ISSN 0025-7680
MEDICINA(Buenos Aires) 37: Supl. 3, 175-181 (1977)
STUDIES ON ARENA VIRUSES IN BRAZIL
F. P. PINHEIRO, J. P. WOODALL, AMÉLlA P. A. TRAVASSOS DA ROSA J. F. TRAVASSOS DA ROSA Ewndro Chagas lmtitute, Fundação SESP, Brazilian Mini.\try of Health, Belém, Brazll and San Juan Laboratorles. CDC, San Juan, Puerto Rico
Two roembers of the Arenavirus group of Amapari vírus during the period of May are presentIy known to occur in BraziI. 1964 through December 1971 is shown in Both of them have onIy been isoIated from Tahle 1. lt can be seen that 12.5 %, of the wiId rodents and ectoparasites and they Oryzomys capito ssp. and 12.1 % of the are found in different geographicaI IocaIi- Neacomys guianae had circulatin~ vírus at ties of the Amazon region. Amapari virus the time they were processed. The vírus has onIv been encountered in the Serra do could not be detected in other wild ani- Navio 'arca, Amapa Territory, where its maIs, mosquitoes or sentineI mice, but 4 occurrence was first recognized in 1964(3). pooIs of ectoparasitic Iaelapid mites com- The other member of the group BeAn bed floro Oryzomys capito ssp. yield the 29.'3022,as yet unnamed, was found in agent. 1975. in the Itaituba- Jacareacanga road There were marked differences of the stction of the TransAmazon highway, infection late in those two rodent species (Fig. 1 ) .Latino virus, which has been durin~ the two periods of studies under- frequentIy iso]ated in Bo]ivia from Calomya taken in Serra do Navio. In the first, which oollosus. but onIy once in BraziI, from a Iasted from May 1004 through August rodent of the same species. caught near 1968, alI animaIs were sacrificed and blood, Corumbá. southwest of BraziI. c]ose to the urine and viscera were 'collected for at- BoIivian border, wilJ .not be discussed in tempted vírus isolation. Subsequently a this paper. retrapping plagIam was started covering the period from September 1968 to Decem- Amapari vinIs ber 1971. During this 40 month period, blood and urine were the specimens collec- This agent is maintained enzootically in ted from the animaIs for the attempted two rodent species. Oryzomys capito vjrus isolation. or viscera from animaIs ~"'P. and Neacomys guianae. which inhabit that died accidentaly. forested regions of the manganese mine of The infection rate was based on actuaI Serra do Navio. Infected animaIs of both virus iso1ations and not on detection of species have aJso been captured in narrow antibody, as the former was considered a ~tretches of secondary growth forest edging more sensitive indicator. lndeed, we failed lhe prirnary forest. In addition, infected to find neutralizing antibodies in the serum Oryzomys capito ssp. have been trapped of infected animaIs, and although comple- near and insjde a hut Iocated some 50 ment fixing (CF) antibodies mar develop, meters outside the primary forest. anticomplementary serum often constitu- A summary of lhe number of animaIs tes a problem. and arthropods examined for lhe presence The use of CF test for the detection of Amapari antigen in the brain of inoculated mice without signs of illness, ~reatly in- Postal /lddress: Evandro Chagas Institute, Flmdação SESP. Brazilian Ministry of Health, creases the number of isolates from N,~a- Belém, Brazil. comys rats. Thus, only about 3070 of the -175 - 11-3;191 MEDICINA Vol. XXXVII. Suplemento N! 3 -1977
strains of Amapari virus derived Eram this the Neacomys the infection rate also gra- rodent species kill suck1ing rnice on the dually increased, peaking in 1006. This first passage.The remaining strains caused peak could be doe, in part, to the fact that asymptomatic infections, that were recog- in this year we introduced the CF techni- nizable by the detection of CF antigen in que for detecting inapparent infections in the mice bmins 10 to 14 days after the suckling mice. However, there was a small
. .:..4" 4'1 ..".o" D,°..
