A machine learning model to assess potential misdiagnosed dengue hospitalization.

Dengue, like other arboviruses with broad clinical spectra, can easily be misdiagnosed as other infectious diseases due to the overlap of signs and symptoms. During large outbreaks, severe dengue cases have the potential to overwhelm the health care system and understanding the burden of dengue hospitalizations is therefore important to better allocate medical care and public health resources. A machine learning model that used data from the Brazilian public healthcare system database and the National Institute of Meteorology (INMET) was developed to estimate potential misdiagnosed dengue hospitalizations in Brazil. The data was modeled into a hospitalization level linked dataset. Then, Random Forest, Logistic Regression and Support Vector Machine algorithms were assessed. The algorithms were trained by dividing the dataset in training/test set and performing a cross validation to select the best hyperparameters in each algorithm tested. The evaluation was done based on accuracy, precision, recall, F1 score, sensitivity, and specificity. The best model developed was Random Forest with an accuracy of 85% on the final reviewed test. This model shows that 3.4% (13,608) of all hospitalizations in the public healthcare system from 2014 to 2020 could have been dengue misdiagnosed as other diseases. The model was helpful in finding potentially misdiagnosed dengue and might be a useful tool to help public health decision makers in planning resource allocation.

Six Cases of Zika/Dengue Coinfection in a Brazilian Cohort, 2015-2019.

Brazil is one of the countries which has been most affected by dengue epidemics. This scenario became more challenging with the emergence of Zika virus after 2014. The cocirculation of dengue and Zika viruses makes their diagnosis and treatment a challenge for health professionals, especially due to their similar clinical outcomes. From 2015 to 2019, we followed a cohort of 2017 participants in Goiania, Goias, Central Brazil. Febrile cases were monitored weekly, and after identification of fever, the physician performed a home visit for clinical evaluation and collection of blood/urine for diagnosis of acute dengue/Zika infection in suspected cases. Dengue acute infection was investigated by NS1 antigen and real time RT-PCR and seroconversion of anti-dengue IgM. ZIKV infection was confirmed by real time RT-PCR. Six cases of Zika/dengue coinfection among participants were reported. The clinical outcomes were suggestive for both DENV and ZIKV infection. No coinfected patient had neurological clinical manifestation, warning signs or need for hospitalization. A continuous specific laboratory confirmation for both dengue and Zika viruses should be enforced as part of the surveillance systems even in the presence of very suggestive cases of dengue fever, minimizing the risk of a late detection of ZIKV circulation.

The decline of dengue in the Americas in 2017: discussion of multiple hypotheses.

OBJECTIVE: Since the 1980s, dengue incidence has increased 30-fold. However, in 2017, there was a noticeable reduction in reported dengue incidence cases within the Americas, including severe and fatal cases. Understanding the mechanism underlying dengue's incidence and decline in the Americas is vital for public health planning. We aimed to provide plausible explanations for the decline in 2017. METHODS: An expert panel of representatives from scientific and academic institutions, Ministry of Health officials from Latin America and PAHO/WHO staff met in October 2017 to propose hypotheses. The meeting employed six moderated plenary discussions in which participants reviewed epidemiological evidence, suggested explanatory hypotheses, offered their expert opinions on each and developed a consensus. RESULTS: The expert group established that in 2017, there was a generalised decreased incidence, severity and number of deaths due to dengue in the Americas, accompanied by a reduction in reported cases of both Zika and chikungunya virus infections, with no change in distribution among age groups affected. This decline was determined to be unlikely due to changes in epidemiological surveillance systems, as similar designs of surveillance systems exist across the region. Although sudden surveillance disruption is possible at a country or regional level, it is unlikely to occur in all countries simultaneously. Retrospective modelling with epidemiological, immunological and entomological information is needed. Host or immunological factors may have influenced the decline in dengue cases at the population level through immunity; however, herd protection requires additional evidence. Uncertainty remains regarding the effect on the outcome of sequential infections of different dengue virus (DENV) types and Zika virus (ZIKV), and vice versa. Future studies were recommended that examine the epidemiological effect of prior DENV infection on Zika incidence and severity, the epidemiological effect of prior Zika virus infection on dengue incidence and severity, immune correlates based on new-generation ELISA assays, and impact of prior DENV/other arbovirus infection on ZIKV immune response in relation to number of infections and the duration of antibodies in relation to interval of protection. Follow-up studies should also investigate whether increased vector control intensification activities contributed to the decline in transmission of one or more of these arboviruses. Additionally, proposed studies should focus on the potential role of vector competence when simultaneously exposed to various arboviruses, and on entomological surveillance and its impact on circulating vector species, with a goal of applying specific measures that mitigate seasonal occurrence or outbreaks. CONCLUSIONS: Multifactorial events may have accounted for the decline in dengue seen in 2017. Differing elements might explain the reduction in dengue including elements of immunity, increased vector control, and even vector and\or viruses changes or adaptations. Most of the results of this expert consensus group meeting are hypothetical and based on limited evidence. Further studies are needed.

