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Revista da Sociedade Br asileir a de Medicina Tr opical 3 8 ( 1 ) :5 3 -5 5 , jan-fev, 2 0 0 5
RELATO DE CASO/CASE REPORT
Chagas’ disease: study of congenital transmission in cases
of acute maternal infection
Doença de Chagas: estudo da transmissão congênita nos casos
da infecção materna aguda
Edgardo Moretti
1, Beatriz Basso
1, Irma Castro
1, Mario Carrizo Paez
2, Marcela Chaul
2,
Gustavo Barbieri
3, Dámaso Canal Feijoo
3, María José Sartori
4and Rubén Carrizo Paez
2ABSTRACT
We stu di e d thre e pre gn a n t wo m e n wi th a c u te c ha ga si c i n f e c ti o n . Two pa ti e n ts, i n f e c te d i n the thi rd tri m e ste r o f pre gn a n c y, h a d u n i n f e c te d c h i ld re n . Th e th i rd p a ti e n t, i n f e c te d e a rli e r, h a d a n i n f e c te d n e wb o rn . Th e se re su lts e n c o u ra ge re se a rc h o n ri sk f a c to rs o f tra n sm i ssi o n a n d o n m e d i c a l d e c i si o n s c o n c e rn i n g p re gn a n t wo m e n wi th a c u te Ch a ga s' d i se a se .
Ke y-words: Ch a ga s' d i se a se . Tr ypa no so ma cr uz i. Co n ge n i ta l i n f e c ti o n . Ac u te m a te rn a l Tr ypa no so ma cr uz i i n f e c ti o n .
RESUMO
Se d e sc re ve m 3 ge sta n te s c o m a d o e n ç a d e Ch a ga s a gu d a . Du a s ge sta n te s i n f e ta d a s n o 3 º tri m e stre d e ge sta ç ã o n ã o ti ve ra m c ri a n ç a s i n f e ta d a s. O 3 º f i lh o , d o q u e lla m a d re f o i i n f e ta d a n o 1 º tri m e stre , n a sc e u c o m d o e n ç a d e Ch a ga s c o n gé n i ta . Este s re su lta d o s i n d u c e m a i n ve sti ga ç ã o so b re o s f a to re s d e ri sc o s d a tra n sm i ç ã o e so b re a s d e si ç õ e s m é d i c a s n a c o n d u c ç ã o d o s c a so s d e ge sta n te s c o m a d o e n ç a d e Ch a ga s a gu d a .
Pal avr as-chave s: Do e n ç a d e Ch a ga s. Tr ypa no so ma cr uz i. In f e c ç ã o c o n gê n i ta . In f e c ç ã o m a te rn a a gu d a .
1 . De par tame nto Diagnó stic o y Tr atamie nto de l Se r vic io Nac io nal de Chagas, Có r do b a, Ar ge ntina. 2 . Ho spital Rawso n, San J uan, Ar ge ntina. 3 . Ce ntr o de Chagas y Pato lo gía Re gio nal, Santiago de l Este r o . 4 . II Cáte dr a de B io lo gia Ce lular, Fac ultad de Cie nc ias Mé dic as, Unive r sidad Nac io nal de Có r do b a, Ar ge ntina.
This wo r k was suppo r te d b y funds fr o m Se r vic io Nac io nal de Chagas and SECYT, Unive r sidad Nac io nal de Có r do b a.
Addr e ss to:Dr. Edgar do Mo r e tti. Güe me s 3 8 3 , 5 0 0 0 Có r do b a, Ar ge ntina Te l: 5 4 3 5 1 4 2 2 - 2 4 2 4
e - mail: e b i@ fc m. unc . e du. ar, o r e mo r e tti@ ho spital- italiano . c o m. ar Re c e b ido par a pub lic aç ão e m 1 9 /7 /2 0 0 4
Ac e ito e m 1 4 /9 /2 0 0 4
Chagas' dise ase is o ne o f the mo st impo r tant par asitic e nde mic dise ase s in Latin Ame r ic a, whe r e ne ar 2 0 millio n pe o ple ar e infe c te d and 6 0 millio n ar e at r isk o f infe c tio n.
