An assessment of false positive rates for malaria rapid diagnostic tests caused by non-Plasmodium infectious agents and immunological factors.

BACKGROUND: Malaria rapid diagnostic tests (RDTs) can produce false positive (FP) results in patients with human African trypanosomiasis and rheumatoid factor (RF), but specificity against other infectious agents and immunological factors is largely unknown. Low diagnostic specificity caused by cross-reactivity may lead to over-estimates of the number of malaria cases and over-use of antimalarial drugs, at the cost of not diagnosing and treating the true underlying condition. METHODS: Data from the WHO Malaria RDT Product Testing Programme was analysed to assess FP rates of 221 RDTs against four infectious agents (Chagas, dengue, Leishmaniasis and Schistosomiasis) and four immunological factors (anti-nuclear antibody, human anti-mouse antibody (HAMA), RF and rapid plasma regain). Only RDTs with a FP rate against clean negative samples less than 10% were included. Paired t-tests were used to compare product-specific FP rates on clean negative samples and samples containing non-Plasmodium infectious agents and immunological factors. RESULTS: Forty (18%) RDTs showed no FP results against any tested infectious agent or immunological factor. In the remaining RDTs significant and clinically relevant increases in FP rates were observed for samples containing HAMA and RF (P<0.001). There were significant correlations between product-matched FP rates for RF and HAMA on all RDT test bands (P<0.001), and FP rates for each infectious agent and immunological factor were also correlated between test bands of combination RDTs (P≤0.002). CONCLUSIONS: False positive results against non-Plasmodium infectious agents and immunological factors does not appear to be a universal property of malaria RDTs. However, since many malaria RDTs have elevated FP rates against HAMA and RF positive samples practitioners may need to consider the possibility of false positive results for malaria in patients with conditions that stimulate HAMA or RF

Cost-effectiveness of interventions to reduce harm from amphetamine/methamphetamine use

