Strict adherence to malaria rapid test results might lead to a neglect of other dangerous diseases: a cost benefit analysis from Burkina Faso

<p>Abstract</p> <p>Background</p> <p>Malaria rapid diagnostic tests (RDTs) have generally been found reliable and cost-effective. In Burkina Faso, the adherence of prescribers to the negative test result was found to be poor. Moreover, the test accuracy for malaria-attributable fever (MAF) is not the same as for malaria infection. This paper aims at determining the costs and benefits of two competing strategies for the management of MAF: presumptive treatment for all or use of RDTs.</p> <p>Methods</p> <p>A cost benefit analysis was carried out using a decision tree, based on data previously obtained, including a randomized controlled trial (RCT) recruiting 852 febrile patients during the dry season and 1,317 in the rainy season. Cost and benefit were calculated using both the real adherence found by the RCT and assuming an ideal adherence of 90% with the negative result. The main parameters were submitted to sensitivity analysis.</p> <p>Results and discussion</p> <p>At real adherence, the test-based strategy was dominated. Assuming ideal adherence, at the value of 525 € for a death averted, the total cost of managing 1,000 febrile children was 1,747 vs. 1,862 € in the dry season and 1,372 vs. 2,138 in the rainy season for the presumptive vs. the test-based strategy. For adults it was 2,728 vs. 1,983 and 2,604 vs. 2,225, respectively. At the subsidized policy adopted locally, assuming ideal adherence, the RDT would be the winning strategy for adults in both seasons and for children in the dry season.</p> <p>At sensitivity analysis, the factors most influencing the choice of the better strategy were the value assigned to a death averted and the proportion of potentially severe NMFI treated with antibiotics in patients with false positive RDT results. The test-based strategy appears advantageous for adults if a satisfactory adherence could be achieved. For children the presumptive strategy remains the best choice for a wide range of scenarios.</p> <p>Conclusions</p> <p>For RDTs to be preferred, a positive result should not influence the decision to treat a potentially severe NMFI with antibiotics. In the rainy season the presumptive strategy always remains the better choice for children.</p

Estimating the burden of rhodesiense sleeping sickness during an outbreak in Serere, eastern Uganda

BACKGROUND: Zoonotic sleeping sickness, or HAT (Human African Trypanosomiasis), caused by infection with Trypanosoma brucei rhodesiense, is an under-reported and neglected tropical disease. Previous assessments of the disease burden expressed as Disability-Adjusted Life Years (DALYs) for this infection have not distinguished T.b. rhodesiense from infection with the related, but clinically distinct Trypanosoma brucei gambiense form. T.b. rhodesiense occurs focally, and it is important to assess the burden at the scale at which resource-allocation decisions are made. METHODS: The burden of T.b. rhodesiense was estimated during an outbreak of HAT in Serere, Uganda. We identified the unique characteristics affecting the burden of rhodesiense HAT such as age, severity, level of under-reporting and duration of hospitalisation, and use field data and empirical estimates of these to model the burden imposed by this and other important diseases in this study population. While we modelled DALYs using standard methods, we also modelled uncertainty of our parameter estimates through a simulation approach. We distinguish between early and late stage HAT morbidity, and used disability weightings appropriate for the T.b. rhodesiense form of HAT. We also use a model of under-reporting of HAT to estimate the contribution of un-reported mortality to the overall disease burden in this community, and estimate the cost-effectiveness of hospital-based HAT control. RESULTS: Under-reporting accounts for 93% of the DALY estimate of rhodesiense HAT. The ratio of reported malaria cases to reported HAT cases in the same health unit was 133:1, however, the ratio of DALYs was 3:1. The age productive function curve had a close correspondence with the HAT case distribution, and HAT cases occupied more patient admission time in Serere during 1999 than all other infectious diseases other than malaria. The DALY estimate for HAT in Serere shows that the burden is much greater than might be expected from its relative incidence. Hospital based control in this setting appears to be highly cost-effective, highlighting the value of increasing coverage of therapy and reducing under-reporting. CONCLUSION: We show the utility of calculating DALYs for neglected diseases at the local decision making level, and emphasise the importance of improved reporting systems for acquiring a better understanding of the burden of neglected zoonotic diseases

