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J. P. Gonznlez and A. A J. Georges LO 11 12 TABLE OF CONTENTS 13 ....................................................................... 14 I. introduction.. 15 II. . ...............................................................

History of Human Cases and Geographical Spread.. ........................

16 Historical Background 17 A. Discovery of Agents.. 18 . 19 C. Social and Economic Impact 20 21 j .. III. Virus Characteristics.. 22 A. Antigenic Relationships 23 B. . Host Range .................................................................. 24 Ci Methods for Assay . . . i ....................................................... 25 ...............................................

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.............................................................. .....................................................

B.

26 . IV; Disease Associations.. ............ L.. .....................................................................

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27 A. Humans 28 B. . Wild and Domestic Animals ................................................. 29 C. ; Diagnostic Procedures..

1, Virus Isolation.. 3,. Serological Diagnosis

30 31 :

32 33 V. Epidemiology ................ ....................................................... 34 A. Geographic Distribution and Seroepidemiology .............................. 35 B. Incidence .................................................................... 36 . . : C, Sesonal Distribution.. 37 ! D.. Risk Factors ..................................................................

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39 ' VI. Transmission Cycles ;. 3s ....................................................... .......

A. Evidence from Field Studies.. ............................ .-. ................. -1. \lectors ..............................................................

...................................................... 2. Vertebrate Hosts -

1. Vectors .............................................................. ..................................................... 7,. Venebrate.Hosts 46 C. Summar)l ....................................................................

48 Vil. Ecological Dynamics..

. B. Evidence from Experimental Studies .........................................

-- _.- 37

49 . 50

............................................................... ....................................... . . . . A. Macre and Microenvironment .... i..

. . .... 7 ....... . '

L._

1, - . .- . C , . .

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/ - - !

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............................................................. ' 51 1.111. l'rcvciiti\m and Control

52 53 Rcfercilccs.. ................................................................................. 54 5.5 I. INTRODUCTION

S3 59 GO 61 62 63 1 : 66

67 65 69, 70 71

73 73 75 76

' 77 78 79 80 81 82 83 84 35 86 87 88 89 90

' 91 91 93

95 96 97 95 99 100 101 102 103

I 104 1 105

106 107 108

I 72

7%- I

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4- 56 57 & Bu-amha, Bun\.;ini\\icm.Gcnniston, Ilcs& arid Taplguine viruscs. all nicmbers of thc family

.~Junynviridnc,'-' are cndcniic in t ' i l and have ncvcr bccn recognized clsewhcrc. All these viruses c a Í h u s c mild fchrile illness, - _ _ --- Lvith or without ïash: nont is rcsponsiblc for impon:lnt enidcmic discasc or lins n y c i t social or economic impact. lntercst in the study of these

* --

- viniscs cciitcrs on both their cpidcmiology and their structure. Among the five viruses. Bunyannilcm, I3tvn;nba (including Bv.mnbs-rclatcd virus such IS Pon;c&l, and Tut:i:uine havc buen isolared niost frcquently.

--. t-.

11. 1-IISTORICAL BACKGROUND

et first described the isolafion of Bwamba virus. I n 1936. they' isolation of Bunyamwera virus, which is considered the prototype of the

virus was isolated in a NiScrian village of the same name from blood of group; i t was rccovercd in Uganda from a pool of Aedes mosquitoes.

a 9-year-old girl.' Gemiiston virus was recognized by Kokcmot et al.x in 1960 in South Africa. The first isolation of Tataguine was made bp Brès et al.' from a mixed pool of Culex and Anopheles mosquitoes collected in Senegal in 1961.

B. History of Human Cases and Geographical Spread Bwamba virus was first recognized in the setting of a small outbreak in westem Uganda;

nine cases were confirmed by virus i so l a t i~n .~ Bwamba infection has been recognized by virus isolation from humans in Uganda.5 Nigeria,'O Cameroon,IL Central African Repub- lic.".'2 Kenya, T a n ~ a n i a , ~ and South Africa." Identification of human infections by Bwamba group viruses was reported in Ethiopia by Ota et al. (unpublished) and, more recently (1978), in Kenya. l4 In Bwamba County (Uganda), where Bunyamwera virus was first isolated, 2.9 to 30% of the human population was found with neutralizing antibodies.s

Tataguine virus is present in Senegal, where 57% of the inhabitants were found to have antibodies. and eight strains were isolated from inhabitants of Dakar s ~ b u r b s . ~ It has also been found in

6After its first isolation in Nigeria,' Ilesha virus was found in Camcroon, Senegal, and the Central African Republic. 1 1 ~ 1 2 Ilesha virus, but not Bunyamwera," is considered to be endemic in souihem Ethiopia.

@one of the five viruses seems to be responsible for epidemics. They are, nevertheless, distributed widely in all of tropical Africa.

Nigeria,*6 the Central African Republic."." and Ethiopia.l* 9

$,L.

C. Social and Economic Impact

social and economic impact. Generally responsible for only m-s, these viruses have a very limited recognized

III. VIRUS CHARACTERISTICS

Bunyaviruses from the Westem Hemisphere show serological cross reactions with those from Africa.'* Nevertheless, it is quite easy to identify each African virus using either complement fixation (CF) or mouse protection neutralization (hlPN)."