OBJECTIF: Depuis les années 1980, l'incidence de la dengue a été multipliée par 30. Cependant, en 2017, il y a eu une réduction notable du nombre de cas d'incidence de dengue rapportés dans les Amériques. Nous voulions fournir des explications plausibles à la baisse en 2017. MÉTHODES: Un groupe d'experts constitué de représentants d'institutions scientifiques et académiques, d'officiels des Ministères de la Santé d'Amérique Latine et de membres du personnel de l'OPS/OMS s'est réuni en octobre 2017 pour proposer et évaluer des hypothèses. RÉSULTATS: En 2017, il y a eu une baisse généralisée de l'incidence, de la sévérité et du nombre de décès dus à la dengue dans les Amériques, accompagnée d'une réduction des cas rapportés d'infections par le virus Zika et par le virus du chikungunya, sans modification dans la répartition entre les groupes d'âge affectés. Il a été déterminé que ce déclin était peu probablement dû aux changements dans les systèmes de surveillance épidémiologique, étant donné que des systèmes de surveillance similaires existaient dans toute la région. Bien que des perturbations soudaines dans la surveillance soient possibles au niveau national ou régional, il est peu probable que cela se produise simultanément dans tous les pays. Une modélisation rétrospective avec des informations épidémiologiques, immunologiques et entomologiques est nécessaire. Des facteurs liés à l'hôte ou immunologiques peuvent avoir influencé le déclin des cas de dengue au niveau de la population par le biais de l'immunité; cependant, l'évidence d'une protection conférée par l'effet du troupeau nécessite des données supplémentaires. Une incertitude subsiste quant à l'effet sur le résultat des infections séquentielles de différents types du virus de la dengue (DENV) et du virus Zika (ZIKV), et vice-versa. Les études à venir devraient examiner (1) l'effet épidémiologique d'une infection antérieure par le DENV sur l'incidence et la sévérité du virus Zika, (2) l'effet épidémiologique d'une infection antérieure par le virus Zika sur l'incidence et la sévérité de la dengue, (3) les corrélats immunitaires basés sur des tests ELISA de nouvelle génération, (4) l' impact d'une infection antérieure à DENV/autres arbovirus sur la réponse immunitaire au ZIKV en fonction du nombre d'infections et de la durée des anticorps en fonction de l'intervalle de protection, (5) si des activités d'intensification de la lutte antivectorielle ont contribué à la diminution de la transmission d'un ou plusieurs de ces arbovirus, (6) le rôle potentiel de la compétence vectorielle lorsqu'ils sont exposés simultanément à différents arbovirus, (7) la surveillance entomologique et son impact sur la circulation d'espèces de vecteurs, dans le but d'appliquer des mesures spécifiques qui réduisent l'occurrence saisonnière d'épidémies. CONCLUSIONS: Des événements multifactoriels pourraient expliquer le déclin observé de la dengue en 2017. La plupart des résultats de cette réunion du groupe de consensus d'experts sont hypothétiques, reposent sur des données limitées et requièrent des investigations supplémentaires.

