176 research outputs found

    Mutation at the Evi1 locus in Junbo mice causes susceptibility to otitis media

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    Otitis media ( OM), inflammation of the middle ear, remains the most common cause of hearing impairment in children. It is also the most common cause of surgery in children in the developed world. There is evidence from studies of the human population and mouse models that there is a significant genetic component predisposing to OM, yet nothing is known about the underlying genetic pathways involved in humans. We identified an N-ethyl-N-nitrosourea-induced dominant mouse mutant Junbo with hearing loss due to chronic suppurative OM and otorrhea. This develops from acute OM that arises spontaneously in the postnatal period, with the age of onset and early severity dependent on the microbiological status of the mice and their air quality. We have identified the causal mutation, a missense change in the C-terminal zinc finger region of the transcription factor Evi1. This protein is expressed in middle ear basal epithelial cells, fibroblasts, and neutrophil leukocytes at postnatal day 13 and 21 when inflammatory changes are underway. The identification and characterization of the Junbo mutant elaborates a novel role for Evi1 in mammalian disease and implicates a new pathway in genetic predisposition to OM

    Epidemiology of Subpatent Plasmodium Falciparum Infection: Implications for Detection of Hotspots with Imperfect Diagnostics.

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    At the local level, malaria transmission clusters in hotspots, which may be a group of households that experience higher than average exposure to infectious mosquitoes. Active case detection often relying on rapid diagnostic tests for mass screen and treat campaigns has been proposed as a method to detect and treat individuals in hotspots. Data from a cross-sectional survey conducted in north-western Tanzania were used to examine the spatial distribution of Plasmodium falciparum and the relationship between household exposure and parasite density. Dried blood spots were collected from consenting individuals from four villages during a survey conducted in 2010. These were analysed by PCR for the presence of P. falciparum, with the parasite density of positive samples being estimated by quantitative PCR. Household exposure was estimated using the distance-weighted PCR prevalence of infection. Parasite density simulations were used to estimate the proportion of infections that would be treated using a screen and treat approach with rapid diagnostic tests (RDT) compared to targeted mass drug administration (tMDA) and Mass Drug Administration (MDA). Polymerase chain reaction PCR analysis revealed that of the 3,057 blood samples analysed, 1,078 were positive. Mean distance-weighted PCR prevalence per household was 34.5%. Parasite density was negatively associated with transmission intensity with the odds of an infection being subpatent increasing with household exposure (OR 1.09 per 1% increase in exposure). Parasite density was also related to age, being highest in children five to ten years old and lowest in those >ā€‰40 years. Simulations of different tMDA strategies showed that treating all individuals in households where RDT prevalence was above 20% increased the number of infections that would have been treated from 43 to 55%. However, even with this strategy, 45% of infections remained untreated. The negative relationship between household exposure and parasite density suggests that DNA-based detection of parasites is needed to provide adequate sensitivity in hotspots. Targeting MDA only to households with RDT-positive individuals may allow a larger fraction of infections to be treated. These results suggest that community-wide MDA, instead of screen and treat strategies, may be needed to successfully treat the asymptomatic, subpatent parasite reservoir and reduce transmission in similar settings

    Geographic Coincidence of Increased Malaria Transmission Hazard and Vulnerability Occurring at the Periphery of two Tanzanian Villages.

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    The goal of malaria elimination necessitates an improved understanding of any fine-scale geographic variations in transmission risk so that complementary vector control tools can be integrated into current vector control programmes as supplementary measures that are spatially targeted to maximize impact upon residual transmission. This study examines the distribution of host-seeking malaria vectors at households within two villages in rural Tanzania. Host-seeking mosquitoes were sampled from 72 randomly selected households in two villages on a monthly basis throughout 2008 using CDC light-traps placed beside occupied nets. Spatial autocorrelation in the dataset was examined using the Moran's I statistic and the location of any clusters was identified using the Getis-Ord Gi* statistic. Statistical associations between the household characteristics and clusters of mosquitoes were assessed using a generalized linear model for each species. For both Anopheles gambiae sensu lato and Anopheles funestus, the density of host-seeking females was spatially autocorrelated, or clustered. For both species, houses with low densities were clustered in the semi-urban village centre while houses with high densities were clustered in the periphery of the villages. Clusters of houses with low or high densities of An. gambiae s.l. were influenced by the number of residents in nearby houses. The occurrence of high-density clusters of An. gambiae s.l. was associated with lower elevations while An. funestus was also associated with higher elevations. Distance from the village centre was also positively correlated with the number of household occupants and having houses constructed with open eaves. The results of the current study highlight that complementary vector control tools could be most effectively targeted to the periphery of villages where the households potentially have a higher hazard (mosquito densities) and vulnerability (open eaves and larger households) to malaria infection