Due to the e ffo r ts to c a r r y o ut ve c to r c o ntr o l in se ve r a l c o untr ie s, the tr ansmissio n thr o ugh the inse c t b ite , the main e pide mio lo gic al way o f infe c tio n, is de c r e asing, at le ast in
B r azil, Ur uguay, Chile and Ar ge ntina. Inde e d, so me o f the se c o untr ie s, and so me pr o vinc e s o f o the r c o untr ie s have b e e n de c lar e d fr e e o f ve c to r tr ansmissio n b y the Pan Ame r ic an
He a l th Or ga n i za ti o n . T h e r e fo r e , n o wa d a ys c o n ge n i ta l tr a n s m is s io n h a s b e c o m e m o r e im po r ta n t. I n fa c t, it is e stimate d that in Ar ge ntina the c o nge nital c ase s ar e at le ast 1 0 tim e s m o r e fr e q ue n t th a n th e a c ute c a s e s b y ve c to r
tr ansmissio n5. B e c ause o f migr atio n o f pe o ple fr o m e nde mic
c o untr ie s, in the Unite d State s the r e we r e r e po r te d c ase s o f in fe c tio n , pr o b a b ly b y b lo o d tr a n s fus io n o r c o n ge n ita l
tr ansmissio n6.
Our gr o up has pe r fo r me d se ve r al studie s o n c o nge nital Chagas' dise ase , and has pr o po se d a pr o to c o l fo r diagno sis and tr eatment8 9. Mo r eo ver, sever al exper imental studies have
b e e n d o n e i n a n a tte m p t to d e te r m i n e th e p o s s i b l e me c hanisms invo lve d in c o nge nital tr ansmissio n, tak ing into ac c o unt that o nly 2 to 1 0 % o f infe c te d mo the r s tr ansmitte d
the infe c tio n to the ir b ab ie s4 1 1. Ne ve r the le ss, to date little is
k no wn ab o ut the fac to r s invo lve d in ve r tic al tr ansmissio n in humans. The r e has b e e n spe c ulatio n ab o ut par asitic fac to r s,
suc h as the str ain o f T. c ru zi o r the par asitic lo ad, and ab o ut ho st fac to r s, suc h as immuno lo gic al o r nutr itio nal status o f pr e gnant wo me n, o b ste tr ic al histo r y and mate r nal stage o f dise ase2 b ut no ne o f the se fac to r have b e e n c o nc lusive ly
de mo nstr ate d ye t. Epide mio lo gic al sur ve ys and studie s ab o ut po ssib le m e c ha nism s o f c o nge nita l Cha ga s' dise a se ha ve b e e n c o nduc te d in m o the r s in the inde te r m inate o r c hr o nic
5 4
Mo r e tti E e t al
Fi gu r e 1 B - Hi stol ogycal se cti on of pl ace n ta ( case 2 ) , stai n e d wi th
he m atox ylin -e osin , showin g am astigote for m s of Tr ypa no so ma cr uz i
( 4 0 0 x ) .
A
B
In this c o mmunic atio n, we r epo r t c linic al, par asito lo gic aland se r o lo gic al patte r ns o f thr e e c ase s o f mo the r-c hild in whic h ac ute Chagas' infec tio n during pregnanc y was detec ted,
as we ll as the pr e se nc e o r ab se nc e o f infe c tio n amo ng the
ne wb o r ns.
CASE REPORTS
The study group inc luded three pregnant women infec ted
during pregnanc y and their babies. Diagnosis of the maternal infection was made by clinical, epidemiological and parasitological
pa r a m e te r s . Th e pa r a s ito lo gic a l m e th o ds us e d we r e th e
mic rohematoc rit c entrifuge tec hnique, as desc ribed by Woo1 2,
Strout and hemoc ultures, essentially performed as previously described in our laboratory1. The classical serological methods
( ELI SA, I n dir e c t I m m un o fluo r e s c e n c e a n d I n dir e c t
Hemagglutination were performed for immunodiagnosis. For
histo lo gic al e xaminatio n, the plac e nta was fixe d with 1 0 % formaldehyde for 2 4 h, dehydrated with alcohol/xylol, embedded
in paraffin and stained with hematoxylin-eosin.
