An overview of

Arbovirology in Brazil and neighbouring countries.

Edited by:

Amélia P. A. Travassos da Rosa Pedro F. C. Vasconcelos

Jorge F. S. Travassos da Rosa

BELÉM INSTITUTO EVANDRO CHAGAS

1998

AN OVERVIEW OF OROPOUCHE FEVER EPIDEMICS..IN BRAZIL AND NEIGHBOUR COUNTRIES

Francisco P. PINHEIROAmelia P.A. TRAVASSOS DA ROSA

Pedro F.C. VASCONCELOS

186

AN OVERVIEW OF OROPOUCHE FEVER EPIDEMICS IN BRAZILAND NEIGHBOUR COUNTRIES

1. INTRODVCTIONOropouche rever is one of the most important arboviral diseases in the Americas, particularly in the

Amazon Region ofBrazil. Since the early 1960s Oropouche rever has caused numerous, extensive and oftenexplosive urban epidemics in the Amazon region, several of which affected large cities such as Belem andManaus. Hundreds ofthousands ofpersons were infected by the vírus during these outbreaks. The infectionmanifests itself in the form of an acute febrile episode, accompanied by headache, myalgia, arthralgia andother systemic symptoms. The symptoms usually reoccur a few days after the end ofthe first febrile episode,at which time they are genera"y less severe. Some patients may develop aseptic meningitis (Pinheiro ~.,1982b). Patients make a fu" recovery, without any apparent after effects, even in the most serious cases. Theincubation period ranges Eram four to eight days. The fatia of symptomatic to asymptomatic cases is roughly2: 1 (Freitas ~., 1982). There are no records of any confirmed fatalities attributab1e to Oropouche rever.Oropouche rever is caused by the Oropouche arbovirus which belongs to the genus Bunyavirus of theBunyaviridae family (Pinheiro ~., 1994); antigenica"y it belongs to the Simbu group which is included inthe Bunyamwera supergroup of arboviruses.

The first case ofthe disease was described in a resident ofVega de Oropouche, Trinidad, in 1955, Eramwhich blood the agent was isolated(Anderson ~., 1961). The disease was detected again in 1961, this timein the city of Belem, Para State, northem Brazi1, where it caused an epidemic that affected at least 11,000persons (Pinheiro ~., 1962). This was fo"owed by the occurrence of many epidemics in urban populationcenters throughout the Brazilian states of Pará, Amapá, Amazonas, Tocantins, Maranhão and Rondônia(Pinheiro ~., 1962; 1976; 1981a; Le Duc ~., 1981; Freitas ~., 1982; Travassos da Rosa ~., 1995;Vasconcelos ~., 1989). The interval between epidemics varied Eram 1 to 7 years and the last outbreakswere recorded in 1996, affecting at least tive urban centers of the Brazilian Amazon Region (Travassos daRosa, A.P.A. and Vasconcelos, P.F., unpublished data, 1996). Outside of Brazil, epidemics of Oropoucherever have been reported in Panama in 1989 (Quiroz, Evelia et ai. Panama, unpublished data, 1989) and inthe Arnazon Region ofPeru in 1992 (Chavez ~., 1992) and in 1994 (Ministry ofHealth,Peru, and V.S.Naval Medical Research Institute Detachment, NAMRID, Lima, 1994).

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2. EPIDEMIOLOGYUp to the present, cases of Oropouche rever have been reported only from Brazil, Panama, Peru and

Trinidad (Figure 1). However, most epidemics of the disease have taken place in the Brazilian Amazonregion. No cases ofthe disease were reported in other areas ofBrazil.

