Severe dengue in travellers: pathogenesis, risk and clinical management

Halstead, Scott B.; Wilder‐Smith, Annelies

doi:10.1093/jtm/taz062

Cited by 88 publications

(67 citation statements)

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“…Plasmodium and DENV infection are endemic in most tropical and subtropical countries, which are also popular tourist destinations, and these infections are increasingly encountered in travellers who return from areas where malaria is endemic, such as Southeast Asia, Latin America or the Caribbean [ 34 – 36 ]. Those travellers also have a risk of malaria, as the two pathogens share similar geographical areas [ 37 , 38 ], and the clinical diagnosis and distinction of malaria and dengue is difficult due to their overlapping symptoms [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

Prevalence of and risk factors for severe malaria caused by Plasmodium and dengue virus co-infection: a systematic review and meta-analysis

Kotepui

Milanez

et al. 2020

Infect Dis Poverty

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Background Co-infection with both Plasmodium and dengue virus (DENV) infectious species could have serious and fatal outcomes if left undiagnosed and without timely treatment. The present study aimed to determine the pooled prevalence estimate of severe malaria among patients with co-infection, the risk of severe diseases due to co-infection, and to describe the complications of severe malaria and severe dengue among patients with co-infection. Methods Relevant studies published between databases between 12 September 1970 and 22 May 2020 were identified and retrieved through a search of the ISI Web of Science, Scopus, and MEDLINE. The pooled prevalence and 95% confidence interval (CI) of severe malaria among patients with Plasmodium and DENV co-infection was estimated with a random-effects model to take into account the between-study heterogeneity of the included studies. The risks of severe malaria and severe diseases due to co-infection were estimated with the pooled odds ratio (OR) and 95% CI with a random-effects model. Results Of the 5653 articles screened, 13 studies were included in the systematic review and meta-analysis. The results demonstrated that the pooled prevalence estimate of severe malaria among patients with co-infection was 32% (95% CI: 18–47%, I2 = 92.3%). Patients with co-infection had a higher risk of severe diseases than those with DENV mono-infection (odds ratio [OR] = 3.94, 95% CI: 1.96–7.95, I2 = 72%). Patients with co-infection had a higher risk of severe dengue than those with DENV mono-infection (OR = 1.98, 95% CI: 1.08–3.63, I2 = 69%). The most severe complications found in severe dengue were bleeding (39.6%), jaundice (19.8%), and shock/hypotension (17.9%), while the most severe complications found in severe malaria were severe bleeding/bleeding (47.9%), jaundice (32.2%), and impaired consciousness (7.43%). Conclusions The present study found that there was a high prevalence of severe malaria among patients with Plasmodium and DENV co-infection. Physicians in endemic areas where these two diseases overlap should recognize that patients with this co-infection can develop either severe malaria or severe dengue with bleeding complications, but a greater risk of developing severe dengue than severe malaria was noted in patients with this co-infection. Trial registration The protocol of this study was registered at PROSPERO: CRD42020196792.

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Section: Discussionmentioning

confidence: 99%

Prevalence of and risk factors for severe malaria caused by Plasmodium and dengue virus co-infection: a systematic review and meta-analysis

Kotepui

Milanez

et al. 2020

Infect Dis Poverty

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“…Despite the recent dengue spread to the Atlixco-Izucar Valley, most of the patients requiring hospitalization during this outbreak had a previous dengue infection (77% SI), possibly from previous outbreaks in the region. This behavior was expected as SI entails a higher risk of severity than PI (Halstead and Wilder-Smith 2019).…”

Section: Discussionmentioning

confidence: 88%

“…However, severe clinical manifestations, including DSS, have also been reported during primary infection (PI) with some DENV serotypes (Soo et al 2016) and the mechanisms involved in severity remain poorly understood. The relative risk of SD in SI versus PI has been estimated as ranging from 2 to 7 (Halstead and Wilder-Smith 2019).…”

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confidence: 99%

“…PI and SI can be discriminated by analyzing denguespecific immunoglobulins during the acute phase of the infection (first 8 days of symptoms). In PI, IgM is the first isotype to appear, detectable in 50% of patients by day 3 and in 80% by day 5 after symptom onset, followed by IgG detectable at low levels around day 10 (WHO 2009b, Halstead and Wilder-Smith 2019). In SI, IgG is the dominant isotype present at high levels from symptom start, with low or undetectable IgM levels during the acute phase (WHO 2009b).…”

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confidence: 99%

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Primary Dengue Infection in Patients Requiring Hospitalization During an Outbreak in a Low Incidence Mexican Region

