Neurocysticercosis (NCC) is a parasitic infection of the brain that accounts for 34% of active epilepsy cases in Vellore district, India. New methods for diagnosing patients with NCC are badly needed. The cost of diagnostic imaging is beyond the means of most patients, and 34% of NCC patients are missed by the gold standard for antibody detection. Recent data suggest that host immune responses are important for determining manifestations of NCC infection. Thus, analyses of non-antibody host responses using state of the art methods present a novel and logical approach for advancing knowledge in detection of NCC. The long-term objective of this US-India proposal is to identify novel circulating biomarkers for diagnosis for NCC-associated epilepsy. The purposes of this proposal are to establish an effective collaboration among investigators from the Univ. of Oklahoma Health Sciences Center (OUHSC), USA, and the Christian Medical College (CMC), India, and to test the extent to which serum profiling by electrospray ionization mass spectrometry (ESI-MS) and analysis of mRNA expression in blood monocytes represent innovative tools for better detection of NCC and its manifestations. The Collaborative partnership aim brings together expertise in epidemiology/biostatistics, monocyte biology and biochemistry with clinical and immunological expertise in NCC.
In Research Aim 1, we will test the extent to which serum profiling by ESI-MS can develop of panel of small molecular markers to distinguish patients with NCC-associated epilepsy identified at CMC from well-characterized controls.
In Research Aim 2, we will analyze mRNA expression of blood monocytes to identify gene expression signatures characteristic of NCC patients among people with epilepsy.
Research Aim 3 will compare a sequential na?ve Bayes statistical classification approach to the traditional approach to classify patients using results from Aims 1 and 2. During an initial meeting in Vellore, India, opportunities for exchange of scientists and graduate students as well as needs in training will be assessed. A workshop on Bayesian statistics will be organized. The research component will include collection of blood and sera from patients attending the clinical services of Dept. of Neurological Sciences, CMC. Four groups of patients will be selected: 1) patients with NCC-associated active epilepsy/seizures;2) NCC patients recovered for at least 2 years;3) patients with active epilepsy/seizures without evidence of NCC or cysticercosis;4) patients without NCC, cysticercosis, and a normal brain CT scan. Serum profiling will be conducted at OUHSC, whereas monocyte isolation and analysis of mRNA expression will be conducted at CMC. Results will be compared with gold-standard antibody and antigen detection methods. This research will allow us to determine if mRNA expression profiling of monocytes and ESI-MS can be used to 1) identify cases of epilepsy, 2) identify cases of NCC-associated epilepsy, 3) describe the evolution of the inflammatory process post resolution of the lesions and 4) differentiate between types of NCC lesions.
Neurocysticercosis (NCC) is a parasitic infection of the brain which occurs when the larval stage of Taenia solium develops in the brain. NCC represents an enormous burden to Indian society. For example, 34% of all patients with active epilepsy in the Vellore district, India have NCC lesions in their brain. Diagnosis of NCC- associated epilepsy relies on computerized tomographic imaging, a technology inaccessible to most people living in India. Moreover current antibody and antigen based tests are sub-optimal. Thus, there is great need to identify novel biomarkers that will complement and extend the ability to diagnose diverse disease states and that will be inexpensive and minimally invasive. Research results from this proposal could provide novel diagnostic methods for NCC, as well as for identifying the stage of NCC infection in the brain. Earlier and more accurate detection of NCC would be a tremendous benefit to public health. Methods in this proposal also could be applied towards developing new diagnostic methods for other central nervous system infections.
|John, Chandy C; Carabin, HÃ©lÃ¨ne; Montano, Silvia M et al. (2015) Global research priorities for infections that affect the nervous system. Nature 527:S178-86|