Dengue Deaths in Puerto Rico: Lessons Learned from the 2007 Epidemic

Dengue is a major public health problem in the tropics and subtropics; an estimated 50 million cases occur annually and 40 percent of the world's population lives in areas with dengue virus (DENV) transmission. Dengue has a wide range of clinical presentations from an undifferentiated acute febrile illness, classic dengue fever, to severe dengue (i.e., dengue hemorrhagic fever or dengue shock syndrome). About 5% of patients develop severe dengue, which is more common with second or subsequent infections. No vaccines are available to prevent dengue, and there are no specific antiviral treatments for patients with dengue. However, early recognition of shock and intensive supportive therapy can reduce risk of death from ∼10% to less than 1% among severe dengue cases. Reviewing dengue deaths is one means to identify issues in clinical management. These findings can be used to develop healthcare provider education to minimize dengue morbidity and mortality

Confirmed adult dengue deaths in Singapore: 5-year multi-center retrospective study

10.1186/1471-2334-11-123BMC Infectious Diseases11-BIDM

Syndromic Surveillance: Adapting Innovations to Developing Settings

The tools and strategies of syndromic surveillance, say the authors, hold promise for improving public health security in developing countries

An Outbreak of Dengue Fever in St. Croix (US Virgin Islands), 2005

BACKGROUND: Periodic outbreaks of dengue fever occur in the United States Virgin Islands. In June 2005, an outbreak of dengue virus (DENV) serotype-2 with cases of dengue hemorrhagic fever (DHF) was detected in St. Croix, US Virgin Islands. The objective of this report is to describe this outbreak of DENV-2 and the findings of a case-control study examining risk factors for DHF. METHODOLOGY/PRINCIPAL FINDINGS: This is the largest dengue outbreak ever recorded in St. Croix, with 331 suspected dengue cases reported island-wide during 2005 (62.2 cases/10,000 population); 54% were hospitalized, 21% had at least one hemorrhagic manifestation, 28% had thrombocytopenia, 5% had DHF and 1 patient died. Eighty-nine laboratory-positive hospitalized patients were identified. Of these, there were 15 (17%) who met the WHO criteria for DHF (cases) and 74 (83%) who did not (controls). The only variable significantly associated with DHF on bivariate or multivariable analysis was age, with an adjusted odds ratio (95% confidence interval) of 1.033 (1.003,1.064). CONCLUSIONS/SIGNIFICANCE: During this outbreak of DENV-2, a high proportion of cases developed DHF and increasing age was significantly associated with DHF

Humoral Immune Responses of Dengue Fever Patients Using Epitope-Specific Serotype-2 Virus-Like Particle Antigens

Dengue virus (DENV) is a serious mosquito-borne pathogen causing significant global disease burden, either as classic dengue fever (DF) or in its most severe manifestation dengue hemorrhagic fever (DHF). Nearly half of the world's population is at risk of dengue disease and there are estimated to be millions of infections annually; a situation which will continue to worsen with increasing expansion of the mosquito vectors and epidemic DF/DHF. Currently there are no available licensed vaccines or antivirals for dengue, although significant effort has been directed toward the development of safe and efficacious dengue vaccines for over 30 years. Promising vaccine candidates are in development and testing phases, but a better understanding of immune responses to DENV infection and vaccination is needed. Humoral immune responses to DENV infection are complex and may exacerbate pathogenicity, yet are essential for immune protection. In this report, we develop DENV-2 envelope (E) protein epitope-specific antigens and measure immunoglobulin responses to three distinct epitopes in DENV-2 infected human serum samples. Immunoglobulin responses to DENV-2 infection exhibited significant levels of individual variation. Antibody populations targeting broadly cross-reactive epitopes centered on the fusion peptide in structural domain II were large, highly variable, and greater in primary than in secondary DENV-2 infected sera. E protein domain III cross-reactive immunoglobulin populations were similarly variable and much larger in IgM than in IgG. DENV-2 specific domain III IgG formed a very small proportion of the antibody response yet was significantly correlated with DENV-2 neutralization, suggesting that the highly protective IgG recognizing this epitope in murine studies plays a role in humans as well. This report begins to tease apart complex humoral immune responses to DENV infection and is thus important for improving our understanding of dengue disease and immunological correlates of protection, relevant to DENV vaccine development and testing

Quantifying the Spatial Dimension of Dengue Virus Epidemic Spread within a Tropical Urban Environment

Global trends in population growth and human redistribution and movement have reshaped the map of dengue transmission risk, exposing a significant proportion of the world's population to the threat of dengue epidemics. Knowledge on the relative contribution of vector and human movement to the widespread and explosive nature of dengue epidemic spread within an urban environment is limited. By analyzing a very detailed dataset of a dengue epidemic that affected the Australian city of Cairns we performed a comprehensive quantification of the spatio-temporal dimensions of dengue virus epidemic transmission and propagation within a complex urban environment. Space and space-time analysis and models allowed derivation of detailed information on the pattern of introduction and epidemic spread of dengue infection within the urban space. We foresee that some of the results and recommendations derived from our study may also be applicable to many other areas currently affected or potentially subject to dengue epidemics

Climate change and the emergence of vector-borne diseases in Europe: Case study of dengue fever

