Rev. Inst. Med. trop. São Paulo 31 (2): 103-109, rnarço-abrü, 1989

RELATIONSHIP BETWEEN THE PREVALENCE OF ANTIBODIES TO ARBOVIRUS AND HEPATITIS B VIRUS IN THE VALE DO RIBEIRA REGION, BRAZIL

C l á u d i o S é r g i o P A N N U T I (1, 3) , L y g i a B u s c h I V E R S S O N (2 ) , J o ã o S i l v a de M E N D O N Ç A (3) ,

A m é l i a P . A , T R A V A S S O S D A R O S A (4) & C e l s o F r a n c i s c o H c r n a n d e s G R A N A T O (5) .

S U M M A R Y

2 8 0 students, between 6 and 1 4 years old, residents in the Iguape county, southern coast of the State of São Paulo, were studied in order to identify the existence of a possible association between the prevalence of specific antibodies to the hepatitis B virus and the exposure to haematophagous mosquitoes, evaluated indirectly through the prevalence of antibodies to 1 7 arboviruses isolated in Braz i l .

The children were from 4 areas with different topographical characterist ics: 89 of the children were from the urban zone of the town of Iguape, 89 were from the per iurban zone, 3 0 were from the rural area with extensive banana plantations, and 7 2 were from the jungle zone. Previous studies had shown signif icantly higher prevalence of antibodies to different arboviruses in the cult ivated zone and the jungle zone, when compared to the urban and peri urban zones of Iguape. The detec¬ tion of antibodies to the H B V surface ant igen ( H B s Ag) was done through the radioimmunoassay (Ausab, Abbott Laboratory). The cases considered positive were confirmed through the presence of anti-core H B V antibodies (anti H B c E I A Roche).

A signif icantly higher prevalence of anti H B V antibodies was observed in chi l¬ dren from the jungle zone ( 2 6 / 7 2 = 3 6 , 1 % ) when compared to those from the urban zone (5/89 = 5 , 6 % ) , peri-urban (6/89 = 6 , 7 % ) or from the cult ivated zone ( 0 / 3 0 = 0 r % ) .

The result suggest the existence of a common factor in the dissemination of the arboviruses and the hepatitis B virus, supporting the hypothesis that mosquitoes may play an important role in the H B V transmission in tropical forested region.

K E Y W O R D S : Hepati t is B transmission; Hepati t is B seroepidemiology. Arbovirus and Hepati t is B

I N T R O D U C T I O N

The higher prevalence of hepatit is B virus regions 3 3 4 suggested that, along with conven-(HBV) markers in human populations in tropical t ional t ransmiss ion mechan isms observed in

(1) I n s t i t u t o de M e d i c i n a T r o p i c a l e L I M do H o s p i t a l d a s C l í n i c a s d a F a c u l d a d e de M e d i c i n a d a U n i v e r s i d a d e de S ã o P a u l o .

S ã o P a u l o . S P , B r a s i l .

(2) F a c u l d a d e de S a ú d e P ú b l i c a d a U n i v e r s i d a d e de S a o P a u l o , S ã o P a u l o , S P , B r a s i l .

(3) H o s p i t a l do S e r v i d o r P ú b l i c o do E s t a d o de S ã o P a u l o . S ã o P a u l o . S P , B r a s i l .

(4) I n s t i t u t o E v a n d r o C h a g a s . M i n i s t é r i o d a S a ú d e . B e l é m , P a r á , B r a s i l .

(5) I n s t i t u t o A d o l f o L u t z . S e c r e t a r i a do E s t a d o d a S a ú d e de S ã o P a u l o , S ã o P a u l o , S P . B r a s i l .

A d d r e s s for c o r r e s p o n d e n c e : D r . C l á u d i o S é r g i o P a n n u t i . I n s t i t u t o de M e d i c i n a T r o p i c a l de S ã o P a u l o . A v . D r . E n é a s de

C a r v a l h o A g u i a r . 470 05403 S ã o P a u l o . S P . B r a s i l .

other parts of the world, addi t ional modes of transmission might be present in the tropics.

