Showing papers on "Dengue fever published in 2010"
TL;DR: A global strategy aimed at increasing the capacity for surveillance and outbreak response, changing behaviours and reducing the disease burden using integrated vector management in conjunction with early and accurate diagnosis has been advocated.
Abstract: Dengue fever and dengue haemorrhagic fever are important arthropod-borne viral diseases. Each year, there are ∼50 million dengue infections and ∼500,000 individuals are hospitalized with dengue haemorrhagic fever, mainly in Southeast Asia, the Pacific and the Americas. Illness is produced by any of the four dengue virus serotypes. A global strategy aimed at increasing the capacity for surveillance and outbreak response, changing behaviours and reducing the disease burden using integrated vector management in conjunction with early and accurate diagnosis has been advocated. Antiviral drugs and vaccines that are currently under development could also make an important contribution to dengue control in the future.
1,732 citations
TL;DR: Viruses such as dengue (DENV) and chikungunya (CHIKV) that have lost the requirement for enzootic amplification now produce extensive epidemics in tropical urban centers, and climate warming could facilitate the expansion of the distributions of many arboviruses.
1,250 citations
TL;DR: It is proposed that the partial cleavage of prM from the viral surface reduces the density of antigen available for viral neutralization, leaving dengue viruses susceptible to ADE by antibody to prM, a finding that has implications for future vaccine design.
Abstract: Dengue virus co-circulates as four serotypes, and sequential infections with more than one serotype are common. One hypothesis for the increased severity seen in secondary infections is antibody-dependent enhancement (ADE) leading to increased replication in Fc receptor-bearing cells. In this study, we have generated a panel of human monoclonal antibodies to dengue virus. Antibodies to the structural precursor-membrane protein (prM) form a major component of the response. These antibodies are highly cross-reactive among the dengue virus serotypes and, even at high concentrations, do not neutralize infection but potently promote ADE. We propose that the partial cleavage of prM from the viral surface reduces the density of antigen available for viral neutralization, leaving dengue viruses susceptible to ADE by antibody to prM, a finding that has implications for future vaccine design.
801 citations
TL;DR: Wolbachia inhibits viral replication and dissemination in the main dengue vector, Aedes aegypti, and is associated with an elevated basal immunity and increased longevity in the mosquitoes, underscoring the potential usefulness of Wolbachia-based control strategies for population replacement.
Abstract: Genetic strategies that reduce or block pathogen transmission by mosquitoes have been proposed as a means of augmenting current control measures to reduce the growing burden of vector-borne diseases. The endosymbiotic bacterium Wolbachia has long been promoted as a potential vehicle for introducing disease-resistance genes into mosquitoes, thereby making them refractory to the human pathogens they transmit. Given the large overlap in tissue distribution and intracellular localization between Wolbachia and dengue virus in mosquitoes, we conducted experiments to characterize their interactions. Our results show that Wolbachia inhibits viral replication and dissemination in the main dengue vector, Aedes aegypti. Moreover, the virus transmission potential of Wolbachia-infected Ae. aegypti was significantly diminished when compared to wild-type mosquitoes that did not harbor Wolbachia. At 14 days post-infection, Wolbachia completely blocked dengue transmission in at least 37.5% of Ae. aegypti mosquitoes. We also observed that this Wolbachia-mediated viral interference was associated with an elevated basal immunity and increased longevity in the mosquitoes. These results underscore the potential usefulness of Wolbachia-based control strategies for population replacement.
669 citations
TL;DR: The results lead to the conclusion that Ae.
