Cost-effectiveness of malaria microscopy and rapid diagnostic tests versus presumptive diagnosis: implications for malaria control in Uganda

BACKGROUND: Current Uganda National Malaria treatment guidelines recommend parasitological confirmation either by microscopy or rapid diagnostic test (RDT) before treatment with artemether-lumefantrine (AL). However, the cost-effectiveness of these strategies has not been assessed at rural operational primary care centres. METHODS: Three health centres (HCs) were randomized to three diagnostic arms (microscopy, RDT and presumptive diagnosis) in a district of low and another of high malaria transmission intensities in Uganda. Some 22,052 patients presenting with fever at outpatients departments were enrolled from March 2010 to February 2011. Of these, a random sample of 1,627 was selected to measure additional socio-economic characteristics. Costing was performed following the standard step-down cost allocation and the ingredients approach. Effectiveness was measured as the number and proportion of patients correctly diagnosed and treated. Incremental Cost-Effectiveness Ratios (ICERs) were estimated from the societal perspective (http://Clinicaltrials.gov, NCT00565071). RESULTS: Overall RDT was most cost-effective with lowest ICER US$5.0 compared to microscopy US$9.61 per case correctly diagnosed and treated. In the high transmission setting, ICER was US$4.38 for RDT and US$12.98 for microscopy. The corresponding ICERs in the low transmission setting were US$5.85 and US$7.63 respectively. The difference in ICERs between RDT and microscopy was greater in the high transmission area (US$8.9) than in low transmission setting (US$1.78). At a willingness to pay of US$2.8, RDT remained cost effective up to a threshold value of the cost of treatment of US$4.7. CONCLUSION: RDT was cost effective in both low and high transmission settings. With a global campaign to reduce the costs of AL and RDT, the Malaria Control Programme and stakeholders need a strategy for malaria diagnosis because as the cost of AL decreases, presumptive treatment is likely to become more attractive

Operational accuracy and comparative persistent antigenicity of HRP2 rapid diagnostic tests for Plasmodium falciparum malaria in a hyperendemic region of Uganda

BACKGROUND: Parasite-based diagnosis of malaria by microscopy requires laboratory skills that are generally unavailable at peripheral health facilities. Rapid diagnostic tests (RDTs) require less expertise, but accuracy under operational conditions has not been fully evaluated in Uganda. There are also concerns about RDTs that use the antigen histidine-rich protein 2 (HRP2) to detect Plasmodium falciparum, because this antigen can persist after effective treatment, giving false positive test results in the absence of infection. An assessment of the accuracy of Malaria Pf immuno-chromatographic test (ICT) and description of persistent antigenicity of HRP2 RDTs was undertaken in a hyperendemic area of Uganda. METHODS: Using a cross-sectional design, a total of 357 febrile patients of all ages were tested using ICT, and compared to microscopy as the gold standard reference. Two independent RDT readings were used to assess accuracy and inter-observer reliability. With a longitudinal design to describe persistent antigenicity of ICT and Paracheck, 224 children aged 6-59 months were followed up at 7-day intervals until the HRP2 antigens where undetectable by the RDTs. RESULTS: Of the 357 patients tested during the cross-sectional component, 40% (139) had positive blood smears for asexual forms of P. falciparum. ICT had an overall sensitivity of 98%, a specificity of 72%, a negative predictive value (NPV) of 98% and a positive predictive value (PPV) of 69%. ICT showed a high inter-observer reliability under operational conditions, with 95% of readings having assigned the same results (kappa statistics 0.921, p 50,000/microl, the mean duration of persistent antigenicity was 37 days compared to 26 days for parasitaemia less than 1,000/microl (log rank 21.9, p < 0.001). CONCLUSION: ICT is an accurate and appropriate test for operational use as a diagnostic tool where microscopy is unavailable. However, persistent antigenicity reduces the accuracy of this and other HRP2-based RDTs. The low specificity continues to be of concern, especially in children below five years of age. These pose limitations that need consideration, such as their use for diagnosis of patients returning with symptoms within two to four weeks of treatment. Good clinical skills are essential to interpret test results

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