The high prevalence in some of these regions of diseases t ransmit ted by haematophagous arthropods and the low frequency of blood trans­fusion or inject ions among their inhabi tants, raised the first suspicion of H B V transmission v ia mosquitoes and other insects as reported by B L U M B E R G et al. 4. Detection of H B Ags in various species of mosquitoes and other haematopha­gous arthropods captured in tropical regions 6

8. i 7 , 27. 35, 40, 41 . 42 a n c j e v e n urban areas of the

United Sta tes 1 3 , has somehow corroborated this hypothesis. Exper imenta l studies showed that when various species of mosquitoes 2 6 7 2 8 3 0

3 i , 38 a n d 0 t he r haematophagous arthropods 1 2 2 6

3 i , 37, 39, 40 w e r e f e c j blood containing H B s Ag , it was possible to detect this marker in mosquitoes for approximately up to 4 days, in most of the studies, and for periods up to several weeks in the other arthropods. I t was observed, however, that the H B s A g disappears once the blood is fully digested, indicat ing that no viral replica­tion occurred in the a n i m a l 6 , 7 - 3 1 .

According to these results, infections of H B V via arthropods would be the result of mechanical t ransmiss ion . I n this mode of t ransmiss ion , which was already been described for several ty­pes of plant and animal viruses, such as the my­xoma virus in rabbits and certain arboviruses 1 1 , the virus would remain viable in the structure of the sucking apparatus of the arthropods and might be transmitted passively from a contami­nated host to a susceptible one, of the refeeding time for the mosquito, or when it completed a feeding which had been interrupted 5. A s is the case with certain viruses such as the Venezuelan equine encephal i t is 1 1 or Ri f t Val ley fever viruses which reach very high concentration in blood; the l ikehood of mechanical transmission of H B V , which is highly infectious and highly resistant to inat ivat ion 3 6 , appears possible.

Th is mechanical transmission should occur more frequently in tropical regions, where there is in tens ive the act iv i ty of haematophagous arthropods.

A seroepidemiologic survey to H B V , carried out in São Paulo State, B raz i l 2 9 , demonstrated

an u n u s u a l l y h i g h p reva lence of a n t i - H B S among children l iv ing in a camping area near Serra do Mar, a rural area near the coastal region of the State. The study showed a prevalence of 31.2% (10/32) among children whose age ranged from 1 to 5 years, and 48.7% (19/39) among those in the 6 to 11 years group. These children were of low socioeconomical status. However, among the adult population of low socioeconomic status l iv ing in the urban area of the city of São Paulo, the prevalence of an t i -HBs was only 14.58% 2 9, suggesting that factors other than the socioeco nomic status determined, the high prevalence of immunological markers to H B V in this loca­lity.

In order to test the hypothesis that wild culi-cidae might be involved in H B V transmission, a seroepidemiologic survey to the H B V was con­ducted in a region with similar ecological charac­teristics, namely the Vale do Ribe i ra , which is also included in the so called Serra do Mar S y s tern. Th i s area is characterized by an abundant Culicidae fauna 1 5 1 6. Since 1977 the Department of Epidemiology of the Publ ic Heal th School of the University of São Paulo, in collaboration with Evandro Chagas Institute, has conducted seroe-pidemiological surveys for arboviruses in the hu­man population. The prevalence of arbovirus an­tibodies should thus provided an indirect indi cator of the r isk of infections transmitted by mosquitoes. The prevalence of immunological markers of the H B V should be correlated with that of arbovirus antibodies.

M A T E R I A L A N D M E T H O D S

T H E A R E A . The serological survey was car­ried out in Iguape, one of the counties of the Vale do Ribe i ra , located in the coastal area of the State of São Paulo, southeast Braz i l , in a region sti l l extensively covered by forests.

I n 1976 an epidemic of arbovirus encepha­l i t i s r e s u l t e d i n a m o r b i d i t y i n d e x of 717.5/100.000 inhabitants in Iguape 2 1 . Seroepide-miological studies showed that arbovirus as be­longing to the Togavir idae and F lav iv i r idae fa­milies, pathogenic for human 2 2 2 5 , are circulat ing in the region.