Case 1 . A 3 0 -year-old pregnant woman, accidentally infected while manipulating T. cruzi in a research laboratory. She was at the
32nd week of pregnancy when she became infected, and developed
severe acute Chagas' disease, with fever, hepatosplenomegaly and schizotrypanids. Parasitemia was high, detectable through direct
blood examination. Due to the severity of the clinical course, the
patient required hospitalisation in the intensive care unit and it was necessary to anticipate parturition. Cesarean delivery was indicated
at 3 5 weeks of pregnancy according to clinical, obstetric, and
therapeutic criteria. Therapy with b enznidazole was successfully
applied to the mother immediately after delivery.
In spite o f the high par asite mia and the se ve r e c linic al
c o ur se pr e se nte d b y the mo the r, the ne wb o r n - a male infant
we ighing 3 .7 k g - was no t infe c te d, as de mo nstr ate d b y the
ab se nc e o f c ir c ulating par asite s and antib o die s at b ir th and
until the twe lfth mo nth o f life . The par asite mia was se r ially
studied by hemo c ulture, a metho do lo gy that previo usly pro ved
to have ne ar 1 0 0 % se nsitivity in c o nge nital and ac ute c ase s.
All the se r o lo gy te sts we r e ne gative up to 1 2 mo nths.
Case 2 . A 1 7 -year-old woman, infected by vector transmission, in whom the acute infection was clinically diagnosed by ophthalmic
ganglio nar c o mplex ( Figur e 1 A) , and was par asito lo gic ally
c o n fir m e d b y th e de te c tio n o f c ir c ula tin g pa r a s ite s b y
microhematocrit technique at the 2 8th week of pregnancy. The
c linic al c ourse of the disease was mild, and the patient was
controlled on an outpatient basis. The delivery took place at 3 8
weeks of pregnancy, by cesarean section. In this case, histological
studies of the placenta were performed, and amastigote forms of
T. cruzi were detected in the free chorionic villi ( Figure 1 B) , as well as alo ng the dec idua plate. The fo llo wing mic ro sc o pic
alter atio ns were o bserved in the pla c e n ta : gr a n ulo m a to us
c hange s, inflammato r y infiltr ate s and foc al nec rosis in the
c horionic villi. The fibrinoid layer was thic ker in some modified
villi in whic h sync ytial m o dific atio ns suc h as e de m a and c alc ific ation foc i were present. Vasc ular thromboses were also
seen.
The newborn was a female infant weighting 3 .4 kg, and did
not present c linic al symptoms of Chagas' infec tion. The absenc e
of infec tion was c onfirmed by the fac t that the parasitologic al e x a m in a tio n s o f c o r d b lo o d - b o th b y m ic r o s tr o ut a n d
hemoc ulture methods - were negative at birth, and also at the 6th
month of life. The infant also have negative serology during the
first year of life. Treatment with benznidazole was administrated
to the mother after delivery.
Case 3 . A 1 9 -year-old woman, in whom the ac ute infec tion was c linic ally and parasitologic ally diagnosed by ophthalmic
ganglionar c omplex and c irc ulating parasites detec ted during the 2 0 th week of pregnanc y. The maternal infec tion oc c urred
by vec tor inoc ulation. The c linic al c ourse of disease was mild, and the patient was c ontrolled on an outpatient basis. The baby
was born by vaginal delivery at 3 8 weeks of gestation, with a
we igh t o f 3 . 1 k g, with h e pa to s ple n o m e ga ly, a n d po s itive parasitemia and serology. B oth, the mother and the newborn
were treated with B enznidazole immediately after delivery, and
examined thro ugh par asito lo gic al and sero lo gic al metho ds. Sera c ollec ted during the longitudinal follow-up of the baby
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Revista da Sociedade Br asileir a de Medicina Tr opical 3 8 ( 1 ) :5 3 -5 5 , jan-fev, 2 0 0 5
Table 1 - Clin ical, parasitological an d serological resu lts of in fected m others an d n ewborn s.
Case Age Week of Week of Clinical Type of Mother Newborn infection delivery symptoms delivery parasitology serology placenta parasitology serology 1 30 32 35 severe cesarea positive doubtful ND* negative negative 2 17 28 38 mild cesarea positive doubtful positive negative negative 3 19 20 38 mild vaginal positive positive ND positive positive * Not done
bec ame negative for Tryp a n o so m a c ru zi as determined by the
same sero lo gic al tests, at 7 mo nths o f age. The parasito lo gic al te st fo r par asite s was ne gative , as we ll.
