2 3 8
Revista da Sociedade Br asileir a de Medicina Tr opical 3 7 ( 3 ) :2 3 8 -2 4 0 , mai-jun, 2 0 0 4
Clinical and labor ator ial evidence of
Rickettsia felis
infections in Latin Amer ica
Evidência clínica e laboratorial de infecções
por
Rick e ttsia fe lis
na América Latina
Már cio Antônio Mor eir a Galvão
1, Cláudio Mafr a
2, Chequer Buffe Chamone
3,
Simone Ber ger Calic
3, Jor ge E. Zavala-Velazquez
4and David Hughes Walker
5ABSTRACT
Af te r th e d i sc o ve ry a n d i n i ti a l c h a ra c te ri za ti o n o f Ric k e ttsia fe lis i n 1 9 9 2 b y Aza d a n d c o ls, a n d th e su b se q u e n t f i rst d e sc ri p ti o n o f a h u m a n c a se o f i n f e c ti o n i n 1 9 9 4 , th e re h a ve b e e n two c o m m u n i c a ti o n s o f h u m a n ri c k e ttsi o si s c a se s c a u se d b y Ric k e ttsia fe lis i n La ti n Am e ri c a . Th e f i rst o n e wa s p u b li sh e d i n 2 0 0 0 b y Za va la - Ve la zq u e z a n d c o ls i n Me x i c o . In 2 0 0 1 Ra o u lt a n d c o ls d e sc ri b e d th e o c c u rre n c e o f two h u m a n c a se s o f Ric k e ttsia fe lis ri c k e ttsi o si s i n Bra zi l. In th e p re se n t d i sc u ssi o n th e se two a rti c le s we re c o m p a re d a n d a f te r th e d e sc ri p ti o n o f th e p ri n c i p a l si gn s a n d sym p to m s, i t wa s c o n c lu d e d th a t m o re stu d i e s a re n e e d e d wi th d e sc ri p ti o n s o f a gre a te r n u m b e r o f p a ti e n ts to e sta b li sh th e tru e f re q u e n c y o f th e c li n i c a l si gn s a n d sym p to m s p re se n t i n Ric k e ttsia fe lis ri c k e ttsi o si s.
Ke y-words: Ri c k e ttsi a f e li s. Ri c k e ttsi o se s. La ti n Am e ri c a .
RESUMO
De p o i s d a d e sc o b e rta e c a ra c te ri za ç ã o i n i c i a l d a Ric k e ttsia fe lis e m 1 9 9 2 p o r Aza d e c o ls, e à d e sc ri ç ã o su b se q ü e n te d o p ri m e i ro c a so d e i n f e c ç ã o h u m a n a e m 1 9 9 4 , h o u ve ra m d u a s c o m u n i c a ç õ e s d e ri c k e ttsi o se s c a u sa d a s p o r Ric k e ttsia fe lis
n a Am é ri c a La ti n a . A pri m e i ra f o i f e i ta po r Za va la - Ve la zq u e z e c o ls e m 2000 n o Mé xi c o . Em 2001, Ra o u lt e c o ls de sc re ve ra m a o c o rrê n c i a d e d o i s c a so s h u m a n o s d e ri c k e ttsi o se p o r Ric k e ttsia fe lis n o Bra si l. Na p re se n te d i sc u ssã o , e sse s d o i s a rti go s f o ra m c o m p a ra d o s, e d e p o i s d a d e sc ri ç ã o d o s p ri n c i p a i s si n a i s e si n to m a s, c o n c lu i - se q u e o u tro s e stu d o s sã o n e c e ssá ri o s, c o m a p a rti c i p a ç ã o d e u m m a i o r n ú m e ro d e p a c i e n te s, p a ra se e sta b e le c e r a ve rd a d e i ra f re q ü ê n c i a d o s si n a i s c lí n i c o s e si n to m a s p re se n te s n a s ri c k e ttsi o se s p o r Ric k e ttsia fe lis.
Pal avr as-chave s: Ri c k e ttsi a f e li s. Ri c k e ttsi o se s. La ti n Am e ri c a .