Development of standard clinical endpoints for use in dengue interventional trials: introduction and methodology.

BACKGROUND: As increasing numbers of dengue vaccines and therapeutics are in clinical development, standardized consensus clinical endpoint definitions are urgently needed to assess the efficacy of different interventions with respect to disease severity. We aimed to convene dengue experts representing various sectors and dengue endemic areas to review the literature and propose clinical endpoint definitions for moderate and severe disease based on the framework provided by the WHO 2009 classification. METHODS: The endpoints were first proposed and discussed in a structured expert consultation. After that, the Delphi method was carried out to assess the usefulness, validity and feasibility of the standardized clinical disease endpoints for interventional dengue research. RESULTS: Most respondents (> 80%) agreed there is a need for both standardized clinical endpoints and operationalization of severe endpoints. Most respondents (67%) felt there is utility for moderate severity endpoints, but cited challenges in their development. Hospitalization as a moderate endpoint of disease severity or measure of public health impact was deemed to be useful by only 47% of respondents, but 89% felt it could bring about supplemental information if carefully contextualized according to data collection setting. Over half of the respondents favored alignment of the standard endpoints with the WHO guidelines (58%), but cautioned that the endpoints could have ramifications for public health practice. In terms of data granularity of the endpoints, there was a slight preference for a categorical vs numeric system (e.g. 1-10) (47% vs 34%), and 74% of respondents suggested validating the endpoints using large prospective data sets. CONCLUSION: The structured consensus-building process was successful taking into account the history of the debate around potential endpoints for severe dengue. There is clear support for the development of standardized endpoints for interventional clinical research and the need for subsequent validation with prospective data sets. Challenges include the complexity of developing moderate disease research endpoints for dengue.

Development of standard clinical endpoints for use in dengue interventional trials.

Dengue is a major public health problem worldwide. Although several drug candidates have been evaluated in randomized controlled trials, none has been effective and at present, early recognition of severe dengue and timely supportive care are used to reduce mortality. While the first dengue vaccine was recently licensed, and several other candidates are in late stage clinical trials, future decisions regarding widespread deployment of vaccines and/or therapeutics will require evidence of product safety, efficacy and effectiveness. Standard, quantifiable clinical endpoints are needed to ensure reproducibility and comparability of research findings. To address this need, we established a working group of dengue researchers and public health specialists to develop standardized endpoints and work towards consensus opinion on those endpoints. After discussion at two working group meetings and presentations at international conferences, a Delphi methodology-based query was used to finalize and operationalize the clinical endpoints. Participants were asked to select the best endpoints from proposed definitions or offer revised/new definitions, and to indicate whether contributing items should be designated as optional or required. After the third round of inquiry, 70% or greater agreement was reached on moderate and severe plasma leakage, moderate and severe bleeding, acute hepatitis and acute liver failure, and moderate and severe neurologic disease. There was less agreement regarding moderate and severe thrombocytopenia and moderate and severe myocarditis. Notably, 68% of participants agreed that a 50,000 to 20,000 mm3 platelet range be used to define moderate thrombocytopenia; however, they remained divided on whether a rapid decreasing trend or one platelet count should be case defining. While at least 70% agreement was reached on most endpoints, the process identified areas for further evaluation and standardization within the context of ongoing clinical studies. These endpoints can be used to harmonize data collection and improve comparability between dengue clinical trials.

Dengue illness index-A tool to characterize the subjective dengue illness experience.

