Viral hepatitis in Bucharest

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1 Virl heptitis in Buchrest C. Pquet,1 V.T. Bbes,2 J. Drucker,3 B. Senemud,4 & A. Dobrescu5 A seroprevlence survey of virl heptitis ws conducted in Buchrest, Romni, between April nd July 1990 on systemtic smple of 1355 persons drwn from the generl popultion nd groups t higher risk of infection. Ser were tested for heptitis A, B, nd C (HA V, HBV nd HCV, resp.) mrkers using n enzyme-linked immunosorbent ssy (ELISA) method. The prevlences of HAV nd HBV mrkers were high in ll groups. A totl of 47% of the dults from the generl popultion nd 39.8% of the children ged 0-16 yers hd t lest one HBV mrker. Of the pregnnt women 7.8% were positive for heptitis B surfce ntigen. Among infnts (0-3 yers of ge) living in orphnges, the prevlence of t lest one HBV mrker ws 54.6%. The findings lso confirmed tht HCV ws circulting in Romni. The results re consistent with ntionl surveillnce dt nd confirm tht virl heptitis is mjor public helth problem in Romni. Preventive mesures will hve to include HBV immuniztion of infnts, with n ppropritely trgeted immuniztion strtegy being determined through further epidemiologicl studies. Introduction Virl heptitis is mjor public helth problem in ll prts of the world. In prticulr, infections with heptitis B virus (HBV) re of concern becuse in some ptients the condition cn led to chronic liver disese, cirrhosis of the liver, nd heptocellulr crcinom (1). Comprtive studies of the morbidity rtes of HBV nd heptitis A virus (HAV) infections in vrious Europen countries indicte tht these diseses re highly endemic in Romni (2). According to ntionl surveillnce dt (3), the reported incidence of ll types of virl heptitis in Romni ws 300 per in Virl heptitis B, which minly ffects young children, ws mjor public helth concern, with n estimted nnul incidence of 50 per The number of reported cses of virl heptitis is very unrelible mesure of the rel epidemiologicl sitution, since it covers only portion of cliniclly mnifested cses. Heptitis infections hving I Medicl Epidemiologist, Epicentre, 8 rue Sint Sbin, Pris, Frnce. Requests for reprints should be sent to this ddress. 2 Director, Lbortory of Virl Heptitis, of Virology, Buchrest, Romni. Stefn Nicolu Institute 3 Professor of Public Helth, University of Medicine, Tours, Frnce. 4 Medecins sns Frontieres, Pris. Current ddress: Nutrition Unit, Food nd Agriculture Orgniztion of the United Ntions, Rome, Itly. 5Director, Lbortory of Epidemiology, Medicine, Buchrest, Romni. Centre for Preventive Reprint No non-icteric course re for the most prt, not officilly reported. For exmple, in Germny, where the surveillnce system is good, the number of unregistered cses of heptitis infections hs been estimted to be twice those tht re registered (4). Also, in Romni, dt on the etiology of virl heptitis re scrce; informtion on its distribution mong the vrious subgroups of the popultion is lso lcking (5-7). Finlly, existing dt must be exmined with cution since lbortory tests for heptitis virus mrkers re rrely crried out with the highly sensitive nd specific third-genertion ssys tht re now vilble. Following the politicl uprising in Romni in December 1989, the newly ppointed Ministry of Helth needed to complete epidemiologicl informtion to implement pproprite virl heptitis prevention mesures. For this purpose, prevlence survey ws designed nd conducted by the Ntionl Institute of Virology, the Centre for Preventive Medicine, Buchrest, nd Epicentre, Pris. The results re reported in this rticle. Mterils nd methods A seroprevlence survey of HAV, HBV nd heptitis C virus (HCV) mrkers ws conducted between April nd July 1990 on smple of 1355 persons who were recruited from the popultion of Buchrest under the supervision of the Centre for Preventive Medicine, Buchrest. Low-risk smple The following groups formed the low-risk smple: 201 children ged 0-16 yers who hd been dmitted Bulletin of the World Helth Orgniztion, 71 (6): (1993) World Helth Orgniztion