The Detectability of Earth's Biosignatures Across Time

Over the past two decades, enormous advances in the detection of exoplanets have taken place. Currently, we have discovered hundreds of earth-sized planets, several of them within the habitable zone of their star. In the coming years, the efforts will concentrate in the characterization of these planets and their atmospheres to try to detect the presence of biosignatures. However, even if we discovered a second Earth, it is very unlikely that it would present a stage of evolution similar to the present-day Earth. Our planet has been far from static since its formation about 4.5 Ga ago; on the contrary, during this time, it has undergone multiple changes in it's atmospheric composition, it's temperature structure, it's continental distribution, and even changes in the forms of life that inhabit it. All these changes have affected the global properties of Earth as seen from an astronomical distance. Thus, it is of interest not only to characterize the observables of the Earth as it is today, but also at different epochs. Here we review the detectability of the Earth's globally-averaged properties over time. This includes atmospheric composition and biosignatures, and surface properties that can be interpreted as sings of habitability (bioclues). The resulting picture is that truly unambiguous biosignatures are only detectable for about 1/4 of the Earth's history. The rest of the time we rely on detectable bioclues that can only establish an statistical likelihood for the presence of life on a given planet.Comment: To appear in "Handbook of Exoplanets", eds. Deeg, H.J. & Belmonte, J.A, Springer (2018). arXiv admin note: text overlap with arXiv:astro-ph/0609398 by other author

Evaluating the impact of screening plus eave tubes on malaria transmission compared to current best practice in central Côte d'Ivoire : A two armed cluster randomized controlled trial

Background: Access to long-lasting insecticidal nets (LLINs) has increased and malaria has decreased globally, but malaria transmission remains high in parts of sub-Saharan Africa and insecticide resistance threatens current progress. Eave tubes are a new tool for the targeted delivery of insecticides against mosquitoes attempting to enter houses. The primary objective of this trial is to test whether screening plus eave tubes (SET) provides protection against malaria, on top of universal coverage with LLINs in an area of intense pyrethroid resistance. The trial will also assess acceptability and cost-effectiveness of the intervention. Methods/design: A two-armed, cluster randomized controlled trial will be conducted to evaluate the effect of SET on clinical malaria incidence in children living in central Côte d'Ivoire. Forty villages will be selected based on population size and the proportion of houses suitable for modification with SET. Using restricted randomization, half the villages will be assigned to the treatment arm (SET + LLINs) and the remainder will be assigned to the control arm (LLINs only). In both arms, LLINs will be distributed and in the treatment arm, householders will be offered SET. Fifty children aged six months to eight years old will be enrolled from randomly selected households in each of the 40 villages. Cohorts will be cleared of malaria parasites at the start of the study and one year after recruitment, and will be monitored for clinical malaria case incidence by active case detection over two years. Mosquito densities will be assessed using CDC light traps and human landing catches and a subset of Anopheles mosquitoes will be examined for parity status and tested for sporozoite infection. Acceptability of SET will be monitored using surveys and focus groups. Cost-effectiveness analysis will measure the incremental cost per case averted and per disability-adjusted life year (DALY) averted of adding SET to LLINs. Economic and financial costs will be estimated from societal and provider perspective using standard economic evaluation methods. Discussion: This study will be the first evaluation of the epidemiological impact of SET. Trial findings will show whether SET is a viable, cost-effective technology for malaria control in Côte d'Ivoire and possibly elsewhere. Trial registration: ISRCTN18145556, registered on 01 February 2017 - retrospectively registered

Modular Formal Specification of Data and Behaviour

We propose a modular approach to the formal specification of the requirements on embedded systems. In this approach, requirements on data are specified as invariants on states. Requirements on behaviour are specified assertionally by temporal logic formulae, restricting the runs of the system. The proposed method is modular, because components can be specified and analysed in isolation, and the views of several components can be combined in an easy way. Requirements can be combined by simply putting them in conjunction. A mathematical framework supporting this approach is developed and implemented in the theorem prover PVS. The method is illustrated by formalising the requirements of a miniature embedded system. This specification is then analysed using the theorem prover, revealing some errors in the original specification

Specification and Checking of Software Contracts for Conditional Information Flow ⋆

Abstract. Information assurance applications built according to the MILS (Multiple Independent Levels of Security) architecture often contain information flow policies that are conditional in the sense that data is allowed to flow between system components only when the system satisfies certain state predicates. However, existing specification and verification environments, such as SPARK Ada, used to develop MILS applications can only capture unconditional information flows. Motivated by the need to better formally specify and certify MILS applications in industrial contexts, we present an enhancement of the SPARK information flow annotation language that enables specification, inferring, and compositional checking of conditional information flow contracts. We report on the use of this framework for a collection of SPARK examples.