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- Duong, Veasna, et al.
(författare)
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Clinical and virological factors influencing the performance of a NS1 antigen-capture assay and potential use as a marker of dengue disease severity
- 2011
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Ingår i: PLoS Neglected Tropical Diseases. - : Public Library of Science. - 1935-2727 .- 1935-2735. ; 5:7
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Tidskriftsartikel (refereegranskat)abstract
- Background: Detection of dengue NS1 antigen in acute infection has been proposed for early diagnosis of dengue disease. The aim of this study was to evaluate the clinical and virological factors influencing the performance of the Platelia NS1 Ag kit (BioRad) and to assess the potential use of NS1 antigen and dengue viral loads as markers of dengue disease severity.Methodology/Principal Findings: Blood specimens were collected from patients hospitalized at the Kampong Cham hospital during the 2006 and 2007 dengue epidemics in Cambodia. Dengue infection was confirmed in 243/339 symptomatic patients and in 17 asymptomatic individuals out of 214 household members tested. Overall sensitivity and specificity of Platelia NS1 Ag kit were 57.5% and 100% respectively. NS1 Ag assay combined with IgM antibody capture ELISA significantly increased the sensitivity for dengue diagnosis. NS1 Ag positivity rate was found significantly higher in DF than in DHF/DSS, in primary than in secondary infections, in patients with a high viremia (>5 log/mL) and in patients infected with DENV-1. In asymptomatic individuals, the NS1 Ag capture sensitivity tends to be lower than that in symptomatic patients. Milder disease severity was observed independently in patients with RNA copy number >5 log10 cDNA equivalents/mL or in high level of NS1 antigen ratio or in DENV-1 infection.Conclusions: Overall sensitivity of NS1 Ag detection kit varied widely across the various forms of dengue infection or disease. Sensitivity was highest in patients sampled during the first 3 days after onset of fever, in patients with primary infection, DENV-1 infection, with high level of viremia and in DF rather than DHF/DSS. In asymptomatic patients, RT-PCR assay has proved to be more sensitive than NS1 antigen detection. The NS1 antigen level correlated significantly with viremia and a low NS1 antigen ratio was associated with more severe disease.Author Summary: Dengue is the most prevalent arthropod-borne disease in tropical regions. The clinical manifestation may vary from asymptomatic to potentially fatal dengue shock syndrome. Early laboratory confirmation of dengue diagnosis is essential since many symptoms are not specific. Dengue non-structural protein 1 (NS1) may be used in simple antigen-capture ELISA for early detection of dengue virus infection. Our result demonstrated that the Platelia NS1 antigen detection kit had a quite low overall sensitivity. However, sensitivity rises significantly when used in combination with MAC-ELISA. When taking into account the various forms of dengue infection, the NS1 antigen detection was found relatively high in patients sampled during the first 3 days of fever onset, in patients with primary infection, DENV-1 infection, with high level of viremia and in mild form of dengue fever. In asymptomatically infected individuals, RT-PCR assay has proved to be more sensitive than NS1 antigen detection. Moreover, the NS1 antigen level correlated significantly with high viremia and low level of NS1 antigen was associated with more severe disease.
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| 2. |
- Haemig, Paul D., et al.
(författare)
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Forecasting risk of tick-borne encephalitis (TBE): Using data from wildlife and climate to predict next year's number of human victims
- 2011
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Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 1651-1980 .- 0036-5548. ; 43:5, s. 366-372
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Tidskriftsartikel (refereegranskat)abstract
- Background: Over the past quarter century, the incidence of tick-borne encephalitis (TBE) has increased in most European nations. However, the number of humans stricken by the disease varies from year to year. A method for predicting major increases and decreases is needed. Methods: We assembled a 25-y database (1984-2008) of the number of human TBE victims and wildlife and climate data for the Stockholm region of Sweden, and used it to create easy-to-use mathematical models that predict increases and decreases in the number of humans stricken by TBE. Results: Our best model, which uses December precipitation and mink (Neovison vison, formerly Mustela vison) bagging figures, successfully predicted every major increase or decrease in TBE during the past quarter century, with a minimum of false alarms. However, this model was not efficient in predicting small increases and decreases. Conclusions: Predictions from our models can be used to determine when preventive and adaptive programmes should be implemented. For example, in years when the frequency of TBE in humans is predicted to be high, vector control could be intensified where infested ticks have a higher probability of encountering humans, such as at playgrounds, bathing lakes, barbecue areas and camping facilities. Because our models use only wildlife and climate data, they can be used even when the human population is vaccinated. Another advantage is that because our models employ data from previously-established databases, no additional funding for surveillance is required.
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| 3. |
- Jourdain, Elsa, et al.
(författare)
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Surveillance for West Nile virus in wild birds from northern Europe.