.... '.," ,. '.
Fig. 1. -Map of amazon r~gion of Brasil, showini ~nzootic ar"as of Amapari and & An 293022 viru..,s and dates of fir.t isolation.
inocuIation. On the other hand, the majo- dec1ine of the rate in 1967, folIowed by a rity of the strains of Amapari vírus from marked decrease in 1968, when it reached Oryzomys capito ssp. kiII suckIing mice 2.5 % during the first eight months of after intracerebraI (i. c.) inocuIation. this year. lt shou1d be noted that no in- As seen in Fig. 2, the annuaI infection fected Neacomys was found between Oc- r~.te af the Oryzomys increased steadiIy tober 1967 and June 1968, aIthough 00 --- . . o
~ ,'\ o , I ~ .., " II " I ., I o , I , \I 'M' 'M' ,...... , -!.'--1 ,... ..,. .."
Fig. 2. -PrrcentaKr isolation of Amapari vírus from OryzomYB capito ssp. and froro NracomV$ [!uianac.
from 4.4% in 1964 to 25% in the period individuaIs of that species were examined. of January-August of 1968. As mentioned ln the Iast four months of 1968 and in the above, during this period alI animaIs were years of 1969-70 the infection raie osciIa- sacrificed. During the Iast four months of ted between 3.0 and 6.7 %. ln 1971, bo- 1968 and in the subsequent years the in- wever, there was a tremendous increase .fection late was Iower but reIativeIy stabIe in the infection raie when isoIations were varying from 8.3 % to 12.77c. Amongst obtained from 34,5 % of the Neacomys. \ -176 -
..,. ARENAVIRUSES IN BRAZIL
The agcnt has been found in the blood, T ABLE1. Amaparl vírus isolations trom Serra do "kidney. liver, spleen, heart, urine and em- Navio, Amapá, BrazU, Mall 1964 through bryos of both rodent species. Tcn per L'ent December 1971. suspensions of these organs in some cases reached titers of more than 4,0 log/O.02 ml Np isolations isolation Specimens Np caught 1 % 'SuckIing mouse LDso. Infected urine Eram -one naturally infected Oryzomys had a 5 Primates O/55 log titre after ovemight freezing. After MarsupiaIs 0/1099 "being held at roam temperature (29-3O"C) Rodents for 12 hours its tine fcll to 2.2 and after Proechiml/ag. gul/annensis 0/008 24 hours to 2.0. In six other naturally in- OfI/zomyacapíto sap. 127/1012 12.5 % fected Oryzomys the original titre of the OfI/ZOmy8capitO(young) 5/41 12.1 % urine ranged Eram0.5 to 2.7 logs. The blood O",zomya macconnelli 0/49 from two other naturally infected Oryzo- Neacomy8gulanae 145/1234 11.7 % mys had titres of 1.0 and 1.5 logo 4/26 Oecomy8sp. 0/44 ( 15 %) and 4/18 (22 %) of pools of em- Other rodents 0/29 oryos Eram infected Oryzomys and Nea- SentineI mOUSegroups 0/910 .comys respectively were vírus positive. Bats 0/1704 Birds 0/427 Persistence of Amapari vírus in the in- Repti)es O/52 fl!fted rodents. Four naturally infected Other vertebrates 0/15 -Dryzomys were kept in lhe laboratory and Mosquitoes 0/56277 examined for presence of virem ia and vi- Ectoparasites2 4/455123 TlJria at approximately monthly intervals {Table 2). Chronic infections were obser- I Over 95 % were examined for presence of virus. ved in all four animaIs, and in two the 2 Combed from Oryzomys capito ssp. and Nea- vírus persisted for 10 months. However, comys. there were some periods during which the 3 Number of positive pools. vírus could not be detected in blood and -others in which the urine was negative. Serum antibodies. 