Dengue virus infections are a major cause of febrile illness that significantly affects individual and societal productivity and drives up health care costs principally in the developing world. Two dengue vaccine candidates are in advanced clinical efficacy trials in Latin America and Asia, and another has been licensed in more than fifteen countries but its uptake has been limited. Despite these advances, standardized metrics for comparability of protective efficacy between dengue vaccines remain poorly defined. The Dengue Illness Index (DII) is a tool that we developed thru refinement of previous similar iterations in an attempt to improve and standardize the measurement of vaccine and drug efficacy in reducing moderate dengue illness. The tool is designed to capture an individual's overall disease experience based on how the totality of their symptoms impacts their general wellness and daily functionality. We applied the DII to a diary card, the Dengue Illness Card (DIC), which was examined and further developed by a working group. The card was then refined with feedback garnered from a Delphi methodology-based query that addressed the adequacy and applicability of the tool in clinical dengue research. There was overall agreement that the tool would generate useful data and provide an alternative perspective to the assessment of drug or vaccine candidates, which in the case of vaccines, are assessed by their reduction in any virologically confirmed dengue of any severity with a focus on the more severe. The DIC needs to be evaluated in the field in the context of vaccine or drug trials, prospective cohort studies, or during experimental human infection studies. Here, we present the final DIC resulting from the Delphi process and offer its further development or use to the dengue research community.

Dengue illness index: a tool to characterize the subjective dengue illness experience

Dengue virus infections are a major cause of febrile illness that significantly affects individual and societal productivity and drives up health care costs principally in the developing world. Two dengue vaccine candidates are in advanced clinical efficacy trials in Latin America and Asia, and another has been licensed in more than fifteen countries but its uptake has been limited. Despite these advances, standardized metrics for comparability of protective efficacy between dengue vaccines remain poorly defined. The Dengue Illness Index (DII) is a tool that we developed thru refinement of previous similar iterations in an attempt to improve and standardize the measurement of vaccine and drug efficacy in reducing moderate dengue illness. The tool is designed to capture an individual’s overall disease experience based on how the totality of their symptoms impacts their general wellness and daily functionality. We applied the DII to a diary card, the Dengue Illness Card (DIC), which was examined and further developed by a working group. The card was then refined with feedback garnered from a Delphi methodology-based query that addressed the adequacy and applicability of the tool in clinical dengue research. There was overall agreement that the tool would generate useful data and provide an alternative perspective to the assessment of drug or vaccine candidates, which in the case of vaccines, are assessed by their reduction in any virologically confirmed dengue of any severity with a focus on the more severe. The DIC needs to be evaluated in the field in the context of vaccine or drug trials, prospective cohort studies, or during experimental human infection studies. Here, we present the final DIC resulting from the Delphi process and offer its further development or use to the dengue research community.

Development of standard clinical endpoints for use in dengue interventional trials

Dengue is a major public health problem worldwide. Although several drug candidates have been evaluated in randomized controlled trials, none has been effective and at present, early recognition of severe dengue and timely supportive care are used to reduce mortality. While the first dengue vaccine was recently licensed, and several other candidates are in late stage clinical trials, future decisions regarding widespread deployment of vaccines and/or therapeutics will require evidence of product safety, efficacy and effectiveness. Standard, quantifiable clinical endpoints are needed to ensure reproducibility and comparability of research findings. To address this need, we established a working group of dengue researchers and public health specialists to develop standardized endpoints and work towards consensus opinion on those endpoints. After discussion at two working group meetings and presentations at international conferences, a Delphi methodology-based query was used to finalize and operationalize the clinical endpoints. Participants were asked to select the best endpoints from proposed definitions or offer revised/new definitions, and to indicate whether contributing items should be designated as optional or required. After the third round of inquiry, 70% or greater agreement was reached on moderate and severe plasma leakage, moderate and severe bleeding, acute hepatitis and acute liver failure, and moderate and severe neurologic disease. There was less agreement regarding moderate and severe thrombocytopenia and moderate and severe myocarditis. Notably, 68% of participants agreed that a 50,000 to 20,000 mm3 platelet range be used to define moderate thrombocytopenia; however, they remained divided on whether a rapid decreasing trend or one platelet count should be case defining. While at least 70% agreement was reached on most endpoints, the process identified areas for further evaluation and standardization within the context of ongoing clinical studies. These endpoints can be used to harmonize data collection and improve comparability between dengue clinical trials.