Abstract: The dramatic global expansion of Aedes albopictus in the last three decades has increased public health concern because it is a potential vector of numerous arthropod-borne viruses (arboviruses), including the most prevalent arboviral pathogen of humans, dengue virus (DENV). Ae. aegypti is considered the primary DENV vector and has repeatedly been incriminated as a driving force in dengue's worldwide emergence. What remains unresolved is the extent to which Ae. albopictus contributes to DENV transmission and whether an improved understanding of its vector status would enhance dengue surveillance and prevention. To assess the relative public health importance of Ae. albopictus for dengue, we carried out two complementary analyses. We reviewed its role in past dengue epidemics and compared its DENV vector competence with that of Ae. aegypti. Observations from “natural experiments” indicate that, despite seemingly favorable conditions, places where Ae. albopictus predominates over Ae. aegypti have never experienced a typical explosive dengue epidemic with severe cases of the disease. Results from a meta-analysis of experimental laboratory studies reveal that although Ae. albopictus is overall more susceptible to DENV midgut infection, rates of virus dissemination from the midgut to other tissues are significantly lower in Ae. albopictus than in Ae. aegypti. For both indices of vector competence, a few generations of mosquito colonization appear to result in a relative increase of Ae. albopictus susceptibility, which may have been a confounding factor in the literature. Our results lead to the conclusion that Ae. albopictus plays a relatively minor role compared to Ae. aegypti in DENV transmission, at least in part due to differences in host preferences and reduced vector competence. Recent examples of rapid arboviral adaptation to alternative mosquito vectors, however, call for cautious extrapolation of our conclusion. Vector status is a dynamic process that in the future could change in epidemiologically important ways.
646 citations
TL;DR: These findings reveal an unexpected degree of cross-reactivity in human antibodies against DENV and illustrate the potential for an antibody-based therapy to control severe dengue.
543 citations
TL;DR: The highest incidence was observed among adolescents and young adults; dengue hemorrhagic fever incidence was highest among infants in Venezuela; and increasing d Dengue morbidity/mortality was observed in the Americas in recent decades.
Abstract: We have reported the epidemic patterns of dengue disease in the Region of the Americas from 1980 through 2007. Dengue cases reported to the Pan American Health Organization were analyzed from three periods: 1980–1989 (80s), 1990–1999 (90s), and 2000–2007 (2000–7). Age distribution data were examined from Brazil, Venezuela, Honduras, and Mexico. Cases increased over time: 1,033,417 (80s) to 2,725,405 (90s) to 4,759,007 (2000–7). The highest concentrations were reported in the Hispanic Caribbean (39.1%) in the 80s shifting to the Southern Cone in the 90s (55%) and 2000–7 (62.9%). From 1980 through 1987, 242 deaths were reported compared with 1,391 during 2000–7. The most frequently isolated serotypes were DENV-1 and DENV-2 (90s) and DENV-2 and DENV-3 (2000–7). The highest incidence was observed among adolescents and young adults; dengue hemorrhagic fever incidence was highest among infants in Venezuela. Increasing dengue morbidity/mortality was observed in the Americas in recent decades.
515 citations
TL;DR: The cases occurring in Nice, southeast France, where Aedes albopictus is established, are evidence of dengue virus circulation in this area, which calls for further enhanced surveillance, active case finding and vector control measures to reduce the spread of the virus.
Abstract: In September 2010, two cases of autochthonous dengue fever were diagnosed in metropolitan France for the first time. The cases occurring in Nice, southeast France, where Aedes albopictus is established, are evidence of dengue virus circulation in this area. This local transmission of dengue calls for further enhanced surveillance, active case finding and vector control measures to reduce the spread of the virus and the risk of an epidemic.
490 citations
University of London1, World Health Organization2, Public Health Agency of Canada3, Pasteur Institute4, Universiti Malaysia Sarawak5, University of Malaya6, University of Oxford7, National University of Singapore8, Centers for Disease Control and Prevention9, University of California, Berkeley10, University of Valle11, Mahidol University12
TL;DR: It has been proposed that the classification of d Dengue disease should be simplified as severe and non-severe dengue, which would make patient management and surveillance easier and permit early intervention to treat patients and prevent or control epidemics.