Abstract Illicit methamphetamine (MA) use is an important public health concern in Australia. MA use is associated with increased health care and criminal justice spending (due to criminal activity associated with addiction). Current knowledge about effective and cost-effective treatments in Australia is limited and there is a clear need to determine the cost-effectiveness of treatment options for MA dependence. This thesis describes the economic evaluation of two community-based treatment programs for MA users. More specifically, this work evaluates the cost-effectiveness of counselling as an outpatient treatment modality and residential rehabilitation as an inpatient treatment modality for MA users, compared with no treatment. This thesis will also assess other criteria, including ‘second filter’ criteria, which may influence policy decisions about current treatment programs in the community. A cost-effectiveness framework was applied to newly available data from Australia – namely, the Methamphetamine Treatment Evaluation Study (MATES) conducted by the National Drug and Alcohol Research Centre (NDARC) of the University of New South Wales. In doing so, the health and cost outcomes associated with the two different treatment options and the non-treatment comparison group of MA users were identified. Both models, as used in the analysis of cost and health outcomes, feature a decision-tree type of models with each decision being a final decision in the decision tree node. Health–Related Quality of Life (HRQL) outcomes were obtained using the SF-6D algorithm to translate responses from the SF-12 Health Questionnaire used in MATES into a single preference-based utility score. The HRQL showed a statistically significant improvement at both 3 and 12 months follow-up compared with baseline among MATES participants for both groups. The HRQL for the residential treatment group was of greater magnitude than the other groups. The cost outcomes were evaluated on the basis of social perspective. Costs measured include treatment, crime, and health service utilisation costs. The analysis of cost and health outcomes (base case scenario discounted at 3% social preference rate and with all costs included in the analysis) indicated a difference in Quality-Adjusted Life Years, ∆QALY = 107 QALYs, costs difference of ∆Costs = -AU$18,364,110, and incremental cost-effectiveness ratio (ICER), ∆C/∆QALY, as dominant for counselling treatment modality compared with no treatment. Cost-effectiveness analysis of residential rehabilitation treatment modality compared with no treatment option indicates a QALY difference, ∆QALY = 68, difference in costs of ∆Costs = AU$1,301,630, and an ICER = AU$23,752 per QALY. Therefore, both interventions meet the cost-effectiveness criterion for cost-effectiveness (threshold below AU$76,000 per QALY), recommended by the Pharmaceutical Benefits Advisory Committee (PBAC) of Australia. The results of uncertainty analysis show the outcomes of the analysis given uncertainty surrounding parameter inputs in the model. Also, sensitivity analysis tested for major cost drivers in the model. Second stage filter criteria are used to address criteria other than cost-effectiveness for the two treatment options. The results of uncertainty analyses suggest that both interventions, counselling and residential rehabilitation when compared with no intervention and under given modelling limitations, are cost-effective strategies for managing the problems of MA dependence in Australian society. Even when different scenarios are considered in various uncertainty analyses, the ICER is either dominant or below the threshold of AU$76,000 per QALY for both interventions when compared with no intervention alternative. The results of sensitivity analyses for both interventions compared with no intervention suggest that costs of crime are major cost drivers for interventions, counselling compared with no intervention and residential rehabilitation compared with no intervention. The results suggest that policy changes towards interventions to reduce current harms in the society as well as on the individual level of users’ dependence are warranted. Firstly, more attention should be given to community treatment services that treat majority of MA users in Australia. Secondly, within the current treatment services for MA dependence in Australia, psychosocial forms of treatment such as counselling and residential rehabilitation treatments should be applied before other interventions are introduced. Thirdly, considerable savings in the Australian society are able to be achieved through the implementation of these two treatment modalities due to lower spending in the criminal justice sector after the application of treatment among MA users. The policy related implementation of the results of this study in the Australian society needs to be considered with caution in relation to the issue of efficacy versus effectiveness, i.e. findings of this study as compared to population wide impact and outcomes. Policy makers should recommend increased funding for the services providing community treatment services for MA users as this would effectively translate the results of this study into better results on cost and health outcomes on population level. Further policy related findings show that the implementation of both interventions, counselling and residential rehabilitation compared with a non-treatment option is suitable for the following reasons: (i) reduction of current inequities among MA users in the community; (ii) acceptance to stakeholders; (iii) feasibility of implementation; (iv) sustainability of the interventions; and (v) the potential for side effects is minimal for both interventions. This thesis demonstrates the cost-effectiveness of two treatment modalities for MA dependence in Australia in a transparent, standardised and evidence-based way. The findings can be used to inform policy-makers about how to better allocate resources and drive better policy decisions for treatment options for MA dependence

Drinking water fluoridation in South East Queensland: a cost-effectiveness evaluation

The aim of this study is to examine cost-effectiveness of fluoridation of drinking water supplies for Brisbane and South East Queensland. The benefits conveyed are expressed in reduced costs of dental treatment and years of life with dental caries as a disability.The analysis utilises a developed life table modelling initial cohort of 36,322 newborns, which when applied to the target population equals to 181,925 persons in the age group 2-100 years, 338,617 persons in the age group 7-100 years and 390,524 persons in the age group 12-100 years respectively. The analysis was conducted using a real discount rate of 3%. Sensitivity analyses investigated the effects of varying the parameters such as: discount rate, costs of dental treatment and costs of fluoridation plant. Uncertainty analysis was also conducted on costs and the measure of ratio of decayed, missing, filled teeth surfaces in deciduous dentition between the cities of Brisbane (non-fluoridated) and Townsville (fluoridated).If fluoridation was implemented there would be a total saving of $10,437.43 (95$ 665,686,529 (95% CI -$973,573,625-$381,322,176). This result is both desirable and dominant as more DALYs are saved along with significant cost savings.Fluoridation remains still a very cost-effective measure for reducing dental decay

Use of PfHRP2-only RDTs rapidly select for PfHRP2-negative parasites with serious implications for malaria case management and control

