Human genetic determinants of dengue virus susceptibility

Coffey, Lark L.; Mertens, Eva; Bréhin, Anne-Claire; Fernandez-Garcia, Maria Dolores; Amara, Ali; Desprès, Philippe; Sakuntabhai, Anavaj

doi:10.1016/j.micinf.2008.12.006

Cited by 115 publications

(87 citation statements)

References 64 publications

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“…On the other hand, people without symptoms may be more likely to visit multiple locations during their daily routines where they are cumulatively bitten by more mosquitoes than sick people who are hospitalized or who stay at home and are exposed to only their resident mosquitoes (24). Additional sources of heterogeneity to consider include duration of the mosquito's EIP (25), genetic variation among DENV strains, and intrinsic differences among human and mosquito populations (26,27).…”

Section: Discussionmentioning

confidence: 99%

Asymptomatic humans transmit dengue virus to mosquitoes

Duong

Lambrechts

Rácz

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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399

367

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Three-quarters of the estimated 390 million dengue virus (DENV) infections each year are clinically inapparent. People with inapparent dengue virus infections are generally considered dead-end hosts for transmission because they do not reach sufficiently high viremia levels to infect mosquitoes. Here, we show that, despite their lower average level of viremia, asymptomatic people can be infectious to mosquitoes. Moreover, at a given level of viremia, DENV-infected people with no detectable symptoms or before the onset of symptoms are significantly more infectious to mosquitoes than people with symptomatic infections. Because DENV viremic people without clinical symptoms may be exposed to more mosquitoes through their undisrupted daily routines than sick people and represent the bulk of DENV infections, our data indicate that they have the potential to contribute significantly more to virus transmission to mosquitoes than previously recognized.mosquito experimental infection | Cambodia | Aedes aegypti | human-to-mosquito transmission | dengue W ith 3.97 billion people living in 128 countries currently at risk for infection, dengue viruses (DENV-1 to -4) cause more human morbidity and mortality worldwide than any other arthropod-borne virus (1, 2). Aedes aegypti mosquitoes are the primary vectors of DENV throughout the tropics (3). Dengue prevention relies on the control of Ae. aegypti populations, which is failing in most parts of the world due to lack of resources, lack of political will, and/or ineffective implementation (4).Virus transmission from infected humans to mosquitoes is a critical step in dengue epidemiology, but due to logistical constraints it has been directly examined only in a handful of studies to date (5). In initial experimental infections of human volunteers during the 1920s (6, 7), the onset of clinical symptoms occurred 4-9 d after virus inoculation by mosquito bite (8). DENV-infected humans were infectious to mosquitoes from 2 d before to 2 d after the onset of symptoms, and Ae. aegypti fed on viremic people were able to transmit virus to another person after at least 11 d of extrinsic incubation (8). Results from later studies indicated that, for naturally infected people with clinically apparent dengue, the duration of detectable viremia was on average 4-5 d after the onset of symptoms, but could range from 2 to 12 d (9, 10). Investigators in Vietnam fed Ae. aegypti directly on 208 symptomatic, hospitalized dengue patients and reported that the probability of successful human-to-mosquito DENV transmission was coincident with the kinetics of viremia (11). Dengue patients were infectious up to 5 d after the onset of symptoms, which generally corresponded with "defervescence" (11).All previous studies on human-to-mosquito DENV transmission were limited to people with overt illness and did not consider subclinical infections. An estimated 300 million of the total 390 million DENV infections per year are clinically inapparent or mildly symptomatic, i.e., no illness that disrupted a person's ...

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Section: Discussionmentioning

confidence: 99%

Asymptomatic humans transmit dengue virus to mosquitoes

Duong

Lambrechts

Rácz

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

399

367

View full text Add to dashboard Cite

show abstract

“…Some HLA alleles are suggested to be associated with different clinical phenotypes of dengue. 90 In addition, there is a suggestion of an association between HLA allele and susceptibility to specific dengue serotypes, for example DENV-1 and HLA *0207 and DENV-2 and HLA *B52. 91 In addition some associations appear to be protective, for example HLA DR alleles in Mexican and Vietnamese populations.…”

Section: Genetic Determinants Of Dengue Susceptibilitymentioning

confidence: 99%

“…Despite these limitations in study design, various single nucleotide polymorphisms (SNPs) have been associated with both protection and vulnerability to dengue infection. 90 The vitamin D receptor modulates the immune response by stimulating cell-mediated immunity and inhibiting lymphocyte proliferation; a polymorphism in the receptor appears to protect against severe dengue. 94 The Fc receptor mediates entry of antibody-coated DENV into target cells; the same study demonstrated that homozygotes for the arginine variant at position 131 of the Fc receptor gene may also be protected from severe disease.…”

Section: Genetic Determinants Of Dengue Susceptibilitymentioning

confidence: 99%

The pathogenesis of dengue

Whitehorn

Simmons

2011

Vaccine

222

185

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“…All the patients survived during 2005, but 4.55%, 25%, and 2.7% of patients died during 2006-2008. Therefore, the highest mortality rate (25%) occurred during 2007, when 25% of patients had Hb levels < 5g/dL, and 50% had severe thrombocytopenia (11)(12)(13)(14)(15)(16)(17)(18)(19)(20),000 platelets/μL). Consequently, 25% of patients required blood and platelet transfusions.…”

Section: Comparison Of the Significant Differences In Clinical Presenmentioning

confidence: 99%

Clinical profile of dengue fever infection in King Abdul Aziz University Hospital Saudi Arabia

Ahmed

2010

J Infect Dev Ctries

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Background: The study aimed to compare the clinical profile of all patients diagnosed with dengue viral infection at King Abdul Aziz University Hospital (KAAUH), during [2005][2006][2007][2008]. Methodology: This retrospective study included 147 patients infected with dengue virus, age ≤ 16 years. Laboratory and haematological data were included. Results: Two peaks of infection occurred during 2006 and another two in 2008. Common clinical symptoms were fever, vomiting, and abdominal pain. Common haematological abnormalities were thrombocytopenia and leucopoenia. Differences existed between the years in the percentage of patients with fever, elevated alanine aminotransferase (ALT), direct bilirubin, lactate dehydrogenase (LDH), fibrin degradation products (FDPs), and haemoglobin (Hb) levels. Differences were found in nationalities between the years, but patient nationality had no effect on disease incidence. Differences were noted in the percentages of patients' immunoglobulin M (IgM) and polymerase chain reaction (PCR) positive. There was a slight inverse correlation of IgM positive with patient age. PCR, fever, ALT, direct bilirubin, LDH, FDPs, Hb, blood transfusion, and platelet transfusion showed no correlation with age or nationality. In 2005, all the patients survived, but there were 4.55%, 25%, and 2.7% deaths during 2006-2008. Conclusions: Significant differences in the clinical presentation of dengue virus (DENV) infection, indicative of a variation in disease severity from dengue fever (DF) to dengue hemhorrhagic fever (DHF)/dengue shock syndrome (DSS), were noted over the years. Possible reasons are infection with different serotypes, concurrent/sequential infection of more than one serotype, and differences in host immune responses associated with host genetic variations.

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Human genetic determinants of dengue virus susceptibility

Cited by 115 publications

References 64 publications

Asymptomatic humans transmit dengue virus to mosquitoes

Asymptomatic humans transmit dengue virus to mosquitoes

The pathogenesis of dengue

Clinical profile of dengue fever infection in King Abdul Aziz University Hospital Saudi Arabia

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