937 sera obtained from Similar observations were made for humans and wild animaIs of the Serra do Neacomys and in two animaIs, trapped Navio regiDo were tested for the presence several times during a period of six of Amapari vírus neutralizing antibody. months. circulating and/or excreted vírus, The source of the sera was the following: was intermittently detected. humans 45, primates 21, Oryzomys capito Six Oryzomys, captured in the forest near ssp. 172, Neacomys172, Proechimys124, Belém, where Tacaribe viruses have Dever Didelphis 148, Oecomys 17, birds 71, rep- been isolated, were inoculated subcutaneo- tiles 38 and bats 128. Of the animaIs exa- usly with 0,2 ml of aI: 100 dilution of mined, 14 Oryzomys and 29 Neacomys mouse brain infected with an Oryzomys \\'ere infected. The test used was a modi- strain of Amapari vírus (Be An 138539 fication in plastic panels of the Miura & 2nd passage) which had a titre of 5,3 log Scherer's method(S). The sera were used I.Dso/0.02 ml in suckling mice. Twice wee- at 1:8 and 1:32 against 40-00 pIaque for- lly their blood and urine were collected ming units of virus. Most surprisingly, not and titrated intracerebrally in infant mice. a single semm showed any neutralization AlI produced viremia and viruria which activity to lhe virus, even those from in- persisted for five weeks, after which the fe.cted animaIs. It .shouId be noted that experiment was terminated. Viremia was sera Eram infected animaIs were aIso tes- oetected in alI on the 4th postinoculation ted in lhe presence of fresh rhesus monkey dar (1st bleeding) and viruria from the serum. 1 lth dar (3rd collection) in all but one CompIement fixing antibodies were animal. Titres ranged from 2,5 to 3,5 log found concurrently with viremia and/or ICLDso/0.02 ml in both blood and urine, viruria in 4/5 naturaIIy infected Oryzomys and vírus was nearly always present in tested. The titres varied from 1:8 to ~ 1:32. both specimens throughout. -177 - MEDICINA Vol. XXXVII -Suplemento N! 3 -J977
T ABLE 2. Persi.stcnce of Anlapan vinIS in naturall" infected Oryzomys capito ssp.
1968 1969 1968 Aug. Oct. Dec. Jan. Feb. Mar. May Jllne July 1969 L 4631 bJood + O + + + + + O + urine + + + O + O O + O L 4635 bJood + + O O -+- NT O O O urine O O + + + NT + + + L 4558 bJood + O + died urine + O + L 4597 blood O O + urine + O + died