Within the l imits of the county, four areas with different topographical and phytological

characteristics, were studied. These areas, have been described in details previously 2 5 . They are briefly:

a) Urban Zone: including Iguape, a town lo­cated in the coast and a health resort in a large ne ighbour ing i s l a n d , wh i ch presents u rban structure;

b) Peri-Urban Zone: Roc io Distr ict , in the outshirts of Iguape, with rural characterist ics, poor houses sparsely located among the vegeta­tion; grass and smal l bushes predominate.

c) Cu l t iva ted Zone: in the coastal p la ins, with a few areas of residual forest. Ex tens ive planting of bananas, and, more recently, of vege­tables and grain, is carried out.

d) Jungle Zone: sti l l extensively covered by forests, made up of tal l trees, dense foliage and high degree of heterogenity, where the uti l iza­tion of land agricultural and cattle-raising pur­poses is stil l l imited.

C A S E S T U D Y

In the 1981-1982 period, blood samples were collected for an arbovirus seroepidemiological study from 337 students (6 to 14 years old) from Iguape county. These children proved to have different prevalences of H I antibodies to 17 arbo­virus isolated in Braz i l , according to the locality where they l ived. Among, these 337 sera, preser­ved at -20°C, 280 presented an enough amount that permited the research of H B V immunolo­gical markers. The 280 children resided in diffe rent areas: 89 of them lived in the Urban Zone; 89 in the Periurban Zone, 30 in the Cul t ivated Zone and 72 in the Jung le Zone. The majority of the children (70.1%) had lived all their lives in the place at which they were residing at the time of the study. Only 2.8% had l ived there for a period of less than one year. The 280 children belonged to 233 different families. In 33 families two or more children were examined.

Socioeconomic status was estimated on the basis of the father's profession, and proved to be low, with no signif icant difference between the areas of residences, since 71(30.5%) of the fathers were agricultural workers, 58(24.9%) were

m a n u a l laborers , 27(11.6%) were f ishermen, 27(11.6% ) were low level public servants, 13(5.6%) were clerks in commercial establishments, and 4(1.7%) were elementary schoolteachers. I n 33 cases (14.2%) this information was not available. A s to sex, 51.7% (135/261) were male and 48.3 (126/261) were female. I n 19 cases, this informa­tion was not available.

An t i -HBs A g was determined by radioimmu­noassay (Ausab-Abbott Laboratories).

The posit ive sera were tested to ant i -HBc antibodies by an immunoenzimat ic technique (Roche Laboratory). To ensure accuracy in the results, only cases where both markers were pre­sent were considered positive. In schoolchildren from the Cul t ivated Zone ant i -HBc antibodies were measured in all sera.

R E S U L T S

Of the 280 sera studied, 37 (13.2%) were posi­tive for ant i -HBs. A prevalence of 27/71 (38.0%) was presented by children of farm workers, 3/27 (11.1%) by children of fishermen and 7/135 (5.2%) by children whose fathers worked at others acti­vities. A s to sex there was no signif icant diffe­rence (p > 0.05) between prevalence in male (12.6%) and female (15.1%). I n one of the positive cases, this information was not available. A s to age distribution, no statist ical ly signif icant diffe­rence (p > 0.05) was observed in the prevalence of ant i -HBs A g antibodies among the groups of 6 to 8 years (11.8%), 9 to 11 years (13.3%) and 12 to 14 years (16.0%).

The prevalence rates of an t i -HBs A g and ar­bovirus antibodies according to the four diffe­rent geographic areas considered may be seen in Tab le 1. In the Jung le area, the rate of sera with positive ant i -HBs was 36.1% (26/72), signifi cant ly higher than other zones (p < 0.001). I n the three localit ies of this Jung le area, preva­lence was 36% (9/25) in the Pavoa district, 37.8% (14/37) in the Pé da Serra district, and 30% (3/10) in the Despraiado district.

