37 research outputs found

    Using molecular data for epidemiological inference: assessing the prevalence of Trypanosoma brucei rhodesiense in Tsetse in Serengeti, Tanzania

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    Background: Measuring the prevalence of transmissible Trypanosoma brucei rhodesiense in tsetse populations is essential for understanding transmission dynamics, assessing human disease risk and monitoring spatio-temporal trends and the impact of control interventions. Although an important epidemiological variable, identifying flies which carry transmissible infections is difficult, with challenges including low prevalence, presence of other trypanosome species in the same fly, and concurrent detection of immature non-transmissible infections. Diagnostic tests to measure the prevalence of T. b. rhodesiense in tsetse are applied and interpreted inconsistently, and discrepancies between studies suggest this value is not consistently estimated even to within an order of magnitude. Methodology/Principal Findings: Three approaches were used to estimate the prevalence of transmissible Trypanosoma brucei s.l. and T. b. rhodesiense in Glossina swynnertoni and G. pallidipes in Serengeti National Park, Tanzania: (i) dissection/microscopy; (ii) PCR on infected tsetse midguts; and (iii) inference from a mathematical model. Using dissection/microscopy the prevalence of transmissible T. brucei s.l. was 0% (95% CI 0–0.085) for G. swynnertoni and 0% (0–0.18) G. pallidipes; using PCR the prevalence of transmissible T. b. rhodesiense was 0.010% (0–0.054) and 0.0089% (0–0.059) respectively, and by model inference 0.0064% and 0.00085% respectively. Conclusions/Significance: The zero prevalence result by dissection/microscopy (likely really greater than zero given the results of other approaches) is not unusual by this technique, often ascribed to poor sensitivity. The application of additional techniques confirmed the very low prevalence of T. brucei suggesting the zero prevalence result was attributable to insufficient sample size (despite examination of 6000 tsetse). Given the prohibitively high sample sizes required to obtain meaningful results by dissection/microscopy, PCR-based approaches offer the current best option for assessing trypanosome prevalence in tsetse but inconsistencies in relating PCR results to transmissibility highlight the need for a consensus approach to generate meaningful and comparable data

    Search for sterile neutrino mixing in the MINOS long-baseline experiment

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    A search for depletion of the combined flux of active neutrino species over a 735 km baseline is reported using neutral-current interaction data recorded by the MINOS detectors in the NuMI neutrino beam. Such a depletion is not expected according to conventional interpretations of neutrino oscillation data involving the three known neutrino flavors. A depletion would be a signature of oscillations or decay to postulated noninteracting sterile neutrinos, scenarios not ruled out by existing data. From an exposure of 3.18×1020 protons on target in which neutrinos of energies between ~500¿¿MeV and 120 GeV are produced predominantly as ¿µ, the visible energy spectrum of candidate neutral-current reactions in the MINOS far detector is reconstructed. Comparison of this spectrum to that inferred from a similarly selected near-detector sample shows that of the portion of the ¿µ flux observed to disappear in charged-current interaction data, the fraction that could be converting to a sterile state is less than 52% at 90% confidence level (C.L.). The hypothesis that active neutrinos mix with a single sterile neutrino via oscillations is tested by fitting the data to various models. In the particular four-neutrino models considered, the mixing angles ¿24 and ¿34 are constrained to be less than 11° and 56° at 90% C.L., respectively. The possibility that active neutrinos may decay to sterile neutrinos is also investigated. Pure neutrino decay without oscillations is ruled out at 5.4 standard deviations. For the scenario in which active neutrinos decay into sterile states concurrently with neutrino oscillations, a lower limit is established for the neutrino decay lifetime t3/m3>2.1×10-12¿¿s/eV at 90% C.L

    An Agent-Based Model of Tsetse Fly Response to Seasonal Climatic Drivers: Assessing the Impact on Sleeping Sickness Transmission Rates

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    ackgroundThis paper presents the development of an agent-based model (ABM) to incorporate climatic drivers which affect tsetse fly (G. m. morsitans) population dynamics, and ultimately disease transmission. The model was used to gain a greater understanding of how tsetse populations fluctuate seasonally, and investigate any response observed in Trypanosoma brucei rhodesiense human African trypanosomiasis (rHAT) disease transmission, with a view to gaining a greater understanding of disease dynamics. Such an understanding is essential for the development of appropriate, well-targeted mitigation strategies in the future.MethodsThe ABM was developed to model rHAT incidence at a fine spatial scale along a 75 km transect in the Luangwa Valley, Zambia. The model incorporates climatic factors that affect pupal mortality, pupal development, birth rate, and death rate. In combination with fine scale demographic data such as ethnicity, age and gender for the human population in the region, as well as an animal census and a sample of daily routines, we create a detailed, plausible simulation model to explore tsetse population and disease transmission dynamics.ResultsThe seasonally-driven model suggests that the number of infections reported annually in the simulation is likely to be a reasonable representation of reality, taking into account the high levels of under-detection observed. Similar infection rates were observed in human (0.355 per 1000 person-years (SE = 0.013)), and cattle (0.281 per 1000 cattle-years (SE = 0.025)) populations, likely due to the sparsity of cattle close to the tsetse interface. The model suggests that immigrant tribes and school children are at greatest risk of infection, a result that derives from the bottom-up nature of the ABM and conditioning on multiple constraints. This result could not be inferred using alternative population-level modelling approaches.ConclusionsIn producing a model which models the tsetse population at a very fine resolution, we were able to analyse and evaluate specific elements of the output, such as pupal development and the progression of the teneral population, allowing the development of our understanding of the tsetse population as a whole. This is an important step in the production of a more accurate transmission model for rHAT which can, in turn, help us to gain a greater understanding of the transmission system as a whole

    Anti-trypanosomatid drug discovery:an ongoing challenge and a continuing need

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    Charge-separated atmospheric neutrino-induced muons in the MINOS far detector

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    14 pages, 15 figuresWe found 140 neutrino-induced muons in 854.24 live days in the MINOS far detector. We looked for evidence of neutrino disappearance in this data set by computing the ratio of the number of low momentum muons to the sum of the number of high momentum and unknown momentum muons for both data and Monte Carlo expectation in the absence of neutrino oscillations. The ratio of data and Monte Carlo ratios is consistent with an oscillation signal. A fit to the data for the oscillation parameters excludes the null oscillation hypothesis at the 94% confidence level. We separated the muons by charge sign in both the data and Monte Carlo events and found the ratio of the total number of negative to positive muons in both samples. The ratio of those ratios is a test of CPT conservation. The result is consistent with CPT conservation

    Observation of Muon Neutrino Disappearance with the MINOS Detectors in the NuMI Neutrino Beam

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    This Letter reports results from the MINOS experiment based on its initial exposure to neutrinos from the Fermilab NuMI beam. The rates and energy spectra of charged current νμ interactions are compared in two detectors located along the beam axis at distances of 1 and 735 km. With 1.27×1020 120 GeV protons incident on the NuMI target, 215 events with energies below 30 GeV are observed at the Far Detector, compared to an expectation of 336±14 events. The data are consistent with νμ disappearance via oscillations with |Δm322|=2.74-0.26+0.44×10-3  eV2 and sin⁡2(2θ23)>0.87 (68% C.L.)
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