(+), positive isolation; O, negative isolation; NT, not tested. Histopathology. Liver, heart, kidney (average 7 %) during 1969. Rates for and spleen of 10 naturally infected ary- Hae11Wlaelaps(probably ali H. fahrenhol- %omysand 13 Neacomys did not show any zi) averaged 33 % for Oryzomys and microscopic 1esions(2). 11 % for Neacomys and for Echinolaelaps E A .'T' bl 1 4 3 % for Neacomys. ctoparasttes.. s seen m 1.a e . strains of Amapari virus were is01ated Eram New Type of Arenamrus. A new type 4.5.512 ectoparasites combed Eram Oryzo- of Arenavirus was iso1ated Eram 3 Oryzo- mys capito ssp. and Neacomys. The 1ae1a- nlYS captured in November 1975 in an pjds were inocu1ated in 484 poo1s.Ali four area 1ocated some 212 km southwest of iro1ates carne Eram Gigantolaelaps oude- the town of Itaituba (Fig. 1). It is an mansi Fonseca taken Eram Oryzomys ca- area of 1?rimary tropical forest, which is pito. An ana1ysis of ali arthropod isola- crossed by the TransAmazon highway. tions of Amapari \irus made to date is The agent was isolated Eram 3 out of 58 given be1ow, for the period 1965-69: Oryzomys spp rodents which were trapped 1965-67(from unselected during a field study carried out between hosts) OryzomysNeacomys October and December 1975. Laelapido pools (positi,'e/ The vírus was obtained Eram the blood total). 3/122 0/104 of ali three anima1s and Eram the viscera Average0001 Slze i9 31 Averagehost infectionrate 13% 14% o f one of the OTfJZGmfjs.In one o f tese h o further identificatioonot rodents the vírus was isolated Eram two dlJne h~ood samples taken about one month 1968-69(from uninfectedhosts) apart. Gigantolaelapspools 1/32 0/21 The agent was considered as an arena- Haemolaelapspools 0/28 0/12 . d - f h . Echinolaelapspool~ O 0/19 VlruS base o.n the act t at !t. cross reac- Other laelapid pools 0/2 0/1 ted strongly m lhe CF test WIth a Tarll- Total ]aelapid pools (lX>Sitive/ ribe group hyperimmune ascitic fluido CF t,ota]) 1/62 O/53 tests performed at lhe Yale Arbovirus Re- Average poo] Si7t' 196 105 h . H . h h . Average host infection Iate 1401; " 5% searcBe An Urnt. 293022 New revealedaven, thatWIt it wast e stramdiffe- It is c1ear Eram lhe above that both the rent Eram Amapari, Junin, LCM, Machupo, number of pool and the numbers of mites Pichinde. Tacaribe and Tamiami viroses processed Eram Neacomys were significan- (Tab1e 3). Furthermore, in CF tests dane t1y 1essthan those from Oryzomys. -at the Evandro Cha~as Institute, Belém, The species of Gigantolaelaps recovered it was observed that ParaDa antiserum cross Eram Oryzomys copito has been almost reacted markedlv with lhe Be An 293022 exc]usive1y G. oudenlonsi, whilst that Eram strain, although the viroses seem antigeni- Neacomys has been a]most exc1usive1yG. cally distinct. Asma)) cross reaction was vitzhumi. Rates for fed specimens or G. scen with I..atino antiserum and there was oudemansi ran fram 5-20 70 (avera~e no cross with Lassa antiserum (Tab1e 4). 12 7é) and for G. ritzhumi Eram 0-21 % The average survival time of infant mi-
-178 - ARENAVJRUSESARENAVIRUSES IN IN BRAZIL
