Changes in hydroxy and carboxylic acid compositions in the supernatant fluids of mosquito cell cultures infected with dengue viruses

Hydroxy and carboxylic acids in the supernatant fluids of mosquito cell cultures infected with four serotypes of dengue viruses (DEN) were analyzed by frequency-pulsed electron capture gasliquid chromatography. The hydroxy acid profiles of all virus-infected cell cultures differed qualitatively and quantitatively from the profile of normal cell culture. Furthermore, the profiles of hydroxy acids in the DEN 1- and DEN 4-infected cultures were type specific. Although quantitative differences of a few peaks could be found between the hydroxy acid profiles of DEN 2- and DEN 3-infected cultures, in the absence of clear qualitative differences the two profiles were considered to be essentially indistinguishable. The carboxylic acid profiles of virus-infected cultures differed from the profile of a normal cell culture, but none of the four serotypes of DEN viruses induced type-specific profiles. Thus, these findings contrasted to previous results with rhesus monkey kidney cell cultures (LLC-MK₂), in which serotype-specific sets of hydroxy acids and a DEN 1-specific set of carboxylic acids were released in the supernatant fluids by the infection with dengue viruses.     

Medical entomology: changes in the spectrum of mosquito-borne disease in Australia and other vector threats and risks, 1972–2004

Abstract   Our paper presents an assessment of research and operational development in relation to medically important mosquito-borne disease, mainly the arboviruses Ross River, Barmah Forest, Murray Valley encephalitis, Japanese encephalitis, Kunjin and dengue, but also with respect to malaria. Since 1972, there have been considerable gains in research output, organisational structure, communication, surveillance including quarantine inspection and operational control. This has been due to the 1974 epidemic of Murray Valley encephalitis virus extending into temperate Australia, increasing occurrence of Ross River and the dengue viruses, the discovery of Barmah Forest virus as a disease entity in 1988, and the introduction of Japanese encephalitis in 1995. Because many of the outputs involve methodologies of global import, this has resulted in an unprecedented upsurge in publications of international standard.     

Hopf and torus bifurcations,torus destruction and chaos in population biology

One of the simplest population biological models displaying a Hopf bifurcation is the Rosenzweig–MacArthur model with Holling type II response function as essential ingredient. In seasonally forced versions the fixed point on one side of the Hopf bifurcation becomes a limit cycle and the Hopf limit cycle on the other hand becomes a torus, hence the Hopf bifurcation becomes a torus bifurcation, and via torus destruction by further increasing relevant parameters can follow deterministic chaos. We investigate this route to chaos also in view of stochastic versions, since in real world systems only such stochastic processes would be observed.However, the Holling type II response function is not directly related to a transition from one to another population class which would allow a stochastic version straight away. Instead, a time scale separation argument leads from a more complex model to the simple 2 dimensional Rosenzweig–MacArthur model, via additional classes of food handling and predators searching for prey. This extended model allows a stochastic generalization with the stochastic version of a Hopf bifurcation, and ultimately also with additional seasonality allowing a torus bifurcation under stochasticity.Our study shows that the torus destruction into chaos with positive Lyapunov exponents can occur in parameter regions where also the time scale separation and hence stochastic versions of the model are possible. The chaotic motion is observed inside Arnol’d tongues of rational ratio of the forcing frequency and the eigenfrequency of the unforced Hopf limit cycle.Such torus bifurcations and torus destruction into chaos are also observed in other population biological systems, and were for example found in extended multi-strain epidemiological models on dengue fever. To understand such dynamical scenarios better also under noise the present low dimensional system can serve as a good study case.     

Identification of Dengue Virus Serotype 3 Specific Antigenic Sites Targeted by Neutralizing Human Antibodies

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Dengue 3 virus distribution in the mosquito Aedes aegyptl: an immunocytochemical study

Abstract. The dissemination of dengue (DEN) 3 virus in parenterally infected female Aedes aegypti mosquitoes was studied imrnunocytochemically. Antigen was first detected in fat body cells near the thoracic site of virus inoculation. The intussuscepted foregut, salivary glands and nervous tissue were the first major tissues infected. Nervous tissue appeared to be the primary site of amplification. Muscles, tracheae, Malphigian tubules and the posterior midgut did not become infected. The only part of the reproductive system to be infected was the calyx (71% of specimens 16–22 days post-infection) consistent with low rates of vertical transmission. After 7 days post-inoculation the salivary glands of 100% of the specimens examined were infected. Virus dissemination was slow and the most common sequence of infection following intrathoracic inoculation was as follows: thoracic fat body, intussuscepted foregut, salivary glands, cardial epithelium, thoracic ganglion, brain, compound eye, anterior midgut, intermediate midgut/anterior abdominal ganglia, and calyx/hindgut/posterior abdominal ganglia. Fat body and intussuscepted foregut tissues lost infections after 16 days post-inoculation.     