Abstract: Dengue is an arthropod-borne flavivirus that comprises four distinct serotypes (DEN-1, DEN-2, DEN-3 and DEN-4) that constitute an antigenic complex of the genus flavivirus, family Flaviviridae. Infection by one serotype induces life-long immunity against reinfection by the same serotype, but only transient and partial protection against infection with the other serotypes1,2. Dengue virus infections can result in a range of clinical manifestations from asymp tomatic infection to dengue fever (DF) and the severe disease dengue haemorrhagic fever/dengue shock syndrome (DHF/ DSS). Most dengue infections are asymptomatic or cause mild symptoms, which are characterized by undifferentiated fever with or without rash. Typical DF is characterized by high fever, severe headache, myalgia, arthralgia, retro-orbital pain and maculopapular rash. Some patients show petechiae, bruising or thrombocytopenia. The clinical presentation of acute dengue infection is non-specific but 5–10% of patients progress to severe DHF/DSS, which can result in death if it is not managed appropriately. Plasma extravasation is the main pathophysiological finding of DHF/ DSS, which differentiates it from DF. DHF/ DSS is characterized by high fever, bleeding, thrombocytopenia and haemoconcentration (an increase in the concentration of blood cells as a result of fluid loss). Approximately 3–4 days after the onset of fever, patients can present with petechiae, rash, epistaxis, and gingival and gastrointestinal bleeding. Pleural effusion and ascites are common. Some patients develop circulatory failure (DSS), presenting with a weak and fast pulse, narrowing of pulse pressure or hypotension, cold and moist skin and altered mental state. Although there are no specific antiviral treatments for dengue infection, patients usually recover when the need for fluid management is identified early and electrolytes are administered3. It has been proposed that the classification of dengue disease should be simplified as severe and non-severe dengue. This simplified classification would make patient management and surveillance easier4. There is a need for specific, inexpensive dengue diagnostic tests that can be used for clinical management, surveillance and outbreak investigations and would permit early intervention to treat patients and prevent or control epidemics. Progress is being made in primary prevention, with several candidate dengue vaccines in late phases of development as well as improved vector control measures. Additionally, new techniques for the early detection of severe disease such as the use of biomarkers have the potential to decrease morbidity and
489 citations
TL;DR: An overview of the infectious life cycle of DENV is given and the viral and host factors that are important in controlling DENV infection are discussed.
Abstract: Dengue virus (DENV 1-4) represents a major emerging arthropod-borne pathogen. All four DENV serotypes are prevalent in the (sub) tropical regions of the world and infect 50-100 million individuals annually. Whereas the majority of DENV infections proceed asymptomatically or result in self-limited dengue fever, an increasing number of patients present more severe manifestations, such as dengue hemorrhagic fever and dengue shock syndrome. In this review we will give an overview of the infectious life cycle of DENV and will discuss the viral and host factors that are important in controlling DENV infection.
419 citations
TL;DR: It is shown that passive administration of anti-DV antibodies is sufficient to enhance DV infection and disease in mice using both mouse-adapted and clinical DV isolates, and a genetically engineered antibody variant that cannot bind FcγR exhibited prophylactic and therapeutic efficacy against ADE-induced lethal challenge.
Abstract: Immunity to one of the four dengue virus (DV) serotypes can increase disease severity in humans upon subsequent infection with another DV serotype. Serotype cross-reactive antibodies facilitate DV infection of myeloid cells in vitro by promoting virus entry via Fcγ receptors (FcγR), a process known as antibody-dependent enhancement (ADE). However, despite decades of investigation, no in vivo model for antibody enhancement of dengue disease severity has been described. Analogous to human infants who receive anti-DV antibodies by transplacental transfer and develop severe dengue disease during primary infection, we show here that passive administration of anti-DV antibodies is sufficient to enhance DV infection and disease in mice using both mouse-adapted and clinical DV isolates. Antibody-enhanced lethal disease featured many of the hallmarks of severe dengue disease in humans, including thrombocytopenia, vascular leakage, elevated serum cytokine levels, and increased systemic viral burden in serum and tissue phagocytes. Passive transfer of a high dose of serotype-specific antibodies eliminated viremia, but lower doses of these antibodies or cross-reactive polyclonal or monoclonal antibodies all enhanced disease in vivo even when antibody levels were neutralizing in vitro. In contrast, a genetically engineered antibody variant (E60-N297Q) that cannot bind FcγR exhibited prophylactic and therapeutic efficacy against ADE-induced lethal challenge. These observations provide insight into the pathogenesis of antibody-enhanced dengue disease and identify a novel strategy for the design of therapeutic antibodies against dengue.