I cece inO<'uIated inoC'uIatcd by lhe the i.c. route varicd from 11.5 to 13.7 days in Iow passagcspassages and by ~ ~ ~ lhethe intrapcritoncaI intrapcritoncaI (i.p.) (i.p.) route route it reachedreachcd ~~tO) 0000000 o o o o o o o '"~ '"~, o0 ]46 d ays. T ltratlons.. pc rf arme d m" m f ant ~ ~ ~ ]4.6 days. Titrations pcnormed in infant mice gave vaIuesvaIucs of 5.5 Iog/O.02 by lhe i.c.i.c. route route and and 4.0 4.0 Iog/ Iogl 0.2 0.2 mI mI by lhe i.p. route. A fcw adult micc mice died followjngfoIlowing i.c. O ~~ illocuIation, but but they they survived survivcd when lhethe -AI~ AI . ~ ip.i.p. route route was was used. used. It It is is interesting interesting that .~.< 000000 000000' '" 00 dIt ' h 1 I .,.,~ L.;~ ~~ ~ a u mlce s ow a partia. a opecla. some 3 .,.,"" Ct> adu1t mice show a partia1 a1opecia some 3 ~~ AI weeks after they are infected, however, .,.,(7)~ one or two weekswceks 1aterIater lhe the mice regain ~ -<~ theirtheir h4ir. . ~~ No cytopathic efect was noted in VeTO ~~ to>U .~ cellsceIls during a 3 week period of observa- ~~ -00000 -00000'0 0 000. O 00 . -~~ ~ ~ bon but pIaque formabon was observed ~ tion but p1aque formation was observed Õ] in this ceIl Iine. EIectron microscopy of .:2 in this cell 1ine. Electron microscopy of 9 VeTOVero cells ceIls infected with lhe Be An 293022 9 ~ ~ strain confirmed that lhethe agent belongsbeIongs ~ O ~ ~ ~~ to lhethe Arenavirus Arenavirus group(4). -:S ~ ~ AI ~ No other arenavirus strains were iso1ated isolated -~.r~ U~ o ~.AI oo~COo o ~ o o . ~ oco o from 731 wiId animaIs captured in 1975, .5 ~ ~ cé ~ from 731 wjld animaIs captured in 1975, ~~ tG ou AI in lhethe area where the the virus virus was foUJld. ~:s j ~ These animaIs included incIuded 19 NeacomyBNeacomys sp., ~ c ~ 59 Proechimys sp., 29 Nectomys sp., 11 ~~ < < ~00 ~ ~ o rodents of other genera, 63 marsupiaIs, 13 -.~ ~ rodents of other genera, 63 marsupia1s, 13 .?,.?, IX: ~ AI AI ~I AI .AI~ AI primates, 530 birds and 7 other anima1s.animaIs. ~~ U "' "'~ooo~ ooo o 00 ., . ~I:~ i-- ~ """"""~ ~Ct>~ ~ ~ ci) CF antibodiesanbbodles to lhethe agent were found min &~ AI l/58] /58 OryzomysDryzom.ys sp. sp. Eram from lhe the enzootic arca, -:SoS Rtat titre of 1:1:16. 16. No antibodies were found .§.§ in lhe the sera of 3 3 OryzomyB Dryzomys that yieldedyieIded lhetbe .,'!; .~~.~0000 ~ ~ ~ virus ~ Ttor in .the~~he-8-eryzomyslhe ~ra of the 8 Ory%omys.I. ~ ~ AI AI AI AI ~ Qecam"Ys-eapt~d-iR tbe aJea-in ~~ U -' AI ,AI '" AI ,AI o o o ., o o ..1..- '--- c- ---1..:-1.. ..1..-' '. Udi -' ~ < 000 00 of'comys captured in lhe area, including3 '"o -C-I.~. ~ c-1~ ~ ~ ~ ..~'WU&runrWftJCIJ -,:T1C"-vrrns-w.as- 1 -~'-'N .c MtO) Ct> ~AI Ct> ~AI ~Ct>AI -E"AI the Jn addition,two from 2/88 whieb seTa the virus of inhabitants was isolated . "N AI AIA! -E Jn addition, 2/88 seTa of inhabitants of ~ .. ;;;:, ~~ Itaituba countycoun ty reacted at 1:8 dilutiondiIution in -"-AI ~E I:I: lhe CF testusingtest using Be An 293022 and Ê-~~.~~ 0000~ ~ ~ ~ ô Amapari sucrose-acetone antigens. Cne Dne of ~"Q.E;~ ~ZZ ' AI AI AI AI 000 ~ ~ 0 Vit' the lhe positive seTa was obtained from a ~ "'" '" '" '" o o o '" '" o AI f b 1 h ' c" .-.~ ~ ~ ~ ~ ~ .~ e n. e case, . m w . lCh bI o od P UJ;slnJ-- od run~ ()..AIc" .-.~...
