Table 1. TDR engagement in development research for field-based RDT for detection of visceral leishmaniasis in the Indian subcontinent.

Author Year Country Reference	Year/Extent of TDR Engagement	Study Design Subjects Sample Size	Results	Conclusion
Chappuis 2003 Nepal [30]	1999–2000 Funding Authorship	Diagnostic evaluation (rK39 ICT, DAT) study 184 VL patients	rK39 ICT sens– 97%, spec– 71%; DAT sens– 99%, spec– 82%;	rK39 ICT compares well with DAT; easy to use in field setting; rK39 ICT can be used for screening test for VL and as a confirmatory test for VL only in high prevalence VL areas due to its high PPV
Boelaert 2004 Nepal [28]	2000–2002 Authorship	Diagnostic (rK39 ICT, FGT, IFAT, DAT) evaluation study 310 VL patients	rK39 ICT sens– 87.4%, spec– 93.1%; FGT sens– 39.9%; IFAT sens– 28.4%; DAT sens– 95.1%	DAT, rK39 ICT can replace parasite diagnosis by bone marrow or splenic aspirate as basis for decision to treat VL in national VL elimination programme
Chappuis 2006 Nepal [31]	2001–2002 Funding Authorship	Diagnostic (rK39 ICT, FGT, KAtex) evaluation study 85 VL patients	rK39 ICT sens– 89%, spec– 90%; FGT sens– 52%; KAtex sens– 57%; Reproducibility higher for rK39 ICT (κ = 0.87) compared to FGT and KAtex;	rK39 ICT meets most criteria of ASSURED [37]
Sundar 2007 India [34]	2005 Funding	Diagnostic (rK39 ICT, rK26 ICT, DAT-FD, KAtex) evaluation study 282 VL patients	rK39 ICT sens– 98.9%, spec– 97%; DAT-FD sens– 98.9%, spec– 94%; KAtex sens– 67%;, spec– 99%; rk26 ICT sens– 21.3%, spec– 100%; Reproducibility high (κ>0.94) for all tests; High agreement between rK39 ICT and DAT-FD (κ = 0.986);	rK39 ICT easy to use in field and preferred RDT for VL elimination programme
Boelaert 2008 India, Nepal, East Africa [29]	2003–2006 Funding Authorship	Diagnostic (rK39 ICT, DAT-FD, KAtex) evaluation study 1,150 VL patients	rK39 ICT, DAT-FD sens > 96%, spec– 90%; DAT-FD sens– 98%, spec– 91%; KAtex sens– 35–66%;, spec– 87–97%; Reproducibility high (κ > 0.94) for DAT-FD, rK39 ICT	DAT-FD, rK39 ICT performance variable and lower in East Africa; DAT-FD, rK39 ICT recommended for clinical practice in Indian subcontinent
Mohapatra 2010 India [26]	Funding	Diagnostic (rK9, rK26, rK39, CSA, ELISA) evaluation study 55 VL patients	rK39 sens– 100%, spec– 96% rK9 sens– 78%, spec– 84% rK26 sens– 38%, spec– 80% CSA sens– 80%, spec– 72%	rK39 most suitable antigen compared to rk9, rk26, CSA; rK9 antigen may be used as adjunct to rK39 for accurate diagnosis of VL or if rK39 antigen not available
WHO 2011 ISC, East Africa, South America [20]	2009 Funding Authorship	Diagnostic (5 commercial RDTs—rK39 ICT, rkE16 ICT) evaluation study 250 VL patients 9 testing laboratories (4 in Indian subcontinent)	Accuracy of RDTs between centres comparable but significantly different between regions; sens, spec, reproducibility (operator to operator, run to run), heat stability high for all RDTs in Indian subcontinent, variable in East Africa, South America	In Indian subcontinent, all brands of RDTs performed well; Need to establish minimal performance limits; Results can be used to guide procurement.
Cunningham 2012 ISC, East Africa, South America[39]	2009 Funding Authorship	Diagnostic (five commercial rK39 ICT) evaluation study 550 VL patients	All rK39 ICTs good sens (92.8–100%) and spec (96–100%) in Indian subcontinent; Lower and variable sens in East Africa and South America; Reproducibility (operator to operator, run to run) high (κ = 0.73–0.99)	Commercial rK39 ICT kits performed well in Indian subcontinent; Need to assess performance in HIV-compromised VL patients
Reviews
Sundar 2002 ISC [24]	Funding	Review	Parasite diagnosis by splenic or marrow or skin lesion remains gold standard but with limitations; DAT limited by cost, multiple steps, incubation, and antigenic variation;	rK39 ICT good sens and spec, rapid results, and can be used in field setting; Need R&D for urine-based KAtex and field-adaptable version of PCR.
Boelaert 2007 [18]	Authorship	Review of considerations for evaluation of diagnostic tests (test for case detection, cure, relapse, surveillance, drug resistance, certification of elimination)	High performance of rK39 ICT (InBios) in India [32]; lower spec (71%) in Nepal in early prototype; higher spec [30] in later generation of InBios ICT [28] and with DiaMed ICT [40];	Need to standardize methodology for evaluation of RDTs to prevent substandard or counterfeit products being used in endemic areas.

Abbreviations: CSA, crude soluble antigen; DAT-FD, direct agglutination test, freeze-dried antigen; FGT, formol gel test; ICT, immunochromatographic card test; IFAT, immunofluorescent antibody test; ISC, Indian subcontinent; KAtex, latex agglutination test for leishmania antigen; R&D, research and development; RDT, rapid diagnostic test; rK9, recombinant kinesin 9; rK26, recombinant kinesin antigen 26; rK39, recombinant kinesin antigen 39; sens, sensitivity; spec, specificity; VL, visceral leishmaniasis.