Seroepidemiology of Asymptomatic Dengue Virus Infection in Jeddah, Saudi Arabia.

BACKGROUND: Although virologically confirmed dengue fever has been recognized in Jeddah, Saudi Arabia, since 1994, causing yearly outbreaks, no proper seroepidemiologic studies on dengue virus have been conducted in this region. Such studies can define the extent of infection by this virus and estimate the proportion that may result in disease. The aim of this study was to measure the seroprevalence of past dengue virus infection in healthy Saudi nationals from different areas in the city of Jeddah and to investigate demographic and environmental factors that may increase exposure to infection. METHODS: Sera were collected from 1984 Saudi subjects attending primary health care centers in six districts of Jeddah. These included general patients of various ages seeking routine vaccinations, antenatal care or treatment of different illnesses excluding fever or suspected dengue. A number of blood donors were also tested. Serum samples were tested by enzyme immunoassay (EIA) for IgG antibodies to dengue viruses 1, 2, 3, 4. A questionnaire was completed for each patient recording various anthropometric data and factors that may indicate possible risk of exposure to mosquito bites and dengue infection. Patients with missing data and those who reported a history of dengue fever were excluded from analysis, resulting in a sample of 1939 patients to be analyzed. RESULTS: The overall prevalence of dengue virus infection as measured by anti-dengue IgG antibodies from asymptomatic residents in Jeddah was 47.8% (927/1939) and 37% (68/184) in blood donors. Infection mostly did not result in recognizable disease, as only 19 of 1956 subjects with complete information (0.1%) reported having dengue fever in the past. Anti dengue seropositivity increased with age and was higher in males than females and in residents of communal housing and multistory buildings than in villas. One of the six districts showed significant increase in exposure rate as compared to the others. Availability of public sewage was associated with lower infection at a nearly significant level. No other clear risk factors were identifiable. Infection was not related to travel abroad. CONCLUSIONS: Our results indicate a relatively high exposure of Jeddah residents to infection by dengue viruses, which must be considered endemic to this region. Infection largely remained asymptomatic or was only associated with minor illness for which patients did not seek treatment. These results call for continued vigilance for clinical cases of dengue that may arise from this wide exposure. They also call for more extensive control efforts to reduce exposure to and transmission of dengue viruses.

Energy and information in Hodgkin-Huxley neurons.

The generation of spikes by neurons is energetically a costly process and the evaluation of the metabolic energy required to maintain the signaling activity of neurons a challenge of practical interest. Neuron models are frequently used to represent the dynamics of real neurons but hardly ever to evaluate the electrochemical energy required to maintain that dynamics. This paper discusses the interpretation of a Hodgkin-Huxley circuit as an energy model for real biological neurons and uses it to evaluate the consumption of metabolic energy in the transmission of information between neurons coupled by electrical synapses, i.e., gap junctions. We show that for a single postsynaptic neuron maximum energy efficiency, measured in bits of mutual information per molecule of adenosine triphosphate (ATP) consumed, requires maximum energy consumption. For groups of parallel postsynaptic neurons we determine values of the synaptic conductance at which the energy efficiency of the transmission presents clear maxima at relatively very low values of metabolic energy consumption. Contrary to what could be expected, the best performance occurs at a low energy cost.

Energy balance in feedback synchronization of chaotic systems.

In this paper we present a method based on a generalized Hamiltonian formalism to associate to a chaotic system of known dynamics a function of the phase space variables with the characteristics of an energy. Using this formalism we have found energy functions for the Lorenz, Rössler, and Chua families of chaotic oscillators. We have theoretically analyzed the flow of energy in the process of synchronizing two chaotic systems via feedback coupling and used the previously found energy functions for computing the required energy to maintain a synchronized regime between systems of these families. We have calculated the flows of energy at different coupling strengths covering cases of both identical as well as nonidentical synchronization. The energy dissipated by the guided system seems to be sensitive to the transitions in the stability of its equilibrium points induced by the coupling.

Actinobacillus pleuropneumoniae iron transport and urease activity: effects on bacterial virulence and host immune response.