1 . De par tame nto de Nutr iç ão Clínic a e So c ial da Esc o la de Nutr iç ão da Unive r sidade Fe de r al de Our o Pr e to , Our o Pr e to . MG. 2 . De par tame nto de B io q uímic a e B io lo gia Mo le c ular da Unive r sidade Fe de r al de Viç o sa, Viç o sa, MG. 3 . Fundaç ão Eze q uie l Dias, B e lo Ho r izo nte , MG. 4 . Unive r sidad Autô no ma de Yuc atán, Me xic o . 5 . Wo r ld He alth Or ganizatio n Co llab o r ating Ce nte r fo r Tr o pic al Dise ase s o f Unive r sity o f Te xas Me dic al B r anc h, Te xas, USA.
Addr e ss to: Dr. Már c io A. Mo r e ir a Galvão . DNCS/EN/UFOP, 3 5 4 0 0 - 0 0 0 Our o Pr e to , MG, B r azil. Te l: 5 5 3 1 3 5 5 9 - 1 8 3 8 .
e -mail: mgalvao @ e nut. ufo p. b r. Re c e b ido par a pub lic aç ão e m 2 0 /1 1 /2 0 0 2 Ac e ito e m 2 3 /4 /2 0 0 4
The patho genic ri c k e ttsi a e are a gro up o f intrac ellular bac teria responsible for a variety of human diseases. Ric k e ttsia ric k e ttsii and Ric k e ttsia typhi and their respec tive diseases, B r azilian spo tte d fe ve r, the e q uivale nt o f Ro c k y Mo untain spotted fever transmitted by the Am b lyo m m a c a je n n e n se tic k, and murine typhus transmitted by the Oriental rat flea, have been known in B razil sinc e the 1 9 2 0 s5 6.
Ro c k y Mo untain spo tte d fe ve r was do c ume nte d in Me xic o dur in g th e 1 9 3 0 s , a lth o ugh e pide m ic typh us c a us e d b y
Ri c k e ttsi a p ro wa ze k i i had impo r tanc e in the o utb r e ak s that have b e e n de sc r ib e d sinc e 1 7 3 6 . Ric k e ttsial dise ase s have sub sequently r ec eived little attentio n in tr o pic al ar eas o f Latin Ame r ic a. Ende mic Ro c k y Mo untain spo tte d fe ve r and o the r r ic k e ttsio se s suc h as e pide mic typhus have b e e n ide ntifie d in c o untr ie s o f Latin Ame r ic a o nly b e c ause the ir high fatality-c ase ratio has demanded investigatio n. It is po ssible that o ther spo tted fever gro up ric kettsio ses have o c c urred unrec o gnized in Me xic o and B r azil fo r lo ng pe r io ds.
2 3 9
Ga lvã o MAM e t al
Serologic al and c linic al evidenc e of severe and mild-to-moderate c ases of ric kettsioses and the applic ation of molec ular m e th o ds in c ludin g de te c tio n b y PCR a m plific a tio n a n d c harac terizatio n by DNA sequenc e analysis has allo wed the identific ation of new spec ies of Rick e ttsia, suc h as R. fe lis in opossums, fleas1 9 1 0 and blood and skin from diseased humans in the USA, Mexic o, Franc e, Brazil, and Germany2 4 7 8 1 1.
MATERIAL AND METHODS
During the 1 9 9 0 ’s reports of serologic al studies in Mexic o 1 2 and Brazil3 disc ussed the possibility of the existenc e of other r ic k e tts io s e s in th e s e c o un tr ie s . I n th e r o le o f th e n e w ric kettsioses, R. fe lis ric kettsiosis c urrently appears to be one of the most important. Some authors7 1 1 have disc ussed the existenc e of human c ases c aused by this bac terium in Mexic o and Brazil. The objec tive of this artic le was to c ompare the data and c linic al symptoms of human ric kettsiosis c ases desc ribed in these two c ommunic ations and to evaluate the severity, epidemiology and c linic al c ourse of this new ric kettsiosis.
RESULTS
In Me xic o thr e e patie nts with fe ve r, e xanthe m, he adac he and c e ntr al ne r vo us syste m invo lve me nt we r e diagno se d with
R. f e li s infe c tio n b y spe c ific PCR o f b lo o d in two c ase s and PCR o f sk in in ano the r c ase . In all thr e e c ase s, ac ute se r um sample s c o ntaine d no de te c tab le antib o die s to ri c k e ttsi a e. The c o nvale sc e nt se r a c o ntaine d antib o die s at a tite r o f 1 :6 4 to Ri c k e ttsi a a k a ri , R. ri c k e ttsi i and R. typ h i1 1.