The genomes of Bunyaviridae consist of a single strand of RNA comprising three segments. Experimental recombination shows that genetic.materia1 can be exchanged between members of Bunyamwera groupand other Bunyaviruses. This could explain the occurrence of "mos- aic" strains of different Bunyavimses with similar geographic and ecologic distribution. as mentioned by Iroegbu.22 The reassortment of RNA 2.gmenFTa - explain the diversity of members of the Bunyaviridae family, as well as the cross reactiocdbserved using serological ~

tests. --. .... t

109 110 I I I 1 I ? I 13 A. :intigenic ~ t i~a t ions i i i p s 114. I I5 -

Gcrmistc.81i viral polypeptides have becn studicd by Ozdcn and Hnnnot&.' consist of three major stmctuial polypeptides (mol wt 115 x IOo, 27 X I O h , 18 X IOh) and one minor larger prntcin t i : i L> l u - t IS5 x IO.'). .

l3unys:!i\i.cn virus is closcly related to othcr members of Bunpam\vcra group. but if prior infcction hy :my nxmhcr of this scrogroup docs not prevent h u m a n infection a i t h another

I I6 IIÏ 11s I 1 0 120 1 1 1 122

I 113 1 1 3 1 176

- 177 118 179 130 I 131 137 133 134 I35 136 137

I 138 139 140 141

143 1 1 3 145 146 137 14s 139 150 15 1 152 153 151

I 155 156 157 15s 159 160

1 161 161

, 163

=e-? 1 ~ I42

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virus o Í tnc smie group. Ukauwa ~ i r u s is now considered to be a strain of Bunyam\vera virus.

Bwanibs virus cross reacts by neutralization test (N) with Pongola virus?' nevertheless, it clcarly differs in a quantit:itive reciprocal manner. Johnson et ;il." demonstrated [hat a Bu;rniba virus variant isolatcd in Kenya could prcscnt antigenic characteristics of Pon_eola virus.

(kOriginally9 Germiston virus was drscribcd as having significant reciprocal neutralization (adult mouse N test) with Bunyamwcra; nevertheless, these two viruses are readily distin- guished by hemagglutination inhibition (HI) and CF. as mentioned by Kokernot et al.n

liesha virus cross reacts to some degree ivith Bunyamwera by the N l est;^^ by HI. the closest relationship is with Cache Valley.26 By CF test. Ilesha virus is related more closcly to Bunyamwera and Cache Valley than to othcr members of the Bunyamwcra serogroup."

I3. Nost Range Table I summarizes the available data conceming natural host range; as evidenced by

virus isolation and antibody tests. All five viruses have been isolated from humans, whereas data on other vertebrate species are scanty. Susceptibility of laboratory hosts is variable. All viruses are pathogenic for newborn mice by the intracercbral (i.c.) route; Bunyamwera and Germiston viruses are the most pathogenic, causing death in weaned mice by the peripheral rouie. Tataguine virus is the least pathogenic and does not produce illness in suckling mice 'ihoculated i.c. or weaned mice by any route. Susceptibility of hamsters, rabbits, and other experimental hosts is described in the Itifernational Catalogue of Arthro- pod-Borne Viruses.27

C. Methods for Assay All of the viruses may be assayed by i.c. inoculation of newborn mice. Cell culture

systems can be used, but the cytopathic effect is not always easy to see and is sometimes absent, Susceptibilities of some cell culture systems are given in Table 2.

Techniques for virus isolation and assay using mosquito cell cultures or mosquitoes inoculated by the intrathoracic route are described below. The sensitivity and specificity of various infectivity assays are different for each virus. The N test performed with Tataguine virus in VERO cells has a high specificity and is more sensitive than the MPN test.28

. .

IV. DISEASE ASSOCIATIONS

A. Humans

cases is their brief duration (4 or 5 days) and benign nature: no fatalities are recorded.

or stiffness of-the neck. I *.I2 Convalescence is characterized by marked asthenia lasting 8 to 10 days.

Bwamba virus is responsible for a relatively sevcre fomi of gcneralized infection. Ex- anthem is nearlv always present, and it is frkquently associated with meninseal involvement."' A case of myocarditis has been reported." Intestinal tract involvement. especially diarrhea, is also seen.74

Bunyamwera virus is generally responsible for pediatric infcction. - - - - Children present with fever. headache, joint pains, and rash. Recovery occurs'in less than 7 days. In some cases, visual disturbances and vertigo have been observed." When infection occurs accidentally or in immunologicnlly compromised patients, severe encephalitis can be observed.2?

The most frequent symptoms are ,fever, h&c&. arthralgia, The hallmark of nearly all

Physical examination is generally normal except. at times. for the presence of conjunctivitis '

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165 166 167 168 169 170 171 172 173 174 175 I76 177 178 179'

.180 181 182 183 181 I85 186 187 188 189 190

,..

Ilesha vin:?, infections are characteristically mild, with the primary symptom being a feeling of malaise. Fever, when present, is generally less than 39°C. A transient discrete exanthem is seen in about half of the cases.3o Recovery occurs without sequelae, but asthenia persists for 8 to 10 days.

Tataguine virus is associated with mild disease in children and more severe symptoms in adults. Rash is present; however, fever is usually less than 39°C. Some patients complain of marked headache, gastrointestinal symptoms, and a florid, nonpruritic rash." .

Only two laboratory-acquired Germiston virus infections have been reported from South Africa; both were characterized by mild disease without specific symptoms 3nd with recovery occumng in 37 hr to 3 days.'

B. Wild and Domestic AnimaLs No natural disease has been reponed.

. - C . Diagnostic Procedures 1. Viriu isolation

Viremia is usually of short duration (24 to 48 hr): Ilesha virus. howevef, has been isolated 3 days after oñset of disease.12 The greatest number of successful virus isolations has been made using both i.c. and subcutaneous (S.C.) or intmp_critoneal Ci.p.) inoculation of suckling mice (usually 1 to 2 days of age). Material for inoculation,consists of blood, serum, or plasma from humans and mammals or of arthropod pools diluted in Hanks' balanced salt solution or similar solution containing a source of protein (bovine albumin or serum). The virus can be identified at the time of harvest of a mouse brain tissue using the Chrom Elisa Technic of Lhuillier and Sarthou,31 or it may be established by passage and identified by use of an appropriate serological test (CF or N tesj).

