Technical handbook for dengue surveillance, dengue outbreak prediction/detection and outbreak response (Model contingency plan)

This handbook was produced by TDR together with WHO’s Neglected Tropical Diseases (NTD) Department and WHO regional offices in the context of a European Union-financed research programme, the International Research Consortium on Dengue Risk Assessment, Management and Surveillance (IDAMS), to develop an evidence-based handbook for the early outbreak detec-tion and management of dengue fever outbreaks. The handbook targets public health providers, in particular those at national level. It is not an implementation guideline, but a framework for developing a national contingency plan with local adaptations that acknowledge micro-level pro-gramme components. Response planning requires contextual details encompassing the structure of the health and vector control services, the availability of infrastructure and budget, and human resources, and the willingness of staff to cooperate, among others. The aim of this “model contingency plan” is to assist programme managers and planners in devel-oping a national, context-specific, dengue outbreak response plan in order to: (a) detect a dengue outbreak at an early stage through clearly defined and validated alarm signals; (b) precisely define when a dengue outbreak has started; and (c) organize an early response to the alarm signals or an “emergency response” once an outbreak has started. A summary of this document, "Dengue Contingency Planning: From Research to Policy and Practice" (PNTD-D-16-00407R1) has also been published in PLOS Neglected Tropical Diseases

The heavy quark search at the LHC

We explore further the discovery potential for heavy quarks at the LHC, with emphasis on the $t'$ and $b'$ of a sequential fourth family associated with electroweak symmetry breaking. We consider QCD multijets, $t\bar{t}+\rm{jets}$, $W+\rm{jets}$ and single $t$ backgrounds using event generation based on improved matrix elements and low sensitivity to the modeling of initial state radiation. We exploit a jet mass technique for the identification of hadronically decaying $W$'s and $t$'s, to be used in the reconstruction of the $t'$ or $b'$ mass. This along with other aspects of event selection can reduce backgrounds to very manageable levels. It even allows a search for both $t'$ and $b'$ in the absence of $b$-tagging, of interest for the early running of the LHC. A heavy quark mass of order 600 GeV is motivated by the connection to electroweak symmetry breaking, but our analysis is relevant for any new heavy quarks with weak decay modes.Comment: 12 pages, 7 figure

Treatment practices for degedege, a locally recognized febrile illness, and implications for strategies to decrease mortality from severe malaria in Bagamoyo District, Tanzania

Malaria remains one of the chief causes of mortality among young children in sub-Saharan Africa. Verbal autopsies for cases of childhood mortality in Bagamoyo District, Tanzania demonstrated that degedege, a locally defined illness of children characterized by fever and convulsions, is frequently treated by traditional healers. To investigate this further, an ethnographic study was carried out in one village that included in-depth interviews with 14 traditional healers and 3 focus groups with parents. Parents and traditional healers were unanimous in their conviction that degedege requires traditional treatments, at least initially, and that these treatments are effective. While traditional healers do refer cases that are not improving to the District Hospital, this frequently occurs late in the course of the illness, after one or more stages of traditional treatments. The prognosis will thus be poor for those children who are suffering from severe malaria. Consideration should be given to enlisting the support of traditional healers in efforts to improve treatment for severe malaria, including teaching them how to distinguish febrile convulsions from cases of severe malaria

t' at the LHC: the physics of discovery

A search for a fourth family at the LHC is presently a low priority, but we argue that an effective search can be conducted early with only a few inverse femtobarns of data. We discuss a method based on invariant masses of single jets for identifying the $W$'s originating from heavy quark decays. This can significantly increase signal to background in the reconstruction of the $t'$ mass. We also study the various types of physics that can impact the background estimate, most notably higher order effects, initial state radiation, and models of the underlying event.Comment: 16 pages, 12 figures, small improvements, version to appear in JHE

Social sciences research in neglected tropical diseases 3: Investment in social science research in neglected diseases of poverty: a case study of Bill and Melinda Gates Foundation

