Human African trypanosomiasis (HAT) is transmitted by tsetse flies and, if untreated, is fatal. Treatment depends on infection stage, and early diagnosis is crucial for effective disease management. The systemic host biochemical changes induced by HAT that enable biomarker discovery or relate to therapeutic outcome are largely unknown. We have characterized the multivariate temporal responses of mice to Trypanosoma brucei brucei infection, using (1)H nuclear magnetic resonance (NMR) spectroscopic metabolic phenotyping of urine and plasma. Marked alterations in plasma metabolic profiles were detected already 1 day postinfection. Elevated plasma concentrations of lactate, branched chain amino acids, and acetylglycoprotein fragments were noted. T. brucei brucei-infected mice also had an imbalance of plasma alanine and valine, consistent with differential gluconeogenesis (parasite)-ketogenesis (host) pathway counterflux, involving stimulated host glycolysis, ketogenesis, and enhanced lipid oxidation in the host. Histopathologic evidence of T. brucei brucei-induced extramedullary hepatic hemopoiesis, renal interstitial nephritis, and a provoked inflammatory response was also noted. Metabolic disturbance of gut microbiotal activity was associated with infection, as indicated by changes in the urinary concentrations of the microbial co-metabolites, including hippurate. Concluding, parasite infection results in multiple systemic biochemical effects in the host and disturbance of the symbiotic gut microbial metabolic interactions. Investigation of these transgenomic metabolic alterations may underpin the development of new diagnostic criteria and metrics of therapeutic efficacy.

https://www.pnas.org/content/pnas/105/16/6127.full.pdf

Global metabolic responses of mice to Trypanosoma brucei brucei infection.

The choroid plexus (CP) forming the blood–cerebrospinal fluid (B-CSF) barrier is among the least studied structures of the central nervous system (CNS) despite its clinical importance. The CP is an epithelio-endothelial convolute comprising a highly vascularized stroma with fenestrated capillaries and a continuous lining of epithelial cells joined by apical tight junctions (TJs) that are crucial in forming the B-CSF barrier. Integrity of the CP is critical for maintaining brain homeostasis and B-CSF barrier permeability. Recent experimental and clinical research has uncovered the significance of the CP in the pathophysiology of various diseases affecting the CNS. The CP is involved in penetration of various pathogens into the CNS, as well as the development of neurodegenerative (e.g., Alzheimer´s disease) and autoimmune diseases (e.g., multiple sclerosis). Moreover, the CP was shown to be important for restoring brain homeostasis following stroke and trauma. In addition, new diagnostic methods and treatment of CP papilloma and carcinoma have recently been developed. This review describes and summarizes the current state of knowledge with regard to the roles of the CP and B-CSF barrier in the pathophysiology of various types of CNS diseases and sets up the foundation for further avenues of research.

/pdf/choroid-plexus-and-the-blood-cerebrospinal-fluid-barrier-in-3llryctrg7.pdf

Choroid plexus and the blood-cerebrospinal fluid barrier in disease.

Oligopeptidase B from Trypanosoma evansi A PARASITE PEPTIDASE THAT INACTIVATES ATRIAL NATRIURETIC FACTOR IN THE BLOODSTREAM OF INFECTED HOSTS

Human trypanosoma infections like the ones seen in Africa and South America are unknown in India. The only exception in literature is of two documented cases of a self-limiting febrile illness, being attributed to Trypanosoma lewisi like parasites. We are reporting an unusual case of trypanosomiasis from the rural parts of Chandrapur district in Maharashtra. An adult male farmhand who used to practice veterinary medicine also, presented with history of febrile episodes on and off since five months and drowsiness before admission to this Institute. Though routine blood and other investigations were within normal limits, the peripheral smear showed a large number of trypanosomes which morphologically resembled the species Trypanosoma evansi, the aetiological agent of surra - a form of animal trypanosomiasis. A battery of assays covering the spectrum of parasitology, serology, and molecular biology confirmed the infecting parasite to be T. evansi. Failure to demonstrate the central nervous system (CNS) involvement, as evidenced by the absence of parasite in cerebrospinal fluid (CSF) advocated the use of suramin - the drug of choice in early stage African trypanosomiasis without any CNS involvement. Suramin achieved cure in our patient. The case is being reported because of its unique nature as the patient was not immunocompromised and showed infestation with a parasite which normally does not affect human beings.

Case Report - A RARE CASE OF HUMAN TRYPANOSOMIASIS CAUSED BY TRYPANOSOMA EVANSI

Experimental Trypanosoma evansi infection in the goat. II. Pathology.

Histopathology of Trypanosoma (Trypanozoon) evansi infection in bandicoot rat. I. visceral organs.

Bandicoot rat, Bandicota bengalensis, received intraperitoneal inoculation of Trypanosoma (Trypanozoon) evansi flagellates and showed acute disease, leading to death during the 2nd peak of parasitaemia [14th day post infection (pi)]. Damage in brain and choroid plexus of the infected bandicoot is studied on the 5th, 8th, 12th and 14th day post inoculation. Sign of histopathological changes in the brain and choroid plexus of the bandicoot are detected after 1st peak of parasitaemia. Infiltration of lymphocyte and plasma cells, congestion, perivascular cuffing, gliosis and brain lesions are observed during 12th–14th day post intection. Multiple sclerosis, neuronophagia, focal haemorrhage, cerebral hyperplasia, oligodendrocytoma, astrocytoma and fatty degeneration of brain tissue are also found. Alteration in the ependymal cells of choroid plexus is noticed. Extensive oedema, infiltration of inflammatory cells and rupture of ventricular ependymal layer are found. Parasites are found both in the brain tissue and choroid plexus. No intracellular stage of the parasite is observed. The nature of damage in the brain tissue and choroid plexus shows similarity with the cases of African trypanosomiasis. This salivarian species cause more deleterious effect in brain much earlier in the disease course than its African relatives.

Histopathology of Trypanosoma (Trypanozoon) evansi infection in Bandicoot rat. II. Brain and choroid plexus

Experimental infection of T. evansi in the cat.

Summary. Life histories of three new coccidian parasites (Protozoa: Apicomplexa: Coccidia) obtained from the larvae of three different coleopteran stored-grain pests, Tribolium castaneum Herbst, Alphitobius piceus Olivier and Palorus ratzeburgii Wissmann, respectively, have been described in detail. These coccidian parasites belong to the genus Adelina Hesse 1911 and are named as Adelina castana sp. n., Adelina picei sp. n. and Adelina palori sp. n. The complete life histories of these parasites are observed on the fat bodies along with the body fluid of the hosts. A comprehensive comparative account of three life histories is presented in tabular form.

https://www1.nencki.gov.pl/pdf/ap/ap3938.pdf

K.K. Misra

Papers

Histopathology of Trypanosoma (Trypanozoon) evansi infection in bandicoot rat. I. visceral organs.

Histopathology of Trypanosoma (Trypanozoon) evansi infection in Bandicoot rat. II. Brain and choroid plexus

Experimental infection of T. evansi in the cat.

Life histories of three new coccidian parasites from three coleopteran stored-grain pests of India.

Letter: Occurrence of amastigote and sphaeromastigote stages of T. evansi in the brain tissue of the cat.