    Spatial heterogeneity of habitat suitability for Rift Valley fever occurrence in Tanzania: an ecological niche modelling approach

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    Despite the long history of Rift Valley fever (RVF) in Tanzania, extent of its suitable habitat in the country remains unclear. In this study we investigated potential effects of temperature, precipitation, elevation, soil type, livestock density, rainfall pattern, proximity to wild animals, protected areas and forest on the habitat suitability for RVF occurrence in Tanzania. Presence-only records of 193 RVF outbreak locations from 1930 to 2007 together with potential predictor variables were used to model and map the suitable habitats for RVF occurrence using ecological niche modelling. Ground-truthing of the model outputs was conducted by comparing the levels of RVF virus specific antibodies in cattle, sheep and goats sampled from locations in Tanzania that presented different predicted habitat suitability values. Habitat suitability values for RVF occurrence were higher in the northern and central-eastern regions of Tanzania than the rest of the regions in the country. Soil type and precipitation of the wettest quarter contributed equally to habitat suitability (32.4% each), followed by livestock density (25.9%) and rainfall pattern (9.3%). Ground-truthing of model outputs revealed that the odds of an animal being seropositive for RVFV when sampled from areas predicted to be most suitable for RVF occurrence were twice the odds of an animal sampled from areas least suitable for RVF occurrence (95% CI: 1.43, 2.76, p < 0.001). The regions in the northern and central-eastern Tanzania were more suitable for RVF occurrence than the rest of the regions in the country. The modelled suitable habitat is characterised by impermeable soils, moderate precipitation in the wettest quarter, high livestock density and a bimodal rainfall pattern. The findings of this study should provide guidance for the design of appropriate RVF surveillance, prevention and control strategies which target areas with these characteristics

    A classification method for neurogenic heterotopic ossification of the hip

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    Background: Existing classifications for heterotopic ossification (HO) do not include all HO types; nor do they consider the anatomy of the involved joint or the neurological injury. Therefore, we performed this study to propose and evaluate a classification according to the location of neurogenic HO and the neurological injury. Materials and methods: We studied the files of 24 patients/33 hips with brain or spinal cord injury and neurogenic HO of the hip treated with excision, indomethacin, and radiation therapy. We classified patients according to the Brooker classification scheme as well as ours. Four types of neurogenic HO were distinguished according to the anatomical location of HO: type 1, anterior; type 2, posterior; type 3, anteromedial; type 4, circumferential. Subtypes of each type were added based on the neurological injury: a, spinal cord; b, brain injury. Mean follow-up was 2.5 years (1-8 years). Results: The Brooker classification scheme was misleading - all hips were class III or IV, corresponding to ankylosis, even though only 14 hips had ankylosis. On the other hand, our classification was straightforward and easy to assign in all cases. It corresponded better to the location of the heterotopic bone, and allowed for preoperative planning of the appropriate surgical approach and evaluation of the prognosis; recurrence of neurogenic HO was significantly higher in patients with brain injury (subtype b), while blood loss was higher for patients with anteromedial (type 3) and circumferential (type 4) neurogenic HO. Conclusions: Our proposed classification may improve the management and evaluation of the prognosis for patients with neurogenic HO

    Topography-derived wetness indices are associated with household-level malaria risk in two communities in the western Kenyan highlands