2 C. Pquet et l. to hospitl for the first time in their life nd who hd non-infectious dignosis; 200 helthy dults who were ttending premritl or recruitment medicl exmintions; nd 204 pregnnt women who were ttending ntentl clinics. The city's two lrgest peditric hospitls recruited ll children who met the inclusion criteri, from the beginning of the study period until the required smple size ws obtined. Helthy dults nd pregnnt women were selected similrly from two specilized clinics nd three mtemity hospitls, respectively. High-risk group The following individuls formed the high-risk group: 214 children under 3 yers of ge selected t rndom from the five orphnges in Buchrest; nd, on voluntry bsis, 336 medicl personnel employed by four different helth fcilities in the city. Ptients with cute heptitis To ssess the reltive distribution of the virl etiologies involved, we lso recruited 100 children nd 100 dults from ptients who were hospitlized for cute virl heptitis in two infectious disese clinics. Risk fctors Although the survey ws not designed to study the risk fctors for virl heptitis, questionnire ws distributed to ech of the study subjects. The informtion collected included their occuption, pst history of prenterl tretment, nd pst history of blood trnsfusions. Lbortory tests Lbortory tests were performed t the Ntionl Institute of Virology, Buchrest. Ser were screened for the following: heptitis B surfce ntigen (HBsAg); ntibody to HBsAg (nti-hbs); ntibody to heptitis B core ntigen (nti-hbc), nti-hbc IgM type; ntibody to HAV (nti-hav) nd nti-hav IgM type; nd ntibody to HCV (nti-hcv) using enzymelinked immunosorbent ssys (ELISA) (Abbott for the HAV nd HBV mrkers; Orthodignostic for the HCV mrkers). HBsAg-positive ser were lso tested for heptitis B envelope ntigen (HBeAg) nd ntibody (nti-hbe). Dt processing nd nlysis Dt were nlysed t Epicentre, Pris, using Epi- Info softwre. The 95% confidence intervl (CI) Centers for Disese Control, Atlnt, GA, USA. ws chosen s the mesure of the precision of the estimtes (prevlence ± 1.96 stndrd devitions). The reltive risk (RR) ssocited with ech of the fctors included in the questionnire ws clculted nd the sttisticl significnce ws ssessed using the 95% CI round the RR (Tylor series 95% confidence limits for the RR). Results Lbortory tests were performed on ll individuls selected for the study (n = 1355). The sex rtios differed widely mong the different subgroups of the smple (Tble 1). Heptitis mrkers The prevlences of HAV nd HBV mrkers were high in ll low-risk groups (Tble 2). There were 121 women of childbering ge (15-45 yers) in the group of helthy dults nd 11 of these women were positive for HBsAg (9.1 ± 5.1%). This is consistent with the rte of HBsAg positivity for the pregnnt women (Tble 2). Of HBsAg-positive women who were pregnnt or, of childbering ge (n = 27), five were positive for HBeAg. A pst history of cute heptitis ws reported by 21 (10.5%) of the helthy dults. None of the children in the low-risk smple hd lived in orphnges, but five (2.5%) hd received blood trnsfusion nd 135 (67.2%) t lest one prenterl tretment. A totl of 166 (81.4%) of the pregnnt women hd received t lest one prenterl tretment, while 17 (8.3%) hd hd blood trnsfusion. The prevlence of nti-hav mrkers incresed with ge (Fig. 1); lmost two-thirds of individuls ged <20 yers hd been infected with HAV. Of the 77 children under 5 yers of ge, 39 (50.7%) were positive for t lest one HBV mrker. The prev- Tble 1: Chrcteristics est, July 1990 of the study smple, Buchr- Age (yers) No. Rnge Medin Children 201 (1.0) 0-16b 6 Adults 200 (0.40) Pregnnt women Helth personnel 336 (0.14) Orphns 214 (1.20) months Children with clinicl heptitis 100 (1.40) Adults with clinicl heptitis 100 (0.80) Figures in prentheses re the rtio of mles to femles. b 30% of the smple were <3 yers of ge. 782 WHO Bulletin OMS. Vol

