Market assessment of tuberculosis diagnostics in China in 2012.

OBJECTIVE: To assess the 2012 served available market for tuberculosis (TB) diagnostics in China in the sector served by the China Centre for Disease Control and Prevention (CDC) and the hospital sector in China, including both designated TB hospitals and general hospitals. DESIGN: Test volumes and unit costs were assessed for tuberculin skin tests, interferon-gamma release assays (IGRAs), smear microscopy, serology, cultures, speciation tests, nucleic-acid amplification tests (NAATs), drug susceptibility tests and adenosine-deaminase tests (ADA). Data were obtained from electronic databases (CDC sector) and through surveys (hospital sector), and were estimated for the two sectors and for the country as a whole. Test costs were estimated by staff at China CDC, and using published literature. RESULTS: In 2012, the China CDC and hospital sectors performed a total of 44 million TB diagnostic tests at an overall value of US$294 million. Tests used by the CDC sector were smear microscopy, solid and liquid culture and DST, while the hospital sector also used IGRAs, NAATs, ADA and serology. The hospital sector accounted for 76% of the overall test volume and 94% of the market value. CONCLUSION: China has a very large TB diagnostic market that encompasses a wide range of diagnostic tests, with the majority being performed in Chinese hospitals.

Market assessment of tuberculosis diagnostics in India in 2013.

BACKGROUND: India represents a significant potential market for new tests. We assessed India's market for tuberculosis (TB) diagnostics in 2013. METHODS: Test volumes and unit costs were assessed for tuberculin tests, interferon-gamma release assays, sputum smear microscopy, serology, culture, speciation testing, nucleic-acid amplification tests (i.e., in-house polymerase chain reaction, Xpert(®) MTB/RIF, line-probe assays) and drug susceptibility testing. Data from the public sector were collected from the Revised National TB Control Programme reports. Private sector data were collected through a survey of private laboratories and practitioners. Data were also collected from manufacturers. RESULTS: In 2013, India's public sector performed 19.2 million tests, with a market value of US$22.9 million. The private sector performed 13.6 million tests, with a market value of US$60.4 million when prices charged to the patient were applied. The overall market was US$70.8 million when unit costs from the ingredient approach were used for the 32.8 million TB tests performed in the entire country. Smear microscopy was the most common test performed, accounting for 25% of the overall market value. CONCLUSION: India's estimated market value for TB diagnostics in 2013 was US$70.8 million. These data should be of relevance to test developers, donors and implementers.

Evaluation of Diagnos TB AG, a flow-through immunoassay for rapid detection of pulmonary tuberculosis.

We evaluated the diagnostic performance of the Diagnos TB AG immunoassay in 171 Tanzanians with suspected pulmonary tuberculosis (TB). The sensitivity and specificity, and positive and negative predictive values of the rapid test for the detection of pulmonary TB in this population were respectively 60.0%, 33.3%, 40.3% and 52.6%. In its current configuration, this test will not help overcome difficulties in the rapid diagnosis of TB.

A prodrug form of a Plasmodium falciparum glutathione reductase inhibitor conjugated with a 4-anilinoquinoline.

Glutathione (GSH), which is known to guard Plasmodium falciparum from oxidative damage, may have an additional protective role by promoting heme catabolism. An elevation of GSH content in parasites leads to increased resistance to chloroquine (CQ), while GSH depletion in resistant P. falciparum strains is expected to restore the sensitivity to CQ. High intracellular GSH levels depend inter alia on the efficient reduction of GSSG by glutathione reductase (GR). On the basis of this hypothesis, we have developed a new strategy for overcoming glutathione-dependent 4-aminoquinoline resistance. To direct both a 4-aminoquinoline and a GR inhibitor to the parasite, double-drugs were designed and synthesized. Quinoline-based alcohols (with known antimalarial activity) were combined with a GR inhibitor via a metabolically labile ester bond to give double-headed prodrugs. The biochemically most active double-drug 7 of this series was then evaluated as a growth inhibitor against six Plasmodium falciparum strains that differed in their degree of resistance to CQ; the ED(50) values for CQ ranged from 14 to 183 nM. While the inhibitory activity of the original 4-aminoquinoline-based alcohol followed that of CQ in these tests, the double-drug exhibited similar efficiency against all strains, the ED(50) being as low as 28 nM. For the ester 7, a dose-dependent decrease in glutathione content and GR activity and an increase in glutathione-S-transferase activity were determined in treated parasites. The drug was subsequently tested for its antimalarial action in vivo using murine malaria models infected with P. berghei. A 178% excess mean survival time was determined for the animals treated with 40 mg/kg 7 for 4 days. No cytotoxicity due to this compound was observed. Work is in progress to extend and validate the strategy outlined here.

Assembly and functional expression of murine glutathione reductase cDNA: a sequence missing in expressed sequence tag libraries.

Glutathione reductase (GR) is a chemotherapeutic target. Murine GRcDNA, which contains 85% GC in the 38 codons following the start codon, was assembled from the PCR-amplified exon 1 and a downstream cDNA prior to expression in Escherichia coli as a His(6)-tagged protein. Recombinant GR, an FAD-containing homodimer, corresponds in its enzymic and spectral properties to GR isolated from murine Ehrlich ascites tumor cells. Another cDNA, representing GR with a mitochondrial targeting sequence, yielded two distinct enzymically active expression products.