Only
zymodemes Z1, Z2 and Z3 are pathogenic for
Homo.
Also
schizodemes (genovars detected by DNA fingerprinting using
EcoRI
on ktDNA) exist.
Obliged intracellular parasite.
Epidemiology
: 18 countries on the American continent in 2 different ecological zones:
-
the Southern Cone
region, where the main vector lives inside human homes and in peridomiciliary
areas
-
Central America
and Mexico where the main vector species lives both inside dwellings and
in uninhabited areas
Country-wide cross-sectional
surveys in the 1980s found an overall prevalence of 17 million cases, with
4.8-5.4 million people exhibiting clinical symptoms, an annual incidence
of 700,000-800,000 new cases and 45,000 deaths every year due to the cardiac
form of the disease At present, estimates indicate an infection prevalence
of 13 million, with 3.0-3.3 million symptomatic cases and an annual incidence
of 200,000 cases in 15 countries; population exposed at risk : 90 millions.
The suspicion that a patient in India may present a patent infection of
some form of trypanosomiasis is not entirely improbable. On the contrary,
suspected human cases of
Trypanosoma
lewisi, another murine parasite, have been reported in India (2
cases, 1974) and Malaysia (1 case, 1933). There have been other incidental
reports as well. However, unlike
T. cruzi,
T. lewisi is transmitted
by
Xenopsylla cheopis
and
Nosopsylla fasciatus
.
The morphology of
T. lewisi can be easily distinguished from
T.
cruzi. Moreover, assuming no travel-related exposure or blood transfusions
in the recent case, it appears nearly impossible that
T. cruzi,
and most certainly the 2 African trypanosomes, would be endemic in India.
Trypanosome parasites are found in a great variety of mammals, but less
well known trypanosomes are found in fish (vectors being leeches), amphibians
(vectors are mainly leeches), reptiles (vectors are phlebotomine sandflies,
tsetse flies and leeches), and finally, avian trypanosomes transmitted
by mosquitoes, simuliid black-flies, hippoboscid flies and the chicken
mite (
Dermanyssus
gallinae)
Genomics
: gene exchange between clones of different genotypes occurs via multiple
and unusual mechanisms
Proteomics :
-
Trypanosoma decay accelerating factor (T-DAF) prevents C-mediated
lysis until it is neutralized by host Abs
-
Tc52 protein binds to TLR2

-
trans-sialidase (both membrane-bound and shed) has anti-AICD
and costimulatory effects on CD4+ T cells, both depending on
CD43
-
pore-forming protein showing immunological crossreactivity to complement
C9
Transmission :
-
a percutaneous zooanthroponoses; reservoir : over 150 species from 24 families
of domestic and wild mammals, including Canis
familiaris
,
Felis
catus
,
Rattus
norvegicus
,
Mus
musculus
,
Didelphis
spp.
,
Dasypus
spp.
,
Tamandua
spp.
,
Desmodes
spp.
,
Glossophaga
spp.
,
Carollia
spp.
,
Aotus
spp.
,
Saimiri
spp.
,
Ateles
spp.
(in the vertebrate host, it infects many different cells, but in the human
host, the disease is conspicuously limited to the myocardium and to gut
nerve fibres); vectors : Rhodnius
prolixus
,
Triatoma
infestans
,
Triatoma
dimidiata
,
Triatoma
sordida
,
Triatoma
brasiliensis
,
Panstrongylus
megistus
,
Rhodnius
pallescens
,
Dipetalogaster
maximum
ref
-
transplacental transmission
-
blood transfusion : only 5 cases of blood transfusion infections have been
confirmed in the US (3) and Canada (2 : both immunocompromised by chemotherapy
for cancer). The risk of infections through blood transfusions has been
estimated to be between 1 per 43 to 1 per 1072 transfusions in different
countries. However, the risk of being infected if receiving blood from
a T.cruzi seropositive donor is most probably overestimated. Recent
seroprevalence studies showed that approximately 0.1% of blood donors likely
to have been born in or have traveled to disease-endemic countries were
seropositive for T. cruzi. Moreover, American Red Cross studies
of recipients of T. cruziseropositive blood and blood products
showed no evidence of transmission. Travellers are rarely exposed to infection,
and T.cruzi infection in travellers is exceedingly rare. The triatomid
bug lives in cracks and crevices in mud walls, and it is therefore immigrants
living under poor conditions for a prolonged time who may carry the infection
and pass it on through blood transfusion
-
oral transmission can cause microepidemics of acute Chagas diseaseref.
No doubt oral transmission to humans has been occurring for a long time.
However, in the context of high levels of vector transmission, these cases
went unnoticed. In the 1990s human cases acquired by the oral route were
reported. Shikanai-Yasuda et al. reported 3 cases by oral transmission,
apart from one possibly by breast-feedingref.
A year later, the same group reported an outbreak in 1986, with 26 patients
that acquired Chagas´ disease with acute phase symptoms after a family
gathering in the Northeastern state of Paraibaref.