TL;DR: Transgenic strains of Aedes aegypti engineered to have a repressible female-specific flightless phenotype are expected to facilitate area-wide control or elimination of dengue if adopted as part of an integrated pest management strategy.
Abstract: Dengue and dengue hemorrhagic fever are increasing public health problems with an estimated 50-100 million new infections each year. Aedes aegypti is the major vector of dengue viruses in its range and control of this mosquito would reduce significantly human morbidity and mortality. Present mosquito control methods are not sufficiently effective and new approaches are needed urgently. A "sterile-male-release" strategy based on the release of mosquitoes carrying a conditional dominant lethal gene is an attractive new control methodology. Transgenic strains of Aedes aegypti were engineered to have a repressible female-specific flightless phenotype using either two separate transgenes or a single transgene, based on the use of a female-specific indirect flight muscle promoter from the Aedes aegypti Actin-4 gene. These strains eliminate the need for sterilization by irradiation, permit male-only release ("genetic sexing"), and enable the release of eggs instead of adults. Furthermore, these strains are expected to facilitate area-wide control or elimination of dengue if adopted as part of an integrated pest management strategy.
TL;DR: It is demonstrated in mice that DENV-specific antibodies can sufficiently increase severity of disease so that a mostly nonlethal illness becomes a fatal disease resembling human DHF/DSS.
TL;DR: The results imply that the antiviral activity of IFN-α is collectively mediated by a panel of ISGs that disrupt multiple steps of the DENV and WNV life cycles.
Abstract: Interferons (IFNs) are key mediators of the host innate antiviral immune response. To identify IFN-stimulated genes (ISGs) that instigate an antiviral state against two medically important flaviviruses, West Nile virus (WNV) and dengue virus (DENV), we tested 36 ISGs that are commonly induced by IFN-α for antiviral activity against the two viruses. We discovered that five ISGs efficiently suppressed WNV and/or DENV infection when they were individually expressed in HEK293 cells. Mechanistic analyses revealed that two structurally related cell plasma membrane proteins, IFITM2 and IFITM3, disrupted early steps (entry and/or uncoating) of the viral infection. In contrast, three IFN-induced cellular enzymes, viperin, ISG20, and double-stranded-RNA-activated protein kinase, inhibited steps in viral proteins and/or RNA biosynthesis. Our results thus imply that the antiviral activity of IFN-α is collectively mediated by a panel of ISGs that disrupt multiple steps of the DENV and WNV life cycles.
TL;DR: The first cases of autochthonous trans- mission of both viruses (dengue and chikungunya) in France are demonstrated, which implies that A. albopictus, which is resident in this region, is the most likely competent vector for dengue virus.
TL;DR: Results of the extensive characterizations are in accordance with the immunogenicity and excellent safety profile of the ChimeriVax-based vaccine candidates, and support their development towards large-scale efficacy trials and registration.
TL;DR: CQ does not reduce the durations of viraemia and NS1 antigenaemia in dengue patients and was associated with significantly more adverse events, primarily vomiting.
Abstract: Background
There is currently no licensed antiviral drug for treatment of dengue. Chloroquine (CQ) inhibits the replication of dengue virus (DENV) in vitro.
TL;DR: The strategies discussed in this report should be applicable to antiviral development of other viruses, including dengue virus and other flaviviruses.
TL;DR: The global spread of dengue fever within and beyond the usual tropical boundaries threatens a large percentage of the world's population, as human and environmental conditions for persistence and spread are present in all continents.
TL;DR: It is demonstrated that prM antibodies facilitate efficient binding and cell entry of immature particles into Fc-receptor-expressing cells and enzymatic activity of furin is critical to render the internalized immature virus infectious.
