Pan American Health Organization PAHO/ACMR 14/4 Original: English

Transcription

1 Pan American Health Organizatin PAHO/ACMR 14/4 Original: English FOURTEENTH MEETING OF THE ADVISORY COMMITTEE ON MEDICAL RESEARCH Washingtn, D.C July 1975 COLLABORATIVE STUDIES ON HEPATITIS B VIRUS e The issue f this dcument des nt cnstitute frmal publicatin. It shuld nt be reviewed, abstracted, r quted withut the cnsent f the Pan American Health Organizatin. The authrs alne are respnsible fr statements expressed in signed papers.

2 COLLABORATIVE STUDIES ON HEPATITIS B VIRUS L. Spence and M.C. Williams Department f Medical Micrbilgy, University f Trnt, Canada and Caribbean Epidemilgic Centre, Trinidad and Tbag.

3 -2-- These studies were undertaken in 1974 in Trnt and Trinidad. The cllabrating labratries were the Department f Medical Micrbilgy f the University f Trnt and the Caribbean Epidemilgical Centre, Pan American Health Organizatin (frmerly the Trinidad Reginal Virus Labratry). INTRODUCTION In many parts f the wrld viral hepatitis is cnsidered t be the rnst imprtant unslved prblem in infectius disease (I). It is well recgnized that persns frm temperate climates may acquire viral hepatitis when residing in the trpics. This was demnstrated in Wrld lwar II when hepatitis became a serius prblem in trps frm Eurpe, Australia and Nrth America wh were statined in the Middle East. Havens and Paul (2) nted that parts f Africa, the Mediterranean littral, the Middle East, the Orient, and varius cuntries f Central and Suth America have been fund t have endemic hepatitis areas which cnstitute a hazard t the nn-indigenus military r t the ever increasing numbers f susceptible immigrant civilians travelling r wrking in such places. This has led in sme instances t the administratin f gamma glbulin n a rutine basis t civilian and military persnnel frm temperate climates during residence in the trpics. e

4 -3- Studies n hepatitis in the trpics have been limited by the lack f suitable techniques and the need t investigate ther infectius diseases. With the successful cntrl f malaria, yellw fever, smallpx and ther infectins in the trpics the time has cme fr an assessment f the rle f viral hepatitis in mrbidity and mrtality in the trpics. The Caribbean is a unique area fr this type f study because it is easily accessible frm Nrth America, has many visitrs and residents frm temperate climates and its ppulatin is cmpsed f peple f many different ethnic grups. Furthermre, there are well established virus labratries in the regin. Within recent years techniques have becme available which make pssible studies f hepatitis B. The discvery by Blumberg et al. (3) in 1961 f a new antigen in the bld f an Australian abrigine and the subsequent demnstratin by Blumberg et a!. (4) f itž_ assciatin wi-h viral hepatitis has prvided a means fr detecting hepatitis B virus by what is believed t be its marker, Australia r- hepatitis B surface antigen (HBsAg). Sn after the antigen was discvered it was nted that it ccurred mre frequently in healthy persns in the trpics than in healthy persns in temperate climates (5). Prince et al. (6) fund the antigen t be 10 t 100 times mre prevalent in clinically well persns frm trpical ppulatins than in vlunteer bld dnrs in New Yrk City. Blumberg et al. (7) thught that this might be due t the existence f an autsmal recessive gene that cnfered an increased susceptibility t chrnic, asymptmatic infectin with Australia antigen. Prince et al. (6)

5 -4- cmmented that the knwn mechanisms f transmissin f serum hepatitis did nt appear t ffer satisfactry explanatins fr the high prevalence f the antigen althugh they might have played an accessry rle. He suggested that mechanical transmissin by arthrpds might play a rle. Blumberg et al. (7) nted that vast numbers f apparently nrmal peple, living primarily in the trpics and suth-east Asia, have Australia antigen in their peripheral bld. Tens f millins f persns in the trpics are asymptmatic carriers and very few f these wuld have received bld transfusin r injectins. They als thught that msquites r ther insects played a rle in transmissin. Studies have als been carried ut n patients with liver disease in the trpics. Bagshawe et al. (8) fund the antigen in 54% f cases f acute viral hepatitis in Nairbi anc Maynard et al. (9) fund the antigen in 60% f acute viral hepatitis cases in Uganda. Als, there is sre evidence that the antigen may play a rle in cirrhsis - the liver in the trpics since Maynard et al. (9) fund the antigen in 15 f 49 patients with cirrhsis and Bagshawe et al. (8) fund the antigen in eight f 39 cases f cirrhsis in Kenya. Vgel et al. (10) fund 18 f 45 patients with hepatcellular carcinma in Uganda psitive fr the antigen. These findings suggest a relatinship between viral hepatitis and hepatcellular carcinma in Uganda but further investigatins need t be undertaken as Smith and Blumberg (11) fund n significant differences with regard t the presence f the antigen in cntrls and patients with hepatcellular carcinma..e