Discussion i~ difficult to explain. li transmjssion is The evidence accumulated up to the through the urine and the placenta, how present time indicates that Oryzomys ca- could the infection disappear Eram the- pito ssp. and Neacomys guianae are tbe Neacomys population? It seems unlikely on]y reservoirs for Amapari virus. The ]ong that alI infected individuaIs were trapped term excretion of Amapari virus in the out, as juveniles were rarely caught, and urine of infected rodents, even though in- capture lates did not falI off until 5 termittent, probab]y rcprcsents an impor- months after the infection rate began to- tant factor fi the spread of the virus to decline. The alterna tive is that the bulk s\lsceptib]e animaIs. Contamination of skin of the Neacomys population had become- or food by infected urine is a most ]ikely immunized, although neutralizin~ antibody method, particu]arJy fi view of the re]a- for Amapari vírus could not be demonstra- tive stability of the virus in the urine. ted in any vertebrate. It should be noted Transmission through the placenta or that the disappearance of the vírus from mi]k can a]so be considered as mechanisms the Neacomys population was preceded by for maintenance of the virus. In fact, 15 % a period in which the infection late was and 22 % respectively of the embryos Eram high. Another peak of the infection in infected Oryzomys and Neacomys yielded Neacomys was observed in 1971 when the virus. It is possible that the embryos 34,5 % of these rodents yielded vírus. cou]d have been contaminated with the'mother'sUnfortunately the program was disconti- fifected blood at the time they nued in 1972, so that it was not possible \vere removed from the uterus. Since only to obtain further information about a cy- 12 % of the Oryzomys bom to infected clical occurrence of the infection among mothers were virus positive (which cou]d the Neacomys. have been infected Eram the motheis uri- On the other hand, infected Oryzomys- ne after birth) it suggests that transmission were captured practically in alI months, through mi]k or placenta probab]y does even during the 10 month period in which not p]ay an important role fi norma] cir~ no vírus was found in the Neacomys. This cumstances, a]thougr it mar be important finding suggests that transmission in each for ]ong term survival. species is unrelated. The evidence for arthropod transmission Although no microscopic lesions were- is sti)) equivoca]. A]though 2,5 % (3/122) seen in the liver, heart, kidney or spleen of poo]s of ]ae]apid mites Eram Oryzomys of naturally infected Oryzomys and Nea- captured during 1005-67 were positive, comys (with the exception of focal dege- 13 % of Oryzomys captured at that time nerative inflamatory lesions of the myo- were known to have been infected. Just cardium, possibly due to cardiac puncture), on the basis of mites containin~ infective \\'e cannot exclude the presence of lesions fJuid, we might have expected to have in other tissues(2). Choroiditis, glial hy- had more positive poo]s. On the other perplasia, vasculitis, perivasculitis with hand, the CF technique for detecting non- infiltration of lymphocytes in central ner- fatal infections was not applied to mice vaus system bas been reported in newbom inoculated with mite material and so some mice inoculated intracerebrally witb Arna- iso]ations mav have been missed. The iso- pari vírus (1). lation in 1968 from Gigantolaelaps taken The garoe type of cbronic, víraemic, in- froro an apparently uninfected rodent is fection caused by Arnapari vírus in o,.y- not conclusive evidence for their impor- zomys and Neacomys has algo been obser- tance as vector, since it is possible that ved with the four other arenaviruses, tbàt they could have fed during a very recent are pathogenic to man, in their natural viraemic phase. Further, arthropod trans- hosts. This pattern of infection, however, mission among Neacomys seems to be ex- does not occur with Latino vírus in Calo- cluded, since not a single vírus iso]ation mys and witb Tamiami vírus in Sigmodon was obtained from over 11.000 lae]apids hispidus(6). taken Eram that. rodent species. With the new arenavírus described in The fact that the infection rate in Nea- this report there are now 11 members in colnys fe)) to"zero during a 9 month period this group. The new agent seems to infect
