Project description:Subarachnoid neurocysticercosis (SANCC) is caused by an abnormally transformed form of the metacestode or larval form of the tapewormTaenia solium. In contrast to vesicular parenchymal and ventricular located cysts that contain a viable scolex and are anlage of the adult tapeworm, the subarachnoid cyst proliferates to form aberrant membranous cystic masses within the subarachnoid spaces that cause mass effects and acute and chronic arachnoiditis. How subarachnoid cyst proliferates and interacts with the human host is poorly understood, but parasite stem cells (germinative cells) likely participate. RNA-seq analysis of the subarachnoid cyst bladder wall compared to the bladder wall and scolex of the vesicular cyst revealed that the subarachnoid form exhibits activation of signaling pathways that promote proliferation and increased lipid metabolism. These adaptions allow growth in a nutrient-limited cerebral spinal fluid. In addition, we identified therapeutic drug targets that would inhibit growth of the parasite, potentially increase effectiveness of treatment, and shorten its duration.
Project description:This study aims to investigate the immunemodulatory effects of excretory-secretory products (ESPs) from the parasite Taenia solium on human macrophages to understand immunopathogenesis of neurocysticercosis (NCC). NCC is an infection of the central nervous system caused by the larvae of T. solium and is a major contributor to acquired epilepsy. Although ESPs from parasites are known to possess immune-modulating properties, the specific mechanisms of their action in NCC remains unclear. Therefore, this expression study seeks to shed light on the exact mechanism by which T. solium ESPs exert their immune-suppressive effects on human macrophages. Understanding this mechanism can provide valuable insights into the pathogenesis of NCC and potentially contribute to the development of novel therapeutic strategies for managing the disease. The study employed miRNA microarray technology to investigate the post-translational effects of excretory-secretory products (ESPs) from Taenia solium on human macrophage function. microRNAs, are small non-coding RNA molecules that play a crucial role in post-transcriptional gene regulation. The aim of study is to identify specific miRNAs that might be responsible for modulating macrophage function. Altered expression of miRNAs can influence the translation and stability of target mRNA molecules, subsequently affecting the production of proteins and the overall function of macrophages, thus affecting immune homeostasis in infection. Understanding the miRNA-mediated regulatory mechanisms involved in the immune response to T. solium infection can contribute to a better understanding of the pathogenesis of neurocysticercosis and potentially uncover novel therapeutic targets for managing the disease.
Project description:We have designed species-specific oligonucleotides which permit the differential detection of two species of cestodes, Taenia saginata and Taenia solium. The oligonucleotides contain sequences established for two previously reported, noncoding DNA fragments cloned from a genomic library of T. saginata. The first, which is T. saginata specific (fragment HDP1), is a repetitive sequence with a 53-bp monomeric unit repeated 24 times in direct tandem along the 1, 272-bp fragment. From this sequence the two oligonucleotides that were selected (oligonucleotides PTs4F1 and PTs4R1) specifically amplified genomic DNA (gDNA) from T. saginata but not T. solium or other related cestodes and had a sensitivity down to 10 pg of T. saginata gDNA. The second DNA fragment (fragment HDP2; 3,954 bp) hybridized to both T. saginata and T. solium DNAs and was not a repetitive sequence. Three oligonucleotides (oligonucleotides PTs7S35F1, PTs7S35F2, and PTs7S35R1) designed from the sequence of HDP2 allowed the differential amplification of gDNAs from T. saginata, T. solium, and Echinococcus granulosus in a multiplex PCR, which exhibits a sensitivity of 10 pg.
