Identification of sVSG117 as an immunodiagnostic antigen and evaluation of a dual-antigen lateral flow test for the diagnosis of human african trypanosomiasis

The diagnosis of human African trypanosomiasis (HAT) caused by Trypanosoma brucei gambiense relies mainly on the Card Agglutination Test for Trypanosomiasis (CATT). There is no immunodiagnostic for HAT caused by T. b. rhodesiense. Our principle aim was to develop a prototype lateral flow test that might be an improvement on CATT.Pools of infection and control sera were screened against four different soluble form variant surface glycoproteins (sVSGs) by ELISA and one, sVSG117, showed particularly strong immunoreactivity to pooled infection sera. Using individual sera, sVSG117 was shown to be able to discriminate between T. b. gambiense infection and control sera by both ELISA and lateral flow test. The sVSG117 antigen was subsequently used with a previously described recombinant diagnostic antigen, rISG65, to create a dual-antigen lateral flow test prototype. The latter was used blind in a virtual field trial of 431 randomized infection and control sera from the WHO HAT Specimen Biobank.In the virtual field trial, using two positive antigen bands as the criterion for infection, the sVSG117 and rISG65 dual-antigen lateral flow test prototype showed a sensitivity of 97.3% (95% CI: 93.3 to 99.2) and a specificity of 83.3% (95% CI: 76.4 to 88.9) for the detection of T. b. gambiense infections. The device was not as good for detecting T. b. rhodesiense infections using two positive antigen bands as the criterion for infection, with a sensitivity of 58.9% (95% CI: 44.9 to 71.9) and specificity of 97.3% (95% CI: 90.7 to 99.7). However, using one or both positive antigen band(s) as the criterion for T. b. rhodesiense infection improved the sensitivity to 83.9% (95% CI: 71.7 to 92.4) with a specificity of 85.3% (95% CI: 75.3 to 92.4). These results encourage further development of the dual-antigen device for clinical use

Proteomic identification of immunodiagnostic antigens for <i>Trypanosoma vivax </i>infections in cattle and generation of a proof-of-concept lateral flow test diagnostic device

Trypanosoma vivax is one of the causative agents of Animal African Trypanosomosis in cattle, which is endemic in sub-Saharan Africa and transmitted primarily by the bite of the tsetse fly vector. The parasite can also be mechanically transmitted, and this has allowed its spread to South America. Diagnostics are limited for this parasite and in farm settings diagnosis is mainly symptom-based. We set out to identify, using a proteomic approach, candidate diagnostic antigens to develop into an easy to use pen-side lateral flow test device. Two related members the invariant surface glycoprotein family, TvY486_0045500 and TvY486_0019690, were selected. Segments of these antigens, lacking N-terminal signal peptides and C-terminal transmembrane domains, were expressed in E. coli. Both were developed into ELISA tests and one of them, TvY486_0045500, was developed into a lateral flow test prototype. The tests were all evaluated blind with 113 randomised serum samples, taken from 37 calves before and after infection with T. vivax or T. congolense. The TvY486_0045500 and TvY486_0019690 ELISA tests gave identical sensitivity and specificity values for T. vivax infection of 94.5% (95% CI, 86.5% to 98.5%) and 88.0% (95% CI, 75.7% to 95.5%), respectively, and the TvY486_0045500 lateral flow test prototype a sensitivity and specificity of 92.0% (95% CI, 83.4% to 97.0%) and 89.8% (95% CI, 77.8% to 96.6%), respectively. These data suggest that recombinant TvY486_0045500 shows promise for the development of a pen-side lateral flow test for the diagnosis of T. vivax animal African trypanosomosis

Cyclin-dependent kinase 12 is a drug target for visceral leishmaniasis

Visceral leishmaniasis causes considerable mortality and morbidity in many parts of the world. There is an urgent need for the development of new, effective treatments for this disease. Here we describe the development of an anti-leishmanial drug-like chemical series based on a pyrazolopyrimidine scaffold. The leading compound from this series (7, DDD853651/GSK3186899) is efficacious in a mouse model of visceral leishmaniasis, has suitable physicochemical, pharmacokinetic and toxicological properties for further development, and has been declared a preclinical candidate. Detailed mode-of-action studies indicate that compounds from this series act principally by inhibiting the parasite cdc-2-related kinase 12 (CRK12), thus defining a druggable target for visceral leishmaniasis

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Not AvailableDesertification is the transformation of productive land into a non-productive one due to poor resource management, and unfavourable biophysical and economical factors. Periodical assessment of desertification status is imperative for a suitable comprehensive and combating plan. In the present study, desertification status maps of Andhra Pradesh (AP), Karnataka and Telangana in South India have been prepared using remote sensing data for two time-frames (2003– 2005 and 2011–2013) and change detection analysis has been carried out. The results reveal that 14.35%, 36.24% and 31.40% of the total geographical area in Andhra Pradesh, Karnataka and Telangana were affected by desertification processes respectively, in 2011–2013. Among the desertification processes, vegetal degradation contributes 7.27% of total area in AP, followed by water erosion (4.93%) and waterlogging (0.83%), whereas in Karnataka water erosion (26.29%) is dominant followed by vegetal degradation (8.93%) and salinization (0.45%). Change detection analysis shows that desertification processes of AP and Karnataka have increased by 0.19% and 0.05% respectively, whereas in Telangana it has decreased by about 0.52% from 2003 to 2005 data. The present database will help the scientists, planners and stakeholders to prepare appropriate land reclamation measures to control the increasing trend of desertification.Not Availabl

Sensitivity and specificity data for <i>T</i>. <i>vivax</i> ISG ELISAs and prototype LFT.

<p>Sensitivity and specificity data for <i>T</i>. <i>vivax</i> ISG ELISAs and prototype LFT.</p

Single- and dual-antigen prototype LFTs.

<p>Photographs of (A) a single-antigen (sVSG117) prototype LFT developed with <i>T. b. gambiense</i> infection serum and (B) a dual-antigen prototype LFT developed with <i>T. b. gambiense</i> infection serum (left) and control uninfected serum (right). The positions of the ‘test complete’ control lines and antigen test lines are as indicated. The band intensities are scored visually by comparison with a test card (C).</p