Dedicated outreach service for hard to reach patients with tuberculosis in London: observational study and economic evaluation.

OBJECTIVE: To assess the cost effectiveness of the Find and Treat service for diagnosing and managing hard to reach individuals with active tuberculosis. DESIGN: Economic evaluation using a discrete, multiple age cohort, compartmental model of treated and untreated cases of active tuberculosis. SETTING: London, United Kingdom. Population Hard to reach individuals with active pulmonary tuberculosis screened or managed by the Find and Treat service (48 mobile screening unit cases, 188 cases referred for case management support, and 180 cases referred for loss to follow-up), and 252 passively presenting controls from London's enhanced tuberculosis surveillance system. MAIN OUTCOME MEASURES: Incremental costs, quality adjusted life years (QALYs), and cost effectiveness ratios for the Find and Treat service. RESULTS: The model estimated that, on average, the Find and Treat service identifies 16 and manages 123 active cases of tuberculosis each year in hard to reach groups in London. The service has a net cost of £1.4 million/year and, under conservative assumptions, gains 220 QALYs. The incremental cost effectiveness ratio was £6400-£10,000/QALY gained (about €7300-€11,000 or $10,000-$16 000 in September 2011). The two Find and Treat components were also cost effective, even in unfavourable scenarios (mobile screening unit (for undiagnosed cases), £18,000-£26,000/QALY gained; case management support team, £4100-£6800/QALY gained). CONCLUSIONS: Both the screening and case management components of the Find and Treat service are likely to be cost effective in London. The cost effectiveness of the mobile screening unit in particular could be even greater than estimated, in view of the secondary effects of infection transmission and development of antibiotic resistance

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

Contribution to the understanding of tribological properties of graphite intercalation compounds with metal chloride

Intrinsic tribological properties of lamellar compounds are usually attributed to the presence of van der Waals gaps in their structure through which interlayer interactions are weak. The controlled variation of the distances and interactions between graphene layers by intercalation of electrophilic species in graphite is used in order to explore more deeply the friction reduction properties of low-dimensional compounds. Three graphite intercalation compounds with antimony pentachloride, iron trichloride and aluminium trichloride are studied. Their tribological properties are correlated to their structural parameters, and the interlayer interactions are deduced from ab initio bands structure calculations

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

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

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 > 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

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

The 'lost child' as figure of trauma and recovery in early post-war cinema: Fred Zinnemann's The Search (1948) and Natan Gross's Unzere Kinder (1948)

The article examines the figure of the ‘lost child’ in feature films of the immediate post-war period. The figure’s enormous symbolic value as innocent victim and future generation, granted the ‘lost child’ a key position in post-war discourse, including films which tried to grapple with the moral and physical destruction of the continent after 1945. National film industries, particularly of the perpetrator nation, employed the ‘lost child’ for genre stories in which the post-war chaos is being mastered and a new, masculine national self is re-built. However, films made by victim groups outside a national context rely on the ‘lost child’ to broach the destruction of their identity by war and persecution. Analysing two films, Fred Zinnemann’s The Search (1948) and Nata Gross’s Unzere Kinder (1948), I argue that they use the child figure to deal with traumatization and make it part of the reconstruction of communal intergenerational relations. This does not result in stories of masculine mastery but in narratives that incorporate moments of trauma process emerging around destroyed mother-child relations. The films, encoding traumatization in film language, develop a rich cinematic language along questions of identity and form a first instance of posttraumatic cinema

Reduction of anti-malarial consumption after rapid diagnostic tests implementation in Dar es Salaam: a before-after and cluster randomized controlled study

ABSTRACT: BACKGROUND: Presumptive treatment of all febrile patients with anti-malarials leads to massive over-treatment. The aim was to assess the effect of implementing malaria rapid diagnostic tests (mRDTs) on prescription of anti-malarials in urban Tanzania. METHODS: The design was a prospective collection of routine statistics from ledger books and cross-sectional surveys before and after intervention in randomly selected health facilities (HF) in Dar es Salaam, Tanzania. The participants were all clinicians and their patients in the above health facilities. The intervention consisted of training and introduction of mRDTs in all three hospitals and in six HF. Three HF without mRDTs were selected as matched controls. The use of routine mRDT and treatment upon result was advised for all patients complaining of fever, including children under five years of age. The main outcome measures were: (1) anti-malarial consumption recorded from routine statistics in ledger books of all HF before and after intervention; (2) anti-malarial prescription recorded during observed consultations in cross-sectional surveys conducted in all HF before and 18 months after mRDT implementation. RESULTS: Based on routine statistics, the amount of artemether-lumefantrine blisters used post-intervention was reduced by 68% (95%CI 57-80) in intervention and 32% (9-54) in control HF. For quinine vials, the reduction was 63% (54-72) in intervention and an increase of 2.49 times (1.62-3.35) in control HF. Before-and-after cross-sectional surveys showed a similar decrease from 75% to 20% in the proportion of patients receiving anti-malarial treatment (Risk ratio 0.23, 95%CI 0.20-0.26). The cluster randomized analysis showed a considerable difference of anti-malarial prescription between intervention HF (22%) and control HF (60%) (Risk ratio 0.30, 95%CI 0.14-0.70). Adherence to test result was excellent since only 7% of negative patients received an anti-malarial. However, antibiotic prescription increased from 49% before to 72% after intervention (Risk ratio 1.47, 95%CI 1.37-1.59). CONCLUSIONS: Programmatic implementation of mRDTs in a moderately endemic area reduced drastically over-treatment with anti-malarials. Properly trained clinicians with adequate support complied with the recommendation of not treating patients with negative results. Implementation of mRDT should be integrated hand-in-hand with training on the management of other causes of fever to prevent irrational use of antibiotic

"Test and treat" or presumptive treatment for malaria in high transmission situations? A reflection on the latest WHO guidelines

Recent WHO guidelines recommend a universal "test and treat" strategy for malaria, mainly by use of rapid diagnostic test (RDT) in all areas. The evidence for this approach is questioned here as there is a risk of over-reliance on parasitological diagnosis in high transmission situations, which still exist. In such areas, when a patient has fever or other malaria symptoms, the presence of Plasmodium spp neither reliably confirms malaria as the cause of the fever, nor excludes the possibility of other diseases. This is because the patient may be an asymptomatic carrier of malaria parasites and suffer from another disease