With a few exceptions alI occurrences of Oropouche rever have been in the forro of urban epidemics,including in Belem and Manaus, the largest cities of the Brazilian Amazon region. Between 1961 and 1981three major outbreaks were recorded in Belem, the capital of Para State. Also in this state, the city ofSantarém and surrounding vilIages were algo affected by a major epidemic in 1974-1975 (Pinheiro ~.,1976). Tbe tirst epidemics occurring outside the State ofPará were reported early in the eighties, striking thecities ofManaus and Barcelos in the State of Amazonas (Borborema~., 1982) andthe city ofMazagão inwhat was then the Amapá Territory (Pinheiro, 1983). After a period of silence lasting until 1988, newoutbreaks ofthe disease struck the cities ofPorto Franco and Tocantinópolis in the states ofMaranhão andTocantins respectively (Vasconcelos ~., 1989). The next reported epidemics occurred in 1991, this time inmore distant locations, namely in the cities of Ariquemes and Ouro Preto D'Oeste in the state ofRondônia;the epidemic's impact on these cities was so great that it was reported in the national press. Subsequentlyanoutbreak occurred in Serra Pelada, Pará State, in 1994, during which 83% of its 6,000 inhabitants wereinfected with the agent (Travassos da Rosa ~., 1995). The last reported outbreaks in Brazil affected tivelocalities in the states of Amazons, Acre and Para (Figure 1).

In addition to the above-mentioned epidemic areas, there are countless smalI vilIages scattered throughoutviftualIy the entire Amazon region whose residents show hemagglutination inhibition (HI) antibodies againstthe Oropouche virus. In general, the prevalence ofthese antibodies is less than 3%, with the exception ofIlhade Gurupá, where the prevalence was 10.7% (Pinheiro ~., 1981a).

Outside of Brazil, outbreaks were reported in Panama and in Peru. The outbreak in Panama occurred in1989, striking the vilIage ofBejuco approximately 50 kilometers west ofthe capital (Quiroz, Evelia et ai.

187

Panama, unpublished data, 1989). The first epidemic in Peru was reported in 1992 in the cityofIquitos in thePeruvian Amazon region (Chavez ~., 1992); subsequently an outbreak occurred in Puerto Maldonado,Madre de Dios, also in the Peruvian Amazon Region (Ministry of Health, Peru, and V.S. Naval MedicalResearch Institute Detachment, Lima,1994). Evidence of immunity to the Oropouche vírus was detected innonhuman primates in Colombia, suggesting its presence in this country as well (Karabatsos, 1985).

./

Figure 1. Map of Latin America showing the places where ~"epidemics of Oropouche rever were reported, between 1961-1996. ~ (..

.:;;;;". C\ oD

As Oropouche rever is not a reportable disease it is difficult to estimate its incidence during outbreaks.However, serological surveys have been useful to determine the incidence of Oropouche rever during outbreaks.In most surveys gera were tested for the presence ofhemagglutination inhibiting antibodies against Oropouchevirus. (Freitas ~., 1982; Pinheiro ~., 1981a; Pinheiro, 1983; Pinheiro ~., 1986). According to thesesurveys at least 357,000 individuaIs are estimated to havebeen infected with the Oropouche vírus between1961 and 1994. However, this estimate is actually quite conservative, considering that the incidence oftheviTal disease had not been computed in a number ofmajor outbreaks as ocurrred in Belém, 1968; Porto Francoand Tocantinópolis, 1988 (Table 1). Accordingly, it is possible that more than half a million people in theBrazilian Amazon region mar have been infected with the Oropouche virus since the beginning of the 1960s.

188

Feb-May/612,50028Nov/80-Mar/81May-JuU80Mar-May/967520,00015,000Jan-Apr/91Jan-Apr/9117,000

Table 1. OROPOUCHE FEVER EPIDEMICS IN BRAZIL, SHOWING NUMBER OF STRAINSISOLATED ESTIMATED INCIDENCE OF PEOPLE INFECTED, 1961-1996

State/MunicipalityLocality

Nr. or strainsIsolated

People InfectedIncidence Total

%

DatePopulation

67,0001 17 11.000Feb-May/61 15

3330U

4006,00

> 101

Feb-Mar/67Mar-Jul/67Feb-Jul/68

28

101

1,20020,000600,000

352,500 >85Jun-Sep/72 o

3035

0-443937

600400

14,0001,600

280

Dez-Apr/75Feb-Apr/75Apr-JuI/75Apr-Jun/75Jul-Augi75

42229O16

2,9001,680

80,0004,000750

28500 420May-Jun/75 9

15-434.8

6.1-50.88

7.2-60.383U

22164628521233

10,0003370002,5,

110,0005812,4095104,77856,00040,000

2,00016,00

11,00065,00037,0005,000

U

Jun-Out/78Apr-Jun/79Mar-Nov/79Feb-0ut/80Mar-Aug/80Nov-De:zJ94Apr-May/96

PARÁBelém

Bragança(Mn)CaratateuaBragançaBelémBaião (Mn)BaiãoSantarém (Mn)Mojuí dos CamposPalhalSantarémBelterraAlter-do-ChãoItupiranga (Mn)ItupirangaTomé-Açu (Mo) ISeveralBelém2; Several3! Belém