- . 7..:.-d

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Job 1386SSSS26 Galley 4x- - - - - - - 12-21-87 11:01-43 . d

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16 17 18 19 20

Lcss cspcricncc has bccn accumulntcd w i t h thc usc of ccll cult~lrc syslcms for thc isal:itions of thcsc viruses. Continuous ccll lincs. such as VERO or BlIK-21 or A C ~ C S ~ 1 ¡ h p i r ~ ~ . ~ (C6/36), niay bc useful. Inoculated C6/36 cclls can hc tcstcd bctwccn dilys 9, and IO for virus by indirect immunofuorcsccncc (IFA) with spccific ascitic fluids or hcld for as lang as 1. wccks wi111 infectious virus dctcctd~lc by an ;ippropri;ltc tccllllicluc suoh 3s mouse inoculation.

T i c viruses under considcration can also be isolatcd hy __.. intrathorack. . inoctilation_o[ To.r- O r / J ~ l l C i l i f C 5 mo~quitoes.~' Antigen is dcmonstratcd by tcsting mosquito hcad squashcs by IFA or pooled mosquitoes by CF.

ff Detection of virus in serum by enzyme immunoassay, as described for yellow f e v ~ r , ' ~ could represent's new approach to diasnosis, but is limited by the probable short duration and low t i > s of viremia in cases of most bunvaviral infccrions.

@

2 . Serologi .-al Diagrtosis =+ One'must' consider th&erological cross reactivity within the Bunyaviridae family." T$e . * 4 "original antigenic sin" phenomenon applies to humans infected with mulIiple Bunyamwera:' ..' . group viruses. Usually, a battery of viruses and tests is required to clarjfy the diagnosis."

Ferological response to infection can be low and/or without seroconversion in the case of 4;" Tataguine virus;" infection can ,be serologically diagnosed by the N test but not the CF test." Methods such as IgM antibody detection, described for other arboviruses,. could represent a new approach to serodiagnosis.

25 26 V. EPIDEMIOLOGY 27 28 29

. . . A. Geographic Distribution and Seroepidemiology

The distribution of these viruses determined bv virus isolation has been described (in 30 31 32 33 34

' 35 36 37 38' 39 -10 41 42 43 44 45 46 47 38 49 50 51

Section 1I.B) and is shown in Table 3, The table also shows the results of seroprevalence surveys in various countries of Africa.

($'NO serological or virological evidence for activity of any of these agents has been found in 9 North Africa, with the exception of Egypt, where a low prevalence (0.9%) of N test antibodies to Bunyamwera but no antibodies to Bwamba virus was rep~r ted .~ '

In tropical parts of West Africa, the prevalence of BUN antibodies has been high in many countries.36 In Equatorial Guinea, the prevalence of antibodies to Bunyamwera and Bwamha viruses appeared to be higher than to most other arboviruses." In contrast, a low prevalence of Bunyamwera antibodies was reported in Togo, Benin, Mali, Niger, and Chad.38*39

@in Central Africa, 100% of the populations inhabiting the rainforest area of the Congo had antibodies after 10 years of age, whereas only 8.0% of persons in the same age group in Gabon w b e immune.j' Considering Bunyamwera antibody prevalence in Africa as a whole, it is apparent that it is highest in the tropics, low in North Africa. and shows a sharp decline in the Republic of South Africa. being 0% in Cape Province and 45% in North N3.taI.4'

In East Africa, Bunyamwera and Bwamba <iruses appear to be endemic in Uganda. Tanzania. and M~zambique .~ '*~ ' A low prevalence of BUN antibodies has been found in Madagascar, with the highest percentage positive on the north coast."

In South Africa, Bunyamwera and Bwamba antibody prevalences are significantly higher in the Simbu Pan area of North Natal than in other regions. Natal seems to be the southern limit for arboviruses, as they require a tropical ecology. Germiston-virus seems to be active only in Austral Africa, with a specific importance in Angola rind Botswana. In South Africa, Germiston antibodies are found in livestock.36*34

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75 76 77 78

1 ' 79

B. Incir!cnce EviJcncc fi)r ]iuman infections has bccn accumulntcd by many stuc lks and is summarized

in Table 3. ~ l ~ , ~ 4'~43.sl.*-sh .\fiCr chikun!pya, Scmliki Forcsr. Sindbis, yellow fcvcr. Up:!nda S, U'cs: :<;!c. K'esselsbron, and Zika. ßuny;imwcra and Bwamba appcar as thc ninth ' and tenth niost frci;,:cn[ arboviruses infecting humans in the African continent."" I n the Ccntral hiriaan Republic. ßw:imba was thc virus most often isolatcd from human cxcs of arboviral inftxiion." Tiil Suine virus ;ilso appears to bc ;L vcry coninlori huiixin infcclion i n sonle arcas. e.g.. wherc multiplc virus isolations havc bccn madc from fchrilc p:itient~. '~

81 82 83 84 85 S6 87 88 s9 90

- 1 91 92 93 94 95 96 97 9s 99 1 O0 101 1 O3 103 103 105

C. Scasonal Distribution Buny:m"era virus has becn isolated in either the middle or. more frcqucntly, at the end

oÎ thc rainy season. I n the Ccntral African Republic, Ilesha and Bwamba viruses were most often isulatrd during the dry season. All Tataguine virus isolations were made during the d n season. Germiston strains from Kenya were isolated 31 the besinning of the rainy caso on.^'

D. Risk Factors

seroprevalcnce in females remains hishcr ßunyamwra antibodies seem to appear earlier in age in feniales than in males, and the

VI. TRANSMISSION CYCLES

A. Evidence from Field Studies 1 . Vectors

Bunyamwera virus has been isolated from mosquitoes belonging to three genera h e d e s Mammzia,and Culc-xj, but Aedes spp. appear to play the predominant role in transmission. h.íultiple strains of the virus were recovered from Ae. cirn¿mluteolus collected at the same time and place as a naturally infected human in South Africa.5s The wide array of mosquito species which have yielded virus suggests that high viremia levels may occur in a variety cf different vcrtebratc hosts.

