DETECTOGEN INC. — Department of Health and Human Services SBIR Phase I: NIAID

Description

DESCRIPTION provided by applicant Antigen detection assays in contrast to conventional serological test detects disease status and not the host antibody response to the disease etiological agent It can therefore be used for both diagnosis and disease treatment follow up purposes Antigen detection assay has been successfully used for the past years for the diagnosis of different infectious diseases including sore throat caused by Streptococcus pyogenes hepatitis pneumonia caused by Streptococcus pneumoniae or Legionella pneumophilla and amoebiasis Although antigen detection assay has the potential to discriminate active visceral leishmaniasis VL from asymptomatic or cured disease paradoxically this approach has not been developed for the diagnosis of this serious parasitic disease Using the ultra sensitive mass spectrometry technology we have recently identified the presence of three Leishmania infantum chagasi proteins in urine of VL patients from the New World These molecules were extensively characterized and used to develop a capture ELISA antigen detection assay for VL diagnosis caused by L infantum A pilot validation studies with this assay using human urine from New World VL patients indicated that the test was sensitive and specific Although this test was excellent for the diagnosis of New World VL caused by L infantum we have recently observed that its sensitivity for the diagnosis of Old World VL caused by L donovani also known as kala azar was not adequate This is likely explained by the fact that these two parasites have substantial differences both in their genomes as well as in the pathologies and clinical manifestations that they cause Therefore the different host handling of the two parasites antigenic repertoires can result in excretion of distinct patterns of biomarkers in the patientsandapos urines Unfortunately the observed low performance of the L infantum biomarkers to diagnose Old World VL is a major hindrance because the highest incidence and prevalence of VL occurs in the Old World Nonetheless this major hindrance can be overcome by unravelling L donovani antigens that are abundantly excreted in the urine of patients with Old World kala azar Hence this Phase I SBIR project proposes to identify these unique L donovani biomarkers with the ultimate goal of developing a non invasive antigen detection assay that will accurately diagnose VL caused by L donovani The Specific Aims are Aim To identify L donovani protein biomarkers present in the urine of kala azar patients Old World VL and to produce diagnostic assay reagents Aim To optimize and to begin the clinical validation of an antigen detection test capture ELISA using select pairs of purified antibodies for the detection of L donovani antigens in the urine of kala azar patients PUBLIC HEALTH RELEVANCE Visceral leishmaniasis VL or kala azar remains a major infectious cause of morbidity and mortality worldwide The incidence of the disease remains high and is increasing in many parts of Southern Europe Africa Asia and South America Diagnosis of VL is either performed with obsolete invasive and inadequate tests or with conventional serological tests that cannot distinguish active disease from asymptomatic VL or from cured infection The present project proposes to validate new biomarkers present in urines of patients with kala azar for the development a novel simple and accurate diagnostic test for this serious disease Such test will detect in the patientandapos s urine a unique group of molecules produced in vivo by the pathogens that cause VL The ability to reliably distinguish between active VL from prior exposure using a non invasive urine sample would rapidly identify persons who require immediate treatment Such a test would save lives and eliminate parasite reservoirs that can spread infection to others in the community