Everywhere else, normally only animals are infected by trypanosomes that, although specific for humans are not pathogenic for them. Yet, in 2004, the first case of human trypanosomiasis was formally identified in India by IRD researcher Philippe Truc, working with the WHO and the Maharashtra State Department of Health (1).
The patient was a farmer living in this State who proved to be infected by a trypanosome, T. evansi, usually a parasite of camels and cattle. In South America, North Africa and in a great part of Asia including India, where this parasite is present, many human populations are currently living in contact with infected animals.
Scientists from the Université Libre de Bruxelles led by Professor Etienne Pays, in conjunction with Philippe Truc and Indian medical specialists, under an agreement with WHO (2), carried out analyses on blood serum from the infected patient, which led them to identify the cause of this first case of human trypanosomiasis in India.
Humans possess natural resistance to this parasite, as they have towards related African trypanosomes, like T. brucei. In the latter case, the innate immunity results from the trypanolytic activity of a specific human protein, apolipoprotein L-1 (APOL-1). Once absorbed inside the parasite, this protein forms pores in the parasite’s organelle membrane, thus inducing the destruction of the trypanosome. However, the two subspecies T. brucei rhodesiense and T. b. gambiense have, with time, overcome human immune defences by acquiring resistance to APOL-1 and thereby causing sleeping sickness in Africa. In T. b. rhodesiense, this resistance mechanism involves a protein that is peculiar to this subspecies, named SRA (Serum Resistance-associated protein), which interacts strongly and specifically with APOL -1, effectively blocking its ability to destroy the trypanosomes.
The major question is whether the first case of T. evansi infection identified in India resulted from the appearance of a mechanism of resistance of this parasite or from a deficiency of the patient’s immune system., The gene coding for the SRA protein, specific to the subspecies rhodesiense, was not detected in the trypanosome that had infected the Indian patient, as could be expected considering its specificity (3).
The researchers then assessed in vitro the ability of the infected serum to destroy the parasites. In this way they brought into evidence a complete absence of any trypanolytic activity on two strains of T. evansi, but also on T. b. brucei. Conversely, these same strains were destroyed on contact with normal serum. The APOL-1 protein, responsible for the trypanolytic action against T. b. brucei, was subsequently looked for in the infected serum. This serum appeared to be extremely deficient in this protein, with a concentration in APOL-1 at least 125 times lower than in normal human serum. However, the addition of a normal quantity of purified APOL-1 to the infected serum was sufficient to restore the latter’s ability to destroy the different strains tested. This APOL-1 deficiency observed in the patient would clearly therefore be the source of the single case of T. evansi infection identified to date.
Analysis of the apoL-1 gene sequence, perfomred on the patient’s DNA, showed that the absence of apolipoprotein results from a double mutation affecting its synthesis (4). In the absence of APOL-1, no other component of the human serum seems capable of forming pores in the parasite membrane and killing the trypanosome.
Furthermore, a serological screening, conducted in 2005 by the Indian authorities in the patient’s village, with the IRD researcher and assigned by WHO, brought to light an intense exposure of individuals to T. evansi, probably favoured by transmission of the parasite from infected animals to humans, via an insect vector. In fact, out of 1806 people examined, 60 proved to be strongly positive to the specific serological test for this trypanosome, although no parasite was detected in these subjects, and no case of infection has since been recorded in the village (5).
However, only study of the frequency of each of the two mutations within exposed populations will allow assessment of the risk of the appearance of other cases and the emergence of this new form of trypanosomiasis.Marie Guillaume-Signoret – IRD
(3) Philippe Truc et al. - Genetic characterization of Trypanosoma evansi isolated from a patient in India, Infection, Genetics and Evolution, 24 August 2006. doi:10.1016/j.meegid.2006.07.004
(4) This occurs in the form of two mutations each of which affects an allele of the same gene apoL-1. The first consists of the absence of two nucleotide bases in position 142, the second is the absence one particular base at position 266. These “frameshift” mutations result in the production of proteins that are cut down in length, and therefore ineffective. And these products are undetectable, as they are probably degraded.
(5) This means that these individuals have been or are still carriers of anti-T. evansi antibodies. They have therefore been carriers of the parasite, no doubt owing to an insufficiency in APOL-1 (mutation of a single allele?). See the reference under “For further information”.
Marie Guillaume | alfa
Fine organic particles in the atmosphere are more often solid glass beads than liquid oil droplets
21.04.2017 | Max-Planck-Institut für Chemie
Study overturns seminal research about the developing nervous system
21.04.2017 | University of California - Los Angeles Health Sciences
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
Two researchers at Heidelberg University have developed a model system that enables a better understanding of the processes in a quantum-physical experiment...
Glaciers might seem rather inhospitable environments. However, they are home to a diverse and vibrant microbial community. It’s becoming increasingly clear that they play a bigger role in the carbon cycle than previously thought.
A new study, now published in the journal Nature Geoscience, shows how microbial communities in melting glaciers contribute to the Earth’s carbon cycle, a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
21.04.2017 | Physics and Astronomy
21.04.2017 | Health and Medicine
21.04.2017 | Physics and Astronomy