A synthetic peptide analog of in silico-predicted immunogenic epitope unique to dengue virus serotype 2 NS1 antigen specifically binds immunoglobulin G antibodies raised in rabbits

Development of a serotyping-capable dengue detection test is hampered by the absence of an identified unique marker that can detect specific dengue virus (DENV) serotype. In the current commercially available antibody-capture diagnostic methods, immobilized nonstructural 1 (NS1) antigen indiscriminately binds and detects immunoglobulin M or immunoglobulin G against any serotype, thus limiting its capability to distinguish existing serotypes of dengue. Identification of dengue serotype is important because certain serotypes are associated with severe forms of dengue as well as dengue hemorrhagic fever. In this study, we aimed to identify an immunogenic epitope unique to DENV2 NS1 antigen and determine the binding specificity of its synthetic peptide mimotope to antibodies raised in animal models. Selection of a putative B-cell epitope from the reported DENV2 NS1 antigen was done using Kolaskar and Tongaonkar Antigenicity prediction, Emini surface accessibility prediction, and Parker hydrophilicity prediction available at the immune epitope database and analysis resource. Uniqueness of the B-cell epitope to DENV2 was analyzed by BLASTp. Immunogenicity of the synthetic peptide analog of the predicted immunogenic epitope was tested in rabbits. The binding specificity of the antibodies raised in animals and the synthetic peptide mimotope was tested by indirect ELISA. A synthetic peptide analog comprising the unique epitope of DENV2 located at the 170th–183rd position of DENV2 NS1 was found to be immunogenic in animal models. The antipeptide antibody produced in rabbits showed specific binding to the synthetic peptide mimotope of the predicted unique DENV2 NS1 immunogenic epitope.     

Recommendations for building out mosquito-transmitted diseases in sub-Saharan Africa: the DELIVER mnemonic

In sub-Saharan Africa, most transmission of mosquito-transmitted diseases, such as malaria or dengue, occurs within or around houses. Preventing mosquito house entry and reducing mosquito production around the home would help reduce the transmission of these diseases. Based on recent research, we make key recommendations for reducing the threat of mosquito-transmitted diseases through changes to the built environment. The mnemonic, DELIVER, recommends the following best practices: (i) Doors should be screened, self-closing and without surrounding gaps; (ii) Eaves, the space between the wall and roof, should be closed or screened; (iii) houses should be Lifted above the ground; (iv) Insecticide-treated nets should be used when sleeping in houses at night; (v) houses should be Ventilated, with at least two large-screened windows to facilitate airflow; (vi) Environmental management should be conducted regularly inside and around the home; and (vii) Roofs should be solid, rather than thatch. DELIVER is a package of interventions to be used in combination for maximum impact. Simple changes to the built environment will reduce exposure to mosquito-transmitted diseases and help keep regions free from these diseases after elimination.This article is part of the theme issue ‘Novel control strategies for mosquito-borne diseases''.     

Influence of the spatial distribution of human hosts and large size containers on the dispersal of the mosquito Aedes aegypti within the first gonotrophic cycle

It is generally accepted that Aedes aegypti (L.) (Diptera: Culicidae) has a short dispersal capacity, and that displacement can be influenced by the availability of oviposition sites in the surroundings of emergence or release sites. In the present article, we observed the influence of spatial heterogeneity of large containers and human hosts on the cumulative flight direction of Ae. aegypti females during the first gonotrophic cycle, testing the hypothesis that they aggregate in resource-rich areas, i.e. where there are higher concentrations of large containers and/or humans per habitation. We analysed data from pupal surveys and mark-release-recapture experiments (non-blood-fed females were released) carried out in two dengue endemic neighbourhoods of Rio de Janeiro, Brazil: Tubiacanga (a suburb, with a human density of 337 inhabitants/ha) and Favela do Amorim (a slum, with a human density of 901 inhabitants/ha). In both areas, host-seeking females of three different release cohorts showed an overall non-uniform and extensive dispersal from their release point within 1–2 days post-release. At 4–5 days post-release, when many of the released females would be expected to be gravid, in Tubiacanga most mosquitoes were collected in areas with a relatively higher density of containers/premise, independently of the density of residents/house, whereas in Favela do Amorim, almost half of the captured mosquitoes were collected in relatively resource-poorer areas. Although Ae. aegypti dispersal patterns varied between sites, overall the distances travelled from the release point and the cumulative flight directions were correlated with the density of containers and hosts, more markedly in Tubiacanga than in Favela do Amorim.