Dengue illness index: a tool to characterize the subjective dengue illness experience

Dengue virus infections are a major cause of febrile illness that significantly affects individual and societal productivity and drives up health care costs principally in the developing world. Two dengue vaccine candidates are in advanced clinical efficacy trials in Latin America and Asia, and another has been licensed in more than fifteen countries but its uptake has been limited. Despite these advances, standardized metrics for comparability of protective efficacy between dengue vaccines remain poorly defined. The Dengue Illness Index (DII) is a tool that we developed thru refinement of previous similar iterations in an attempt to improve and standardize the measurement of vaccine and drug efficacy in reducing moderate dengue illness. The tool is designed to capture an individual’s overall disease experience based on how the totality of their symptoms impacts their general wellness and daily functionality. We applied the DII to a diary card, the Dengue Illness Card (DIC), which was examined and further developed by a working group. The card was then refined with feedback garnered from a Delphi methodology-based query that addressed the adequacy and applicability of the tool in clinical dengue research. There was overall agreement that the tool would generate useful data and provide an alternative perspective to the assessment of drug or vaccine candidates, which in the case of vaccines, are assessed by their reduction in any virologically confirmed dengue of any severity with a focus on the more severe. The DIC needs to be evaluated in the field in the context of vaccine or drug trials, prospective cohort studies, or during experimental human infection studies. Here, we present the final DIC resulting from the Delphi process and offer its further development or use to the dengue research community.

Dengue in pregnant women: characterization of cases in Brazil, 2007-2015. / Dengue em gestantes: caracterização dos casos no Brasil, 2007-2015.

OBJECTIVE: to characterize the probable cases of dengue in pregnant women reported in Brazil, from 2007 to 2015. METHODS: descriptive study of sociodemographic, epidemiological, clinical and laboratory characteristics, with data from the Information System for Notifiable Diseases (Sinan). RESULTS: the annual incidence of dengue in pregnant women ranged from 3.3 (2009) to 816.6 (2010) cases per 100 thousand live births; of the 43,772 probable cases of dengue in pregnant women, 81.6% were investigated, 34.1% were confirmed by laboratory tests, and 1.7% were severe cases; hospitalization and fatality rates were of 5.4% and 1.6‰, respectively; the risk of death due to dengue was higher in pregnant women than in the population of non-pregnant women at reproductive age (ratio=3.95; 95%CI=3.07;5.08), and higher in the third trimester of pregnancy (ratio=8.55; 95%CI=6.08;12.02). CONCLUSION: the results show the burden of dengue in pregnant women and their vulnerability to worsening of the disease and death.

Sensitivity of the Dengue Surveillance System in Brazil for Detecting Hospitalized Cases.

We evaluated the sensitivity of the dengue surveillance system in detecting hospitalized cases in ten capital cities in Brazil from 2008 to 2013 using a probabilistic record linkage of two independent information systems hospitalization (SIH-SUS) adopted as the gold standard and surveillance (SINAN). Sensitivity was defined as the proportion of cases reported to the surveillance system amid the suspected hospitalized cases registered in SIH-SUS. Of the 48,174 hospitalizations registered in SIH-SUS, 24,469 (50.7%) were reported and registered in SINAN, indicating an overall sensitivity of 50.8% (95%CI 50.3-51.2). The observed sensitivity for each of the municipalities included in the study ranged from 22.0% to 99.1%. The combination of the two data sources identified 71,161 hospitalizations, an increase of 97.0% over SINAN itself. Our results allowed establishing the proportion of underreported dengue hospitalizations in the public health system in Brazil, highlighting the use of probabilistic record linkage as a valuable tool for evaluating surveillance systems.

A comparative study on active and passive epidemiological surveillance for dengue in five countries of Latin America.