This report has become a classic, and the situation resembles the one now
seen in Santa Catarina, Brazil. Since the decline of vector-transmitted
disease in Brazil, 1st in the State of Sao Paulo in the 1970s and then
in other states in the 1990s, oral transmission has been a subject of growing
concern. The Southern state of Santa Catarina has never been an endemic
area for Chagas´disease. Although Panstrongylus
megistus
can be found in forest areas, they have not moved into homes, as in Bahia
or Minas Gerais, states well North of Santa Catarina. Chagas´ disease
in wildlife is common in Santa Catarina, as well as in coastal areas in
South and Southeastern Brazil. A rather recent paperref
reported that oral sporadic transmission seems to be rather common in certain
rural areas. This has been reported also from the Amazon, associated with
acai,
a rain-forest fruit that is rather a fad in urban areas, causing a small
boom in the acai industry. This fruit is processed much in the same way
as sugar-cane, in order to obtain a paste. As the fruit is found in palm-like
trees, a favorite habitat of triatomid bugs, the result is a fruit paste
contaminated with Trypanosoma cruzi. The most probable explanation
for the outbreak in Santa Catarina is that sugar-cane was harvested and
kept in some kind of makeshift shed that harbored triatomid bugs, and the
droppings of these bugs contaminated the sugarcane, resulting in a juice
with T.cruzi. As sugarcane juice (locally called "garapa")
is drunk fresh, immediately after processing, the risk of infection is
high. Oral transmission of T.cruzi to mammals was first demonstrated
experimentally in 1958 (Phillips NR, Thesis, University of London, cited
by Hoare CA in "The Trypanosomes of mammals, Blackwell Scientific Publ.,
London 1972), when 50% of mice became infected after being fed T.cruzi-infected
triatomid bugs. Ingestion of infected vectors was also found to be the
main mode of transmission among wood-rats in north America (Ryckman &
Olsen, J Med Entomol 1972,2:99). Triatomid bugs have a preference for feeding
from the face of sleeping humans and shed the parasites in their feces
after the blood meal. The parasites are then thought to infect humans through
the mucus membranes in the mouth or the conjunctiva. There is no information
on how long the epimastigotes of T.cruzi remain infective after
being passed in bug feces, which seems to be a key parameter for food-borne
transmission. Sugar cane juice, also known as "garapa," is a very common
beverage all over the country and is made by crushing the cane. The triatomid
insect vector may have been crushed during this process, or the cane could
have become contaminated with infected bugs' feces. So far there have been
31 confirmed cases and 5 deaths; additional 64 suspected cases under
investigation. There may have been > 50 000 possible exposures (which includes
international travellers). All cases were apparently related to drinking
garapa in cities along the northern beaches of the State (to name all the
suspicious cities: Itapoa, Garuva, Joinville, Araquari, Sao
Francisco do Sul, Balneario Barra do Sul, Barra Velha, Picarras, Penha,
Navegantes, Itajai, Balnearion Camboriu, Camboriu, and Itapema) : 91% of
the cases had ingested sugar cane juice at the Kiosk Barracao da Penha
2, between the municipalities of Navegantes and Pen-ha, on the side of
the BR-101 highway by Kilometer 111. The test, conducted by the Department
of Microbiology and Parasitology of the Federal University of Santa Catarina,
proved the presence of the protozoan in a triatomid bug hidden in a towel
-- a product that is also sold in this kiosk. Norms aimed specifically
for the sale of sugar cane juice will take effect on 31 Mar 2005. ANVISA
(the National Sanitary Surveillance Unit) announced that all persons who
drank sugar cane juice
from the kiosks along highway BR-101, between Picarras and Italjai,
during the period 1 Feb 2005 through 23 Mar 2005 are to be considered inappropriate
for blood donation. There are 2 research papers referring to previous
outbreaks of Chagas disease associated with the oral route of transmission
(1968 in Teutonia RSref
and 1991 - Catole do Rocha PBref),
the larger of which presents 26 confirmed cases. Incubation period seems
to be around 7-28 days, and the main signs and symptoms include high fever
for > 5 days; myalgia; headache; orbital swelling and hepatosplenomegaly.
In such cases diagnosis must be confirmed with serology (remember that
many labs perform only IgG); IgM and direct visualization on smears. Treatment
with either benzonidazol or nifurtimox must be provided ASAP for all acute
cases, especially symptomatic ones. Cure rates are around 70%. For diagnosis
in asymptomatic cases, we are recommending just serology IgG and IgM. In
negative cases with > 30 days elapsed from exposure, close the case; <
30 days, repeat serology within 2-4 weeks. All positive cases must be confirmed
with a 2nd serological exam or direct visualization of T. cruzi.
