Slow parasite clearance, absent K13-propeller gene polymorphisms and adequate artesunate levels among patients with malaria: A pilot study from southern India.

Background: Artemisinin-based combination therapy (ACT) is widely used in India and many generic preparations are available. Delayed response has been reported, suggesting inadequate response to artesunate (AS) or genotypic resistance. We designed a prospective observational study to assess the therapeutic response, elaborate pharmacokinetics of AS and identify Plasmodium falciparum kelch 13 (pfk13) propeller gene polymorphisms among hospitalized Indian patients with severe malaria. Methods: We collected blood samples from adult patients with severe P. falciparum or mixed (P. falciparum and P. vivax) malaria on ACT. We calculated the parasite clearance (CL) half-life using the Worldwide Antimalarial Resistance Network (WWARN) online parasite clearance estimator (PCE). We used the liquid chromatography tandem mass spectrophoto-metry method for simultaneous quantification of AS and dihydroartemisinin. We genotyped longitudinally archived DNA samples obtained pre-treatment (day 0) to study the point mutations in the pfk13 propeller domain. Results: A total of 54 patients with malaria were included, with a majority fulfilling the definitions of severe malaria. The median parasite CL slope half-life was estimated to be 6.44 hours (interquartile range 4.79-10.24). AS pharmacokinetics, assessed in 17 patients, were found to be similar in the groups with rapid (<48 hours) and slow CL (>48 hours) of parasites. No known mutations associated with artemisinin resistance in Southeast Asia were observed in our study participants. Conclusions: Slow parasite CL was seen with a high parasite burden without genotypic evidence of AS resistance. There is a need to standardize definitions of therapeutic efficacy of AS in cases of severe malaria.

Comparative evaluation of validity and cost-benefit analysis of rapid diagnostic test (RDT) kits in diagnosis of dengue infection using composite reference criteria: A cross-sectional study from south India.

BACKGROUND & OBJECTIVES: Rapid diagnostic test (RDT) kits are widely used in India for the diagnosis of dengue infection. It is important to evaluate the validity and reliability of these RDTs. The study was aimed to determine the sensitivity, specificity and predictive value of four commercially available RDTs [Panbio Dengue Duo cassette, Standard Diagnostics (SD) Bioline Dengue Duo, J. Mitra Dengue Day-1 test and Reckon Dengue IgG/IgM] against composite reference criteria (CRC), and compare the cost of the tests. METHODS: In this prospective observational study for diagnostic accuracy, we tested stored blood samples from 132 cases of dengue and 149 controls of other infections as classified based on CRC, with all the four RDTs. The CRC was based on the epidemiological considerations, common clinical features and laboratory abnormalities. The non-dengue controls were the cases of proven alternative diagnosis. The diagnostic performances of the tests were compared in terms of sensitivity, specificity and predictive value along with the cost involved per test. RESULTS: The sensitivity of the Panbio and SD RDT kits was found to be 97.7 and 64.3% respectively, and the specificities were 87.8 and 96.6% respectively. The sensitivity of the NS1 antigen capture by SD Duo, Reckon, J. Mitra RDTs was 20.9, 18.6 and 27.1% respectively. The prevalence of dengue specific IgG antibody with Panbio RDT kits was 49.3%. The cost per test for Panbio, SD, Reckon and J. Mitra is US$ 6.90, 4.27, 3.29 and 3.61 respectively. CONCLUSION: It was concluded that in dengue outbreak, Panbio IgM capture RDT alone is reliable and easily available test which can be used in acute phase of dengue infection in any resource limited set up. NS1 capture rates by any of the other three RDTs might not be reliable for the diagnosis of acute dengue infection.