BACKGROUND: Dengue is a notifiable infectious disease in many countries, but under-reporting of cases to National Epidemiological Surveillance Systems (NESSs) conceals the true extent of the disease burden. The incidence of dengue identified in a cohort study was compared with those reported to NESSs. METHODS: A randomized, placebo-controlled study was undertaken in Brazil, Colombia, Honduras, Mexico, and Puerto Rico to assess the efficacy of a tetravalent dengue vaccine (CYD-TDV) in children aged 9-16 years. The incidence of dengue in the placebo group was compared with that reported to NESSs in a similar age group (10-19 years) from June 2011 to April 2014. RESULTS: Three thousand six hundred and fifteen suspected dengue cases were identified in the study over 13527 person-years of observation. The overall incidence of confirmed dengue was 2.9 per 100 person-years (range 1.5 to 4.1 per 100 person-years). In the NESSs combined, over 3.2 million suspected dengue cases were reported during the same period, corresponding to over 1 billion person-years of observation. The incidence of confirmed dengue reported by the NESSs in the same locality where the study took place was 0.286 per 100 person-years across Brazil, Colombia, and Mexico (range 0.180 to 0.734 per 100 person-years). The incidence of confirmed dengue was 10.0-fold higher in the study than that reported to NESSs in the same localities (range 3.5- to 19.4-fold higher). CONCLUSIONS: There is a substantial under-reporting of dengue in the NESSs. Understanding the level of under-reporting would allow more accurate estimates of the dengue burden in Latin America.

Economic Impact of Dengue: Multicenter Study across Four Brazilian Regions.

BACKGROUND: Dengue is an increasing public health concern in Brazil. There is a need for an updated evaluation of the economic impact of dengue within the country. We undertook this multicenter study to evaluate the economic burden of dengue in Brazil. METHODS: We estimated the economic burden of dengue in Brazil for the years 2009 to 2013 and for the epidemic season of August 2012- September 2013. We conducted a multicenter cohort study across four endemic regions: Midwest, Goiania; Southeast, Belo Horizonte and Rio de Janeiro; Northeast: Teresina and Recife; and the North, Belem. Ambulatory or hospitalized cases with suspected or laboratory-confirmed dengue treated in both the private and public sectors were recruited. Interviews were scheduled for the convalescent period to ascertain characteristics of the dengue episode, date of first symptoms/signs and recovery, use of medical services, work/school absence, household spending (out-of-pocket expense) and income lost using a questionnaire developed for a previous cost study. We also extracted data from the patients' medical records for hospitalized cases. Overall costs per case and cumulative costs were calculated from the public payer and societal perspectives. National cost estimations took into account cases reported in the official notification system (SINAN) with adjustment for underreporting of cases. We applied a probabilistic sensitivity analysis using Monte Carlo simulations with 90% certainty levels (CL). RESULTS: We screened 2,223 cases, of which 2,035 (91.5%) symptomatic dengue cases were included in our study. The estimated cost for dengue for the epidemic season (2012-2013) in the societal perspective was US$ 468 million (90% CL: 349-590) or US$ 1,212 million (90% CL: 904-1,526) after adjusting for under-reporting. Considering the time series of dengue (2009-2013) the estimated cost of dengue varied from US$ 371 million (2009) to US$ 1,228 million (2013). CONCLUSIONS: The economic burden associated with dengue in Brazil is substantial with large variations in reported cases and consequently costs reflecting the dynamic of dengue transmission.

Costing Dengue Fever Cases and Outbreaks: Recommendations from a Costing Dengue Working Group in the Americas.

OBJECTIVES: The overall aim of this article was to present a step-by-step guideline for determining the costs associated with dengue in dengue-endemic countries of the Latin American and the Caribbean region and to illustrate how each of these steps can be applied in dengue costing studies. METHODS: An expert panel was convened to develop standards for costing dengue so that over the next decade, decision makers will have access to improved information on the true cost of dengue in endemic countries of the Latin American and the Caribbean region. We described the outcome of the expert panel meeting, which resulted in the provision of a step-by-step dengue costing guideline that aims to provide direction to planners and program managers on how to estimate dengue economic burden studies, and provide a discussion forum of the methods used to cost dengue fever cases and outbreaks in a manner that should be accessible to persons with some familiarity with a cost study. RESULTS: The guideline includes nine sequential steps: 1) definition of the scope of the study; 2) identification of the target population; 3) description of the study perspective; 4) definition of the time horizon; 5) calculation of the sample size; 6) definition of the unit of analysis; 7) identification of the cost items; 8) measurement and valuation of the cost items; and 9) handling of uncertainty. The trade-off between accurate, patient-level cost estimates and data availability constraints is discussed. CONCLUSIONS: The current guideline is the result of constructive collaboration among a multidisciplinary research team to better ascertain the true economic burden of dengue across countries of the region.