This article has been made available through the Brunel Open Access Publishing Fund.BACKGROUND: The level of funding provides a good proxy for the level of commitment or prioritisation given to a particular issue. While the need for research relevant to social, economic, cultural and behavioural aspects of neglected tropical diseases (NTD) control has been acknowledged, there is limited data on the level of funding that supports NTD social science research. METHOD: A case study was carried out in which the spending of a major independent funder, the Bill and Melinda Gates Foundation (BMGF) - was analysed. A total of 67 projects funded between October 1998 and November 2008 were identified from the BMGF database. With the help of keywords within the titles of 67 grantees, they were categorised as social science or non-social science research based on available definition of social science. A descriptive analysis was conducted. RESULTS: Of 67 projects analysed, 26 projects (39%) were social science related while 41 projects (61%) were basic science or other translational research including drug development. A total of US$697 million was spent to fund the projects, of which 35$ 241 million) went to social science research. Although the level of funding for social science research has generally been lower than that for non-social science research over 10 year period, social science research attracted more funding in 2004 and 2008. CONCLUSION: The evidence presented in this case study indicates that funding on NTD social science research compared to basic and translational research is not as low as it is perceived to be. However, as there is the acute need for improved delivery and utilisation of current NTD drugs/technologies, informed by research from social science approaches, funding priorities need to reflect the need to invest significantly more in NTD social science research

Searching for Lee-Wick Gauge Bosons at the LHC

In an extension of the Standard Model(SM) based on the ideas of Lee and Wick, Grinstein, O'Connell and Wise have found an interesting way to remove the usual quadratically divergent contributions to the Higgs mass induced by radiative corrections. Phenomenologically, the model predicts the existence of Terascale, negative-norm copies of the usual SM fields with rather unique properties: ghost-like propagators and negative decay widths, but with otherwise SM-like couplings. The model is both unitary and causal on macroscopic scales. In this paper we examine whether or not such states with these unusual properties can be uniquely identified as such at the LHC. We find that in the extended strong and electroweak gauge boson sector of the model, which is the simplest one to analyze, such an identification can be rather difficult. Observation of heavy gluon-like resonances in the dijet channel offers the best hope for this identification.Comment: 17 pages, 4 figs; discussion adde

Laboratory demonstration of a prozone-like effect in HRP2-detecting malaria rapid diagnostic tests: implications for clinical management

Background: Malaria rapid diagnostic tests (RDTs) are now widely used for prompt on-site diagnosis in remote endemic areas where reliable microscopy is absent. Aberrant results, whereby negative test results occur at high parasite densities, have been variously reported for over a decade and have led to questions regarding the reliability of the tests in clinical use. Methods. In the first trial, serial dilutions of recombinant HRP2 antigen were tested on an HRP2-detectiing RDT. In a second trial, serial dilutions of culture-derived Plasmodium falciparum parasites were tested against three HRP2-detecting RDTs. Results: A prozone-like effect occurred in RDTs at a high concentration of the target antigen, histidine-rich protein-2 (above 15,000 ng/ml), a level that corresponds to more than 312000 parasites per L. Similar results were noted on three RDT products using dilutions of cultured parasites up to a parasite density of 25%. While reduced line intensity was observed, no false negative results occurred. Conclusions: These results suggest that false-negative malaria RDT results will rarely occur due to a prozone-like effect in high-density infections, and other causes are more likely. However, RDT line intensity is poorly indicative of parasite density in high-density infections and RDTs should, therefore, not be considered quantitative. Immediate management of suspected severe malaria should rely on clinical assessment or microscopy. Evaluation against high concentrations of antigen should be considered in malaria RDT product development and lot-release testing, to ensure that very weak or false negative results will not occur at antigen concentrations that might be seen clinically

Investigating portable fluorescent microscopy (CyScope®) as an alternative rapid diagnostic test for malaria in children and women of child-bearing age