Several4Serra PeladaOriximináAltamira (Mn)Brasil NovoVitória do Xingu

uu

Jan-Feb/96Jun-JuU96

73

12,0008,000

uu

AMAZONASManausBarcelosNovo Airão

15UU

9O40

650,00010,00010,000

97,000171

U

Nov/80-Mar/81

May-JuV80Mar-May/96

AMAP Á

Mazagão 5,000 u u1980 o

MARANBÃOPorto Franco u75 20,000 uDec/87 -Mar/88

15,000 u uDec/87 -Mar/88 10

210,837130,125

27.7827.21

58,57435,413

Jan-Apr/91Jan-Apr/91

163

TOCANTINSTocantinópolis

RONDÔNIAAriquemesOuro Preto D'oeste

uMar-Apr/96 4 17,000 uACREXapuri

Estimated

>356.413

TOTAL

U. Unknown.1. Population of 2 district (Marco and Pedreira).2. Population of six districts (Marco, Marambaia, Cidade Velha, Guamá, Umarizal and Telégrafo).3. Abaetetuba, Benfica, Benevides, Sta. Izabel, Castanhal, Capanema.4. Ananindeua, Augusto Correa, Bragança.5. Susceptible population.

189

Gender-specitic attack rales vary, with female rales slightly higher than attack rales for males in villagesin lhe Bragantina area, Eastem Pará State, struck by lhe virus in 1979 (Freitas tlill., 1982), with lhe oppositetrue in lhe outbreak in Belém that same year. However, in lhe reported epidemics in Santarém, lhe infectionstruck females twice as often as males (Dixon tlill., 1981). Oropouche fever strikes ali age groups, although,in certain outbreaks, its incidence was higher among children and young adults.

In several outbreaks a wide range of localities within a particular geographic area were affected by lhevirus. This situation was observed in Bragança in 1967, in Santarém in 1974-1975 and, even more so, inBelém and in lhe Bragantina area in 1978-1980 (where at least 10 towns were stricken), as well as in Rondôniain 1991. Most likely virus spread is due to lhe movement of viremic individuais throughout areas in which lhevirus vector is present.

Most epidemics ofOropouche fever typically occur during lhe rainy season which, ln lhe case ofthe StateofPará, corresponds to lhe period between lhe months of January and June. However, some epidemics havealgo extended into lhe dry season, although with less intensity. The seasonal nature ofthe Oropouche fever ismost likely linked to lhe higher density of populations of Culicoides paraensis commonly known as bitingmidge, lhe urban virus vector, in months with higher levels of rainfall, combined with a higher concentrationof exposed individuais. Downward trends in epidemics of Oropouche fever are generally associated with lhearrival of lhe dry season and lhe resulting lower density of biting midge populations and smaller numbers ofexposed individuais.

Laboratory studies and broad-based surveys conducted by lhe Evandro Chagas Institute (IEC) during lhecourse of epidemics point to lhe importance of lhe insect C. paraensis belonging to lhe Ceratopogonidaefamily as lhe urban vector for lhe Oropouche virus (Pinheiro tlill., 1981 b; Pinheiro tlill., 1982a). These tinyinsects commonly known as "maruins" (biting midges) in lhe Amazon region, are active during lhe day,particularly in lhe late aftemoon hours. They crave human blood, biting people inside as well as outside theirhomes (Hoch ~., 1990; Pinheiro tlill., 1976; Roberts tlill., 1981). The disease is transmitted by lhe bitesof infected midges inoculating lhe virus into exposed individuais.