-180 - ARENAVIRUSES IN BRAZIL
only rodents of the genus Oryzomy.\',which dos o no infectados. Ellos pueden. sin em- apparently deveJop a chronic infection. bargo, tener víremia o viruria y, aI miamo The finding of two peopJe from the tiempo, anticllerpos fijadores de comple- Itaituba arca with positive CF reactions mento circulantes. Estudios de recaptura at 1:8 serum diJution against Be An 293022 1/ observaciones de laboratorio han mos- and Amapari viroses, must be interpreted irado que el vírus Amapari puede producir with caution in the absence of any infor- viremia o viruria intermitente en Oryzomyz mation on cross-reactions with other agents capito ssp. y en Neacomys guianae durante (e.g. LCM virus). un período de meses. El segundo miembro deI grupo Be An 293022, aun innomÍ1U1do, fue aislado en Summary noviembre de 1975 a pariir de Oryzomys. E.\tos roedO1'es fueron capturados en una Two members of the Arenavirus group zona localizada a 10 largo de Ia Ruta occur enzooticaUy among cricetine rodents Trans-Amaz6nica, en el Estado de Pará. which inhabit forested areas of the Ama- Hasta ahora, no ha!1 evidencias que sugie- zon region of Brazil. The first, Amapari ran que alguno de estos dos Arenavírus t-'Írus, produces chronic viremic infection in Oryzomys capito ssp. and in Neacomys ptledan producir infecciones naturales en el hombre. guianae and it has been found only in the Serra do Navio region, Amapá Territory. No neutralizing antibodies have been de- Acknowledgements monstrated in infected and uninfected "0- The studies and observations on which this dents by conventional techniques. They paper is based were undertaken with the support may, though, produce viremia or viruria and under the auspices of the Polamazônia and circulate compZement fixing antibodies program, Tropico UrDido program (CNPq) USAF grant N9 68-1430 and PHSR6 N9 RO-l-AI 08085- at the some time. Recapture studies and 02 and the Rockefeller Foundation. laboratory observations show that Ama- We are greatly indebted to the lndustria e pari vírus ma!! present intermittent viremia Comércio de Minérios SI A for the invaluable or viruria in Oryzomys capito ssp. and in support provided to the work carried out at Serra do Navio. We are grateful to Dr. J. J. Shaw of Neacomys guianae over a period of months. the Wellcome Parasitology Unit, Belem, for nis The second member of the group, as yet suggestionsand commentsdurin~ revision of the unnamed, Be An 29:xJ22, roas isolated in manuscript. Thanks are also due to the staff of November lfll5, from Oryzomys rodents the IEC, especially to Joel P. Souza, Joaquim Contente, Emanuel Nazareno de Freitas, Manoel captured in one area located along the Santa Brígida, Geraldo P. Silva, José Luis C. Baía, T,.ans Amazon highway in Pará State. Carlos Marques Cabeça, F. F. Ramos, Antonio There is tiU now, no sound evidence sugges- Pires Martíns, Célia Nakauth, for their technical ting that these viruses can cause natural assistance. infection of man: References
1. Besuchio, S. C.; Weissenbacher, M. C.; Schmu- Resumen fiis, G. A.: Different histopathological re..ponse to Arenavirus infection in Thymectomized mice. E&'TUDIOS SOBRE ARENAVIRUS EN BRASn.. Arch. ges. Virusforscll. 40: 21, 1973. 2. Días, L. B.: Personal communication, 1970. Dos miembros deZ grupo Arenavirus se 3. Pinheiro, F. P.; Shope, R. E.; Andrade, A. H. P.; Bensabath,G.; Cacios.G. V. and CasaIs encuent,.an en forma enz06tica en roedores T.: Amapari a new virus of the Tacaribe group cricétidos Que habitan zonas forestadas de ttom rodents and mites of Arnapa territory, la regi6n deZ Amazonas. El primero, vírus Brazil, Proc. SocoExp. Btol. Med., 122: 531, Amapari, produce. una infecci6n cr6nica 1966. 4. Webb, P. A.: Personnalcommunication, 1976. con víremia en Oryzomys capito ssp. y en 5. Webb, P. A.; Johnson, K. M.; Mackenzie, Neacomys guianae, y ha sido encontrado R. B.: The measurementof specific antibodies s610 e.n la ,.egi6n Serra do Navio, en el in bolivian hemorrhagic fever by neutralization territorio de Amapá. EmpZeando técnicas of virus plaques, Proc. Soc. Exp. Biol. Med., 130: 1013, 1969. convencionaZesno se han encontrado anti- 6. Webb, P. A.; JustinesG. and Johnson,K. M.: cuerpos neutraZizantesen roedores infecta- Buli. WHO, 52: 493, 1975. -181 -