Abstract: Cells infected with dengue virus release a high proportion of immature prM-containing virions. In accordance, substantial levels of prM antibodies are found in sera of infected humans. Furthermore, it has been recently described that the rates of prM antibody responses are significantly higher in patients with secondary infection compared to those with primary infection. This suggests that immature dengue virus may play a role in disease pathogenesis. Interestingly, however, numerous functional studies have revealed that immature particles lack the ability to infect cells. In this report, we show that fully immature dengue particles become highly infectious upon interaction with prM antibodies. We demonstrate that prM antibodies facilitate efficient binding and cell entry of immature particles into Fc-receptor-expressing cells. In addition, enzymatic activity of furin is critical to render the internalized immature virus infectious. Together, these data suggest that during a secondary infection or primary infection of infants born to dengue-immune mothers, immature particles have the potential to be highly infectious and hence may contribute to the development of severe disease.
TL;DR: The described arboviruses associated with acute undifferentiated febrile illness in participating clinics in four countries in South America and detailed epidemiological analysis in Iquitos, Peru are provided to provide a better understanding of the geographic range of arbaviruses in SouthAmerica.
Abstract: Background: Arthropod-borne viruses (arboviruses) are among the most common agents of human febrile illness worldwide and the most important emerging pathogens, causing multiple notable epidemics of human disease over recent decades. Despite the public health relevance, little is know about the geographic distribution, relative impact, and risk factors for arbovirus infection in many regions of the world. Our objectives were to describe the arboviruses associated with acute undifferentiated febrile illness in participating clinics in four countries in South America and to provide detailed epidemiological analysis of arbovirus infection in Iquitos, Peru, where more extensive monitoring was conducted. Methodology/Findings: A clinic-based syndromic surveillance system was implemented in 13 locations in Ecuador, Peru, Bolivia, and Paraguay. Serum samples and demographic information were collected from febrile participants reporting to local health clinics or hospitals. Acute-phase sera were tested for viral infection by immunofluorescence assay or RT-PCR, while acute- and convalescent-phase sera were tested for pathogen-specific IgM by ELISA. Between May 2000 and December 2007, 20,880 participants were included in the study, with evidence for recent arbovirus infection detected for 6,793 (32.5%). Dengue viruses (Flavivirus) were the most common arbovirus infections, totaling 26.0% of febrile episodes, with DENV-3 as the most common serotype. Alphavirus (Venezuelan equine encephalitis virus [VEEV] and Mayaro virus [MAYV]) and Orthobunyavirus (Oropouche virus [OROV], Group C viruses, and Guaroa virus) infections were both observed in approximately 3% of febrile episodes. In Iquitos, risk factors for VEEV and MAYV infection included being male and reporting to a rural (vs urban) clinic. In contrast, OROV infection was similar between sexes and type of clinic. Conclusions/Significance: Our data provide a better understanding of the geographic range of arboviruses in South America and highlight the diversity of pathogens in circulation. These arboviruses are currently significant causes of human illness in endemic regions but also have potential for further expansion. Our data provide a basis for analyzing changes in their ecology and epidemiology.
TL;DR: There was a very strong association between the magnitude of the response and disease severity in dengue-infected children from Thailand, and in DHF, cytokine-high CD107a-negative cells predominated.
Abstract: Dengue infections are increasing at an alarming rate in many tropical and subtropical countries, where epidemics can put health care systems under extreme pressure. The more severe infections lead to dengue hemorrhagic fever (DHF), which can be life threatening. A variety of viral and host factors have been associated with the severity of dengue infections. Because secondary dengue infection is more commonly associated with DHF than primary infections, the acquired immune response to dengue, both B cells and T cells have been implicated. In this study, we set out to study T-cell responses across the entire dengue virus proteome and to see whether these were related to disease severity in a cohort of dengue-infected children from Thailand. Robust responses were observed in most infected individuals against most viral proteins. Responses to NS3 were the most frequent, and there was a very strong association between the magnitude of the response and disease severity. Furthermore, in DHF, cytokine-high CD107a-negative cells predominated.
TL;DR: As the major transmission vectors of dengue viruses, the biological behavior and vectorial capacity of Aedes mosquitoes have undergone significant changes in the last two decades in mainland China, most likely the result of urbanization and global climate changes.