PCR amplific atio n o f DNA fr o m sk in b io psy and b lo o d s a m ple s with s pe c ific pr im e r s fo r th e Ri c k e ttsi a 1 7 k Da pr o te in ge n e wa s c o n fir m e d b y DNA s e q ue n c in g, wh ic h sho we d that the se que nc e was 1 0 0 % ide ntic al to R. f e li s1 1. In the two human c ase s o f R. f e li s r ic k e ttsio sis in B r azil, fir st s us pe c te d to b e B r a zilia n s po tte d fe ve r, th e dis e a s e wa s c o n fir m e d in s e r um b y I FA ( I gG/I gM) with h igh tite r s to
R. f e li s ( 1 0 2 4 /6 4 a n d 5 1 2 /6 4 ) a n d b y ide n tific a tio n o f
R. f e li s in o ne c ase b y DNA se que nc ing fo llo wing ne ste d-PCR amplific atio n fr o m a se r um sample8.
In both reports from Mexic o and B razil ( Figure 1 ) , the patients ( five) initially had systemic symptoms ( fever, headac he and m yalgia) . All the c ase s also sho we d a r ash. Visc e r al involvement was suggested in all patients with abdominal pain, nausea and vomiting and diarrhea in four patients. Four patients had involvement of c entral nervous system with photophobia in two pa tie nts fr o m Me xic o a nd he a r ing lo ss a nd signs o f meningismus in the other one and the presenc e of c oma in one of the Brazilian cases. One patient from Mexico had conjunctivitis. Laboratory data in the Brazilian c ases revealed thromboc ytopenia ( platelets < 1 0 0 ,0 0 0 /mm3) and inc reased serum c onc entration of aspartate transaminase assoc iated with hepatosplenomegaly. One of the three Mexic an c ases manifested anemia, leukoc ytosis, thromboc ytosis and prolonged prothrombin time. The third one showed leukopenia.
DISCUSSION
The c linic al manife statio ns in the se patie nts inc r e ase o ur k no wle dge o f the illne ss c ause d b y R. f e li s infe c tio n.
Fe ve r, he adac he , and myalgia sugge ste d syste mic ac ute -phase r espo nse, the exanthem r eflec ts a vasc ulitis, a c o mmo n manife statio n o f r ic k e ttsial dise ase s, and the o c c ur r e nc e o f a b do m ina l pa in, na us e a , vo m iting a nd dia r r he a indic a te po ssible visc eral invo lvement. Neuro lo gic al sympto ms suggest that we ar e fac ing a po te ntially se ve r e ne w r ic k e ttsial dise ase . The epidemiologic data suggested c ontac t with an opossum in one of the Mexic an c ases, and with fleas and tic ks in the B razilian patients and o ne o f the Mexic an c ases. Regarding treatment, the Brazilian c ases rec eived c hloramphenic ol, and in the Mexican cases one patient received doxycycline after the acute illness. All these c ases survived in the two c ountries studied.
Mo r e studie s ar e ne e de d to e stab lish the r e al fr e que nc y o f the sympto ms present in R. f e li s ric kettsio sis, the true c ase-fatality r atio o f this dise ase , the e pide mio lo gy and the r o le o f
R. f e li s as an impo r tant patho ge n.
Central nervous
system involvement
Fever, headache
and myalgia
Cutaneous
lesions
Diarrhea Conjunctivitis Abdominal pain
nausea and vomiting 4
3
2
1
0
Clinical signs and symptoms
Brazil
Mexico
2 4 0
Revista da Sociedade Br asileir a de Medicina Tr opical 3 7 ( 3 ) :2 2 8 -2 4 0 , mai-jun, 2 0 0 4
REFERENCES
1 . Azad AF, Sac c i J r J B , Ne lso n WM, Dasc h GA, Sc hmidtmann ET, Car l M. Ge ne tic c har ac te r izatio n and tr anso var ial tr ansmissio n o f a typhus- lik e
Ri c k e ttsi a fo und in c at fle as. Pr o c e e dings o f Natio nal Ac ade my o f Sc ie nc e
o f the Unite d State s o f Ame r ic a 8 9 : 4 3 - 4 6 , 1 9 9 2 .