Little field evidence has been accumulated for Ilesha virus; the virus has been isolated from Anophe s garnbiae in the Central Airican Republic and Senegal and from Cx. rhalassiits in Senegal.57 Germiston virus has becn recovered repeatedly from Cx. rirbinorrts in South A i r i ~ a , ~ , ~ ~ Zimbabwe,5B M o ~ a m b i q u e , ~ ~ Ken>*a,s7 and Uganda.59 High minimum infection rates in this species suggest that transovmhl transmission of the virus may occur.

Senegal, lu'igcria," Central African and the Ivory Coasts7 and from An. gambiae andAe.jircifer in Senegal.57 Twelve strains of Bwamba virus were isolated during field studies in riverine forest in Nigeria in 1971 the majority from Ae. (Neornelunoconion) s p p and Ae. (N . ) circirmlu-. rcolus, but also from An. cousrani and Ma. uniformis. The Aedes were captured on human bait. suggesting that these mosquitoes. as well as anophelines, may be responsible for human infections. -

Tataguine virus has been isol3tcd principally from anopheline mosquitoes. Multiple strains have been recovered from An. gambiac in Camero~n; '~ Central African Republic, Senegal, and Ethiopia; from An. fiincstlts in Nigeria, Central African R e p ~ b l i c , ' ~ ~ ~ ~ and Ethiopia; and from An. nifi in S e n ~ p a l . ' ~ . ~ ~ An ísolate has also been made from Coquillerridiu arrritrs in Camer~on.'~.'' The association between virus isolations from humans and anopheline mos- quitoes suggests that transmission occurs in the domestic habitat with humans serving as a viremic host. Is

Bwamba virus has been isolated from An.furzcsriis in

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- .. 2. Vertebrate Hosts

I

l

106 107 I os

I IO I I I 1 12 1 I3 1 1 1 115 I I6 1 I7 1 I8 I I9 130 111 113 13-3 124 115 126 1-77

. . 128

109 !.

119 130 131 132 133 I34 135 136 137 138 139 140 131

, ! 142 143 1 4 4 -i 152 153 153 155 156 157 158 159

No isolxi.:r.. ../ Runyamwcra, Ilesha. Bwaniba. or Tataguine viruscs have been made frani namr:di! :i: ..:cd vertebrates. Germiston virus has becn is*( on multiple occasions from ro-+rlb t'Ï., .! 1): from Dasyri!ys i,icomtus in Kcnya'X.and from Rarfrcs rCiftiis. An?- c tmhn r i i ! o r i c x , .!q/;lrronz>'s sikapsi, and L. flavopunctatus in U_~anda .~"*~ ' A n isolate tvas mnd: fmn n niongoosc (Ifrrpcsres ichnr~imon) in Kcnya.4x hlultiplc isolations of Gemlision virus wcrc also made from scntincl hamsters in Sourh Arica and hlazm~bique.h'

The interprctation of s c r o l o $ d evidcncc for involvement of vertcbrate hosts ivith Bun- yamwen group viruses is lirnitcd somenhat by the problcm of antigenic cross reactivity among inembcrs of the seroyoup. Neutralizing antibodics to Bunymwcra, B\vamha. and Gcrmiston viruses have been found in domestic livestock (Table 4). .4 high seroprevalence to Gcmiiston virus has also been found in rodents, in accord with virus js01:ition dat'a implicating them as hosts. A high prcvalcnce of antibodies to Tataguine virus in humans and abscncc of antibodics in wild and domestic animalsd5 further support the conclusion thnt humans serve as hosts in thc transniission cycle. Antibodics to Bwamba virus have been found in birds in South and East Afri~a. '~. '~ A high prevalence of antibodies in monkcys was repnncd in Uganda.63 In South Africa, the scroprevalence in humans to Bwaniba and Bunpmwcrn viruses was significantly higher than in monkeys. birds, or domestic livestock."'

B. Evidence from Experimental Studies 1 . Vectors . I

.4fter intrathordcic inoculation, Bunyamwera virus has been shown to replicate in Ae. w.rans,- Ac. canadensis,0J.6s Ae. ac,qpri,--" Ae. triseriatus, b5.66 Psorophora ferox," Cx. pipiens," and An. q~cadrimacularus.~~ Oral infection of and transmission by Ae. aegypti has been demonstrated for both B u n y a m ~ e r a " . ~ ~ . ~ ~ and Ilesha viruses.67 CI. rubinotus has been shown to become infected after feeding on virus and to transmit

virus to ham~ters. '~ Bwamba virus has been shown to infect Ae. aegypti, An. quadrima- culurus. and Cx. pipiens after intrathoracic inoc~lation,~' but susceptibility to oral feeding has not. been investigated. Cx. pipiens fed on virus-soaked pledgets become infectcd with but are incapable of transmitting Tataguine virus.68

2 . Vertebrate Hosts Wild Afrjcan rodents (Anicanthus abyssinicus and CricetomYs gambianus) experimentally

infected with Bunyamwera virus develop viremias sufficient to infect mosquitoes, suggesting that rodents could play a role in natural transmission cycles.69 Similar results have been reported for Tadarida hlonkeys develop viremia, fever, and inapparent or mild illness.71 Germiston virus behaves similarly in experimental animals, including rodents (Anicanthus nilori~us5~ and Torera branrsi7') and monkey^.^' Little or no useful information is available regarding experimental infections with Bwamba or Ilesha viruses.