None of the cases from the Banana l Zone presented ant i -HBc or ant i -HBs antibodies.

When we only considered the families where no more than one child was studied, the anti-

H B s prevalences were of 26.7% in the Jung le Zo­ne, 8.2% in the Periurban Zone and 6.1% in Ur­ban Zone showing a signif icant difference bet­ween Jung le Zone and Urban and Periurban Zo­nes ( X 2 = 10.5050 p < 0.01).

D I S C U S S I O N

There are signif icant differences in the pre­valence of H B s antibodies according to the geo graph ic area cons idered. T h e preva lence of

T A B L E 1 Prevalence of H B s Ag antibodies (anti-Ags H B ) and H I antibodies against 17 arbovirus in school

children, aged 6 to 14 years, for different areas of Vale do Ribe i ra , São Paulo, Braz i l .

Geographic area N? tested

N? positive (%) An t i -HBs A g

N? positive (%) Anti-arbovirus

Urban Zone (Iguape and I lha Comprida)

89 5 ( 5.6%) 2 ( 2.2%)

Per iurban Zone (Rocio)

89 6 ( 6.7%) 3 ( 3.4%)

Cul t ivated Zone 30 0 ( 0.0%) 7 (23.3^ )

Jung le Zone 72 26 (36.1%) 13 (18.0%)

To ta l 280 37 (13.2%) 25 ( 8.9%)

x 2 - 36.2883 p < 0.001

36.1% in children from 6 to 4 years old, the vast majority of whom (73% ) were children of farmers who lived in the Jung le Zone, is unusual , both in relation to children from other areas of the present study and in relation to the rates obser­ved in the adult population of low socioeconomic status in the city of São Paulo, where the preva­lence of an t i -HBs antibodies was 14.58%2 9. The rates were similar to those of h igh prevalence (48 7%) observed in 6 to 11 year-old children li­v ing in the Serra do Mar region 2 9 , also in the southern coast of São Paulo State, which pre­sents cl imatic and phytological conditions simi­lar to those of the Vale do Ribei ra.

In the present study, the children had a ho­mogeneous socioeconomical status. Also, there were no signif icant differences as to sex and age of those infected by H B V (p > 0.05). Thus, it is pro­bable that a factor l inked to the geographic area could be influencing the larger dissemination of the H B V in the Jung le Zone. The fact that similar rates were found in three different localities of the Jung le Zone somehow removes the possi­

bil ity of a local epidemic of infection by H B V , since these populations have almost no contact at all among themselves. Besides even we exclu­de 33 families where two or more children were studied (15 from Jungle zone), the prevalence of positive sera to an t i -HBs antibodies remains sig­nificantly higher in the Jung le Zone than other areas.

Previous study, carried out among these ve­ry same children, also detected a clear pattern in the prevalence of H I antibodies to 17 arbovi­ruses in Braz i l , depending on the geographical area under considerat ion 2 5 . The prevalence of ar­bov i rus an t ibod ies was s ign i f i can t l y h igher among those l iv ing in the rural zone (Jungle and Cul t iva ted Zones) than observed among chi l ­dren l iv ing in the Urban and Peri-Urban Zones 2 5 .

The results suggest the existence of a com­mon factor in the dissemination of V H B and of the arboviruses in forested areas, one of the pos­sibil it ies being that of transmission by means

of anthropophilic mosquitoes, extremely abun­dant in that region 1 5 1 6 .

Neve r the less , the t r a n s m i s s i o n m e c h a ­nisms for both viruses would have totally diffe­rent characteristics. Thus , is relation to the arbo­viruses, there is a continuous maintenance cy­cle of these agents in the forest, with part ici­pation of wild vertebrates, especially mammals and birds, and of haematophagous mosquitoes in which the virus multiplies. When humans enter this ecosystem, they face a high probabil i ty of becoming infected. The H B V , on the other hand, would be mechanical ly transmitted by haemato­phagous arthropods; this requires, besides the high density of this arthropods, exogenous intro­duction of the virus by infected humans. Th is might occur in one area and not in another, even though the second area might be just a few kilo­meters away from the first, due to the fact that this transmission depends on the degree of dis­persion of the mechanical vectors. Furthermore, there are no know animal reservoirs to H B V ex­cept man. The association between the preva­lence of arbov i rus ant ibodies and a n t i - H B s , which seem to be directed proportional (the hi gher the prevalence of anti arbovirus antibodies, the higher the prevalence of an t i -HBs A g antibo­dies), is sharply interrupted in the Cul t ivated Zone, the very place of highest prevalence of ar­bovirus antibodies.