Risk of dengue for tourists and teams during the World Cup 2014 in Brazil.

BACKGROUND: This year, Brazil will host about 600,000 foreign visitors during the 2014 FIFA World Cup. The concern of possible dengue transmission during this event has been raised given the high transmission rates reported in the past by this country. METHODOLOGY/PRINCIPAL FINDINGS: We used dengue incidence rates reported by each host city during previous years (2001-2013) to estimate the risk of dengue during the World Cup for tourists and teams. Two statistical models were used: a percentile rank (PR) and an Empirical Bayes (EB) model. Expected IR's during the games were generally low (<10/100,000) but predictions varied across locations and between models. Based on current ticket allocations, the mean number of expected symptomatic dengue cases ranged from 26 (PR, 10th-100th percentile: 5-334 cases) to 59 (EB, 95% credible interval: 30-77 cases) among foreign tourists but none are expected among teams. These numbers will highly depend on actual travel schedules and dengue immunity among visitors. Sensitivity analysis for both models indicated that the expected number of cases could be as low as 4 or 5 with 100,000 visitors and as high as 38 or 70 with 800,000 visitors (PR and EB, respectively). CONCLUSION/SIGNIFICANCE: The risk of dengue among tourists during the World Cup is expected to be small due to immunity among the Brazil host population provided by last year's epidemic with the same DENV serotypes. Quantitative risk estimates by different groups and methodologies should be made routinely for mass gathering events.

Epidemiological trends of dengue disease in Brazil (2000-2010): a systematic literature search and analysis.

UNLABELLED: A literature survey and analysis was conducted to describe the epidemiology of dengue disease in Brazil reported between 2000 and 2010. The protocol was registered on PROSPERO (CRD42011001826: http://www.crd.york.ac.uk/prospero/display_record.asp?ID=CRD42011001826). Between 31 July and 4 August 2011, the published literature was searched for epidemiological studies of dengue disease, using specific search strategies for each electronic database. A total of 714 relevant citations were identified, 51 of which fulfilled the inclusion criteria. The epidemiology of dengue disease in Brazil, in this period, was characterized by increases in the geographical spread and incidence of reported cases. The overall increase in dengue disease was accompanied by a rise in the proportion of severe cases. The epidemiological pattern of dengue disease in Brazil is complex and the changes observed during this review period are likely to have been influenced by multiple factors. Several gaps in epidemiological knowledge regarding dengue disease in Brazil were identified that provide avenues for future research, in particular, studies of regional differences, genotype evolution, and age-stratified seroprevalence. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number: CRD42011001826.

Dermatological diseases of compulsory notification in Brazil.

The development of a Brazilian National Surveillance System in 1975 led to a compulsory reporting of selected infectious diseases aiming to reduce the burden of these events in the country. However, shifts in the epidemiology of these diseases associated with modern life style, demand constant revision of surveillance activities. In this manuscript we present the epidemiology, trends and differential diagnosis of the following compulsory notifiable diseases in Brazil: Aids, dengue fever, hanseniasis, American tegumentary leishmaniasis, measles, rubella and congenital rubella syndrome and syphilis. Additionally, the current challenges for control and prevention of each disease are presented.

Quality of life among adults with confirmed dengue in Brazil.