C. Summary Except for Germiston virus, for which convincing evidence of a rodent-Cx. rubinotus

cycle is available, the natural history of the viruses under consideration remains obscure. All viruses are mosquitobome; for Ilesha, Bwamba, and Tataguine viruses. anophelines appear to be the principal vectors', especiaIly endo- and anthropophilic s p i e s (An. gamhiae and funesrus).-A human-Anopheles cycle is suggested for Tataguine and possible Bwamba viruses, but a role for wild vertebrate hosts cannot he - . excluded.

VIL. ECOLOGICAL DYNAMICS

A. hlacro- and Microenvironment Bunyamwera virus serological studies show vi& activity in,As>ociation with rivers and

riverine forests," HI antibody prevalence in Nigeria was higher in forest and savannah zones than in swamljy Xeas.36 Virus activity in the Centra! African Republic is associated with gallery forests in the moisf savannah zone.'""

I’

i: j i

, -.

- . .. . . . . -

.. .. .. . .. . , ,~ . , .

160 161

I 163 ’ 163 164

Ilesha antibody prevalence in the endemic area of Nigeria appears to be highest in the savannah than in the plateau and rain forest. and the virus seems IO be more active in rural than in urban communities.’’ Germiston virus isolations have been associated with irrigated areas, where cattle have a high antibody prevalence. Tataguine antibodies have been found in highest prevalence in the derived savannah vegetational

165 166 VIII. PREVENTION AND CONTROL 167 168 169 170 diseases. -- _ _ 171

Vaccines are not available. Because of their relatively low pathogenicity and lack of economic impact, specific efforts have not been developed to reduce the incidence of these

-- .. -.

. .. ... . ... . . . . . - I . . . ., ... I *I . . .. . , ... .:.’!: .l. . , ... . .. . . ... I . .. ... . . .. , . I .. . .., . . - . . . . ” * .., . ..* . ~ . ... . , . . .. . ... . . . ... 1

,’. 6 3 . . . . . . .

, 34

35

3 6

37

38 , I

I 39

! JO

11 12

43

45

46

17

48

19 50

51

52

53 . . 54

f .. .. .

55

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60 61

' 62

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-.

\'cric+riir,-s,' .,rd.ed.. Xiiierican Sc~lety of 'Tropii4 hlrdisinc :tnd tlyFisnc. \Va\liinFton. D.C.. l9S5. 2s. Fagh:rmi,, h. II . . Gmwth. pl;iqur msay and immunulluorcscsnt studies on Tataguine virus in cell culture.

29. Southsn;. C. >l. and Xltme. h. E., WCSI Xlc. Ilhcus. and Bunyamwera virus infections in nian. Am. J. Trcy .!led. H J . ~ . . 31, 724. 1951.

30. Rrottez. I f . and Salaun, J. J., Isolenient au Cameroun d'une souche d'arbovirus a pad r d'une ficvre ex~n:hciii~::qur. Arch. Inst. Pasrmr Tunis. I . 77. 1965.

31. Lhuillirr. \i. and Sarthnu, T. L., Chrom Elisa: a new technique for npid identification of arboviruscs, Ann. \'irrt: ( ! ,zJt . Pnsrciirj, 131E. 349. lYS3.

32. Conulez. J . I'.. Saluzzo. J. F., and Hcrve, J . P., Interet de la technique d'inoculation intrathor;lcique a ,Ar&*.í ,wg>pri dans I'isolcmcnt ct IC reisolemcnt dcs arhvtrus. Ann. Virol. Ilnsr. Pasrcurj. I l l E . 5 19, I U S l .

33. Xlocnth, T. P. and N!strom, R. R.. Lktcction of yellow fever virus in seruin by cnzymc immunoassay. ;\m. J. Trop, Med. HT.~.. 33. 151. 1984.

YI. I'ctcrs. C. J . and LeDuc. J. \Y., Bunyauiruscs. Phlchoviruscs. and rclatcd viruses. in Tc.uhook of f f iunun Virology. Belshe. R. B.. Ed.. PSF Publishing. Littleton. Xluss., 19S1.

35. Smithburn, K. C.. Taylor, K. Al.. Kirk, F.. and Kidcr. A.. Am. J. Trop. Affd. Hyg.. 3. 9. 19%. 36. Bres. P.. Ktcent data from serological survey on the prevalence of arbovirus infections in Africa. with

37. I'into, hl. R., Survey for antibodirs to arboviruses in the srri of childrcn in Ponuguesc Guinea., B i d l .

3s. Rres. P., Carrie, J., Desbois, A.. Lartigue. J. J., and hIace. G.. Les arhovirus en Haute Volta. Ann.

39. Robin. Y.. BrPs, P.. Lartigue. J. J.. Gidel, R., Lefevre, hi.. Athawet. B.. and Hery, G.. Arboviroses

40. Chambon. L.,, Brès. P., Chippaux. C. L., et al.. Role des arbovirus dans I'etiolopie des fievrcs exan-

41. Knkernot. R. H.. Smithburn, K. C.. and Weinbren. Xi . P., Neutralizing antibodies to arthropod-borne

42. Iiokernot. 'R, HI. Smithburn, K. C., Gandara. A. F.. hlclntosh. B. hi.. and Heymann, C. S.. Provas

C.IVO~IO: 26. 37. 1979.

spcial reference to yellow fever, ß d l . N'HO. 43. 213. 1970.

lt'H0. 37. 101. 1967.