Tab le 1 summar izes the main c linic al, par asito lo gic al and
se r o lo gic al findings in the thr e e infe c te d mo the r s and the ir
b ab ie s.
DISCUSSION
Th e in c ide n c e o f c o n ge n ita l tr a n s m is s io n h a s a lwa ys
b e e n de te r m ine d in wo m e n dur ing the inde te r m ina te o r
c hr o nic pe r io d o f infe c tio n2 7. Dur ing the se phase s o f the
dise ase , the par asite m ia is lo w and r e c ur r e nt, unde te c tab le
b y dir e c t par asito lo gic al m e tho ds and o nly de te c tab le in
so m e c ase s b y xe no diagno sis o r he m o c ultur e . The r e ar e
fe w pr e vio us r e po r ts o n ac ute infe c tio n o f pr e gnant wo m an. I n fac t, Rassi e t al1 0 in 1 9 5 8 in B r azil, r e po r te d a c ase , the n
r e vie we d b y B r ab in3. I n the pr e se nt wo r k we studie d thr e e
ac ute c ase s in pr e gnant wo m e n, with high par asite m ia and, at le ast in o ne o f tho se c ase s, plac e ntal infe c tio n and se ve r e
histo lo gic al c hange s. Tak e n to ge the r, the lac k o f c o nge nital
infe c tio n in two o f the thr e e studie d c ase s, sugge sts that the
par asitic lo ad do e s no t se e m to b e a m ain fac to r invo lve d in
the m ate r nal- fe tal tr ansm issio n o f T. c ru z i, at le ast dur ing ac ute infe c tio n o f the m o the r. Mo r e o ve r, in c ase 2 , the o nly
o n e in wh ic h it wa s po s s ib le to s tudy th e pla c e n ta , th e
pr e se nc e o f am astigo te s and the se ve r e histo lo gic al c hange s
we r e no t asso c iate d with fe tal infe c tio n, r e sults that ar e in agr e e m e nt with Rassi e t al1 0 and Mo ya e t al7, who r e po r te d
th a t p l a c e n ta l i n fe c ti o n i s n o t s yn o n ym o u s wi th fe ta l
infe c tio n. Eve n tho ugh we studie d o nly thr e e c ase s, it is in te r e s tin g to n o te th a t in b o th n o n - in fe c te d c a s e s th e
m ate r nal infe c tio n to o k plac e dur ing the thir d tr im e ste r o f
pr e gn a n c y, wh ile in th e c a s e in wh ic h th e n e wb o r n wa s
infe c te d, the infe c tio n o c c ur r e d in the e a r lie r pe r io d o f
pr e gnanc y. This finding sugge sts that the tim e o f infe c tio n c o uld b e a r isk fac to r fo r T. c ru zi tr ansm issio n, in the ac ute
infe c tio n o f the m o the r. On the o the r hand, it sho uld no t b e
disc ar de d that, as in o the r b ac te r ial o r vir al infe c tio ns, the
tr ansmissio n c o uld also tak e plac e at the mo me nt o f de live r y. I n this se nse , in o ur pr e vio us e xpe r ie nc e8 we have fo und
b ab ie s who we r e par asito lo gic ally ne gative at b ir th and who
b e c am e po sitive at 1 0 - 1 5 days o f life ; with no po ssib ility o f o the r po ssib le fo r m s o f tr ansm issio n.
Fi n a l l y, a s s p e c i fi c a n ti p a r a s i te th e r a p y c a n n o t b e
administr ate d dur ing pr e gnanc y with the availab le dr ugs, it will b e ne c e ssar y to disc uss po ssib le me dic al and the r ape utic
de c isio ns in pr e gnant wo me n with ac ute c hagasic infe c tio n.
ACKNOWLEDGEMENTS
We thank Dr. Pe dr o Mo ya and Dr. So fía Par issi de Fab r o
fo r the ir impo r tant sugge stio ns and Ms. Patr ic ia Gil fo r he r
te c hnic al c o llab o r atio n. This wo r k was suppo r te d b y funds fr o m Se r vic io Nac io nal de Chagas and SECYT, Unive r sidad
Nac io nal de Có r do b a.
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