3 Virl heptitis in Buchrest Tble 2: Prevlence of virl heptitis mrkers in the low-risk smple, Buchrest, July 1990 Children Adults % prevlence of: No. HBsAg HBV nti-hav (5.5)b 39.8 (6.7) 51.7 (6.9) (4.3) 47.0 (6.8) 88.0 (4.5) Pregnnt women (3.6) 45.5 (6.8) -c At lest one HBV mrker. b Figures in prentheses re the 95% confidence intervls. c Not determined. lence of HBV ws higher mong 0-4-yer-olds thn mong 5-19-yer-olds (50.7% versus 34.8%; RR = 1.45, 95% CI: ). High-risk smple The prevlences of HAV, HBV, nd HCV mrkers were very high for this smple (Tble 3). All the orphns hd received prenterl tretments nd vccine injections, but there ws no trnsfusion record in the orphnges. The number of hospitl dmissions (referrls from the orphnges) rnged from 0 to 9 (medin, 1). The risk of being the crrier of n HBV mrker incresed with the number of hospitl dmission (X2 test for trend = 7.7; P = 0.005). Etiologicl dignosis of cute heptitis Among individuls hospitlized with cute heptitis, the virl etiology ws ssessed by nti-hav nd nti-hbc IgM type (Tble 4). A totl of 91% of the children (0-16 yers of ge) nd 70% of the dults hd n HAV on HBV eti- Fig. 1. Age distribution for heptitis A virus (HAV) nd heptitis B virus (HBV) mrkers in the low-risk smple (children, dults, nd pregnnt women, n = 605), Buchrest, July Age (yers) WHO Bulletin OMS. Vol Tble 3: Prevlence of heptitis A virus (HAV) nd heptitis B virus (HBV) mrkers in the high-risk groups, Buchrest, July 1990 % prevlence of: HBsAg HBV nti-hav Orphns 27.1 (5.9) 54.6 (6.6) 45.3 (6.6) Helth personnel 9.2 (3.1) 56 (85.2) -c At lest one HBV mrker. b Figures in prentheses re the 95% confidence intervls. c Not determined. ology; this suggests tht bout third of cses of cute heptitis mong dults in Buchrest hve non-a, non-b etiology. The proportions of HBV infection were similr for the dults nd children. Heptitis C Anti-HCV ws found in ll the groups tested, with prevlences tht differed mrkedly from one group to nother (Tble 5). Institutionlized children ppered, once gin, to be the most frequently ffected group. As with HBV mrkers, there were no differences in the nti-hcv prevlences of helth personnel nd helthy dults (3.9% versus 4.5%; RR = 0.85, 95% CI: ). Discussion Smple representtiveness The socioeconomic representtiveness of the lowrisk smple ws ensured by the number of institutions tht prticipted in the study nd by their loction in vrious res of the city. Also, Buchrest is reltively homogeneous in terms of the socioeconomic sttus of its popultion. The children t low risk were hospitlized nd hence my not hve been representtive of the generl popultion. Conditions ssocited with higher risk of HBV or HAV infections, such s socioeconomic or ethnic sttus, might be more prevlent mong hospitlized thn nonhospitlized children. To minimize potentil selection bises, we smpled Tble 4: Prevlence of mrkers of recent virl infection, Buchrest, July 1990 heptitis % prevlence of: No. nti-hav IgM nti-hbc IgM NA-NB Children (8.2)b 14.0 (6.8) 9.0 (5.6) Adults (9.4) 34.0 (9.2) 30.0 (8.9) NA-NB = no HAV or HBV mrker. bfigures in prentheses re the 95% confidence intervls. 783

4 C. Pquet et l. Tble 5: Prevlence of heptitis C virus (HCV) mrkers, Buchrest, July 1990 % prevlence of No. HCV mrkers Low-risk dults (4.5) Adults with clinicl heptitis (5.0) Children with clinicl heptitis (2.1) Helth personnel (2.0) Orphnges (4.9) Figures in prentheses re the 95% confidence intervls. children who hd been hospitlized for the first time in their life nd for noninfectious complint, from two hospitls. None of these children hd lived in orphnges. Among this group of children, 0-3-yerolds were overrepresented: 30% of the study smple, versus 17% of the sme ge group in the generl popultion of Buchrest, ccording to dt from the Ntionl Centre for Helth Sttistics. Since the prevlence of heptitis mrkers increses with ge, this bis, rther thn those ssocited with the selection of hospitlized children, might hve led to n underestimtion of the seriousness of the problem mong the children. The overrepresenttion of women in the helthy dult group (M/F rtio = 0.25) ws probbly due to recruitment bis. Since the prevlence of heptitis mrkers ws similr for mles nd femles, the sex rtio of the smple probbly did not ffect the estimte of the level of endemicity mong the helthy dults. The helth personnel enrolled in the study were volunteers. This might hve introduced selection bis, leding to n overestimte of the rel prevlence of virl