Dengue virus infection and leptospirosis represent important causes of acute febrile illness whose diagnosis and management in resource-poor settings remains challenging. Both diseases are potentially fatal, and represent important causes of morbidity and mortality globally. As emerging or re-emerging vector- and water-borne pathogens, respectively, dengue and leptospirosis are increasingly important considerations in patients with acute febrile illness, particularly in the context of decreasing malaria transmission in many areas of the world [1]. The burden of illness attributable to dengue viruses is estimated to be million annually [2].

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A systematic literature review was conducted to describe the epidemiology of dengue disease in Colombia. Studies in English or Spanish published between 1 January and 23 February were included. The searches identified relevant citations, 30 of which fulfilled the inclusion criteria defined in the review protocol. The geographical spread of dengue disease cases showed a steady increase, with most of the country affected by the outbreak.

Gaps identified in epidemiological knowledge regarding dengue disease in Colombia may provide several avenues for future research, namely studies of asymptomatic dengue virus infection, primary versus secondary infections, and under-reporting of the disease.

Improved understanding of the factors that determine disease expression and enable improvement in disease control and management is also important. Dengue disease is caused by one of four serologically related, but antigenically distinct dengue virus serotypes DENV-1, -2, -3 or It is the most prevalent arthropod-borne viral disease, with a global distribution. Resource-poor countries are particularly vulnerable to transmission of dengue disease and it is present throughout the Americas.

Colombia is one of the countries in the Americas most affected by epidemics of dengue disease, which is a significant public health concern. We conducted this systematic literature review to consolidate knowledge regarding the epidemiology of dengue disease in Colombia using well-defined methods to search and identify relevant research, according to predetermined inclusion criteria.

The findings reveal that despite vector control measures and constant improvement in diagnosis and clinical management of dengue disease cases by health services, there has been no success in the effective control of the disease. This systematic review identifies important epidemiological characteristics of dengue disease in Colombia, as well as identifying several avenues for future research.

This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: Sanofi Pasteur sponsored this survey and analysis. The Literature Review Group including members of Sanofi Pasteur were responsible for the conception of the literature analysis, development of the protocol, data collection, analysis and interpretation of data, provision of critical comments, writing the paper and approving the final version to be published.

This does not alter our adherence to all PLOS policies on sharing data and materials. All authors confirm that they had full access to all data and had final responsibility for the decision to submit for publication. Dengue disease is the most prevalent arthropod-borne viral disease in humans and is caused by any one of four serologically related, but antigenically distinct dengue virus serotypes DENV-1, -2, -3 or The primary vector for viral transmission is the Aedes aegypti Linnaeus mosquito.

Dengue disease is a rapidly increasing public health priority with a global distribution. Resource-poor countries are particularly vulnerable to transmission of dengue disease [ 1 ], and it is present in urban and suburban areas in the Americas, eastern Mediterranean, western Pacific, South-East Asia and mainly rural areas in Africa [ 2 ]. However, a new classification was proposed by the WHO in based on levels of severity: non-severe dengue disease with or without warning signs, and severe dengue disease, which encompasses DHF and DSS [ 4 ].

The WHO estimates that more than 50 million dengue virus infections and 20, dengue disease-related deaths occur annually worldwide [ 2 , 5 ]. A recent disease distribution model using a boosted regression tree framework estimated there to be million dengue disease infections in , of which 96 million are clinically apparent [ 1 ]. In , the countries of the Americas notified in excess of 1. In Colombia, Ae.

Approximately 23 million individuals are considered to be at-risk areas for dengue disease, [ 7 ] however, recent reports of dengue disease and Ae. Colombia has about 46 million inhabitants. Its land area is 1,, km 2 , and three branches of the Andean mountain range dominate its topography [ 6 ]. These regions also have some distinct demographic, socio-economic, political and cultural features. Colombia comprises 32 administrative states called departments that vary considerably in geographical area and size of population.

Historically, Colombia is one of the countries in the Americas most affected by epidemics of dengue disease [ 9 , 10 ], first recognized as a significant public-health target in the s [ 11 ]. Although the number of annual DF cases ranged from 6, to 17, during the s [ 13 ], there was a clear increase over the decade which continued through the s, with large outbreaks documented in , , and Between and , more than 1, cases of DHF were reported and the frequency of fatal infections increased rapidly [ 15 ].

