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Revista da Sociedade Br asileir a de Medicina Tr opical 3 9 ( 5 ) :5 0 1 -5 0 3 , set-out, 2 0 0 6
RELATO DE CASO/CASE REPORT
Vertical transmission of
Cryptococcus neoformans
from a mother
coinfected with human immunodeficiency virus. Case report
Transmissão vertical de Cryptococcus neoformans a partir de mãe co-infectada
com o vírus da imunodeficiência humana. Relato de caso
Gleusa Castro
1, Maria Célia Cervi
2and Roberto Martinez
1ABSTRACT
Disse minate d infe c tio n with Cr ypto c o c c us ne o fo r mans was o b se r ve d in a ne wb o r n infant who pr e se nte d fe ve r and r e spir ato r y sympto ms sinc e the 5 2nd
day o f life . The mo the r was infe c te d b y human immuno de fic ie nc y vir us and pr e se nte d pulmo nar y and me ninge al c r ypto c o c c al infe c tio n. This is a r ar e c ase o f c r ypto c o c c al infe c tio n with pr o b ab le mate r nal-fe tal tr ansmissio n.
Ke y- wo r ds: Cr ypto c o c c us ne o fo r m ans. Ac q uir e d im m uno de fic ie nc y syndr o m e . Pr e gnanc y. Mate r nal- fe tal tr ansm issio n. Human immuno de fic ie nc y vir us.
RESUMO
Infecção disseminada por Cryptococcus neoformans foi observada em um recém-nascido que apresentava febre e sintomas respiratórios desde o 5 2 º dia de vida. A mãe tinha infec ç ão pelo vírus da imunodefic iênc ia humana e apresentou infec ç ão pulmonar e meningite c riptoc óc ic a. Este é um c aso raro de uma infec ç ão c riptoc óc ic a c om provável transmissão materno-fetal.
Pa la vr a s- cha ve s: Cr ypto c o c c us ne o fo r mans. Síndr o me da imuno de fic iê nc ia adquir ida. Gr avide z. Tr ansmissão mate r no -fe tal. Vír us da imuno de fic iê nc ia humana.
1 . De par tame nt o f Inte r nal Me dic ine , Fac ulty o f Me dic ine o f Rib e ir ão Pr e to , Unive r sity o f São Paulo , Rib e ir ão Pr e to , SP, B r asil. 2 De par tame nt o f Pe diatr ic , Fac ulty o f Me dic ine o f Rib e ir ão Pr e to , Unive r sity o f São Paulo , Rib e ir ão Pr e to , SP, B r asil.
Addr e ss to : Pr o f. Ro b e r to Mar tine z. De pto de Clínic a Mé dic a/FMRP/USP. Av. B ande ir ante s 3 9 0 0 , 1 4 0 4 8 - 9 0 0 Rib e ir ão Pr e to , SP, B r asil.
Te l: 5 5 1 6 3 6 0 2 - 2 4 6 8 , Fax: 5 5 1 6 3 6 3 3 - 6 6 9 5 e - mail: r mar tine @ fmr p. usp. b r
Re c e b ido par a pub lic aç ão e m 2 1 /1 0 /2 0 0 5 Ac e ito e m 1 0 /8 /2 0 0 6
Cr ypto c o c c o sis is a syste mic myc o sis c ause d b y var ie tie s o f Cr yp to c o c c u s n e o fo r m a n s a n d i s p r e do m i n a n tl y a n o ppo r tunistic infe c tio n o b se r ve d in adults with ac q uir e d im m uno de fic ie nc y syndr o m e ( AI DS) o r in o the r c e llular immuno de fic ie nc y c o nditio ns. A B r azilian study sho we d a 1 5 % pr e vale nc e o f c r ypto c o c c o sis amo ng adults with AIDS2.
Ano the r pr o spe c tive study c o nduc te d in the Unite d State s b e twe e n 1 9 9 2 and 2 0 0 0 r e po r te d that 8 8 .7 % o f the c ase s o f c r ypto c o c c o sis we r e asso c iate d with HIV infe c tio n6.
This is a dise ase r ar e ly de te c te d in c hildr e n, e ve n in tho se immuno depr essed, with so me r epo r ts o f o lder c hildr en4 9 and
almo st no nexistent in newbo rn infants3. There are few repo rts
o f c r ypto c o c c o sis diagno se d dur ing pr e gnanc y1 8, inc luding
iso latio n o f the fungus fr o m the plac e nta.
Th e tr a n s m i s s i o n o f Cr yp to c o c c u s fr o m m o th e r to newbo rn infant with evidenc e o f the disease has been repo rted pr e vio usly and is c o nside r e d to b e quite r ar e7.
A c ase of probable vertic al transmission of Cr ypto c o c c us neoformans from an HIV-infec ted mother is desc ribed here, with manifestations of pulmonary and disseminated c ryptoc oc c osis in an infant by fungal dissemination during the peripartum period.
CASE REPORT
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Ca str o G e t a l
Cryptoc oc c osis was diagnosed 4 8 days after delivery. She presented headac he and vomiting, whic h started 4 0 days after delivery, and persistent fever beginning 1 5 days before delivery. She was c ac hec tic , pale and c o nsc io us and sho wed nuc hal rigidity. Subsidiary tests revealed 8 .9 g/dL of hemoglobin and white cell number of 6 ,2 5 0 /mm3, with 6 8 % granulocytes. Cerebrospinal
fluid ( CSF) obtained by spinal punc ture revealed 9 6 c ells/mm3,
2 4 mg/dL of protein, and 3 3 mg/dL of gluc ose, with numerous enc apsulated fungi identified as Cryptoc oc c us spp by the Indian ink test. Cryptoc oc c us neoformans was isolated from both the blood c ulture and the CSF.