Abstract: Dengue is an acute emerging infectious disease transmitted by Aedes mosquitoes and has become a serious global public health problem. In mainland China, a number of large dengue outbreaks with serious consequences have been reported as early as 1978. In the three decades from 1978 to 2008, a total of 655,324 cases were reported, resulting in 610 deaths. Since the 1990s, dengue epidemics have spread gradually from Guangdong, Hainan, and Guangxi provinces in the southern coastal regions to the relatively northern and western regions including Fujian, Zhejiang, and Yunnan provinces. As the major transmission vectors of dengue viruses, the biological behavior and vectorial capacity of Aedes mosquitoes have undergone significant changes in the last two decades in mainland China, most likely the result of urbanization and global climate changes. In this review, we summarize the geographic and temporal distributions, the serotype and genotype distributions of dengue viruses in mainland China, and analyze the current status of surveillance and control of vectors for dengue transmission.
TL;DR: Until the availability of a licensed vaccine, disease surveillance and vector population control remain the mainstay of dengue prevention.
Abstract: Dengue virus is the most widespread geographically of the arboviruses and a major public health threat in the tropics and subtropics. Scientific advances in recent years have provided new insights about the pathogenesis of more severe disease and novel approaches into the development of antiviral compounds and dengue vaccines. Phylogenetic studies show an association between specific subtypes (within serotypes) and severity of dengue. The lack of association between maternal antibodies and development of severe dengue in infants in a recent study has called for the rethinking or refinement of the current antibody-dependent enhancement theory of dengue hemorrhagic syndrome in infancy. Such studies should stimulate new directions of research into mechanisms responsible for the development of severe dengue. The life cycle of dengue virus readily shows that virus entry and replication can be targeted by small molecules. Advances in a mouse model (AG 129 mice) have made it easier to test such antiviral compounds. The efforts to find specific dengue inhibitors are intensifying and the tools to evaluate the efficacy of new drugs are now in place for rapid translation into trials in humans. Furthermore, several dengue vaccine candidates are in development, of which the chimeric dengue/yellow fever vaccine has now entered phase 3 trials. Until the availability of a licensed vaccine, disease surveillance and vector population control remain the mainstay of dengue prevention.
TL;DR: The best methods of surveillance in general, the stakeholders in d Dengue surveillance, and the steps from mosquito bite to reporting of a dengue case are described to explore how best to carry out dengu surveillance.
Abstract: Background
Dengue fever is a virus infection that is spread by the Aedes aegypti mosquito and can cause severe disease especially in children. Dengue fever is a major problem in tropical and sub-tropical regions of the world.
TL;DR: Results support the development of a dengue virus tetravalent vaccine based on the four 80E subunits produced in the Drosophila S2 cell expression system, which are highly immunogenic and capable of eliciting protective responses in both mice and monkeys.
TL;DR: The spectrum and evolution of disease manifestations among 644 adults with d Dengue who were prospectively recruited on admission to a major infectious disease hospital in southern Vietnam are described and a group of patients with similar illnesses not caused by dengue is compared.
Abstract: Globally, the number of adults hospitalized with dengue has increased markedly in recent years. It has been suggested that hepatic dysfunction is more significant in this group than among children. We describe the spectrum and evolution of disease manifestations among 644 adults with dengue who were prospectively recruited on admission to a major infectious disease hospital in southern Vietnam and compare them with a group of patients with similar illnesses not caused by dengue. Transaminase levels increased in virtually all dengue patients and correlated with other markers of disease severity. However, peak enzyme values usually occurred later than other complications. Clinically severe liver involvement was infrequent and idiosyncratic, but usually resulted in severe bleeding. Chronic co-infection with hepatitis B was associated with modestly but significantly increased levels of alanine aminotransferase, but did not otherwise impact the clinical picture.
TL;DR: In this article, the authors used paired Wolbachia-infected and uninfected Aedes-derived cell lines and dengue virus to confirm the phenomenon of viral inhibition at the cellular level.
