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not be reproduced in later studies.10,11 Maternal-fetal HLA incompatibility was also investigated.Different workers claimed that the production ofHLA antibodies was significantly increased,12 un-changed,13,14 or decreasedls in cases of pre-eclamp-sia. Only the last finding would fit the observationsthat maternal HLA antibodies increase with parity,whereas the incidence of pre-eclampsia diminishes.

Evidence for excessive maternal-fetal HLA in-

compatibility was not found by the indirectapproach of typing pre-eclamptic women and theirhusbands. On the contrary, in one of the studies

significantly more sharing of the antigens wasreported than was predicted from population genefrequencies.16 No particular maternal HLA antigenwas associated with the disorder. However, in thelargest study, of 80 pre-eclamptic women, REDMANand co-workersl7 found an unpredicted but highlysignificant excess of apparent maternal HLA homo-zygosity. It was more pronounced at the B than atthe A locus, and correlated with the severity of thecondition. REDMAN et al. suggested that this couldindicate homozygosity for recessive maternal im-mune response genes linked to HLA, which couldpredispose to severe pre-eclampsia. This hypothesiswould not explain the report that pre-eclampsiawas diminished in an inbred population 7but wouldaccount for the very high incidence of eclampsia inone highly inbred family in Newfoundland. 18The hypothesis of REDMAN et al,17 has now

received support from work by COOPER and Lis-TON,19 suggesting that genetic control of severe pre-eclampsia may depend on mendelian inheritance ofa single recessive gene. Because pre-eclampsia ismanifest only in pregnancy, the genotype of eithermother or fetus may be the determining factor. Ifthere is recessive inheritance the two possibilitiescannot be distinguished by study of mother/daughter pairs. But the issue can be resolved bydetermining the incidence of pre-eclampsia in sis-ters of affected women (higher than expected inci-dence if the maternal genotype hypothesis is cor-

10 McFarlane A, Scott JS. Pre-eclampsia/eclampsia in twin pregnancies. J MedGenet 1976; 13: 208-11.

11.Juberg RR, Gaar DG, Humphries JR, Cenac P, Zambie MF. Sex ratio inthe progeny of mothers with toxaemia of pregnancy. J Reprod Med 1976;16: 299-302.

12. Carretti N, Chiaramonte P, Pasini C, Zanetti M, Fagiolo U. Association ofanti-HLA antibodies with toxemia in pregnancy. In: Centaro A, CarrettiN, Addison GM, eds. Immunology in obstetrics and gynaecology. Amster-dam: Excerpta Medica, 1974; 221-25.

13. Fingleton AM. Leucocytotoxic antibodies and pre-eclampsia of pregnancy.Transplantation 1971; 12: 319-21.

14 Nymand G. Complement-fixing and lymphocytotoxic antibodies in serum ofpregnant women at delivery. Vox Sang 1975; 28: 101-09.

15. Jenkins DM, Need J, Rajah SM. Deficiency of specific HLA antibodies insevere pregnancy pre-eclampsia/eclampsia. Clin Exp Immunol 1977; 27:485-86.

16 Jenkins DM, Need JA, Scott JS, Morris H, Pepper M. Human leukocyteantigens and mixed lymphocyte reaction in severe pre-eclampsia. Br MedJ 1978; i: 542-44.

17. Redman CWG, Bodmer JG, Bodmer WF, Beilin LJ, Bonnar J. HLAantigens in severe pre-eclampsia. Lancet 1978; ii: 397-99.

18 Brocklehurst JC, Ross R. Familial eclampsia. J Obstet Gynœcol Br Emp1960; 67: 971-74.

19. Cooper DW, Liston WA. Genetic control of severe pre-eclampsia J MedGenet 1979; 16: 409-16.

rect) or in the husband’s female relatives (higherthan expected incidence if the fetal hypothesis is

correct). COOPER and LISTON19 reanalysed the

family data collected and previously reported byCHESLEY.1,4 The incidence of toxaemia in the sis-ters, daughters, and sisters-in-law of eclampticwomen proved to fit closely with the notion ofmaternal homozygosity for a recessive gene. Butwhen they extended their analysis to two furthersets of data collected from Aberdeen, they found in-stead evidence for the fetal-genotype hypothesis;there was a significant deficit of toxaemic illness insisters of affected women. Thus they cannot cometo a final judgment on this matter. ’