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    <p>Abstract</p> <p>Background</p> <p>Transmission of <it>Plasmodium falciparum </it>generally decreases with increasing elevation, in part because lower temperature slows the development of both parasites and mosquitoes. However, other aspects of the terrain, such as the shape of the land, may affect habitat suitability for <it>Anopheles </it>breeding and thus risk of malaria transmission. Understanding these local topographic effects may permit prediction of regions at high risk of malaria within the highlands at small spatial scales.</p> <p>Methods</p> <p>Hydrologic modelling techniques were adapted to predict the flow of water across the landscape surrounding households in two communities in the western Kenyan highlands. These surface analyses were used to generate indices describing predicted water accumulation in regions surrounding the study area. Households with and without malaria were compared for their proximity to regions of high and low predicted wetness. Predicted wetness and elevation variables were entered into bivariate and multivariate regression models to examine whether significant associations with malaria were observable at small spatial scales.</p> <p>Results</p> <p>On average, malaria case households (n = 423) were located 280 m closer to regions with very high wetness indices than non-malaria "control" households (n = 895) (t = 10.35, p < 0.0001). Distance to high wetness indices remained an independent predictor of risk after controlling for household elevation in multivariate regression (OR = 0.93 [95% confidence interval = 0.89ā€“0.96] for a 100 m increase in distance). For every 10 m increase in household elevation, there was a 12% decrease in the odds of the house having a malaria case (OR = 0.88 [0.85ā€“0.90]). However, after controlling for distance to regions of high predicted wetness and the community in which the house was located, this reduction in malaria risk was not statistically significant (OR = 0.98 [0.94ā€“1.03]).</p> <p>Conclusion</p> <p>Proximity to terrain with high predicted water accumulation was significantly and consistently associated with increased household-level malaria incidence, even at small spatial scales with little variation in elevation variables. These results suggest that high wetness indices are not merely proxies for valley bottoms, and hydrologic flow models may prove valuable for predicting areas of high malaria risk in highland regions. Application in areas where malaria surveillance is limited could identify households at higher risk and help focus interventions.</p

    The effect of octopaminergic compounds on the behaviour and transmission of Gyrodactylus

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    Background: The high transmission potential of species belonging to the monogenean parasite genus Gyrodactylus, coupled with their high fecundity, allows them to rapidly colonise new hosts and to increase in number. One gyrodactylid, Gyrodactylus salaris Malmberg, 1957, has been responsible for devastation of Altantic salmon (Salmo salar L.) populations in a number of Norwegian rivers. Current methods of eradicating G. salaris from river systems centre around the use of non-specific biocides, such as rotenone and aluminium sulphate. Although transmission routes in gyrodactylids have been studied extensively, the behaviour of individual parasites has received little attention. Specimens of Gyrodactylus gasterostei Gl&auml;ser, 1974 and G. arcuatus Bychowsky, 1933, were collected from the skin of their host, the three-spined stickleback (Gasterosteus aculeatus L.), and permitted to attach to the substrate. The movements of individual parasites were recorded and analysed. Results: The behaviour patterns of the two species were similar and parasites were more active in red light and darkness than in white light. Four octopaminergic compounds were tested and all four inhibited the movements of parasites. Treatment ultimately led to death at low concentrations (0.2 &mu;M), although prolonged exposure was necessary in some instances. Conclusions: Octopaminergic compounds may affect the parasite's ability to locate and remain on its host and these or related compounds might provide alternative or supplementary treatments for the control of G. salaris infections. With more research there is potential for use of octopaminergic compounds, which have minimal effects on the host or its environment, as parasite-specific treatments against G. salaris infections

    Malaria risk factors in north-east Tanzania

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    BACKGROUND: Understanding the factors which determine a household's or individual's risk of malaria infection is important for targeting control interventions at all intensities of transmission. Malaria ecology in Tanzania appears to have reduced over recent years. This study investigated potential risk factors and clustering in face of changing infection dynamics. METHODS: Household survey data were collected in villages of rural Muheza district. Children aged between six months and thirteen years were tested for presence of malaria parasites using microscopy. A multivariable logistic regression model was constructed to identify significant risk factors for children. Geographical information systems combined with global positioning data and spatial scan statistic analysis were used to identify clusters of malaria. RESULTS: Using an insecticide-treated mosquito net of any type proved to be highly protective against malaria (OR 0.75, 95% CI 0.59-0.96). Children aged five to thirteen years were at higher risk of having malaria than those aged under five years (OR 1.71, 95% CI 1.01-2.91). The odds of malaria were less for females when compared to males (OR 0.62, 95% CI 0.39-0.98). Two spatial clusters of significantly increased malaria risk were identified in two out of five villages. CONCLUSIONS: This study provides evidence that recent declines in malaria transmission and prevalence may shift the age groups at risk of malaria infection to older children. Risk factor analysis provides support for universal coverage and targeting of long-lasting insecticide-treated nets (LLINs) to all age groups. Clustering of cases indicates heterogeneity of risk. Improved targeting of LLINs or additional supplementary control interventions to high risk clusters may improve outcomes and efficiency as malaria transmission continues to fall under intensified control
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