Abstract: Background: Dengue is currently the most important arthropod-borne viral disease of humans. Recent work has shown dengue virus displays limited replication in its primary vector, the mosquito Aedes aegypti, when the insect harbors the endosymbiotic bacterium Wolbachia pipientis. Wolbachia-mediated inhibition of virus replication may lead to novel methods of arboviral control, yet the functional and cellular mechanisms that underpin it are unknown. Methodology/Principal Findings: Using paired Wolbachia-infected and uninfected Aedes-derived cell lines and dengue virus, we confirm the phenomenon of viral inhibition at the cellular level. Although Wolbachia imposes a fitness cost to cells via reduced proliferation, it also provides a significant degree of protection from virus-induced mortality. The extent of viral inhibition is related to the density of Wolbachia per cell, with highly infected cell lines showing almost complete protection from dengue infection and dramatically reduced virus titers compared to lines not infected with the bacteria. Conclusions/Significance: We have shown that cells infected with Wolbachia display inhibition of dengue virus replication, that the extent of inhibition is related to bacterial density and that Wolbachia infection, although costly, will provide a fitness benefit in some circumstances. Our results parallel findings in mosquitoes and flies, indicating that cell line models will provide useful and experimentally tractable models to study the mechanisms underlying Wolbachia-mediated protection from viruses.
TL;DR: The spatio-temporal pattern of a large dengue virus-2 (DENV-2) outbreak that affected the Australian city of Cairns in 2003 was analyzed, the relationship between d Dengue transmission and distance to the epidemic's index case (IC) was quantified, the effects of indoor residual spraying (IRS) on the odds of dengingue infection were evaluated, and recommendations for city-wide denge surveillance and control were generated.
Abstract: Background
Dengue infection spread in naive populations occurs in an explosive and widespread fashion primarily due to the absence of population herd immunity, the population dynamics and dispersal of Ae. aegypti, and the movement of individuals within the urban space. Knowledge on the relative contribution of such factors to the spatial dimension of dengue virus spread has been limited. In the present study we analyzed the spatio-temporal pattern of a large dengue virus-2 (DENV-2) outbreak that affected the Australian city of Cairns (north Queensland) in 2003, quantified the relationship between dengue transmission and distance to the epidemic's index case (IC), evaluated the effects of indoor residual spraying (IRS) on the odds of dengue infection, and generated recommendations for city-wide dengue surveillance and control.
TL;DR: The overall picture in this case was one of systemic malaria infection that fit the WHO classification for severe malaria, including cerebral pathology, which suggests that further study of knowlesi malaria will aid the interpretation of, often conflicting, information on malaria pathophysiology in humans.
Abstract: Background: Zoonotic malaria caused by Plasmodium knowlesi is an important, but newly recognized, human pathogen. For the first time, post-mortem findings from a fatal case of knowlesi malaria are reported here. Case presentation: A formerly healthy 40 year-old male became symptomatic 10 days after spending time in the jungle of North Borneo. Four days later, he presented to hospital in a state of collapse and died within two hours. He was hyponatraemic and had elevated blood urea, potassium, lactate dehydrogenase and amino transferase values; he was also thrombocytopenic and eosinophilic. Dengue haemorrhagic shock was suspected and a postmortem examination performed. Investigations for dengue virus were negative. Blood for malaria parasites indicated hyperparasitaemia and single species P. knowlesi infection was confirmed by nested-PCR. Macroscopic pathology of the brain and endocardium showed multiple petechial haemorrhages, the liver and spleen were enlarged and lungs had features consistent with ARDS. Microscopic pathology showed sequestration of pigmented parasitized red blood cells in the vessels of the cerebrum, cerebellum, heart and kidney without evidence of chronic inflammatory reaction in the brain or any other organ examined. Brain sections were negative for intracellular adhesion molecule-1. The spleen and liver had abundant pigment containing macrophages and parasitized red blood cells. The kidney had evidence of acute tubular necrosis and endothelial cells in heart sections were prominent. Conclusions: The overall picture in this case was one of systemic malaria infection that fit the WHO classification for severe malaria. Post-mortem findings in this case were unexpectedly similar to those that define fatal falciparum malaria, including cerebral pathology. There were important differences including the absence of coma despite petechial haemorrhages and parasite sequestration in the brain. These results suggest that further study of knowlesi malaria will aid the interpretation of, often conflicting, information on malaria pathophysiology in humans.