2 . B o uye r DH, Ste no s J , Cr o q ue t- Valde s P, Mo r o n CG, Po po v VL, Zavala-Ve lazq ue z J E, Fo il LD, Sto thar d DR, Azad AF, Walk e r DH. Ri c k e ttsi a f e li s: mo le c ular c har ac te r izatio n o f a ne w me mb e r o f the spo tte d fe ve r gr o up. Inte r natio nal Jo ur nal o f Syste matic and Evo lutio nar y Epide mio lo gy 5 1 :3 3 9 -3 4 7 , 2 0 0 1 .
3 . Galvão MAM, Chamo ne , CB , Calic SB , Mac hado MC, Oto ni MEA, Die tze R, Mo r o n C, Fe ng HM, Olano J P, Walk e r DH . Se r o lo gic e vide nc e o f spo tte d fe ve r gr o up Ri c k e ttsi a in No vo Cr uze ir o Munic ipalityMinas Ge r ais State -B r azil. In : Rao ult D, B r o uq ui P ( e ds) Ric k e ttsial Dise ase s at the Tur n o f the Thir d Mille nnium, Mar se ille , Else vie r p. 2 4 0 - 2 4 3 , 1 9 9 9 .
4 . Higgin s J A, Sa c c i J B , Sc h r ie fe r ME, En dr is R G, Aza d AF. Mo le c ula r ide ntific atio n o f Ri c k e ttsi a-lik e mic r o o r ganisms asso c iate d with c o lo nize d c at fle as (Cte n o c e p h a li d e s f e li s) . Inse c t Mo le c ular B io lo gy 3 :2 7 -3 3 , 1 9 9 4 .
5 . Mo nte ir o JL, Fo nse c a F. Typho e ndê mic o de São Paulo . No vas e xpe r iê nc ias so b r e a tr ansmissão e xpe r ime ntal po r c ar r apato s Bo o p h i lu s m i c ro p lu s e
Am b lyo m m a c a je n n e n se. Me mó r ias do Instituto B utantan ( São Paulo ) 1 0 : 3 3 - 5 0 , 1 9 3 2 .
6 . Piza JT. Co nsider aç õ es epidemio ló gic as e c línic as so br e o Tifo Exantemátic o
de São Paulo . São Paulo , So c iedade Impr esso r a Paulista 1 1 -1 1 9 , 1 9 3 2 .
7 . Raoult D, Fournier P-E, Abboud P, Caron F. First doc umented human Rick e ttsia a e sc hlim a nnii infec tion. Emerging Infec tious Diseases 8 :7 4 8 -7 4 9 , 2 0 0 2 .
8 . Rao ult D, La Sc o la B , Ene a M, Fo ur nie r P- E, Ro ux V, Fe no llar F, Galvão MAM, Lamb alle r ie X. A fle a asso c iate d Ri c k e ttsi a patho ge nic fo r humans. Eme r ging Infe c tio us Dise ase s 7 : 7 3 - 8 1 , 2 0 0 1 .
9 . Sc hr ie fe r ME, Sac c i J B J r, Dumle r J S, B ulle n MG, Azad AF. Ide ntific atio n o f a no ve l r ic k e ttsial infe c tio n in a patie nt diagno se d with mur ine typhus. J o ur nal o f Clinic al Mic r o b io lo gy 3 2 : 9 4 9 - 9 5 4 , 1 9 9 4 .
1 0 . Sc hr ie fe r ME, Sac c i J r J B , Taylo r J P, Higgins J A, Azad AF. Mur ine typhus: update d r o le s o f multiple ur b an c o mpo ne nts and a se c o nd typhus- lik e
Ri c k e ttsi a. J o ur nal o f Me dic al Ento mo lo gy 3 1 : 6 8 1 - 6 8 5 , 1 9 9 0 .
1 1 . Zavala-Ve lazq ue z JE, Ruiz-So sa JA, Sanc he z-Elias RA, B e c e r r a-Car mo na G, Walk e r DH. Ri c k e ttsi a f e li s r ic k e ttsio sis in Yuc atan. Lanc e t 3 5 6 : 1 0 7 9 -1 0 8 0 , 2 0 0 0 .
