Leprosy Mailing List – April 19, 2013
Ref.: (LML) New Diagnostic Test
From: Diana NJ Lockwood, London, UK
Dear Pieter,
The new Diagnostic Test (LID and |PGL-I) for Leprosy – what does it add to PGL testing? Thank you Wim van Brakel (LML Mar 4 2013 – see attached file) for laying out some useful points about the new leprosy diagnostic test. I agree that the press coverage was unfortunate using phrase such as "Taking diagnosis out of the Dark Ages". This portrays a very negative view of the work of the leprosy world and acts against those working to lessen leprosy stigma.
There are some aspects of the new test that it would be useful to be aware of and discuss:
1. What is the new test and what data supports its use?
The new test detects antibodies against PGL-1 and two protein antigen which are a fusion protein (LID). Serological testing for PGL-1 has been done for over 40 years and there is a large literature on the strengths and weakness of this test. People should be aware that this is not a new test, it is an "Old test Plus"
2. The new component of the test is the detection of antibodies against LID.
Duthie et al have published several papers looking at the antibody produced by leprosy patients of different types to different protein antigens.
- In Venezuela (1) (Duthie 2011) patients across the Ridley-Jopling spectrum were tested for sero-positivity to LID with rates of 97% for LL patients, 96.4 % for BL and 76.9 % for BB. Tthe figures for BT and TT sero-positivity are not given but from their figures appear to be low and zero for BT and TT patients respectively.
- In Brazil (1) (Duthie 2011) sero-positivity rates across the spectrum can be compared for PGL-1 and LID. Numerical data is not given but the sero-positivity rates look very similar. So it is not clear what extra value is gained from adding in testing for LID antibodies. What Duthie et al have shown is that leprosy patients produce antibodies to protein antigens in a manner that correlates with bacterial load. This is a long way from a new diagnostic test.
3. Any new diagnostic test has to be compared against the old test.
In Brazil (2) (Hungria 2012) compared PGL-1 and LID sero-positivity rates and found rates of 89% and 83% for LL patients respectively. There is also no analysis of the differences between the patients responses to these two tests. So there is little evidence to show that adding testing for these protein antigens will detect more or new patients.
4. The major drawback of the test is that is BT and TT patients do not produce antibodies to LID or PGL-1 so the test cannot be used to exclude leprosy. This significantly reduces the field applicability of the test.
5. The usefulness of the test is further limited by the relatively high rate of sero-positivity, 11.5% in house hold contacts of new leprosy patients.
6. There are no publications in peer reviewed journals on the dipstix format of this test. So this is another aspect that cannot be reviewed.
7. Dr Shen Jiaping (LML Mar 7 2013) has also commented on his field experience of serological testing for PGL-1 antibodies reminding us that not all people with detectable antibodies to PGL-1 go on to develop disease and pointing out other shortcomings found with PGL antibody testing. I am sure that the same shortcomings will be found with this new diagnostic test because it is based on PGL-1.
8. The test has been promoted as a test for early leprosy but this is unlikely to happen because patients with early leprosy are more likely to be BT type.
9. These limitations also mean that testing for positive and negative predictive values will be difficult to do – will they be done just in patients with MB leprosy?
10. The test also needs to be done in the general clinic setting where patients with other diagnoses are attending. Since it is negative in BT leprosy patients it will not be useful in the differential diagnosis of other skin granulomatous conditions such as Tuberculosis and sarcoid.
11. This test has been promoted as a new test for leprosy is in fact an old test that will detect some patients with leprosy.
12. The problem with over-promoting a new test for leprosy is that it obscures the reality that we badly need a field friendly test for paucibacillary leprosy. This will need the skill and effort of researchers doing smart translational work on cellular immunology. The best options at the moment are probably the T cell based tests that are being developed and use a new detection method for detecting interferon gamma using up-converting phosphor technology.(3) The possibility of combining these with a serological test offers the possibility of a test that could be used to detect patients across the spectrum.
I would also concur with Wim that we still need to focus on health education so that people report early, this remains the best way of detecting new patients.
Diana NJ Lockwood
London School of Hygiene & Tropical Medicine.
Apr 16 2013
References
1. Duthie MS, Hay MN, Rada EM, Convit J, Ito L, Oyafuso LK, et al. Specific IgG antibody responses may be used to monitor leprosy treatment efficacy and as recurrence prognostic markers. European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology. 2011 Oct;30(10):1257-65. PubMed PMID: 21544695. Epub 2011/05/06. eng.
2. Hungria EM, de Oliveira RM, de Souza AL, Costa MB, de Souza VN, Silva EA, et al. Seroreactivity to new Mycobacterium leprae protein antigens in different leprosy-endemic regions in Brazil. Memorias do Instituto Oswaldo Cruz. 2012 Dec;107 Suppl 1:104-11. PubMed PMID: 23283461.
3. Geluk A. Biomarkers for leprosy: would you prefer T (cells)? Lepr Rev. 2013;84(1):3-12.
LML - S Deepak, B Naafs, S Noto and P Schreuder
The link for the LML archives is http://www.aifo.it/english/leprosy/mailing_list/index.htm
Contact: Dr Pieter Schreuder << editorlml@gmail.com >>.
LML - S Deepak, B Naafs, S Noto and P Schreuder
LML Archives: http://www.aifo.it/english/resources/online/lml-archives/index.htm
Contact: Dr Pieter Schreuder << editorlml@gmail.com >>.
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