/ILCI. Pnsreur, IoS. 311. 1965.

en Afrique de l'Ouest. Bull. Soc. Parhol. €.rot.! 61. 833. 1968.

thematiques CII Afrique Centrale. Mel. Afr. Noire, 185. 1969.

virus in hur m being and animals in the union of Soulh Africa. J . Immunol.. 77, 313. 1956.

de ncuualizai com soros de individuos residentes en Mozambique conm determinados virus isoladas em Africa transmiditospar mhropodcs. AR. Inst. Med. Trop.. 17. 201. 1960.

43. Sureau, P., A r b o v M a Madagascar. .4rch. Insf. Pasreur Mada.qascar. 38. 27, 1965. trQoscs 44. Kokernot, R. H., Szlamp, E. L., Levitt. J., and DehleilIon. B., Survey for antibodies against arthropod-

bome viruses in the sera of indigenous residents of Caprivi sVip and Bechuanaland Protectorate. Trans. R. Soc. Trop. Med. Hyg.. 59. 553, 1965.

45. Fagbami, A. H., hlonath, T. P., Tomori, O., Lee, V. H.. and Fabiyi, A., Studies on Tataguine infection in Nigeria, Trop. Geogr. Med.. 24. 298. 1972.

46. Fagbami. A. H. and Tomori, O., Tataguine virus isolations from humans in Niseria, 1971-1975, Trans. R. Soc. Trop. Med. Hyg.. 75. 788. 1981.

47. Johnson, B. K., Shockley, P., Chanas, A. C., et al., Arbovirus isolations from mosquitoes: Kano Plain. Kenya, Trans. R. Soc. Trop. hfed. Hyg., 71, 518. 1977.

48. Johnson, B. IC., Chanas, A. C., Shockley, P., et al., Arbovirus isolations from, and serological studies on, wild and domestic vertebrates from Kano Plah. Kenya, Trans. R. Soc. Trop. Med. Hyg., 71, 512,

49. Gonzalez. J. P.. Saluuo, J. F., Herve. J. P., and Geoffroy. B., Enquetes semlo_eiqucs sur l'incidence des arbovirus chez l'homme en milieu forestier et periforestier de la region de la Basse Lobaye (Empire Centrafricain). Bull. Soc. Parhol. Exor., 72. 416, 1979.

50. Saluuo. J. F., Gonzalez, J. P., Herve. J. P., and Georges, A. J., Enquetes serologiques sur la prevalence de cenains arbovirus dans la population humaine du Sud-Est de la Republique Centrafricaine en 1979, Bull. Soc. Pathol. Exot.! 74, 490. 1981.

51. Rickenbach,.X., Germain, hi., Eouzan, J. P., and Poirier, A., Recherches sur I'cpidemiologie des arbovimxs dans une region forestiere du Sud-Cameroun. Bull. Soc. Pathol. Exot.. 61. 266, 1968.

52. Booman, J. P. T. and Draper, C. C., Isolation of arboviruses in the Lagos area of Nigeria. and a survey of antibodies to them in man and animals, Trans. R. Soc. Trop. Med. Hyg.. 62, 269. 1968.

53. hlcIntosh.,B. hi.. Serafini. E. T., Dickinson, D. B., et al., Antibodies against cenain arboviruses in sera from hiiman beings resident in the coasml areas of Southern Natal and Eastem Cape Provinces of South Africa. S.'. f i . J . Med. Sci.. 17, 1962.

' ' 1977.

54. Courtois, G., Osterrieth. P., and Blanes-Ridaura, G., Ann. Soc. BelRe Med. Trop,, JO. 29. 1960. 55. 'Kokernot, R. H.. Smithburn, K. C.. Dehleillon. B., and Paterson, H. E., Isolation of Bunyamwera

virus from a naturally infectcd human k i n g and further isolation h m Aedes (Banksinella) cirrumlureolus

56. Kokernot, R. H., Heymann, C. S., hluspratt, J., et al.. Studies on arihropod-bome viruses of Tonplund. V. Isolation of Bunyamwen and Rifi Valley fever viruses ¡rom mosquitoes, S. AJr. J , bled. Sri., 92, 71. 1957.

Theo.. Am. J. Trop. Med. Hyg.. 7. 579, 1958. -- ..

57. Dakar. Senegal. Annual Report. Institut Pasteur, P d s . 1985, 58. hlclntosh, U. hl., Jupp, P. G., Santos, I. S. L.. and hleenehnn, C. hl., Culex (Eumelunomyia) ruhinorus

Theohld as' vectors of Banzi, Germiston. and Witwa!esmd virus%: f: Isolation of virus from wild populations of Cx. ribinorus. J. Med. Enromol.. 12. 637, 1976.

59. h{onath, T. p., Hendemon, 8. E.. and K i r p . G. B., Chvacteritation of viru:es (Witwatersrand and Gemiston) isolated from-mosquitoes and rodents collected near Lunyo Forest, Uuanda, in 1978. Arch. Ges. Vir,~sforsch.. 38. 125. 1971.

h i I

, -.

61 1

65 . I 69

i 70 -1 :;

75

8 76 17

; 75

I 79 ' 80

81 82

60. Lee, V. H., hlonalh, T. P., Tomori. O., Fagbami, A., and Wilson. D. C., Arbovirus studies in Nupeko Forest. a possible na+ focus of yellow fever in Nigeria. U. Entomological investigations and viruses isolated. Trrms. R. Soc. Trop. Mcd. Hyg.. 68. 39, 1974. ,

61, Henderson. B. E., hIcCrae. A. \V. R., Kirya, G. B.. Sscnkubuge, Y., and Scmpala. S. D. IC., Arbovirus epizootics involving mai, mosquitoes, and vertebrates at Lunyo..Uganda, 1968, Ann. Trop. Medi Purasirol., 66, 343. 1972.