Studies conducted by lhe IEC (Pinheiro ~., 1981a) suggest that lhe Oropouche virus is perpetuated innature through two different cyc1es, namely an urban cycle and a wi1d cycle. In lhe urban or epidemic cycle,lhe virus is transmitted from person to person by lhe bite of C. paraensis. One ofthe most conclusive piecesof evidence attesting to lhe truth ofthis assertion 1ies in lhe demonstration ofthe ability of C. paraensis, afterfeeding on lhe blood of viremic patients, to transmit lhe virus to hamsters bitten by lhe midges tive or moredays later (Pinheiro ~., 1982a). Moreover, these midges are typically found in high densities duringperiods of epidemics. They breed mostly in decomposing trunks of felled banana trees, in rotting husks ofcocoa beans (Hoch ~., 1990) and in piles of detritus formed in tree hollows (Linley ~., 1983). Theyarescattered throughout tropical and subtropical areas ofthe Americas (Linley ~., 1983).

Attempts to transmit the virus from one hamster to another through lhe bite ofthe Culex p. quinquefasciatusmosquito (a species commonly found in urbanareas throughout lhe Amazon region) showed that it wastransmitted only in lhe presence of extremely high levels of viremia, which is rare in infected humans (Pinheiro~., 1981b). Thus, this tinding virtually roles out ali likelihood of lhe epidemic vector being Cx. p.quinquefasciatus. Curious1y enough, lhe virus isolation rale from C.paraensis during periods of epidemics isonly 1:12,500 (Le Duc & Pinheiro, 1988), which suggests that we are dea1ing here with a low-efficiencyvector. Apparently, man is lhe only vertebrate involved in lhe urban cycle of Oropouche virus, since studiesof domestic animais conducted during lhe course of a number of outbreaks ruled out lhe possibility of theseanimais playing an amplifying role.

As far as its wild, silent cyc1e is concemed, there is evidence that, among lhe vertebrates, lhe Edentata(sloths), nonhuman primates and possibly certain species ofwi1d birds serve as hosts. Although lhe vector isstill unknown, lhe possib1e involvement of biting midges in lhe virus' wi1d cycle should nevertheless be

investigated.The link between lhe two cycles is most likely man himself who, after contracting lhe infection in enzootic

forested areas and then retuming to an urban setting during lhe viremic phase, becomes a source of infectionfor biting midges. The virus replicates in lhe tissues ofbiting midges which, following lhe extrinsic incubationperiod which lasts tive or more days (Pinheiro tlill., 1982a), bite and infect exposed individuaIs who, in tum,serve as source of infection for other midges, thereby forming a chain of transmission, resulting in lhe un1~ashingof an epidemic. The b100d of infected patients is infectious to C. paraensis during lhe first three or four daysafter lhe onset of symptoms, when lhe levei of viremia is high enough to infect lhe midges.

190

3. PREVENTION AND CONTROL

The most effective way to prevent, avert or curb the impact of epidemics of Oropouche fever is to combatits vector C. paraensis. In order to be effective, vector control efforts will need to focus on the midges's adultand larval forms. Considering how C. paraensis is habitually active during the day, applications ofinsecticidesto its habitats through thermonebulization or ultra-low volume aerosolization may help reduce adult bitingmidge populations. Since this Culicoides species is most active during the late aftemoon hours (Roberts ~ill., 1981), ultra-low volume spraying may be more effective during this period of the day. However, carefullyplanned-out studies are needed to assess how to maximize the effectiveness of spraying, in arder to determinethe type and concentration of insecticide to be used, lhe necessary volume of insecticide per treatment area, lhesize of the droplets, the frequency and timing of applications, etc. At lhe same time, it is essential that aneffort be made to contrai its larvae by larviciding corresponding habitats ar, better yet, by conducting drivesto eliminate or bum breeding sites such as rotting cocoa bean husks, decomposing trunks of felled bananatrees, etc. (Hoch ~., 1990). Obviously, lhe success ofthese measures will be largely dependent on communityinvolvement. Hence the importance of proper community education. IndividuaIs can protect themselves byapplying insecticides directly to the skin. However, lhe action of these types of products is only temporaryand they may be unaffordable to the poor.

There is no vaccine against Oropouche fever at this time. In light of the relatively benign nature of thisviral disease, it is hard to justify developing a general-purpose vaccine for at-risk populations living in areaswhere they are exposed to contracting the disease.

191

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