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Serum proteome changes in dengue virus-infected patients from a dengue-endemic area of India: towards new molecular targets?

ABSTRACT: The global burden of dengue continues to worsen, specifically in tropical and subtropical countries, and has evolved as a major public health problem. We investigated the changes in serum proteome in dengue fever (DF) patients from a dengue-endemic area of India to obtain mechanistic insights about the disease pathogenesis, the host immune response, and identification of potential serum protein biomarkers of this infectious disease. In this study, serum samples from DF patients, healthy subjects, and patients with falciparum malaria (an infectious disease control) were investigated by 2D-DIGE in combination with MALDI-TOF/TOF MS. The findings were validated with Western blotting. Functional clustering of the identified proteins was performed using PANTHER and DAVID tools. Compared to the healthy controls, we found significant changes in the expression levels of 48 protein spots corresponding to 18 unique proteins (7 downregulated and 11 upregulated) in DF patients (p<0.05). Among these differentially-expressed proteins, 11 candidates exhibited different trends in dengue fever compared to falciparum malaria. Importantly, our results suggest that dengue virus infection leads to alterations in expression levels of multiple serum proteins involved in diverse and vital physiological pathways, including acute phase response signaling, complement cascades, hemostasis, and blood coagulation. For the first time we report here that the serum levels of hemopexin, haptoglobin, serum amyloid P, and kininogen precursor, are altered in DF. This study informs the pathogenesis and host immune response to dengue virus infection, as well as the current search for new diagnostic and molecular drug targets.

SUBMITTER: Ray S

PROVIDER: S-EPMC3459427 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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Serum proteome changes in dengue virus-infected patients from a dengue-endemic area of India: towards new molecular targets?

Ray Sandipan S Srivastava Rajneesh R Tripathi Karnika K Vaibhav Vineet V Patankar Swati S Srivastava Sanjeeva S

Omics : a journal of integrative biology 20120823 10

The global burden of dengue continues to worsen, specifically in tropical and subtropical countries, and has evolved as a major public health problem. We investigated the changes in serum proteome in dengue fever (DF) patients from a dengue-endemic area of India to obtain mechanistic insights about the disease pathogenesis, the host immune response, and identification of potential serum protein biomarkers of this infectious disease. In this study, serum samples from DF patients, healthy subjects ...[more]

PMID: 22917478

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Project description:IntroductionDengue has become a major health problem in globally as well as locally. The delay in health-seeking is significantly associated with complications leading to severe dengue and active engagement of communities needs to minimize the delays in management to control epidemics. The aim of the study was to evaluate the relationship between sociodemographic characteristics and householders' Health-Seeking Behaviours (HSB), Dengue-Prevention Behaviours (DPB), and Community Capacities (CC) for sustained dengue prevention in Sri Lanka, a country with a high dengue endemicity.MethodsA cross-sectional analytical study was carried out in a district with the highest dengue endemicity from January to April 2019. Of the householders, 532 were chosen randomly. A pre-tested, validated, and interviewer-administered questionnaire was used to assess HSB and DPB. The HSB was assessed using three aspects, initial response for fever management, the duration of blood testing and initial response if suspected dengue. The DPB assessment was evaluated using 'waste, outdoor water container, indoor water container, roof gutter and water storage management'. 'Dengue Community Capacity Assessment Tool', with 14 key items was used to assess the level of community capacity for dengue prevention. Out of the total, ≥ 50% was considered as an "adequate" HSB, DPB and CC. Multiple logistic regression was performed to control confounding effects. The results were expressed as adjusted Odds-Ratios (aOR) and 95% Confidence Intervals (CI).ResultsThe response rate was 93.2% (n = 496). Among them, 44.6% (n = 221) had adequate overall HSB, and 19.2% (n = 95) had adequate DPB. Householders who have ≤ 4 family members are 1.74 times (aOR = 1.74; 95% CI: 1.17 - 2.61) more likely to have adequate HSB and 1.85 times (aOR = 1.85; 95% CI: 1.11 - 3.09) more likely to have adequate DPB. The age group of 46 to 70 years' individuals (aOR = 1.74; 95% CI:1.12 - 2.92), and who engaged in employment (aOR = 1.68; 95% CI: 1.05 - 2.67) were more likely to have adequate DPB than the group of 18 to 45 years and the non-employed individuals respectively. Of them, 24.6% (n = 122) perceived that they have adequate CC. The householders who have per-capita income < USD 50 are 1.95 times (aOR = 1.95; 95%CI:1.11 - 3.40) more likely to have adequate CC.ConclusionThe HSB, DPB and CC need to be improved to change the behaviour for sustainable dengue prevention and community capacity-building programmes need to be conducted in the Kurunegala district, Sri Lanka.