6 -5- Cckburn (12) has reviewed the epidemilgy f viral hepatitis in trpical cuntries. He nted that in 1967 ntificatins f infectius diseases hepatitis came secnd nly t measles in Cuba and Uruguay and third in Puert Ric. He cncluded that viral hepatitis was a prly ntified but cmmn and widespread disease in the trpics. There was evidence f higher mrtality frm viral hepatitis in indigenus trpical ppulatins than in Eurpeans and Cckburn thught that malnutritin and a higher incidence f serum hepatitis might be respnsible fr the higher mrtal ity. It is clear frm the studies already undertaken that infectins with hepatitis viruses are f frequent ccurrence in the trpics. It is als apparent that much remains t be learned abut the mdes f transmissin f hepatitis viruses and the rle f these viruses in liver disease in the trpics. These are the reasns fr prpsing this study. Ntificatins f Hepatitis in the Caribbean Mrris and Standard (13) reprted ntificatins f infectius hepatitis in the Caribbean fr the tw year perid, These are shwn in Table i. It is prbably true that many cases are nt ntified and that sme f the cases ntified as infectius hepatitis (hepatitis A) are cases f serum hepatitis (hepatitis B). Nevertheless, these ntificatins indicate that viral hepatitis is recgnized as an infectius disease in many f the Caribbean Islands.

7 -6-- OBJECTIVES OF STUDY The bjectives f the study were as fllws: 1. T cnfirm the presence f HBsAg in hea[l-hy persns and patients in Trinidad and Tbag and pssibly ther islands; 2. T assess the rle f this virus in mrbidity and mrtality in Trinidad and Tbag; 3. T draw t the attentin f the Public Health authrities in the Caribbean the imprtance f hepatitis B in pst-transfusin hepatitis and liver disease and the methds available fr preventin; 4. T intrduce int the Caribbean sme f the technlgy that has becme available within recent years in Nrth America fr diagnsing viral hepatitis B infectin; 5. T ensure that lcal persnnel wuld be trained in the new methds available fr diagnsing viral hepatitis B; 6. T draw attentin t the hazard that viral hepatitis presents t health care persnnel. METHODS In February 1974 Miss Micheline Fauvel f the Trnt labratry visited Trinidad and set up the cunterimmunelectrphresis test fr hepatitis B antigen and antibdy (anti-hbs). Fllwing her departure the test was perfrmed rutinely at the Trinidad Labratry by Miss Barbara Hull. e

8 -7- The fllwing assignments were given t the labratries: Caribbean Epidemilgic Centre (CAREC) I. Test by cunterimmunelectrphresis (CIEOP) fr HIBsAg 1000 sera frm healthy Trinidadian residents; 2. Test by CIEOP fr hepatitis B surface antibdy (anti-he) the same 1000 sera frm Trinidadian residents; In selecting sera the fllwing is taken int cnsideratin: a) ethnic rigin, b) sci-ecnmic status, c) age, d) ccupatin, e) histry f transfusin r drug usage, f) past histry f jaundice, g) presence f venereal disease. 3. Tests fr HBsAg and anti-hb s will be carried ut n sera frm special grups: labratry technicians, retarded children and cases f Hansen's disease. Patients with liver disease will als be tested by CIEOP fr HB Ag and anti-hbs; 4. When carriers f the antigen are detected husehld cntdcts will be tested and blded msquites cllected in their hmes. Sera frm msquites will be shipped t Trnt n filter paper discs fr testing by radi immune assay fr HBsAg (RIA). Other epidemilgic studies t determine methd f transmissin within the husehld will be undertaken; 5. Carriers will be referred t their dctrs r a gastrenterlgist fr further investigatin.