<p>Abstract</p> <p>Background</p> <p>Prompt and correct diagnosis of malaria is crucial for accurate epidemiological assessment and better case management, and while the gold standard of light microscopy is often available, it requires both expertise and time. Portable fluorescent microscopy using the CyScope^®offers a potentially quicker, easier and more field-applicable alternative. This article reports on the strengths, limitations of this methodology and its diagnostic performance in cross-sectional surveys on young children and women of child-bearing age.</p> <p>Methods</p> <p>552 adults (99% women of child-bearing age) and 980 children (99% ≤ 5 years of age) from rural and peri-urban regions of Ugandan were examined for malaria using light microscopy (Giemsa-stain), a lateral-flow test (Paracheck-Pf^®) and the CyScope^®. Results from the surveys were used to calculate diagnostic performance (sensitivity and specificity) as well as to perform a receiver operating characteristics (ROC) analyses, using light microscopy as the gold-standard.</p> <p>Results</p> <p>Fluorescent microscopy (qualitative reads) showed reduced specificity (<40%), resulting in higher community prevalence levels than those reported by light microscopy, particularly in adults (+180% in adults and +20% in children). Diagnostic sensitivity was 92.1% in adults and 86.7% in children, with an area under the ROC curve of 0.63. Importantly, optimum performance was achieved for higher parasitaemia (>400 parasites/μL blood): sensitivity of 64.2% and specificity of 86.0%. Overall, the diagnostic performance of the CyScope was found inferior to that of Paracheck-Pf^®.</p> <p>Discussion</p> <p>Fluorescent microscopy using the CyScope^®is certainly a field-applicable and relatively affordable solution for malaria diagnoses especially in areas where electrical supplies may be lacking. While it is unlikely to miss higher parasitaemia, its application in cross-sectional community-based studies leads to many false positives (i.e. small fluorescent bodies of presently unknown origin mistaken as malaria parasites). Without recourse to other technologies, arbitration of these false positives is presently equivocal, which could ultimately lead to over-treatment; something that should be further explored in future investigations if the CyScope^®is to be more widely implemented.</p

Should colloid boluses be prioritized over crystalloid boluses for the management of dengue shock syndrome in the presence of ascites and pleural effusions?

<p>Abstract</p> <p>Background</p> <p>Although the WHO guideline for the management of dengue fever considers the presence of ascites or pleural effusions in the diagnosis of DSS, it does not emphasize the importance of their presence when selecting fluids for resuscitation.</p> <p>Case presentation</p> <p>We highlight three patients with DSS who received boluses of crystalloids on priority basis as recommended by WHO guidelines during resuscitation. All three patients had varying degrees of third space fluid loss (ascites and pleural effusions) at the time of development of DSS. Ascites and pleural effusions were detected in all 3 patients at the time of shock irrespective of whether iv fluids were given or not. All three patients had documented liver involvement at the time of shock evidenced by elevation of AST (4800 iu/L, 5000 iu/L and 1960 iu/L). One patient who had profound shock died 6 hours after admission with evidence of acute pulmonary oedema in the convalescence phase. All of them needed CPAP ventilator support and potent diuretics.</p> <p>Conclusions</p> <p>We therefore feel that resuscitation of patients with DSS who already have third space fluid accumulation with crystalloid boluses on priority basis may contribute to recovery phase pulmonary oedema.</p

A cost-effectiveness analysis of provider and community interventions to improve the treatment of uncomplicated malaria in Nigeria: study protocol for a randomized controlled trial.

BACKGROUND: There is mounting evidence of poor adherence by health service personnel to clinical guidelines for malaria following a symptomatic diagnosis. In response to this, the World Health Organization (WHO) recommends that in all settings clinical suspicion of malaria should be confirmed by parasitological diagnosis using microscopy or Rapid Diagnostic Test (RDT). The Government of Nigeria plans to introduce RDTs in public health facilities over the coming year. In this context, we will evaluate the effectiveness and cost-effectiveness of two interventions designed to support the roll-out of RDTs and improve the rational use of ACTs. It is feared that without supporting interventions, non-adherence will remain a serious impediment to implementing malaria treatment guidelines. METHODS/DESIGN: A three-arm stratified cluster randomized trial is used to compare the effectiveness and cost-effectiveness of: (1) provider malaria training intervention versus expected standard practice in malaria diagnosis and treatment; (2) provider malaria training intervention plus school-based intervention versus expected standard practice; and (3) the combined provider plus school-based intervention versus provider intervention alone. RDTs will be introduced in all arms of the trial. The primary outcome is the proportion of patients attending facilities that report a fever or suspected malaria and receive treatment according to malaria guidelines. This will be measured by surveying patients (or caregivers) as they exit primary health centers, pharmacies, and patent medicine dealers. Cost-effectiveness will be presented in terms of the primary outcome and a range of secondary outcomes, including changes in provider and community knowledge. Costs will be estimated from both a societal and provider perspective using standard economic evaluation methodologies. TRIAL REGISTRATION: Clinicaltrials.gov NCT01350752