Cárdenas-Perea

Flores-Mendoza

Pérez-Contreras

et al. 2020

Vector-Borne and Zoonotic Diseases

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Background: Dengue manifestations can range from subclinical to fatal. The study of factors that influence dengue's clinical severity can provide information to potentially limit or predict severe cases. Secondary infection (SI) with a different dengue serotype has been recognized as an important determinant of severity. However, severe dengue (SD) manifestations, including shock, can happen during primary infection (PI) too and the mechanisms involved are less understood. To characterize the severe manifestations associated to PI, we distinguished between primary and secondary dengue cases in hospitalized patients from a region of low and recent dengue incidence in central Mexico. This region can serve as a model for dengue's behavior as it spreads to new areas worldwide. Methods: Dengue-specific immunoglobulin M (IgM) and IgG concentrations were measured in the serum of 78 hospitalized patients with dengue hemorrhagic fever, and their ratios were used to discriminate between PI and SI, as recommended by World Health Organization. Clinical and laboratory manifestations were compared between PI and SI. Results and Conclusions: PI was detected in 23% of hospitalized dengue cases, a proportion similar to that reported in high-incidence regions in Mexico. PI was more frequent in 16-to 40-year-olds, and was absent in patients older than 60 years. Only dengue with warning signs and SD were present in the studied population of hospitalized patients, and case frequency decreased with clinical severity both in PI and SI groups. No significant differences in demographics, laboratory tests, or symptoms were found between PI and SI, which illustrates that cases requiring hospitalization during outbreaks can be severe, even if they are PI. This information can help plan for sanitary contingencies in places where dengue is recently emergent and numerous PI cases are expected. The mechanisms involved in PI clinical severity need to be studied further.Keywords: dengue primary infection, dengue outbreak, dengue IgG and IgM Introduction D engue is a common infection worldwide, with 4.0 billion people (half the world's population) currently at risk (Brady et al. 2012). It is caused by dengue virus (DENV), an arbovirus (arthropod-borne virus) with four serotypes (DENV-1 to 4) that circulate periodically (Wash et al. 2015). Because of its recent and rapid spread all over the world, DENV is considered an emerging pathogen and it is endemic in at least 128 countries (Brady et al.

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“…Over 25 million people are now at risk of this infection every year that affects world economies [6,7]. This infection affects not only local people, but also travelers who visit high-risk regions [8]. The major fatal cases are caused by the mechanism of antibody-dependent enhancement during the secondary infection by different serotypes [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Target Identification Using Homopharma and Network-Based Methods for Predicting Compounds Against Dengue Virus-Infected Cells

et al. 2020

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Drug target prediction is an important method for drug discovery and design, can disclose the potential inhibitory effect of active compounds, and is particularly relevant to many diseases that have the potential to kill, such as dengue, but lack any healing agent. An antiviral drug is urgently required for dengue treatment. Some potential antiviral agents are still in the process of drug discovery, but the development of more effective active molecules is in critical demand. Herein, we aimed to provide an efficient technique for target prediction using homopharma and network-based methods, which is reliable and expeditious to hunt for the possible human targets of three phenolic lipids (anarcardic acid, cardol, and cardanol) related to dengue viral (DENV) infection as a case study. Using several databases, the similarity search and network-based analyses were applied on the three phenolic lipids resulting in the identification of seven possible targets as follows. Based on protein annotation, three phenolic lipids may interrupt or disturb the human proteins, namely KAT5, GAPDH, ACTB, and HSP90AA1, whose biological functions have been previously reported to be involved with viruses in the family Flaviviridae. In addition, these phenolic lipids might inhibit the mechanism of the viral proteins: NS3, NS5, and E proteins. The DENV and human proteins obtained from this study could be potential targets for further molecular optimization on compounds with a phenolic lipid core structure in anti-dengue drug discovery. As such, this pipeline could be a valuable tool to identify possible targets of active compounds.

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Severe dengue in travellers: pathogenesis, risk and clinical management

Cited by 88 publications

References 147 publications

Prevalence of and risk factors for severe malaria caused by Plasmodium and dengue virus co-infection: a systematic review and meta-analysis

Prevalence of and risk factors for severe malaria caused by Plasmodium and dengue virus co-infection: a systematic review and meta-analysis

Primary Dengue Infection in Patients Requiring Hospitalization During an Outbreak in a Low Incidence Mexican Region

Target Identification Using Homopharma and Network-Based Methods for Predicting Compounds Against Dengue Virus-Infected Cells

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