9 -8- Medical Micrbilgy Dept., University f Trnt: _ 1. Standardizatin f tests and training f technicians at CAREC; 2. Cnfirmatin f psitive sera; 3. Additinal tests (electrn micrscpy and radi immune assay) n psitive sera; 4. Test sme CIEOP negative sera by radiimmune assay; 5. Study antigenic determinants f psitive sera; 6. Test blded msquites by radi immune assay. RESULTS The results f testing fr HB Ag at CAREC by CIEOP and at the University f Trnt by radi immune assay are shwn in Table II. These results are preliminary but seem t indicate a lw rate f HBsAg carriage by healthy Trinidadian residents. Nt a single psitive was fund amng 1011 residents tested by CIEOP. One labratry technician was fund t be carrying the antigen. Fifty-five cases f Hansen's disease were tested by CIEOP and RIA and ne was fund t be psitive by the mre sensitive test, RIA. Patients frm the venereal disease clinic and mentally retarded children were fund t be free frm antigen. in their bld. Twenty f the 100 patients with liver disease had HBsAg As was t be expected mre cases were detected by the RIA test. All f the sera fund psitive by CIEOP were cnfirmed psitive by RIA.

10 -9- The passive haemaggiutinatin (PHA) test was used in Trnt t test sera frm Trinidad and Tbag fr anti-hb s (antibdy t hepatitis B surface antigen). The results are shwn in Table IIl and IV. The distributin f antibdy titre is als shwn fr healthy residents. In the latter, antibdy was lw in infants (5%) and rse t 20% in lder peple. Antibdy was fund in 14.7% f patients with liver disease and 17% f cntacts f persns wh were carrying antigen. It was als fund in 17 (30.9%) f 55 cases f Hansen's disease and in 7 (28.0%) f 25 mentally retarded children. Our surveys detected n HB Ag carriers. Hwever, thrugh the curtesy f Dr. Val Massiah f the Prt f Spain General Hspital we btained the names f tw carriers wh had been detected during the screening f bld dnrs. Msquit cllectins were made at the hmes f these tw individuals. The msquites were identified and the bld frm each msquit was expressed n t small filter papers which were then frwarded t Trnt fr testing by RIA. The results f these tests are shwn in Table V. Of the msquites cllected 12 f 36 engrged female Culex fatigans were fund t be psitive. DISCUSSION These preliminary investigatins n hepatitis B in Trinidad and Tbag have demlistrated the presence f HB Ag in the bld f lcal residents. Hwever, the level f antigen carriage is much lwer than wuld have been expected frm the studies reprted by Blumberg and Prince. The pattern f antigen carriage in Trinidad and Tbag is

11 -I 0- clser t that f Canada and the United Kingdm than the pattern fund in the Middle East, the Mediterranean and suth-east Asia. The presence f antibdy indicates that transmissin f HBsAg is ccurring but it appears that infectin is mre lilkely t result in antibdy prductin than in the develpment f antigen carriage. The msquit studies cnfirm that msquites will shw detectable antigen after feeding n HB Ag carriers but n evidence f transmissin f HBsAg frm msquites t man has been btained. The methds f transmissin f HB Ag in Trinidad remains t be elucidated. The highest rate f HBsAg detectin was in cases f acute viral hepatitis. Many f these cases were diagnsed clinically as infectius hepatitis which suggested n past histry f inculatin by a parenteral rute. Our studies t date prvide n infrmatin n the rle f HBsAg in liver disease ther than acute viral hepatitis. N infrmatin is available n the effects f HBsAg n the liver f malnurished persns. SUMMARY Studies ver a perid f ne year n virus B hepatitis in Trinidad and Tbag have shwn hepatitis B virus t be respnsible fr cases f viral hepatitis n the island f Trinidad. N carriers f antigen (HBsAg) were fund amng 1011 healthy persns whse bid was tested fr antigen

