515JAUNDICE AFTER YELLOW FEVER INOCULATION

THE LANCETT ONDON SATURDAY, OOTOBER 31, 1942

JAUNDICE AFTER YELLOW FEVERINOCULATION

THE Secretary of State for War told the House lastweek that all the British troops proceeding to endemicareas have been vaccinated against yellow fever sincebefore the war. During the war three cases of thedisease have been diagnosed in British troops but thevaccine itself has produced no cases of jaundice orother ill effects. This question was no doubt raisedbecause of the recent cases of jaundice followingyellow fever vaccination in United States soldiers, ofwhich a full official account was published a fewweeks ago.1

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Occasional instances of jaundice have been recordedafter the inoculation of vaccines and sera in the pastbut little significance was attached to them until 1938,when MACNALTY 2 and PROPERT 3 observed a numberof cases of jaundice with a considerable death-rate inchildren inoculated with a batch of convalescentmeasles serum. This batch was a pool of the sera ofmany donors from different parts of the country,none of whom gave any history of jaundice. Atabout the same time jaundice after the inoculation ofyellow fever vaccine was reported by FINDLAY andMACCALLUM 4 in England. It was shown that thiswas not the result of the action of the yellow fevervirus, and it was suggested that it might be caused byan infectious agent present in the human serum usedfor suspending the virus, and that this agent wascarried in the tissue cultures used for growing thevirus.5 A similar occurrence was recorded in Brazil

by SOPER and SMITH.6 In England a fresh start wasmade in November, 1937, with a strain of yellow fevervaccine virus from the laboratories of the InternationalHealth Division of the Rockefeller Foundation in NewYork and the human serum used was heated to56-60° C. for at least 30 minutes before inoculation. Nocases of jaundice have been attributed to the vaccinein many thousands of inoculations since that time.Fox and others have recently reported a similaroccurrence in 1939-41 in Brazil. Among approxi-mately 107,000 people who were inoculated with theincriminated batches of vaccine in 1940-41 there were1072 cases of icterus. Several batches of vaccinewere incriminated with varying percentages of icterusin the groups inoculated with them but the most

interesting fact was that the incidence of jaundicecovered a wide range of 0-19% in different groups indifferent areas inoculated with the same lot of vaccine.This suggested the probability of some causative factorin addition to the inoculation. Another interestingfinding was the preponderance of cases among adults.The latest addition to this extraordinary series ofevents is the report 8 of 28,585 cases of jaundice among1. J. Amer. med. Ass. 1942, 120, 51.2. MacNalty, A. S. Rep. med. Offr Minist. Hlth, Lond. for 1937.3. Propert, S. A. Brit. med. J. 1938, ii, 677.4. Findlay, G. M. and MacCallum, F. O. Trans. R. Soc. trop. Med.

Hyg. 1937, 31, 297.5. Findlay, G. M., MacCallum, F. O. and Murgatroyd, F. Trans. R.

Soc. trop. Med. Hyg. 1939, 32, 575.6. Soper, F. L. and Smith, H. N. Amer. J. trop. Med. 1938, 18, 111.7. Fox, J. P., Manso, C., Penna, H. A. and Para M. Amer. J. Hyg.

1942, 36, 68.8. J. Amer. med. Ass. 1942, 119 ,1110.

USA army personnel inoculated with yellow fevervaccine between Jan. 1 and July 4, 1942. The evid-ence points to the same sequence of events and clinicalfindings as in the previous instances. The incubation

period ranges from 6 weeks to as long as 6 months,with the majority of cases 10-15 weeks after inocula-tion. The cases greatly resemble those seen in infec-tive hepatitis or catarrhal jaundice, though the incuba-tion period in the latter disease is generally acceptedas about 20-35 days. One point of note is the pres-ence of urticaria in about 20% of cases, a conditionhardly ever seen in ordinary infective hepatitis ; thatdisease, too, is usually a disease of children and adoles-cents, who seemed more or less immune to the post-vaccination condition in Brazil. One of the mostnotable differences has been the absence of contactcases in places where there were cases of jaundice inthe midst of many times their number of unvaccinatedor non-icteric postinoculation men. The cases whichfollowed the use of measles convalescent serum fit intothe same picture as the postvaccination cases exceptfor the two possible contact cases and the much

greater severity of the disease. But here again theseverity has varied widely in the different postvaccina-tion incidents, and if the serum is to be incriminatedone must realise that the measles children receivedseveral hundred times the dose given in yellow fevervaccine.The last two " outbreaks " tend to confirm the

earlier view that the normal human serum used in

production was responsible, and in Brazil, wherefertile eggs are sufficiently plentiful to make it pos-sible, the serum has been dispensed with and no caseshave occurred in 164,000 people vaccinated with thenew vaccine. The vaccine produced in New Yorkhas also been modified, presumably along the samelines. All the evidence clearly indicates that thelesion is not the work of the yellow fever virus.Pathological material has not revealed any new

specific lesion, the main feature being various degreesof subacute and acute necrosis beginning in the centralzone of the liver lobule. The condition has not yetbeen reproduced in animals.

MASKED HYPERTHYROIDISMFRANK hyperthyroidism is easy to diagnose, but it

was realised as early as 1883 that cases do not alwaysconform to type. In that year MARIE pointed outthat cases of Graves’s disease did not necessarily havegoitre or exophthalmos, and CHARCOT, a little later,described formes frustes in which struma, exophthal-mos and even tachycardia were lacking. These casesof atypical hyperthyroidism have periodicallyattracted attention, and cardiologists have for sometime emphasised the importance of considering occulthyperthyroidism as a cause of cardiac failure withauricular fibrillation. It is not only as a circulatorydisorder that hyperthyroidism may be disguised, forcases presenting as gastro-intestinal disease have beendescribed, while SHORR,1 and McEACHERN and Ross 2have recently drawn attention to a group suggestingmyasthenia gravis or progressive muscular atrophy.Many cases of masked hyperthyroidism continue topass unrecognised, and BREIDENBACH and APPEL-BAUM 3 of New York report 12 further examples.

1. Personel communication to Breidenbach and Appelbaum.2. McEachern, D. and Ross, W. D. Brain, 1942, 65, 181.3. Breidenbach, L, and Appelbaum, E. Ann. Surg. 1942, 115, 184.