DENV-3 is generally believed to have been absent from most of Colombia throughout the s and s [ 12 , 16 ] re-emerging during the outbreak [ 7 , 17 ]. Probable and confirmed cases are reported weekly, and cases of serious dengue disease and mortality due to dengue disease are notified immediately. Not all cases of dengue disease are laboratory-confirmed, although all deaths due to dengue disease must be confirmed [ 19 ]. The sentinel surveillance system that began in comprises sentinel institutions that routinely test five patients each week to monitor circulating DENV serotypes.

In , the surveillance system for dengue disease in Colombia began to transition from collective to individual notification. Both systems were used until , after which the collective notification system was no longer used. Discrepancies between local and national data sources may have arisen during the transition period.

The newer system generates more data, contributing to an enhanced knowledge of dengue disease in Colombia. Since , the Instituto Nacional de Salud has provided regular disease updates through weekly bulletins and annual reports detailing national and regional incidence information and annual data for dengue-related deaths.

Case definitions of dengue disease used in Colombia were changed in January , as the new WHO definitions of dengue disease were adopted [ 7 ]. Our systematic literature review describes the epidemiology of dengue disease in Colombia between 1 January and 23 February in the context of national and regional state and district trends.

Incidence by age and sex , seroprevalence and serotype distribution, and other relevant epidemiological data are described. We also identify gaps in epidemiological knowledge, and aim to provide a basis for defining research priorities for epidemiological studies of the disease and inform evidence-based policies in dengue disease prevention.

A Literature Review Group, comprised of epidemiology and dengue specialists, developed a protocol based on previous literature surveys and analyses [ 21 ]. The protocol reflects the preferred reporting items of systematic literature reviews and meta-analyses PRISMA guidelines [ 22 ] and details well-defined methods to search, identify and select relevant research, and predetermined inclusion criteria to guide study selection.

Papers, theses, dissertations, reports, statistical tables, official web sites and grey materials e. A heterogeneous group of articles with respect to data selection and classification of cases was anticipated. As these would not be methodologically comparable, a meta-analysis was not planned. Searches for epidemiological data relating to dengue disease in Colombia were conducted in a broad range of online sources S1 Table between 9 February and 23 February To help increase sensitivity and specificity, combinations of different search strings were used for each electronic database.

Sources were included or excluded according to the criteria defined by the Literature Review Group, which also guided the search and selection process described below, reaching consensus via teleconferences. The criteria allowed for the inclusion of sources containing information related to general epidemiological indicators of dengue disease incidence and seroprevalence ; intensity of dengue epidemics frequency of hospitalization and severity of attack , populations at increased risk of dengue disease, dengue serotype information, geography of dengue disease and dengue surveillance systems.

To reduce selection bias, studies published in English or Spanish between 1 January and 23 February were included. This systematic review utilised a protocol common to other reviews in this collection.

Within that protocol it was estimated that at least one decade of data would be necessary to provide an accurate image of recent evolution of epidemiology and to observe serotype distribution over time and through several epidemics and to limit any bias that might be introduced by changes in surveillance practices over time; 1 January was selected as the lower end of the date range for this systematic review due to the sentinel surveillance system in Colombia also began in and because a summary country surveillance data was presented into the introduction The 23 February cut-off date reflects when the searches for this systematic review began.

No limits by sex, age and ethnicity of study participants or by study type were imposed, although single-case reports and studies that only reported data for the period before 1 January were excluded. To reduce repetition of published data repeated in meta-analyses or review publications, these duplicate data sets were excluded, unless reporting different outcome measures. Unpublished reports were included if they were identified in one of the sources listed in S1 Table.

Data from other sources were included to complement articles selected in the primary systematic literature review: online reports and guidelines published by relevant organizations; papers and posters from infectious disease, tropical medicine or paediatric conferences; and grey literature were identified through general internet searches e.