- 2011
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Ingår i: Vector Borne and Zoonotic Diseases. - : Mary Ann Liebert Inc. - 1530-3667 .- 1557-7759. ; 11:1, s. 77-79
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Tidskriftsartikel (refereegranskat)abstract
- A total of 1935 migratory birds from 104 different species were captured in southeastern Sweden in 2005-2006 and tested for antibodies against West Nile virus (WNV). Overall, 46 birds (2.4%; binomial confidence limits, 1.8-3.2) were positive by blocking-ELISA, but only 2 (0.10%; binomial confidence limits, 0.0-0.4) had antibodies detectable by both blocking-ELISA and WNV neutralization test. ELISA-positive birds included long- and short-distance migrants likely exposed to WNV while wintering in or migrating through areas enzootic for WNV. Exposure to a cross-reactive Flavivirus was suspected for short-distance migrants of the Turdidae family, but no cross-neutralization with tick-borne encephalitis and Usutu viruses was observed.
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| 4. |
- Järhult, Josef D., et al.
(författare)
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Environmental levels of the antiviral oseltamivir induce development of resistance mutation H274Y in influenza A/H1N1 virus in mallards
- 2011
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Ingår i: PLOS ONE. - San Francisco, CA : Public Library of Science (PLoS). - 1932-6203. ; 6:9
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Tidskriftsartikel (refereegranskat)abstract
- Oseltamivir (Tamiflu®) is the most widely used drug against influenza infections and is extensively stockpiled worldwide as part of pandemic preparedness plans. However, resistance is a growing problem and in 2008-2009, seasonal human influenza A/H1N1 virus strains in most parts of the world carried the mutation H274Y in the neuraminidase gene which causes resistance to the drug. The active metabolite of oseltamivir, oseltamivir carboxylate (OC), is poorly degraded in sewage treatment plants and surface water and has been detected in aquatic environments where the natural influenza reservoir, dabbling ducks, can be exposed to the substance. To assess if resistance can develop under these circumstances, we infected mallards with influenza A/H1N1 virus and exposed the birds to 80 ng/L, 1 µg/L and 80 µg/L of OC through their sole water source. By sequencing the neuraminidase gene from fecal samples, we found that H274Y occurred at 1 µg/L of OC and rapidly dominated the viral population at 80 µg/L. IC₅₀ for OC was increased from 2-4 nM in wild-type viruses to 400-700 nM in H274Y mutants as measured by a neuraminidase inhibition assay. This is consistent with the decrease in sensitivity to OC that has been noted among human clinical isolates carrying H274Y. Environmental OC levels have been measured to 58-293 ng/L during seasonal outbreaks and are expected to reach µg/L-levels during pandemics. Thus, resistance could be induced in influenza viruses circulating among wild ducks. As influenza viruses can cross species barriers, oseltamivir resistance could spread to human-adapted strains with pandemic potential disabling oseltamivir, a cornerstone in pandemic preparedness planning. We propose surveillance in wild birds as a measure to understand the resistance situation in nature and to monitor it over time. Strategies to lower environmental levels of OC include improved sewage treatment and, more importantly, a prudent use of antivirals.
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| 5. |
- Kindberg, Elin, et al.
(författare)
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A Functional Toll-Like Receptor 3 Gene (TLR3) May Be a Risk Factor for Tick-borne Encephalitis Virus (TBEV) Infection
- 2011
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Ingår i: JOURNAL OF INFECTIOUS DISEASES. - : University of Chicago Press. - 0022-1899 .- 1537-6613. ; 203:4, s. 523-528
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Tidskriftsartikel (refereegranskat)abstract
- Background. Tick-borne encephalitis virus (TBEV) infections may be asymptomatic or cause severe symptoms in the central nervous system. A mutation in the chemokine receptor 5 gene has been associated with increased risk of TBE but explains only a limited number of cases. Investigations of further risk factors are needed. Method. To investigate the importance of the innate immune response, we analyzed 128 TBE patients, 77 patients with aseptic meningoencephalitis (AME) and 135 healthy controls, for 3mutations: 2 in the Toll-like receptor 3 (TLR3) gene and 1 in the 2-5-oligoadenylate synthetase (OAS1) gene. Results. Although no association was found between the mutation in the OAS1 gene and TBE, the genotype distribution ofrs3775291, a mutation in TLR3, differed significantly between TBE patients and controls; 61%, 32%, and 7% of the TBE patients were carriers of the wild-type, heterozygous, and mutant genotype of rs3775291, respectively. The corresponding percentages among healthy controls (n = 126) were 52%, 29%, and 19% (P = .02), and among AME patients (n = 75) were 47%, 32%, and 21% (P = .009). Additionally, the wild-type rs3775291 allele was more common among TBE patients than among healthy controls (allele frequency, .768 vs .663; P = .01). Conclusion. A functional TLR3 is a risk factor for TBEV infection.
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