August i, 191 8] 



NATURE 



425 



disease .are (i) its frequently mild, indefinite, and 

 irregxilar clinical course, with the consequent diffi- 

 culty in diagnosis ; (2) our lack of knowledg-e as 

 to the nature of the infecting virus ; and (3) the 

 difficulty, if not impossibility, of infecting experi- 

 mental animals. 



When the two cardinal features of the disease 

 are present — i.e. the characteristic relapses of 

 fever, occurring at fairly regular intervals of four, 

 six, seven, or ten days, and severe pain in the 

 lower part of the shins — its recognition is fairly 

 easy, but in numerous cases only one or neither of 

 these symptoms is present, and diagnosis has to 

 depend on a general survey of the clinical symp- 

 toms. The causal micro-organism is un- 

 known ; though a spirochaete, a hsemogregarine, a 

 bacterium, or a Rickettsia body similar to that 

 described as the cause of typhus fever has each 

 its advocates. 



A few experiments on the transmission of trench 

 fever by the louse were made before 1918, but 

 the evidence published is scanty. Weldon and 

 Davis allowed two lice to bite each of them after 

 first starving the insects, and then feeding them on 

 a trench-fever patient. Weldon developed the 

 disease after eighteen days. The evidence for the 

 transmission by these lice is, however, not quite 

 convincing. Xankivell and Sundell failed to 

 transmit by feeding lice and doubted the hypothesis 

 of transmission by these insects. 



In October, 191 7, the American Red Cross 

 Society, in conjunction with representatives of the 

 British Expeditionary Force, formed a committee 

 to investigate trench fever. This body has carried 

 out much very valuable work, but its full report 

 has not yet been made. 



About the same time a War Office Committee, 

 under the chairmanship of Major-General Sir 

 David Bruce, was formed in England, in order to 

 advance the knowledge of trench fever with a view- 

 to its prevention, and the research in progress at 

 Hampstead was merged in that of the Committee, 

 of which Major Byam became a member. 



Up to the close of the year the work was con- 

 ' fined to the study of clinical evidence, the exami- 

 nation of the blood and urine of patients, together 

 with the feeding of lice on them during their 

 febrile periods, followed by the subsequent micro- 

 scopical examination of the insects with a view to 

 the discovery of the infecting organism. 



With the commencement of 1918, thanks to the 

 financial assistance of the Lister Institute and the 

 courageous and patriotic action of a number of 

 volunteers, it became possible to widen the scope 

 of the research, and very valuable results speedily 

 followed. A confirmation was obtained of McNee's 

 main results of direct inoculation from patient to 

 patient by blood, and the problem of transmission 

 by the louse was seriously attacked. The 

 Committee was fortunate in having at its 

 disposal ample stocks of lice, free from suspicion 

 of previous infection, which had been reared under 

 the direct supervision of Mr. Bacot, entomologist 

 to the Lister Institute. 



The first experiments in which the insect vector 

 NO. 2544, VOL. lOl] 



was concerned consisted in two of the volunteers 

 submitting themselves to the bites of several 

 hundred hce daily, the insects having been pre- 

 viously fed ,on patients during febrile periods both 

 before and during the month of experiment. The 

 lice, therefore, had many opportunities of becom- 

 ing infected, and the men received the bites of these 

 lice three times each day for thirty days. Neither 

 showed any of the symptoms of trench fever. 



Next, following the analogies of relapsing and 

 typhus fevers, two volunteers were inoculated 

 from lice which had fed repeatedly on trench-fever 

 patients. In both the inoculation was made by 

 scratching the skin and rubbing in, eleven 

 crushed lice in one case, and excreta voided 

 by the lice in the other. Both men developed 

 typical symptoms of the disease, with a relapse in 

 six to eight days. The inoculation of louse excreta 

 into scratches has been repeated a number of times, 

 and in every case an attack of the disease has 

 resulted. 



It was found that the incubation in man, when 

 infected by scarification, was remarkably constant, 

 i.e. six to eight days, and the ease and certainty 

 with which infection could be produced pointed to 

 the inoculation of the contents of crushed lice or 

 louse excreta as in all probability the common, if 

 not the invariable, method of transmission. 



The excreta obtained by shaking through the 

 gauze cover of the boxes in which the lice were 

 confined were used in the form of a dry powder, 

 which remained infective for at least sixteen days. 

 In parallel experiments with the excreta of normal 

 lice which had not been fed on trench-fever 

 patients no symptoms of the disease were 

 produced. 



That a very small amount of blood, such as 

 might be contained in ten lice, does not directly con- 

 vey the disease through an excoriation of the skin, 

 is indicated by the negative result obtained h|r rub- 

 bing 5 c.mm. of infective blood into scratches on 

 the skin of a volunteer. 



Moreover, the following series of experiments 

 points to the fact that the louse, after a meal of 

 infected blood, does not void infective excreta for 

 some days. Lice were fed on a trench-fever 

 patient on one day only, and then on healthy men. 

 Excreta collected on the first, third, fifth, and 

 eighth days after infection gave negative results, 

 while those collected on the twelfth and twenty- 

 third days proved virulent. The virus, therefore, 

 would apf)ear to undergo some preparation in the 

 insect before it becomes infective. Whether this 

 change in the louse is due to a simple multipli- 

 cation on the part of the hypothetical micro- 

 organism, or to a cycle in its development, is as 

 yet undetermined. Further, it was shown that the 

 ingestion of louse excreta did not produce trench 

 fever in two men who daily swallowed a dose for 

 seven and fourteen days respectively. 



Incidentally, the transmission experiments by 

 McNee and at Hampstead have proved that the 

 different clinical types of the disease are really due 

 to the same infective virus. The disease may per- 

 sist in man for a very long period. A case i<^ 