12 -I I- by cunterimmunelectrphresis, indicating a lw rate f antigen carriage n the island. Other grups studied fr carriage f antigen were patients with Hansen's disease, mentally retarded persns, labratry technicians, and persns attending venereal diseases clinics. The mentally retarded children and the venereal disease clinic patients were fund t be free frm antigen. One f 55 Hansen's disease patients was fund t be antigen psitive and ne f 101 labratry technicians was psitive fr antigen. The passive haemagglutinatin test was used t study the presence f anti-hb s (antibdy t hepatitis B surface antigen) in the bld f lcal residents. Twelve (12.6%) f 95 healthy residents tested were fund t have antibdy, the antibdy rate rising frm 5% in infants t 20% in adults. Antibdy was als detected in jaundiced patients, cntacts f carriers, patients with venereal disease and Hansen's disease and menta l y retarded chi Idren. Engrged msquites cllected in the hmes f antigen carriers were fund psitive fr antigen but n evide.ice f msquit transmissin was btained. e

13 -12- TABLE I NOTIFICATION OF INFECTIOUS HEPATITIS IN ENGLISH SPEAKING CARIBBEAN, Territry Number Territry Number Antigua O Guyana 4 Bahamas 25 Jamaica 65 Baibads 10 St.Kitts, Nevis 14 0 Belize 136 St. Lucia O Dminica 10 St. Vincent 63 Grenada 45 Trinidad/Tbag 5 Mrris & Standard. W. Ind. Med. J. 23, 212, *

14 -1 3- z ci O) <' - L OO z 0 Zz Uf) b-5, 00 O - - OO - ic F- en z w F- LL LU (rl - 2: 0 z - O (LO <- C L 0W ) r- 0 i N (N z _J _ < 1-- c i - -u O1) Uf) C) 2: C: - O Ln O CO " O O U O O0D - O O n O O O O W u) CO LL vr U) 0 5: z L O U) 4 ( e) U- C <3 U +n - U ) U) _ C - 0 L L <' D C O) > X L O) O - O O L L CLa - E u O Uln ) >- - - J - < <u U) 4-- Oi t- WL +- L L L - O n ) ) U f- - c > t- I2 -J I > J-

15 -14-- O) O O N - O r_ O C- go Z 0_n L Uf) ní- J,; 0 O O N O N u- Cf) wz LL O Ci~ - 2: ~I O) O - - N Cf) 2: ' LL [Z3 >- I- > 0- - Ln Nc cd ii cd N ca mo - mz r 0 O_ LtL L - E L a> - E z 2: a) tn - a> U) O) 1-1 -O b n i 0 O O NcJ - N - N N. LL O Z O a cn O O L L C9 : a> u) Ln N (I ' li\ O m

16 -15- e TABLE IV DISTRIBUTION OF HEPATITIS B ANTIBODY IN PATIENTS AND CONTACTS IN TRINIDAD Categry N. Tested N. Ps. % Ps. Hansen's disease Venereal disease Livar disease Retarded children Fllw up sera frm antigen-ps. cases Cntacts f psitive cases e

17 -16- TABLE V RESULTS OF RIA TESTS FOR HBSAg ON MOSQUITOES COLLECTED IN THE HOMES OF HBsAg CARRIERS IN TRINIDAD Categry N. Tested N. Psitive Gravid female Empty female Culex fatigans 7 0 Cu(ex fatigans 6 0 A. aegyptli I O Engrged female Culex fatigans TtaIs io 12 1 e

18 -17- REFERENCES 1. Krugman, S., Ward, R. Clinical Virlgy, ed. Debre, R., Celers, J., Saunders, , Havens, W.P., Paul, J.R. Viral and Rickettsial Infectins f Man, ed. Hrsfall, F.L., Tamm, 1. Lipinctt, , Blumberg, B.S. Bull. N.Y.Acad. Med. 40, 377, Blumberg, B.S., Gertsley, B.J.S., Hungerfrd, D.A., et al. Ann. Intern. Med. 66, , Blumberg, B.S., Sutnick, A.l., Lndn, W.T., et al. New Engl.J.Med. 283, , Prince, A.M. Am. J. Trp. Med. 19, , Blumberg, B.S., Melartin, L., Guint, R.A., et al. AM. J. Human Gen. 18, , Bagshawe, A.F., Parker, A.M., Jindani, A. Brit. Med. J. 1, 88-89, Mayndard, E.P., Sadikali, -., Anthny, P.P., et al. Lancet ii, , Vgel, C.L., Anthny, P.P., Mdy, N. et al. Lancet, ii, , II. Zavatne, V. cited in Smith, J.B., Blumberg, B.S. Lancet, ii, 953, Cckburn, W.C. Am. J. Dis. Children, 123, , 1972.