A reasonable explanat ion to this discrepan­cy (0% of ant i -HBs and 23,3% of arbovirus anti­bodies) would be the total absence of H B V car­riers in the Cult ivated Zone. The total absence of H B V markers among children in this zone cor­roborates this hypothesis. Should H B V be intro­duced in this locality, the expectation would be for an infection prevalence comparable to that of Jung le Zone since in the open areas of the extraforest environment of Iguape there is a high frequency of different species of Cu l i c idae 1 5 1 6 . Addi t ional research directed to this area beco­mes necessary. I n the Urban and Peri-Urban Zo­nes of the town of the Iguape, the epidemiolo­gical behavior would be equivalent to that obser­ved in the Urban Zone of the city of São Paulo.

Other studies have attempted to stabl ish a correlation between H B V markers and the pre­sence of mosquitoes 1 1 4 2 0 3 2 ; the results are con­

flicting. However, the different conditions under which these studies were carried out and the different techniques employed for the detection of H B V immunological markers make the com­parison of the results difficult.

Unusual ly high prevalences of H B V immu­nological markers have been consistently obser­ved among Ind ian tribes in the western Ama­zon area, varying, in the adult individuals from 60,7% to 100%9 1 0 1 8 1 9. A s for inhabitants of the rural zone in the Vale do Ribe i ra these popula­tions live in relative isolation, in close contact with the forest. H igh rates of infection by arbo­virus, such as Mayaro, have also been observed in the Amazon region 3 3 . Even if there is a wide gap between the Indians of the Amazon regions and the inhabitants of the Vale do Ribe i ra area, both populations have something in common: they both live in close contact with the forest environment and its fauna. The present study seems to support the hypothesis that mosqui­toes may play an important role in the trans­mission of hepatit is B in the tropical forested regions, However, further research becomes ne­cessary to shed further l ight on the matter.

R E S U M O

Relação entre prevalência de anticorpos para arbovirus e v i rus de hepatite B na região do

Vale do Ribeira , Bras i l .

280 escolares de 6 a 14 anos de idade, residen¬ tes em Iguape, Vale do Ribe i ra , sudeste do Es ta ­do de São Paulo, foram estudados com o objetivo de verificar possível associação entre a preva­lência de anticorpos para hepatite B e a expo¬ sição a mosquitos hematófagos, aval iada indire­tamente pela prevalência de anticorpos de arbo­virus. A s cr ianças eram originárias de 4 áreas com característ icas topográficas e fitográficas diferentes: 89 residiam em área urbana, 89 em área periurbana, 30 em área de cultivo extensivo de banana e hortal iças e 72 em área florestal. Estudos prévios mostraram significante maior prevalência de anticorpos de arbovirus nas áreas cul t ivada e florestal do que nas áreas urbana e periurbana. A pesquisa de ant i -HBs foi feita por radioimunoensaio (Ausab, Laboratório Ab­bott) e de ant i -HBc por ensaio imunoenzimático (Roche). Observou-se que os escolares residentes

na área florestal apresentaram mais alta preva­lência (26/72 = 36.1%) de anticorpos para hepa­tite B de que os residentes nas áreas urbana (5/89 = 5,6%), periurbana (6/89 = 6.7%) e cul t ivada (0/30 = 0% ). Os resultados sugerem a existência de fator comum na transmissão de arboviruses e de hepatite B , apoiando a hipótese que nas regiões tropicais com presença de mata mosqui­tos possam desempenhar importante papel na transmissão da hepatite B .

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