heptitis mong them, since the professionls most concemed bout the problem re usully those who hve hd the gretest exposure. Level of endemicity The min objective of the survey ws to estblish, using sensitive lbortory methods, the level of endemicity of virl heptitis in Buchrest, with specil regrd to heptitis B. The results re consistent with vilble surveillnce dt (3). The prevlence of HBsAg mong the generl dult popultion is the most useful mrker of heptitis B endemicity.b Preb Besley, R. Immuniztion strtegies ginst heptitis B. Unpublished document WHO/EPI/GEN/88.5. vious studies in Romni hve reported similr prevlence, rnging from 5.7% (6) to 10.8% (2). The HBsAg crrier rtes for dults nd pregnnt women were, respectively, 11.0 ± 4.0% nd 7.8 ± 3.6%. The prevlence of HBsAg in pprently helthy dults vries from 0.1% in prts of Austrli, North Americ, nd northem Europe, to 15% in severl tropicl countries (9). WHO hs defined the following brod virl heptitis B endemicity pttems mong dults: low prevlence (<1% positive for HBsAg); moderte (2-7% prevlence of HBsAg); nd high (>8% positive for HBsAg) (2). Our results therefore indicte tht Romni belongs to the group of countries of high endemicity. The prevlence of HBV mrkers ws higher mong 0-4-yer-olds thn mong 5-19-yer-olds (Fig. 1). This uncommon distribution pttern suggests tht the risk of heptitis infection hs incresed in recent yers in Buchrest. The difference between the prevlence of HBV mrkers mong helth personnel (58.6 ± 5.3%) nd helthy dults (47.0 ± 6.8%) ws not sttisticlly significnt. The medin ge of the helth personnel smple ws 10 yers greter thn tht of the helthy dults nd this probbly led to n underestimte of the prevlence of HBV mong the helth personnel. Thus in Buchrest, the risk of HBV infection ppered to be s high mong the generl popultion s mong those exposed to it professionlly. In our study HCV testing ws performed using first-genertion ssy tht hs subsequently proved to be of low specificity. The results obtined therefore hve to be interpreted with cution, since they my contin n unknown proportion of flse-positives. Trnsmission ptterns In ddition to confirming the high level of heptitis B endemicity in Buchrest, the results of the survey highlighted vrious spects of the trnsmission of HBV in the city. The prevlence of HBsAg mong women of childbering ge suggested tht the mother-to-newborn mode might ply substntil role in trnsmission. However, the size of our smple did not permit us to ssess properly the presence of HBeAg, the min indictor of infectivity, mong this popultion. Further studies therefore need to be crried out to mesure the exct risk of this mode of trnsmission - one of the key fctors for estblishing n pproprite immuniztion strtegy. Orphnges The level of heptitis infection in the orphnges in Buchrest is of gret concern. The prevlence of HBV mrkers in this popultion of newborns nd 784 WHO Bulletin OMS. Vol

5 Virl heptitis in Buchrest infnts (under-3-yer-olds) is ssocited with poor prognosis. The risk of becoming chronic HBV crrier, nd thus of developing long-term complictions, such s cirrhosis of the liver or primry heptocellulr crcinom, is directly relted to n individul's ge t infection; the risk tht 1-4-yer-old child who is infected with HBV will become chronic crrier hs been estimted to be 20-30% (10, 11) nd 60-80% for under-l-yer-olds (11). An epidemic of cquired immunodeficiency syndrome (AIDS) in orphnges in Romni ws described t the beginning of 1990, with prevlences reching 50% in some of the country's institutions (12). For both humn immunodeficiency virus (HIV) nd HBV infections, the itrogenic route ws suspected to be the min mode of trnsmission. Although the informtion to mke proper epidemiologicl ssessment is not vilble, the lck of disposble needles nd medicl supplies, together with the policy of regulrly trnsfusing smll quntities of untested blood for the mngement of growth retrdtion nd mlnutrition, re probbly responsible for the extensive spred of blood-borne diseses in Romnin orphnges (12, 13). The high prevlence of HCV mrkers tht we found mong the study children further