The main factor for the risk of spreading Chagas disease by food and drink
is the survival of the trypanosomes after they have left the intestine
of the triatomid bug. How sensitive are they to changes in temperature,
pH, and osmolarity? This will determine how long they can stay infective
in bug feces on sugar cane. In 1968, a member of a farming community in
Teotonia (Rio Grande do Sul) fell ill with a severe febrile illness. No
one suspected Chagas disease, as there were no Reduviid bug vectors in
the local dwellings. After much investigation, food borne transmission
through vegetables served in the common dining-room was accepted as the
cause. Possibly, marsupials had contaminated the vegetables by droppings
from their anal glands, usually rich in T.cruzi. In 1986, another
outbreak occurred, this time in Catole do Rocha (Paraiba). A large wedding
anniversary party had been held on a farm. Days later, some of the guests
fell ill with a febrile illness, similar to the one in Teotonia. Sugarcane
juice and other foodstuffs or beverages had been contaminated by animal
droppings. The couple that had celebrated their 50th anniversary eventually
died as a consequence of Chagas disease acquired at the party. Recently,
oral transmission of T.cruzi has been responsible for small outbreaks
in the state of Para. Entire families acquired Chagas disease in the absence
of insect vectors in their homes. These insects live in palm trees and,
attracted by the lights, fall into the machinery used to grind acai to
obtain juice (much the way sugarcane juice is obtained). The insects are
ground and contaminate the juice with T.cruzi, transmitting the
infection to those drinking it. All of these cases in Rio Grande do Sul,
Paraiba and Para attracted the attention of scientists. The question which
was brought forward was why didn't gastric juice destroy T.cruzi ?
The physician Sonia Gomes Andrade from CPqGM, who specializes in experimental
pathology, formulated an experiment: she introduced T.cruzi through
a tube directly into the stomach of mice,. She studied the strains isolated
from cases in Paraiba and Para. She observed that the parasite not only
survived gastric juice but was able to infect the mice. They developed
disease identical to the one produced when mice are infected directly via
the bloodstream. The findings of the researcher confirm that T.cruzi,
when swallowed, can cause infection through the digestive system. In the
most common manner of infection, scratching, T.cruzi is able to
penetrate the skin. It is easy to imagine that, when someone ingests a
large quantity of parasites, the infection will be more severe. There is
no reason to stop eating vegetables or drinking sugarcane or acai juice.
The problem lies not with the kind of food but with T.cruzi. These
are mainly parasites of biodem type III -- from wildlife -- that are able
to cause infection through the digestive system. A biodem is a group of
genetically close T.cruzi strains with similar characteristics.
Biodem type III strains are, as a rule, highly pathogenic. In the experiment,
a strain of this type showed a higher capacity to cross the gastric barrier
and cause infection in mice than strains from biodems I and II. It
is significant to point out that biodem III strains are associated with
wildlife disease cycles, causing outbreaks in places where Reduviid bugs
are not domiciled. It seems beyond doubt that T.cruzi can infect
hosts, including humans, by the oral route, but it still remains unclear
how important this route of transmission is for maintaining infections
in humans and causing outbreaks like the present one. The mouse experiment
cited above confirms previous reports Hoft et al. Infect Immun 1996,64:3800-10]
that T.cruzi can indeed infect the host through the gastric mucosa.
The key question is how long a time T.cruzi can survive in feces
outside the triatomid bug, and how long a time in different forms of fluids
after the triatomid bugs have been crushed. Oral transmission, either from
bug feces or from crushed bugs, presumes that T.cruzi can survive
for at least several hours, possibly days, in juice. Information on this
survival time is key to determining whether the present outbreak is a rare
coincidence or just part of a more widespread problem
During the past decades, after urban migrations, Chagas disease became
frequent in cities and a health problem in non-endemic countries, where
it can be transmitted vertically and by blood transfusion or organ transplantation.
Pathogenesis : parasite-derived danger
signal (
parasitokines, ...) => breakdown of self-tolerance => autoimmunity.
It induces up-regulation of both Fas and FasL on parasite-specific IgG
+
B cells and renders them susceptible to B cell-B cell killing (fratricide).
Integration of
T.cruzi kinetoplast DNA (kDNA) into the genomes of
infected patients, as well as chicken and rabbit animal models, suggesting
that horizontal gene transfer may play a role in
T.cruzi host–parasite
interactions. In the human chromosomes, 5 loci were identified as integration
sites, and the beta-globin locus and LINE-1 retrotransposons were frequently
targeted. Short repeated sequences in the parasite and the target host
DNAs favor kDNA integration by homologous recombination. Introduced kDNA
was present in offspring of chronically infected rabbits and in chickens
hatched from
T. cruzi-inoculated eggs. kDNA incorporated into the
chicken germline was inherited through the F
2 generation in
the absence of persistent infection. If this process involves the germline,
integrated kDNA could theoretically alter human genetics through disruption
of protein-coding sequences and promotion of recombination events between
kDNA integration sites. kDNA integration represents a potential cause for
the autoimmune response that develops in a percentage of chronic Chagas
patients, which can now be approached experimentally
ref
=>
Chagas'
disease / American trypanosomiasis :
-
90% asymptomatic
-
10% symptomatic :