Any hypothesis on the aetiology of pre-eclampsiahas to account for the first-pregnancy preponder-ance. If pre-eclampsia depended on a fetal gene theinfluence of parity would be extremely difficult toexplain. It is easier to accept the conclusion basedon CHESLEY’S data and suggest that the evidence infavour of the fetal-genotype hypothesis may bebiased by problems of under-ascertainment. Parouswomen who conceive for the first time by a newpartner seem to have an increased risk of pre-eclampsia20—i.e., they behave as virtual primigra-vidae. This leads to the concept that pre-eclampsiaresults from an absent or deficient maternal im-mune response to the fetus, which is necessary fornormal pregnancy, and more likely to be imper-fectly developed on first exposure to fetal

antigens.21 Thus the first-pregnancy preponderanceof pre-eclampsia, its familial occurrence, and theHLA data can be gathered together by one genetichypothesis: the putative gene and its function havenot been identified, but circumstantial evidence

suggests that it may be an immune-response gene.COOPER and LISTON conclude that more detailedexamination of family histories should help to dis-criminate between their fetal and maternal geno-type hypotheses. It would be equally important tosearch for other genetic markers, particularly thoserelated to the histocompatibility complex, whichmay be associated with pre-eclampsia.

PRAZIQUANTEL: A NEW HOPE FORSCHISTOSOMIASIS

THOSE who look to drugs for better control of schisto-somiasis have long been awaiting better agents. Withexisting drugs the individual with schistosomiasis canusually be cured or at least rid of most of his worms; buttreatment as a tool for mass control of the infection isa different matter altogether. Whereas an individualwith the infection may tolerate uncomfortable side-

effects, an entire population may not. Most of those in-

20. Feeney JG. Pre-eclampsia and changed paternity. Proceedings of first con-gress of the International Society for the Study of Hypertension in Preg-nancy 1980 (in press).

21. Scott JS, Jenkins DM, Need JA. Immunology of pre-eclampsia. Lancet 1978;i: 704-05.

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fected have no symptoms from the disease, and representa danger more to others than to themselves, so they forma group particularly intolerant of the toxic effects ofdrugs. In the past, the pharmaceutical industry hassometimes been reluctant to cooperate with interna-tional bodies interested in disease-control programmes,but the case of the drug praziquantel is a worthy excep-tion : a series of papers prepared jointly by a WHO staffmember and a member of a pharmaceutical companylnow shows that this drug is effective against all threespecies of schistosome parasite affecting man. The valueof the papers produced is greatly enhanced by adoptionof a uniform method of assessment of drug effectivenessand drug toxicity, and in particular, the use of quantita-tive methods to arrive at an accurate mathematical

expression of schistosomicidal effect.In Zambia, one year after praziquantel treatment for

Schistosoma hxmatobium infection, only 2 out of 80 pa-tients were still excreting viable eggs.2 This is a remark-able result by any standards, and even more so in viewof the infrequency and mildness of toxic effects. A singleoral dose of 50 mg/kg proved as effective as three spacedoral doses of 20 mg/kg, so making the drug of enormouspotential value as a tool in control of the infection. Asimilarly well-conducted trial of praziquantel againsthuman infection with S. mansonz’3 showed that the drugwas equally effective against this species. Here again, thecure rate was extremely high-all but 1 of 26 patientsfollowed up at one year-and again there seemed to beno difference between three doses of 20 mg/kg or one doseof 50 mg/kg. There was no biochemical or other evi-dence of serious toxicity, although nausea, abdominalpain, headache, giddiness, and drowsiness were com-moner than with placebo. The administration of a singlelarge dose seemed to be associated with a higher inci-dence of side-effects than with the repeated smallerdoses, but in no case were the side-effects severe enoughto cause alarm. Before praziquantel, S. japonicum infec-tions were the most difficult to treat with drugs. How-ever, a trial carried out in the Philippines4 has reportedexcellent results with three doses of 20 mg/kg, and onlyslightly less good results with a single oral dose of 50mg/kg. Although more than half of the patients on bothregimens had side-effects, these were mild, consistingmainly of abdominal discomfort, fever, and giddiness.The cure rate was high but perhaps more impressive wasthe mean reduction in egg output of 90% or more in pa-tients receiving either regimen. Very similar results wereobtained in S. japonicum infection in Japans and thelack of serious side-effects was again noted.