Google and Yahoo; limited to the first 50 search results. Publications not identified by the approved search strategy and unpublished data sources meeting the inclusion criteria were included if recommended by members of the Literature Review Group. Following removal of duplicate citations, the Literature Review Group evaluated the list of titles and abstracts, and selected articles considered potentially relevant.

A second review was undertaken on the full texts of these documents to select the final list of relevant articles. The Literature Review Group ensured each study complied with the search inclusion and exclusion criteria. Articles and other data sources were not excluded or formally ranked on the basis of the quality of evidence. Although we recognize that assessment of study quality can potentially add value to a systematic literature review, the consensus of the Literature Review Group was that, in this instance, quality assessment would not add value given the expected high proportion of surveillance data among the available data sources and the nature of surveillance data passive reporting of clinically suspected dengue disease.

We therefore retained all available data sources that met our criteria. The data extraction instrument developed and used for a systematic literature review conducted for Brazil [ 21 ] was used to collate and summarize the selected data sources in the form of a series of Excel Microsoft Corp.

Data were extracted into the spreadsheets according to the following categories for descriptive review: incidence, age, sex and serotype distribution, serotype data, seroepidemiology or seasonality and environmental factors, by national or regional groups. Data from literature reviews of previously published peer-reviewed studies and pre data published within the search period were not extracted. All members of the Literature Review Group had the opportunity to review and analyse the original data sources and extraction tables.

No attempt was made to contact researchers for additional information. Searches identified relevant citations, following the initial removal of duplicates and papers not matching the study criteria 63 papers were evaluated. Of these 33 were excluded after detailed review of the publication because on further examination data collection occurred outside the search criteria date range, they contained little epidemiological data relevant to the study objectives or because they provided similar but less extensive data to that provided by sources already included and thus provided insufficient information to be included in the review.

Some studies were excluded for more than one of these reasons. Consequently, 30 dengue-related sources were included Fig. Six were cross-sectional studies usually limited to specific geographic regions. Only two prospective studies were identified, four studies were phylogenetic studies and one was a disease awareness survey.

The searches identified relevant citations, 28 of which were dengue-related sources fulfilling the inclusion criteria. All references identified in the on-line database searches were assigned a unique identification number.

Following the removal of duplicates and articles that did not satisfy the inclusion criteria from review of the titles and abstracts, the full papers of the first selection of references were retrieved either electronically or in paper form. A further selection was made based on review of the full text of the articles.

Between and , the annual number of non-severe dengue disease cases reported in nationwide surveillance data ranged between 22, and , Fig.

The epidemiology of dengue disease in Colombia was characterized by fluctuations in the number of DF cases there was a slight baseline increase over time with major outbreaks in — and Widespread dengue disease epidemics were observed during — and A significant outbreak of dengue disease occurred between and The annual number of severe dengue disease was highest in , and lowest in A significant outbreak of dengue disease occurred between and Fig.

In this outbreak, the annual number of cases of severe dengue disease peaked in approximately 6, cases and 5,—5, cases [ 7 , 23 ]. During the period —, the annual number of cases was within the range 22,—39, Fig. A slight increase in the number of notified cases of non-severe dengue disease was observed in [ 7 ] 44, [ 26 ]; 41, [ 27 ]. A record number of cases of non-severe dengue disease was reported for range: , [ 7 , 27 ]—, [ 22 ].

The estimated incidence was per , population [ 7 , 28 ] Fig. Fewer than half of the cases were confirmed using serological or virological tests.


Why are people with dengue dying? A scoping review of determinants for dengue mortality

Metrics details. Dengue is a viral disease whose clinical spectrum ranges from unapparent to severe forms and fatal outcomes. We consider that, along with biological factors, social determinants of health SDHs are related to dengue deaths as well. A scoping review was conducted to explore what has been written about the role of SDHs in dengue mortality. The inclusion criteria were that documents grey or peer-reviewed had to include information about dengue fatal cases in humans and be published between and and written in English, Spanish, Portuguese or French. Information on SDHs was categorized under individual, social and environmental, and health systems dimensions. A summative content analysis using QDA Miner was conducted to assess the frequency of information on SDHs and its contextual meaning in the reviewed literature.


Host biomarkers distinguish dengue from leptospirosis in Colombia: a case-control study


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