Project description:BackgroundDengue is a major international public health concern, one of the most important arthropod-borne diseases. More than 3.5 billion people are at risk of dengue infection and there are an estimated 390 million dengue infections annually. This prolific increase has been connected to societal changes such as population growth and increasing urbanization generating intense agglomeration leading to proliferation of synanthropic mosquito species. Quantifying the spatio-temporal epidemiology of dengue in large cities within the context of a Geographic Information System is a first step in the identification of socio-economic risk factors.Methodology/principal findingsThis Project has been approved by the ethical committee of Institut Pasteur. Data has been anonymized and de-identified prior to geolocalisation and analysis. A GIS was developed for Delhi, enabling typological characterization of the urban environment. Dengue cases identified in the Delhi surveillance system from 2008 to 2010 were collated, localised and embedded within this GIS. The spatio-temporal distribution of dengue cases and extent of clustering were analyzed. Increasing distance from the forest in Delhi reduced the risk of occurrence of a dengue case. Proximity to a hospital did not increase risk of a notified dengue case. Overall, there was high heterogeneity in incidence rate within areas with the same socio-economical profiles and substantial inter-annual variability. Dengue affected the poorest areas with high density of humans, but rich areas were also found to be infected, potentially because of their central location with respect to the daily mobility network of Delhi. Dengue cases were highly clustered in space and there was a strong relationship between the time of introduction of the virus and subsequent cluster size. At a larger scale, earlier introduction predicted the total number of cases.Conclusions/significanceDENV epidemiology within Delhi has a forest fire signature. The stochastic nature of this invasion process likely smothers any detectable socio-economic risk factors. However, the significant finding that the size of the dengue case cluster depends on the timing of its emergence emphasizes the need for early case detection and implementation of effective mosquito control. A better understanding of the role of population mobility in contributing to dengue risk could also help focus control on areas at particular risk of dengue virus importation.

Project description:BACKGROUND:Mosquitoes belonging to genus Aedes are the prime vectors of several arboviral diseases such as Dengue, Zika and Chikungunya worldwide. Every year numerous cases of dengue infections occur throughout the world, proper control of which depends on efficient vector control. However the onset of insecticide resistance has resulted in failure of vector control approaches. PRINCIPAL FINDINGS:This study was carried out to unveil the degree of prevailing insecticide resistance along with its underlying mechanisms among the primary dengue vector in dengue endemic districts of West Bengal, India through standard WHO protocol. It was observed that, the majority of the tested populations were found to possess resistance to more than one insecticide. In adult bioassay, the toxicity levels of the six tested insecticides was found to decrease in the following order: deltamethrin > lambdacyhalothrin > malathion > propoxur > permethrin > DDT. In larval bioassay, one of the tested populations was found to possess moderate resistance against temephos, mortality percentage 92.5% and 79.8% for WHO (0.0200 ppm) and National Vector Borne disease Programme, India recommended dose (0.0125 ppm) respectively. Carboxylesterases were found to be involved in conferring resistance as revealed in synergistic and quantitative assay against temephos in North Dinajpur (NDP) population and malathion in Alipurduar (APD) and Darjeeling (DAR) populations. Similar correlations were also observed in the majority of the tested populations between reduced susceptibilities against pyrethroid insecticides and Cytochrome P450s activity. CONCLUSION:Efficient disease management in this region can only be achieved through proper integrated vector management along with tools to minimize insecticide resistance. This study may help the concerned authorities in the formulation of an effective vector control strategy throughout this region incorporating the knowledge gained through this study.

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Serum proteome changes in dengue virus-infected patients from a dengue-endemic area of India: towards new molecular targets?

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Serum proteome changes in dengue virus-infected patients from a dengue-endemic area of India: towards new molecular targets?

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