Background Rapid diagnostic tests (RDTs) are an important tool for malaria diagnosis, with most utilising antibodies against histidine-rich protein 2 (PfHRP2). Reports of Plasmodium falciparum lacking this protein are increasing, creating a problem for diagnosis of falciparum malaria in locations without quality microscopy. Methods An agent-based stochastic simulation model of P.falciparum transmission was used to investigate the selective pressure exerted on parasite populations by use of RDTs for diagnosis of symptomatic cases. The model considered parasites with normal, reduced or no PfHRP2, and diagnosis using PfHRP2-only or combination RDTs. Results Use of PfHRP2-only RDTs in communities where a PfHRP2-negative parasite was introduced during the simulation resulted in transmission of the parasite in over 80% of cases, compared to less than 30% for normal or PfHRP2-reduced parasites. Using PfHRP2-only RDTs in the presence of PfHRP2-negative parasites caused an increase in prevalence, reduced RDT positivity within symptomatic patients, but no change in number of antimalarial treatments due to false negative RDT results. Diagnosis with PfHRP2/Pf-pLDH combination RDTs didn’t select for PfHRP2-negative parasites. Conclusions Use of PfHRP2-only RDTs is sufficient to select P.falciparum parasites lacking this protein, thus posing a significant public health problem which could be moderated by using PfHRP2/Pf-pLDH combination RDTs

A review of psychological and pharmacological treatment options for methamphetamine dependence

Methamphetamine (MA) is a public health problem both in Australia and internationally and very little is known about the most cost-effective treatment options. This study is a review of recent studies and an assessment of current treatment options for MA dependence. Treatment options for MA dependence can be divided into outpatient and inpatient modality settings according to the level of drug use. Moderate improvements through higher rates of retention in treatment (especially residential rehabilitation) have been found in individuals who completed either cognitive-behavioural therapy or counselling as a form of outpatient treatment and in those users who completed a residential rehabilitation treatment programme at an inpatient treatment modality. There remains a need for further research to investigate the efficacy of existing treatment options in individuals with MA use problems and to address the economic impact of those interventions in terms of cost-effectiveness/cost utility

A review of psychological and pharmacological treatment options for methamphetamine dependence

Methamphetamine (MA) is a public health problem both in Australia and internationally and very little is known about the most cost-effective treatment options. This study is a review of recent studies and an assessment of current treatment options for MA dependence. Treatment options for MA dependence can be divided into outpatient and inpatient modality settings according to the level of drug use. Moderate improvements through higher rates of retention in treatment (especially residential rehabilitation) have been found in individuals who completed either cognitive-behavioural therapy or counselling as a form of outpatient treatment and in those users who completed a residential rehabilitation treatment programme at an inpatient treatment modality. There remains a need for further research to investigate the efficacy of existing treatment options in individuals with MA use problems and to address the economic impact of those interventions in terms of cost-effectiveness/cost utility. © 2012 Informa UK Ltd

Cost-effectiveness of counselling as a treatment option for methamphetamine dependence

© 2015 Informa UK Ltd. Introduction and aims: Illicit methamphetamine (MA) use is an important public health concern. There is a dearth of knowledge about effective and cost-effective treatments for methamphetamine (MA) dependence in Australia. This article evaluates the cost-effectiveness of counselling as a treatment option for illicit MA use compared with no treatment option. Design and methods: Data are from 501 individuals recruited into Methamphetamine Treatment Evaluation Study (MATES). The population of MA users from MATES is extrapolated to a total number of 1000 MA users in the intervention group (counselling treatment) and control group (non-treatment group). A decision analytic model is developed that examines the costs and health outcomes [measures as quality adjusted life years (QALYs) gained] for the treatment and comparison group over a 3-year period. A societal perspective is adopted and model inputs are subject to sensitivity and uncertainty analysis to test the robustness of results to parameter variability. Results are discounted by using 3% discount rate and expressed in 2011 Australian dollars. Results: The incremental cost-effectiveness analysis suggests that counselling is a dominant health care intervention, i.e. saves money and is more effective than a do nothing intervention. The incremental difference in costs is -AU$18.36 million (95$22.80 million to -AU$14.31 million) and the incremental difference in QALY is 107 (95$63832 per QALY in the Australian society. The results of the sensitivity analysis show that the ICER is most sensitive to change in five major inputs: baseline utility, utility at 3 months, dealing crime costs, property crime costs and fraud crime costs. Discussion and Conclusions: The economic evaluation of the cost-effectiveness of counselling for MA dependence, as a first cost-effectiveness study to assess psychosocial treatment options for MA dependence, shows that greater investment in this cost-effective strategy will produce significant cost-savings and improve health outcomes as well as improve a lot of externality issues associated with drug use