Actinobacillus pleuropneumoniae, a porcine respiratory tract pathogen, has been shown to express transferrin-binding proteins and urease during infection. Both activities have been associated with virulence; however, their functional role for infection has not yet been elucidated. We used two isogenic A. pleuropneumoniae single mutants (DeltaexbB and DeltaureC) and a newly constructed A. pleuropneumoniae double (DeltaureC DeltaexbB) mutant in aerosol infection experiments. Neither the A. pleuropneumoniae DeltaexbB mutant nor the double DeltaureC DeltaexbB mutant was able to colonize sufficiently long to initiate a detectable humoral immune response. These results imply that the ability to utilize transferrin-bound iron is required for multiplication and persistence of A. pleuropneumoniae in the porcine respiratory tract. The A. pleuropneumoniae DeltaureC mutant and the parent strain both caused infections that were indistinguishable from one another in the acute phase of disease; however, 3 weeks postinfection the A. pleuropneumoniae DeltaureC mutant, in contrast to the parent strain, could not be isolated from healthy lung tissue. In addition, the local immune response-as assessed by fluorescence-activated cell sorter and enzyme-linked immunosorbent spot analyses-revealed a significantly higher number of A. pleuropneumoniae-specific B cells in the bronchoalveolar lavage fluid (BALF) of pigs infected with the A. pleuropneumoniae DeltaureC mutant than in the BALF of those infected with the parent strain. These results imply that A. pleuropneumoniae urease activity may cause sufficient impairment of the local immune response to slightly improve the persistence of the urease-positive A. pleuropneumoniae parent strain.

Macrophages during avian optic nerve development: relationship to cell death and differentiation into microglia.

Cell death is frequent during the development of the nervous system. In the developing optic nerve of chicks and quails, neuroepithelial cell death was first observable on the third day of incubation, slightly after the first cell ganglion axons appeared in the stalk. Specialized phagocytes were observed within the stalk in chronological and topographical coincidence with cell death. These cells were identified as macrophages because of their morphological features, intense acid phosphatase activity and, in quail embryos, labeling with QH1, a monoclonal antibody recognizing quail hemangioblastic cells. Macrophages in areas of cell death were round and actively phagocytosed cell debris. We used electron microscopy and histochemical and immunocytochemical labeling to study macrophagic cells of the optic nerve in avian embryos of 3-6.5 days of incubation. As development proceeded, phagocytosing, round macrophages became ameboid macrophages that migrated from areas of cell death toward regions occupied by optic axonal fascicles. Macrophages in these locations were thin and elongated, with a few processes. To elucidate the final fate of macrophagic cells in the optic nerve, sections taken from older embryonic and hatched quails were stained with the QH1 antibody. On the 8th day of incubation some slightly ramified QH1+ cells were present among axonal fascicles. In subsequent stages these cells increased in number and acquired more complex ramifications. In adult optic nerves, QH1+ cells had a small body and sent out slender processes, sometimes with secondary and tertiary branches, which were frequently orientated parallel to the course of the optic axons. These cells were considered to be microglial cells. The appearance of macrophages within the developing optic nerve at the same time as neuroepithelial cell death suggests that cell death influences the recruitment of macrophages into the nerve. When macrophages reach the areas invaded by optic axonal fascicles, they undergo structural and probably also physiological changes that appear to signal differentiation into microglia.

Origin of microglia in the quail retina: central-to-peripheral and vitreal-to-scleral migration of microglial precursors during development.