Background: Dengue fever is the most prevalent mosquito-borne viral disease worldwide. Dengue transmission is critically dependent on climatic factors and there is much concern as to whether climate change would spread the disease to areas currently unaffected. The occurrence of autochthonous infections in Croatia and France in 2010 has raised concerns about a potential re-emergence of dengue in Europe. The objective of this study is to estimate dengue risk in Europe under climate change scenarios. Methods. We used a Generalized Additive Model (GAM) to estimate dengue fever risk as a function of climatic variables (maximum temperature, minimum temperature, precipitation, humidity) and socioeconomic factors (population density, urbanisation, GDP per capita and population size), under contemporary conditions (1985-2007) in Mexico. We then used our model estimates to project dengue incidence under baseline conditions (1961-1990) and three climate change scenarios: short-term 2011-2040, medium-term 2041-2070 and long-term 2071-2100 across Europe. The model was used to calculate average number of yearly dengue cases at a spatial resolution of 10 × 10 km grid covering all land surface of the currently 27 EU member states. To our knowledge, this is the first attempt to model dengue fever risk in Europe in terms of disease occurrence rather than mosquito presence. Results: The results were presented using Geographical Information System (GIS) and allowed identification of areas at high risk. Dengue fever hot spots were clustered around the coastal areas of the Mediterranean and Adriatic seas and the Po Valley in northern Italy. Conclusions: This risk assessment study is likely to be a valuable tool assisting effective and targeted adaptation responses to reduce the likely increased burden of dengue fever in a warmer world

Incidence and mortality rates of selected infection-related cancers in Puerto Rico and in the United States

<p>Abstract</p> <p>Background</p> <p>In 2002, 17.8% of the global cancer burden was attributable to infections. This study assessed the age-standardized incidence and mortality rates of stomach, liver, and cervical cancer in Puerto Rico (PR) for the period 1992-2003 and compared them to those of Hispanics (USH), non-Hispanic Whites (NHW), and non-Hispanic Blacks (NHB) in the United States (US).</p> <p>Methods</p> <p>Age-standardized rates [ASR(World)] were calculated based on cancer incidence and mortality data from the PR Cancer Central Registry and SEER, using the direct method and the world population as the standard. Annual percent changes (APC) were calculated using the Poisson regression model from 1992-2003.</p> <p>Results</p> <p>The incidence and mortality rates from stomach, liver and cervical cancer were lower in NHW than PR; with the exception of mortality from cervical cancer which was similar in both populations. Meanwhile, the incidence rates of stomach, liver and cervical cancers were similar between NHB and PR; except for NHB women who had a lower incidence rate of liver cancer than women in PR. NHB had a lower mortality from liver cancer than persons in PR, and similar mortality from stomach cancer.</p> <p>Conclusions</p> <p>The burden of liver, stomach, and cervical cancer in PR compares to that of USH and NHB and continues to be a public health priority. Public health efforts are necessary to further decrease the burden of cancers associated to infections in these groups, the largest minority population groups in the US. Future studies need to identify factors that may prevent infections with cancer-related agents in these populations. Strategies to increase the use of preventive strategies, such as vaccination and screening, among minority populations should also be developed.</p

Host Gene Expression Profiling of Dengue Virus Infection in Cell Lines and Patients

Dengue is the most prevalent mosquito-born viral disease affecting humans, yet there is, at present, no drug treatment for the disease nor are there any validated host targets for therapeutic intervention. Using microarray technology to monitor the response of virtually every human gene, we aimed to identify the ways in which humans interact with dengue virus during infection in order to discover new therapeutic targets that could be exploited to control viral replication. From the activated genes, we identified three pathways common to in vitro and in vivo infection; the NF-κB initiated immune pathway, the type I interferon pathway, and the ubiquitin proteasome pathway. We next found that inhibiting the ubiquitin proteasome pathway, or activating the type I interferon pathway, resulted in significant inhibition of viral replication. However, inhibiting the NF-κB initiated immune pathway had no effect on viral replication. We suggest that drugs that target the ubiquitin proteasome pathway may prove effective at killing the dengue virus, and, if used therapeutically, improve clinical outcome in dengue disease

Dengue Virus Type 2 Infections of Aedes aegypti Are Modulated by the Mosquito's RNA Interference Pathway

A number of studies have shown that both innate and adaptive immune defense mechanisms greatly influence the course of human dengue virus (DENV) infections, but little is known about the innate immune response of the mosquito vector Aedes aegypti to arbovirus infection. We present evidence here that a major component of the mosquito innate immune response, RNA interference (RNAi), is an important modulator of mosquito infections. The RNAi response is triggered by double-stranded RNA (dsRNA), which occurs in the cytoplasm as a result of positive-sense RNA virus infection, leading to production of small interfering RNAs (siRNAs). These siRNAs are instrumental in degradation of viral mRNA with sequence homology to the dsRNA trigger and thereby inhibition of virus replication. We show that although dengue virus type 2 (DENV2) infection of Ae. aegypti cultured cells and oral infection of adult mosquitoes generated dsRNA and production of DENV2-specific siRNAs, virus replication and release of infectious virus persisted, suggesting viral circumvention of RNAi. We also show that DENV2 does not completely evade RNAi, since impairing the pathway by silencing expression of dcr2, r2d2, or ago2, genes encoding important sensor and effector proteins in the RNAi pathway, increased virus replication in the vector and decreased the extrinsic incubation period required for virus transmission. Our findings indicate a major role for RNAi as a determinant of DENV transmission by Ae. aegypti