Sheet n°256 - December 2006-January 2007
The new form of trypanosomiasis
discovered in India stems from a deficiency
in a particular immune-system protein
© IRD/ Olivier Barbary
I
n December 2004, the
first case of human
Trypanosoma evansi -induced trypanosomiasis was
formally identified in India,
in a farmer living in the central state of Maharashtra, by
Philippe Truc, researcher at
IRD research unit UR 177
commissioned by the World
Health Organization (WHO)
Department of Neglected
Tropical Diseases Control,
at the request of the Indian
Directorate
of
Health
Services (1). The causative trypanosome was up to
then known only to infect
certain animals, especially
camels and cattle. Scientists
from Université Libre de
Bruxelles, Philippe Truc
and Indian medical specialists and the WHO (2) sought
explanations for this atypical
infection. Their work found
the cause of this infection
lay in the absence from the
patient’s blood serum of
apolipoprotein L-1 (APOL1),
a protein that provides
human subjects with their
natural immunity against
such animal trypanosomes.
A double mutation on the
gene apoL-1 turned out to be
responsible. Determination
of the frequency of each of
these mutations, by screening within populations in
contact with affected animals, should lead to improved assessment of the risk
of emergence of this new
form of trypanosomiasis.
Transplanting of rice, Gudi Pudi (A.P., Guntur district), India.
The two known types of human trypanosomiasis, endemic in two regions of the world,
are sleeping sickness in Africa, caused by the
parasites Trypanosoma brucei gambiense or
T. b. rhodiense, and Chagas’ disease in South
America induced by T. cruzi. 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, apolipo-
>>
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Sheet n°256 - December 2006-Janua
For futher information
CONTACTS :
PHILIPPE TRUC
IRD Angola UR 177
Instituto de Combate e Controlo
das Tripanosomiases (ICCT)
Luanda, Angola
+244 222 330065 / 334841,
truc@ird.fr
ETIENNE PAYS
Université Libre de Bruxelles,
Laboratoire de Parasitologie
Moléculaire, Gosselies,
Belgique.
00 32 (0)71 37 87 59,
epays@ulb.ac.be
Press office ULB :
00 32 (0)71 60 02 03
IRD PRESS OFFICE:
+33 1 48 03 75 19 ;
presse@paris.ird.fr
INDIGO BASE, IRD PICTURE LIBRARY
+33 1 48 03 78 99 ;
indigo@paris.ird.fr
IRD AUDIOVISUEL
+33 (0)1 48 02 56 24 ;
audiovisuel@bondy.ird.fr
www.audiovisuel.ird.fr/
REFERENCES:
BENOÎT VANHOLLEBEKE, PHILIPPE
TRUC, PHILIPPE POELVOORDE,
ANNETTE PAYS, PRASHANT P.
JOSHI, RAVINDRA KATTI, JEAN
G. JANNIN AND ETIENNE PAYS
– Human trypanosomiasis
caused by Trypanosoma
evansi in India is due to the
absence of the trypanolytic
factor apolipoprotein L-1, New
England Journal of Medicine,
vol. 355:2752-2756, 28
décembre 2006.
FOR FURTHER INFORMATION:
SHEGOKAR, VR, POWAR
RM, JOSHI PP, BHARGAVA
A, DANI VS, KATTI R, ZARE
VR, KHANANDE VD, JANNIN
J, TRUC P (2006). Human
trypanosomiasis caused by
Trypanosoma evansi in India:
a preliminary serological survey of the local population in
the patient’s village, American
Journal of Tropical Medicine
and Hygiene, 75, 869-870.
KEY WORDS
HUMAN TRYPANOSOMIASIS,
TRYPANOSOMA EVANSI, APOLIPOPROTEIN, GENETIC MUTATION,
INDIA.
protein 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.
(1) See scientific sheet n°230, AugustSeptember
2005,
accessible
at:
www.ird.fr/fr/actualites/fiches/2005/fiche230.htm
(2) This research was conducted by scientists from the ‘Laboratoire de Parasitologie
Moléculaire (IBMM)’ of the Université Libre de
Bruxelles (Belgium), jointly with a researcher
from IRD research unit UR 177, medical specialists from the Department of Medicine of
the Government Medical College of Nagpur
(India), from the Department of Health at
Mumbai (India) and from the WHO (Geneva,
Switzerland).
(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-Signoret - IRD
Translation : Nicholas Flay
Marie Guillaume - Signoret, coordinatrice
Délégation à l’information et à la communication
Tél. : +33(0)1 48 03 76 07 - fax : +33(0)1 40 36 24 55 - fichesactu@paris.ird.fr