62. Annual Repon, South African Institute of Medical Reseasch. Johannesburg. 1972. 63. Dick, G . W. A.. Epidemiologic notes on some viruses isolated in Ugmda. Trans. R . Soc. Trop. Ned.

64. Peers. R. R.. Bunyamwen virus replication in mosquitoes. Can. J. Microbiof., 18. 741. 1972. 65. O y n b i , O., Ukauwa virus proliferation in mosquitocs. Can. J . Microbid.. 14. 125. 1968. 66. Hayes, C. C., A comparison of suckling mou= and mosquito susceptibility to infection hy the Bunyamwera

67. Boorman. J. P. T., Srudies on the growth and transmission of N D viruses of the Bunyamwcra group in

68. Fagbami, A. H.. Studies on transmission of Tataguine virus by Culex Ipipiens)furigans mosquitoes. Afr.

69. Simpson.-D. I. H.. Experimental Bunyamwen virus infection in Iwo species of African rilts. Trans. R .

70. Annual Repon. East African Virus Research Inslirute. 1964. 5 and 46. 71. Schwartz, A. and Allen, W. P.. Experimental infection of monkeys with Bunyamwera and Germiston

72. hlcln,tosh, B. hi.. Susceptibility of some African wild rdents to infection with various arthropod-bome

73. Faphami, A. H. and Fabiyi, A., A survey for llesha (Bunymwera :roup) virus antibodies in sera from

74. G u n d e z . J. P. and Georges, A. J., unpublished data.

Hyg., 47. 13, 1953.

group arboviruses. hfosq. NCWS. 32. 172. 1972.

Aedes aexypri Linn.. Trans. R. Soc. Trop. hfed. H q . . 60. 332, 1966.

J. Med. Sci., 8. 31. 1979.

Soc. Trop. Mcd. Hyg.. 59. 198, 1965. -.

viruses, Infecr. Immun.. 2, 762. 1970.

viruses. Trans. R. Soc. Trop. Mcd. Hyg., 55, 63. 1961.

domestic animals and humans in three ecological zones, of.Nigeria. Vlrologia. 76. 27. 1975.

- . -

I 2

Job 4386555529 Galley - - - - - - - 12-21-87 1 1-06-07

p;:? ;?Gr,-;-. . , ,- < , .. . , - , .

d- l 3 . 4

.- ! 5 ' Table 1. ._ __- .. '6 : 7 I

' 8 AND TATAGUISE) 9 10

-i ! .

ORIGIN OF VIRUS ISOLATIONS (ISOL) AND ANTIBODIES (AB) AGAINST FIVE ARBOVIRUSES (BUNYAMWERA, BWAMBA, GERR-IISTON, ILESHA,

4 BUN BWA GER ILE TAT @> - c_c_ - .-.

Origin h l AB Is01 AB Is01 AB Is01 AB Is01 AB 11

13 1 Chimpanzee NDb + ND ND ND ND ND ND ND ND ' I4 hfonkeys S D + ND ND ND N D ND ND ND ND IS Domestic animals ND + ND ND ND ND ND ND ND ND

' 16 Rodents ND + ND ND + + ND ND ND ND ' 17 Birds ND t ND + ND ND ND ND ND ND ' 18 Donkeys N,D ND ND + ND ND ND ND ND ND

19 Cattle ND ND ND ND N D . . + ND ND ND ND 20 Hamster (sentinel) ND NI) ND ND + ND ND . ND ND ND

22

12 Man +' + + + + + + t + +

+ + + + ? I Anhropods + + + + + -_ + ' 23 Positive isolation or presence of antibodies. . 24 ND, nodata.

-

2s .. 26

-. . I . . . .-.-. ... ~ - .. -.--.-. .- . -. . - -. - . . -

i Job 338655553 GdIiy lx------- - 12-21-87 11-46-07

2

' \ -. 3 .- 4

5

6 7 8 9 10

A II I.strl :i 1)

hllln Chimpanzee hliiilkcys Domcatlc Itnlnlds Rotlents Birds Donkcp Cattlc Hamiter (sentinel) hnhropods ,

+ ' + , + NEh + ND ND + ND ND -t ND ND + S D ND + ND ND ND ND ND ND ND ND ND ND + + +

+ S D ND ND ND + 4-

S D ND -k

+ ND ND ND +

ND ND ND + i.

+ + ND ND ND ND ND ND + ND

ND ND NI> ND + ND

ND ND -k 4-

4- ND ND ND ND ND ND ND ND 4-

' N D S D ND ND ND SU ND S D ND ND ND S D ND ND ND ND + +

19 20 'I

23 24

77 -- ' Positive isolation or presence of antibodies.

ND. no data.

Job 4356SSSS29 Galley 1%- - - - - -- 12-21-87 11-06-07

.*y * I I

I L

I

Job 4386SSSS30 G d k y - - - - - - - 12-2 1-87 1 1-09-19

' 3

5 i---i 6

: 7

4 Table 2 SUSCEPTIBILITY OF CELL-WTURE SYSTEMS FOR FIVE BUNYAVIRUSES

BUN -> L GER T,LT ILE - -- L

Cell system E P Dayb Eff Day Eff Day Eff Day Eff , Day

Chickembryo CPE 2-5 CPE 2 PLQ 3 PLQ 4-5 ND' ND VERO PLQ 5 PLQ 5 PLQ 3 PLQ 6 PLQ . 6 BHK-21 CPE 4 CPE 2 PLQ 2 ND ND ND ND LLC-MK, PLQ 4 PLQ 3 PLQ 4 PLQ 4 NP NP

1 , a * 9

1 I I 1.7 13 I4

. 15 16 17

' 18

' 20

1 IO

i 19

I 21

Nofe: Results given can v q with the virus passage history.