The main objective of this study was to measure the quality of life (QoL) during a dengue episode. We conducted a facility-based survey in central Brazil in 2005 and recruited 372 laboratory-confirmed dengue patients greater than 12 years of age in hospital and ambulatory settings. We administered the World Health Organization QoL instrument approximately 15 days after the onset of symptoms. We used principal component analysis with varimax rotation to identify domains related to QoL. The median age of interviewees was 36 years. Most (85%) reported their general health status as very good or good before the dengue episode. Although ambulatory patients were mainly classified as having dengue fever, 44.8% of hospitalized patients had dengue hemorrhagic fever or intermediate dengue. Principal component analysis identified five principal components related to cognition, sleep and energy, mobility, self-care, pain, and discomfort, which explained 73% of the variability of the data matrix. Hospitalized patients had significantly lower mean scores for dimensions cognition, self-care, and pain than ambulatory patients. This investigation documented the generally poor QoL during a dengue episode caused by the large number of domains affected and significant differences between health care settings.

Is routine dengue vector surveillance in central Brazil able to accurately monitor the Aedes aegypti population? Results from a pupal productivity survey.

OBJECTIVE: To assess how well the Aedes aegypti infestation rapid survey, Levantamento Rapido de Indice para Aedes aegypti (LIRAa), is able to accurately estimate dengue vector densities and target the most important breeding sites in Goiania, Brazil. METHODS: In February 2009, a pupal productivity survey was conducted in 2 districts of the city of Goiania, central Brazil. The results were compared to those of LIRAas conducted in the same districts during the months before and after the pupal productivity survey. RESULTS: In the pupal productivity survey, 2,024 houses were surveyed and 2,969 water-holding containers were inspected. Discarded small water containers most frequently contained immature Ae. aegypti. The most pupal-productive containers were elevated water tanks, roof gutters and water holding roofs. Combined, these three containers accounted for <40% of all positive containers but produced >70% of all pupae. In the two districts where the pupal productivity survey was conducted, the house indices were 5.1 and 4.6 and the Breteau indices were 5.9 and 6.0. In contrast, the two LIRAs conducted in the same two districts resulted in an average house index of 1.5 and Breteau index of 2.5, with discarded items identified as the most frequently infested container type. CONCLUSION: Both the LIRAa and the pupal productivity survey identified discarded items as being most frequently infested with immature stages of Ae. aegypti, but the pupal productivity survey showed that elevated containers produced the greatest proportion of Ae. aegypti pupae (a proxy measure of adult vector density) and that the values of the Stegomyia indices were substantially underestimated by LIRAa. Although both surveys differ considerably in terms of sampling method and manpower, in the case of this study the LIRAa did not accurately identify or target the containers that were the most important to adult mosquito production.

Dengue and dengue hemorrhagic fever among adults: clinical outcomes related to viremia, serotypes, and antibody response.

BACKGROUND: Clinical manifestations of dengue vary in different areas of endemicity and between specific age groups, whereas predictors of outcome have remained controversial. In Brazil, the disease burden predominantly affects adults, with an increasing trend toward progression to dengue hemorrhagic fever (DHF) noted. METHODS: A cohort of adults with confirmed cases of dengue was recruited in central Brazil in 2005. Patients were classified according to the severity of their disease. Associations of antibody responses, viremia levels (as determined by real-time polymerase chain reaction [PCR]), and serotypes (as determined by multiplex PCR) with disease severity were evaluated. RESULTS: Of the 185 symptomatic patients >14 years of age who had a confirmed case of dengue, 26.5% and 23.2% were classified as having intermediate dengue fever (DF)/DHF (defined as internal hemorrhage, plasma leakage, manifested signs of shock, and/or thrombocytopenia [platelet count, < or =50,000 platelets/mm3]) and DHF, respectively. The onset of intermediate DF/DHF and DHF occurred at a late stage of disease, around the period of defervescence. Patients with DHF had abnormal liver enzyme levels, with a >3-fold increase in aspartate aminotransferase level, compared with the range of values considered to be normal. Overall, 65% of patients presented with secondary infections with dengue virus, with such infection occurring in similar proportions of patients in each of the 3 disease category groups. Dengue virus serotype 3 (DV3) was the predominant serotype, and viremia was detected during and after defervescence among patients with DHF or intermediate DF/DHF. CONCLUSIONS: Viremia was detected after defervescence in adult patients classified as having DHF or intermediate DF/DHF. Secondary infection was not a predictor of severe clinical manifestation in adults with infected with the DV3 serotype.