So, what part will this drug play in controlling seriousschistosomal disease throughout the world? One of the

1. Davis A, Wegner DHG. Multicentre trials of praziquantel in human schisto-somiasis: design and techniques. Bull World Health Org 1979; 57:767-71.

2. Davis A, Biles JE, Ulrich A-M. Initial experiences with praziquantel in thetreatment of human infections due to Schistosoma haematobium. BullWorld Health Org 1979; 57: 773-79.

3. Katz N, Rocha RS, Chaves A. Preliminary trials with praziquantel in humaninfections due to Schistosoma mansoni. Bull World Health Org 1979; 57:781-85.

4. Santos AT, Blas BL, Nosenas JS, Portillo GP, Ortega OM, Hayashi M,Boehme K. Preliminary clinical trials with praziquantel in Schistosomajaponicum infections in the Philippines. Bull World Health Org 1979; 57:793-99

5. Ishizaki T, Kamo E, Boehme K. Double-blind studies of tolerance to prazi-quantel in Japanese patients with Schistosoma japonicum infections. BullWorld Health Org 1979; 57: 787-91.

unanswered questions concerns cost. If, as is rumoured,a course of treatment for an adult comes to 2, it willbe too expensive for those parts of the world where thedisease is endemic. It would be tragic if, on these

grounds, praziquantel were to be priced out of the mar-ket.

A TRADE UNION LOOKS AT CANCER

A WORK by S. S. Epstein has set out vividly thesorrier chapters in the history of occupational cancer.Prevarication, cover-up, and worse have filled the some-times long intervals between the earliest hint that some-thing might be very wrong with a substance-for in-stance, asbestos, the naphthylamines, and vinylchloride-and effective action. Trades unions are enti-tled to be angry, and the Association of Scientific, Tech-nical, and Managerial Staffs should not be criticised forallowing some of this emotion to spill over into a policydocument issued last week.2 ASTMS wants employers toknow (or find out) and disclose the carcinogenicitystatus of all materials handled in their plants. If thereare no carcinogens, then employers could be asked toagree never to deal with any substance known to be acancer agent; substitutes would be needed for car-

cinogens that are used; and, in the rare instances whereremoval would be economically impossible, containmentshould be the best that money can buy. Cancer epidemi-ology is a matter for experts, but even experts disagreeabout saccharin, low-dose radiation, and reserpine, tochoose just three topical examples. ASTMS is contemp-tuous of holding things up while "bodies are counted"and is unconcerned about the large gap between mouseand man;3 it wants a clean sweep.ASTMS accepts an extrapolation published in the

United States in September, 1978,4 suggesting that infuture 20-40% of cancer will be occupationally linked.This figure, which is prodigiously higher than previousones, has been criticised.s Many epidemiologists thinkthat it is simply nonsense: the current trends and extra-polations do not seem to fit. As ASTMS says, the pathto recognition as a prescribable industrial disease is ahard one, and even for non-disputed associations thenumbers of workers receiving benefit are small andalmost certainly are underestimates of the totalsaffected. But ASTMS then makes another big jump: ofa table extracted from an OPCS report6 it says "everyline ... could be a candidate for prescription as an in-dustrial disease". OPCS is more cautious in its lists of

large numbers of occupations where the risk of death

1. The Politics of Cancer. By SAMUEL S. EPSTEIN, M.D., School of PublicHealth, University of Illinois. Garden City, N.Y.. Anchor Press/Double-day. 1979. Pp. 628. $6.95.

2. The Prevention of Occupational Cancer: an ASTMS policy documentObtainable from ASTMS, 10-26a Jamestown Road, London NW1 DT£3.

3. Editorial. Seventeen principles about cancer, or something. Lancet 1976571-73.

4. Bridport K, and others. Estimates of the fraction of cancer in the UnitedStates related to occupational factors. NCI/NIEHS/NIOSH, 1978

5. Editorial. What proportion of cancers are related to occupation ? Lancet

1978; ii: 1238.