Project description:Taeniids exhibit a great adaptive plasticity, which facilitates their establishment, growth, and reproduction in a hostile inflammatory microenvironment. Transforming Growth Factor-? (TGF?), a highly pleiotropic cytokine, plays a critical role in vertebrate morphogenesis, cell differentiation, reproduction, and immune suppression. TGF? is secreted by host cells in sites lodging parasites. The role of TGF? in the outcome of T. solium and T. crassiceps cysticercosis is herein explored. Homologues of the TGF? family receptors (TsRI and TsRII) and several members of the TGF? downstream signal transduction pathway were found in T. solium genome, and the expression of Type-I and -II TGF? receptors was confirmed by RT-PCR. Antibodies against TGF? family receptors recognized cysticercal proteins of the expected molecular weight as determined by Western blot, and different structures in the parasite external tegument. In vitro, TGF? promoted the growth and reproduction of T. crassiceps cysticerci and the survival of T. solium cysticerci. High TGF? levels were found in cerebrospinal fluid from untreated neurocysticercotic patients who eventually failed to respond to the treatment (P?=?0.03) pointing to the involvement of TGF? in parasite survival. These results indicate the relevance of TGF? in the infection outcome by promoting cysticercus growth and treatment resistance.
Project description:Neurocysticercosis (NCC) is a parasitic infection of the central nervous system caused by Taenia solium larval cysts. Its epidemiology in cysticercosis-nonendemic regions is poorly understood, and the role of public health institutions is unclear. To determine the incidence of NCC and to pilot screening of household contacts for tapeworms, we conducted population-based active surveillance in Oregon. We screened for T. solium infection by examining hospital billing codes and medical charts for NCC diagnosed during January 1, 2006-December 31, 2009 and collecting fecal and blood samples from household contacts of recent case-patients. We identified 87 case-patients, for an annual incidence of 0.5 cases per 100,000 general population and 5.8 cases per 100,000 Hispanics. In 22 households, we confirmed 2 additional NCC case-patients but no current adult intestinal tapeworm infections. NCC is of clinical and public health concern in Oregon, particularly among Hispanics. Public health intervention should focus on family members because household investigations can identify additional case-patients.
Project description:BACKGROUND:Taeniasis and cysticercosis are major causes of seizures and epilepsy. Infection by the causative parasite Taenia solium requires transmission between humans and pigs. The disease is considered to be eradicable, but data on attempts at regional elimination are lacking. We conducted a three-phase control program in Tumbes, Peru, to determine whether regional elimination would be feasible. METHODS:We systematically tested and compared elimination strategies to show the feasibility of interrupting the transmission of T. solium infection in a region of highly endemic disease in Peru. In phase 1, we assessed the effectiveness and feasibility of six intervention strategies that involved screening of humans and pigs, antiparasitic treatment, prevention education, and pig replacement in 42 villages. In phase 2, we compared mass treatment with mass screening (each either with or without vaccination of pigs) in 17 villages. In phase 3, we implemented the final strategy of mass treatment of humans along with the mass treatment and vaccination of pigs in the entire rural region of Tumbes (107 villages comprising 81,170 people and 55,638 pigs). The effect of the intervention was measured after phases 2 and 3 with the use of detailed necropsy to detect pigs with live, nondegenerated cysts capable of causing new infection. The necropsy sampling was weighted in that we preferentially included more samples from seropositive pigs than from seronegative pigs. RESULTS:Only two of the strategies implemented in phase 1 resulted in limited control over the transmission of T. solium infection, which highlighted the need to intensify the subsequent strategies. After the strategies in phase 2 were implemented, no cyst that was capable of further transmission of T. solium infection was found among 658 sampled pigs. One year later, without further intervention, 7 of 310 sampled pigs had live, nondegenerated cysts, but no infected pig was found in 11 of 17 villages, including all the villages in which mass antiparasitic treatment plus vaccination was implemented. After the final strategy was implemented in phase 3, a total of 3 of 342 pigs had live, nondegenerated cysts, but no infected pig was found in 105 of 107 villages. CONCLUSIONS:We showed that the transmission of T. solium infection was interrupted on a regional scale in a highly endemic region in Peru. (Funded by the Bill and Melinda Gates Foundation and others.).