supports this hypothesis. Conclusions Our findings together with vilble surveillnce dt indicte tht prevention nd control of HBV infection re mjor helth priorities in Romni. Since Jnury 1990 vrious mesures hve been tken by the Ministry of Helth to reduce itrogenic trnsmission of HBV, including vccintion cmpigns in orphnges nd peditric fcilities. Moreover, severl blood bnks re crrying out HBsAg screening using sensitive tests. There is now enough epidemiologicl evidence to recommend heptitis B immuniztion, not only for identified risk groups, but lso for the generl popultion. However, further studies re needed to elborte n pproprite strtegy for integrting this procedure into the current childhood immuniztion progrmme. Acknowledgements Lbortory tests nd equipment were provided by Medecins sns Frontieres, Frnce. We thnk the following individuls for their ssistnce; Dr T. lonescu, Director, Romnin Centre for Helth Sttistics; Dr N. Beldescu, Director, Preventive Medicine, Romnin Ministry of Helth; Dr N. Nedelcu, Centre for Preventive Medicine, Buchrest, for supervising the ser collection; nd Dr A. Moren, Epicentre, Pris, for reviewing the mnuscript. Resume H6ptite virle Bucrest Entre vril et juillet 1990, une enquete sur l s6roprevlence de l'h6ptite virle ete effectuee Bucrest (Roumnie) sur un 6chntillon syst6mtique de 1315 personnes choisies dns l popultion generle et prmi des groupes risque. On recherch6 dns le s6rum de ces sujets les mrqueurs des virus de l'h6ptite A, B et C (HAV, HBV, HCV), u moyen d'epreuves immunoenzymtiques (ELISA). Dns tous les groupes etudi6s, l pr6vlence des mrqueurs du HAV et du HBV 6tit 6lev6e. Au totl, 47% des dultes de l popultion gen6- rle et 39,8% des enfnts de 0 16 ns 6tient porteurs d'u moins un mrqueur du HBV. Prmi les femmes enceintes, 7,8% 6tient positives pour l'ntigene de surfce de l'h6ptite B. Chez les enfnts de 0 3 ns vivnt en orphelint, l pr6- vlence d'u moins un mrqueur du HBV etit de 54,6%. L'enquete confirme l circultion du HCV en Roumnie. Ces r6sultts concordent vec les donn6es de l surveillnce ntionle et confirment que l'h6ptite virle est un probleme mjeur de snt6 publique en Roumnie. Les mesures pr6ventives devront comprendre une vccintion des nourrissons contre l'h6ptite B, selon une strt6gie vccinle convenblement ciblee d'pres les r6sultts d'6tudes 6pidemiologiques venir. References 1. Protection ginst virl heptitis. Morbidity nd mortlity weekly report, 39 (No. RR-2) (1990). 2. Sobeslvsky, 0. Prevlence of mrkers of HBV infection in vrious countries: WHO collbortive study. Bulletin of the World Helth Orgniztion, 58: (1980). 3. Buletin Informtiv, vol. 1, No. 2. Buchrest, Directi Medicinei Preventive, Februry-My 1991 (in Romnin). 4. Lnge, W. & Msihi, K.N. Epidemiology nd economic importnce of heptitis B in the Federl Republic of Germny. Journl of postgrdute medicine, 63(suppl. 2): (1987). 5. Bbes, V.T. & Berc, C. Heptitele virle cute. Timisor, Fcl Edit, 1988 (in Romnin). 6. Bbes, V.T. Prevlence of HBsAg in more or less recent foci of cute virl heptitis. Revue Roumine de medicine: virologie, 32: 247 (1981). 7. Ksz, L. et l. [Study of the etiology of virl heptitis in the zone Tirgu-Mures]. Vit medicl, 31: (1984) (in Romnin). 8. Sbu, M. et l. [Epidemiologicl dt on the circultion of heptitis viruses in the zone Tirgu-Mures]. Revue m6decine et de chirurgie de lsi, 90: WHO Bulletin OMS. Vol

6 C. Pquet et l (1986) (in Romnin). 9. McCollum, R.W. & Zuckermn, A.J. Virl heptitis: report on WHO informl consulttion. Journl of medicl virology, 8: 1-29 (1981). 10. Besley, L.P. et l. Incidence of heptitis B virus infections in preschool children in Tiwn. Journl of infectious diseses, 146: (1982). 11. Coursget, P. et l. Age- nd sex-relted study of heptitis B virus chronic crrier stte in infnts from n endemic re (Senegl). Journl of medicl virology, 22: 1-5 (1987). 12. Hersh, B. et l. Acquired immunodeficiency syndrome in Romni. Lncet, 338: (1991). 13. Rudin, C. et l. HIV-1, heptitis (A, B, nd C), nd mesles in Romnin children. Lncet, 336: (1991). 786 WHO Bulletin OMS. Vol

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