The patient was treated with amphoteric in B at a total dose of 4 ,0 7 5 mg, for about 8 0 days. Cryptoc oc c us was detec ted in the CSF by the Indian ink test, but the CSF c ulture bec ame negative afte r 6 6 days o f tr e atme nt. Fluc o nazo le was intr o duc e d as maintenanc e treatment, but the patient returned for evaluation only two months later. She presented intrac ranial hypertension and died nine days after hospitalization.
T h e i n fa n t wa s b o r n b y va gi n a l d e l i ve r y, we i gh i n g 2 , 8 8 0 g with an Apgar sc o r e o f 9 and 1 0 at the 1st and 5th
minute , r e spe c tive ly. He was no t b r e ast-fe d. He e vo lve d with insuffic ie nt we ight gain and o n the 5 2nd day o f life manife ste d
a c o ugh and ir r egular fever. The infant was anemic , pr esented a n e n l a r ge d l i ve r a n d s p l e e n , d i ffu s e c r a c k l e s u p o n ausc ultatio n o f the lung, as we ll as c andidiasis o f the o r al m uc o s a . A c h e s t X- r a y r e ve a le d a n in te r s titia l in filtr a te pr e do m in a tin g in th e b a s e s . Th e c h ild wa s tr e a te d with amoxic illin and nystatin. At 1 2 0 days of life he was hospitalized due to wo r se ning r e spir ato r y sympto ms and pe r siste nt fe ve r. He pr e se nte d dyspne a, c yano sis, inte r c o stal r e tr ac tio ns and ta c h yc a r di a . A c h e s t X- r a y r e ve a l e d a di ffu s e b i l a te r a l inte r stitial infiltr ate with alve o lizatio n in the pulmo nar y r ight b a s e . He wa s tr e a te d wi th a m p i c i l l i n , ge n ta m i c i n a n d sulfame tho xazo le -tr ime tho pr im ( 2 0 mg/k g/day) fo r 1 8 days, with n o im p r o ve m e n t in s ign s a n d s ym p to m s . He th e n manife ste d r e spir ato r y insuffic ie nc y and pe te c hial le sio ns o n the ar ms and tr unk , r e quir ing o r o tr ac he al intub atio n, with de ath o c c ur r ing 2 0 days afte r ho spitalizatio n. Cr ypto c o c c us ne o fo r mans was iso late d fr o m a b lo o d c ultur e pe r fo r me d 2 days b e fo r e de ath. Histo patho lo gic al e xaminatio n o f the pla c e n ta wa s n o t pe r fo r m e d. Th e in fa n t did n o t r e c e ive antifungal tr e atme nt b e c ause the c r ypto c o c c al infe c tio n was no t diagno se d while he was alive . The anti-HIV te st c ar r ie d o ut by immuno enzymatic metho d at 5 days o f life was reac tive, b ut PCR fo r HIV was no t ac c e ssib le in that time .
DISCUSSION
I n th e c a s e r e po r te d h e r e , ve r tic a l tr a n s m is s io n o f C. neoformans probably oc c urred, sinc e the disease began in the mother at the end of pregnancy and was later diagnosed as c ryptoc oc c osis. Infec tion of the blood stream permitted the dissemination of the fungus to the meninges and the child was presumably infected inside the uterus. Although it was not possible to examine the placenta, the transmission of C. neoformans during
the peripartum period was suggested by the early occurrence of respiratory infec tion in the c hild, whic h progressed despite antibacterial treatment, with the yeast isolated later from a blood c ulture. However, there was no epidemiologic al data suggesting the ac quisition of C. neoformans from an environmental sourc e.
In addition to the fac t that AIDS favors the oc c urrenc e of c r ypto c o c c o sis, the r e is e vide nc e that the ho r m o nal and immunological changes inherent to the gestational state favor the onset of diseases caused by intracellular pathogens. Several cases of cryptococcosis affecting pregnant women have been reported, either as pneumo nia in previo usly healthy wo men o r, mo re commonly, as an infection of the central nervous system 1 8. In
general, C. neoformans is not transmitted to a fetus during pregnancy even when cryptococcal infection is observed in the maternal space of the placenta in a patient5. A case of
mother-child Cryptococcus transmission with isolation of the yeast from both was reported in 1 9 4 87. Another probable case of vertical
transmission of C. neoformans was recently observed in Thailand. The mother, a 2 6 -year-old woman with HIV-1 infection detected dur ing pr e gnanc y, de ve lo pe d pne umo nia and c r ypto c o c c al meningitis three days after delivery. The child, which was premature and showed insufficient weight gain, but was not infected with HIV, manifested pulmonary and meningeal cryptococcosis at 8 0 days of age1 0. In this case, whose characteristics were similar to those
of the present report, it was also not possible to perform a histological examination of the placenta.
Cr ypto c o c c us n e o fo r m a n s in fe c tio n is in fr e q ue n t in c hildren, tho ugh its inc idenc e has inc reased due to the greater numb e r o f immuno de pr e sse d patie nts and e spe c ially due to the inc r e asing sur vival o f c hildr e n with AI DS4 9, altho ugh
c r ypto c o c c o sis is r ar e ly o b se r ve d amo ng ne o nate s3.
The pr e se nt r e po r t c o r r e spo nds to a r ar e c ase o f mo the r-c hild tr ansmissio n o f Cr ypto c o c c us neo fo r mans b y pr o b ab le he mato ge no us disse minatio n dur ing the pe r ipar tum pe r io d, wi th a n i n s i di o u s i n s ta l l a ti o n o f th e i n fe c ti o n a n d th e o c c ur r e nc e o f de ath in b o th mo the r and infant.
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