*

,

Eff, effcct in cell culture (CPE, cytopathic effects: PLQ. plaque>). Day, mean of days after isolation. ND. no data. NP, no plaque.

. .

lob 1386SSSS30 Galley 1%- - - - - - - 12-2l-S7 1 1 9 - 2 9

I

I -

2 I

Table 3 DETECTION OF IhIhIUNITY TO U\Y.L\hIBA (BWA). LiUNYAhIl\.'ERA (I)UN), ILESHA (ILE), GERhIISTON (GER), AND TXTAGUINE (TAT) VIRUSES IN

mnims: ANTIBODY PREVALENCE AND VIRUS ISOLATIONS

G 7 .8

.: 9 ; 10

1 12

1 15

! 11

1 ' :: , 16 1 17 I , . I 8 j 19

?O

BWA DUN ILE GER TAT

Nonh Africa AlFeria Egypt Lihya hltrrroco Tunisia

Benin Burkina faso Bameroon . CAR Chad Gambia Ghana Guinea Guinea-Bissau Ivory coa5t Liberia Mali Niger. Kigeria Senepl Sierra Leone Togo

Ethiopia Somalia

West Equatorial Africa Congo Equatorial Guinea Gibon ,

Rwanda . .

Kenya Tanzania

Wcst Tropical ATwa

East Tropical Africa

EasI Equalorial Africa

ND' 0.0 O.Ob 0.9 ND 0.0 ND 0.0 ND 0.0

0.0 ND ND, 0.0 0.0

ND ND ND ND ND

ND ND ND ND ND

ND ND

*d

* ND +*

ND ND

43.0 ND ND ND ND

33.WO.O' ND ND ND

3.0 17.0 8.0'

* 24.0' 0.0 + +

11.0 14.0 19.0 2.0 3.0

0.0;-23.0* . 19.0*

0.5

*

ND ND *

ND ND ND ND ND ND ND ND ND ND ND ND ND 10.0 ND ND w

ND * *

* * ND ND 6.5* ND 3.0 ND

. ND ND ND

27 .O*

ND ND

*

ND

ND ND ND ND ND ND ND ND ND 26.w1 .O*

ND ND

ND ND

*

29 -52.2 I 30

I 31 32

I 33

' 35 36 ! 31 38

' 39

41

I 34

-Il 40

' 49 50 51 52 53 54 55 56

+ 1.8-19.2. ND *

+ ND

ND 7 .?25.0 + +

ND 8 ND 0.0-10.0

\

* + 75.0* 1 1 . 1

ND ND ND ND

ND ND ND ND

ND ND ND ND

ND *

ND ND ND

Upanda M.O* 37.0' 1 *

Angola hfadagascar Moumbique Zimbibwe

Ausu-al Africa Botswana Namibia SAR

+ 52.0 , ND ND 0 . 0 4 . 5 ' ND

24.7. 24.1' ~ - ND ND 15.9 ND

3.3 53.3 ND ND 42. I ND

18.0 ND ND ND ND ND 2.3 ND -

90.1 ND 56.0 ND

I .4* ND ..

0.0440.0 0 . y 5 . 7 ' ND .I 'I . .

-.

.. . . -- ... -A. ... ...% _... , ...Is ... - , . , -. . i..

. z -.._ . . - .... . . ,

. - .

62 63

.

I

8 I - - a m u i . ,

I ' l o

11 ' 12 s 13

I4

15 16

17 18 19 20 21 22

--

Job 4386555532 Galley - - - - - - - 12-21-87 10-5439

Table 4 EI'IDENCE OF VIRUS CIRCULATION IN WILD AND DOMESTIC

VERTEBRATE HOSTS

Serological evidence c

RWA No

BUN NO

virus isolation

ILE No GER Herpestes ichneumon

D q m y s incomrus Rairus ruttus '

Lophurom?\c spp. Anicanrhus nilorirus

TAT No

Wild animals Domestic animak

Goast, sheep, cattle

Monkeys Chimpanzee. cattle. sheep, rodents. nonhu- Goats. sheep

No ..

No Goats. sheep, cattle

No

103 104 105

, 106 107 . . I08 1 o9 I10 111 I12 113 114 115 116 117 118 119

121 122 123 124 125 126 127 128 129 130

' 131 132 133

' 120

Andrew Spielman, Sc. D. Professor Departmeqkof Tropical Public Health H m w d Sc.hoo1, of Public Health Boston, hlassachusetts

Dennis W. Trent, Ph. D. Chief Molecular Virology Branch Centers for Disease Control Fort Collins, Colorado

Michael J. Turell, Ph. D., RI. P. M. Microbiologist Department of Arboviral Entomology USAMRIID, Fort Detrick Disease Assessment Division Frederick, Maryland

- CONTRIBUTORS

G. Stephen Bowen, M. D., hf. P. H. Deputy Director, AIDS Center for Prevention Services Centers for Disease Control Atlanta, Ggergia

AIain-Jean Georges, M. D. Director Department of Microbiology

<

134 Institut Pasteur 135 Bangui,Central African Republic

Department of Infectious Diseases College of Veterinary hledicine

133 144 Laboratory Chief 145 Department of Virology

Jean Paul Gonzalez, M. D., Ph. D.

I 1 . i 146 Institut Pasteur

- 1 I 147

149 ' 148

Ellis C . Greiner, Ph. D. 150 Associate Professor 15 1 152 College of Veterinary Medicine 153 University cif Florida 154 Gainesville, Florida 155 156

Departmen6 of Infectious Diseases

Paul fi. Grimstad, Ph. D.