The origin, migration, and differentiation of microglial precursors in the avascular quail retina during embryonic and posthatching development were examined in this study. Microglial precursors and developing microglia were immunocytochemically labeled with QH1 antibody in retinal whole mounts and sections. The retina was free of QH1+ macrophages at embryonic day 5 (E5). Ameboid QH1+ macrophages from the pecten entered the retina from E7 on. These macrophages spread from central to peripheral areas in the retina by migrating on the endfeet of the Müller cells and reached the periphery of the retina at E12. While earlier macrophages were migrating along the inner limiting membrane, other macrophages continued to enter the retina from the pecten until hatching (E16). From E9 on, macrophages were seen to colonize progressively more scleral retinal layers as development advanced. Macrophages first appeared in the ganglion cell layer at E9, in the inner plexiform layer at E12, and in the outer plexiform layer at E14. Therefore, it seems that macrophages first migrated tangentially along the inner retinal surface and then migrated from vitreal to scleral levels to gain access to the plexiform layers, where they differentiated into ramified microglia. Macrophages appeared to differentiate shortly after arrival in the plexiform layers, as poorly ramified QH1+ cells were seen as early as E12 in the inner plexiform layer and at E14 in the outer plexiform layer. Radial migration of macrophages toward the outer plexiform layer continued until posthatching day 3, after which retinal microglia showed an adult distribution pattern. We also observed numerous vitreal macrophages intimately adhered to the surface of the pecten during embryonic development, when macrophages migrated into the retina. These vitreal macrophages were not seen from hatching onwards, when no further macrophages entered the retina.

Microglia in the avian retina: immunocytochemical demonstration in the adult quail.

Immunocytochemical techniques were used in conjunction with the QH1 antibody to study the morphological characteristics and distribution of microglia in the avascular retina of an avian species (the quail). The majority of microglial cells appeared in the outer and inner plexiform layers throughout the entire retina, whereas a few microglial cells in the nerve fiber layer were seen only in the central zone of the retina, near the optic nerve head. In the outer plexiform layer, microglial cells were star-shaped, with processes that ramified profusely in the horizontal plane. Fine process tips extended outward radially, insinuating themselves among the photoreceptors. A regular mosaic-like arrangement of microglial cells was evident in the outer plexiform layer, with no overlapping between adjacent cell territories. Microglial cells in the inner plexiform layer ramified through the entire width of this layer, showing radial and horizontal processes. Microglia in the inner plexiform layer also tended to be regularly distributed in a mosaic-like fashion, although there was slight overlapping between adjacent cell territories. Microglia density in this layer was approximately twice that in the outer plexiform layer. This pattern of microglial distribution was similar to that described in vascular retinae of several species of mammals, a finding that suggest that blood vessels are not responsible for the final locations of microglia in the adult retina, and that microglial precursors must migrate through long distances before they reach their precise destination.

Development of microglia in the quail optic tectum.

The development of microglia in the quail optic tectum from embryonic day 6 to adulthood was studied by using the QH1 monoclonal antibody. In youngest tecta, microglial cells were scarcely present, but their number rose in subsequent stages. A clear pattern of microglial cell distribution was observable in embryos of 9-16 days. (1) Round cells appeared close to the ventricular layer. (2) Large numbers of ameboid and round labeled cells were seen in the stratum album centrale during development. A gradient of cell density was observable in this layer, as fewer labeled cells appeared in medial regions of the tectum than in lateral regions. (3) Maturing ramified cells were found in layers external to the stratum album centrale, where they increased in number and in branching complexity during development. In adult tecta, almost all microglial cells were of the mature ramified type and were distributed homogeneously in the different tectal layers, although in some layers they had particular morphological features. The distribution of microglia in the developing tectum and in adjacent regions provided insight into the routes of microglial cell invasion of the tectum during development. Apparently, a proportion of microglial cells reached the tectal parenchyma from the meninges and from the ventricular lumen, but the majority of them migrated along nerve fiber tracts from their entry point at the pial surface of the ventromedial caudal tectum. After they reached the stratum album centrale, microglial cells continued their migration toward more external layers, where they differentiated into ramified microglia.

Microglia in the mature and developing quail brain as revealed by a monoclonal antibody recognizing hemopoietic cells.

The monoclonal antibody QH1, which recognizes quail endothelial and hemopoietic cells, was found to label microglia in the developing and mature brain of the quail. Forms of microglia similar to those described in mammals were labelled. Ameboid microglia predominated at embryonic stages, became less numerous in late embryonic development, and disappeared completely by day 10 post-hatch (P10). Poorly ramified microglia were present as early as day 5 of incubation (E5), and were progressively replaced by mature ramified microglia from E14 onwards. From P10 onwards, ramified microglia were the only microglial form seen in the quail brain.