BACTERIOPHAGE TREATMENT OF TYPHOID FEVER CARRIER WITH BONE ABSCESS FIorida MedicaI Center FRED
H. ALBEE, NEW YORK
I
M.D.,
W. H. HOSKINS, M.D. AND CRESTON COLLINS, M.S. VENICE, FLORIDA
N an active bone and joint and orthopedic practice of over thirty years, 9 post-typhoid bone abscesses of the spine have been seen. This is the first found in the tibia or any Iong bone, and aIso the first instance where the bIoodstream, urine, biIe and stoo1 have proved to be infected with the same organism. Whether, in this instance, the bIoodstream infection came via the bone Iesion, it is difficuIt to say. However, Alessandrini and Doria demonstrate that typhoid fever is associated with a bIoodstream invoIvement and because of this, it is aIways advisabIe to administer a bacteriophage not onIy by mouth but aIso intravenousiy. Previous to 1904, there had been repeated outbreaks of typhoid fever in Strassburg, Germany, which Koch traced to a certain bakeshop. Upon investigation that he found the bakery was in every respect cIean and the water suppIy pure, but the woman who ran the shop admitted that years before she had been iI of typhoid fever. Tests reveaIed that, aIthough she seemed in good health and was able to go about her business, her excreta showed the presence of typhoid baciIIi. By this case the carrier principIe was proved for the first time by Koch. In 1904, Dr. George A. Soper, of the Department of HeaIth of New York City, was puzzIed by repeated outbreaks of typhoid fever in homes where the food and water suppIy were above suspicion. The most outstanding of the outbreaks were in Mamaroneck in 1900, and in a home in Dark Harbor, Maine, where seven members were affected. In 1904, typhoid broke out in individua1 homes in Sands Point and Oyster Bay, Long IsIand and Tuxedo Park. Dr. Soper, in investigating these out-
VENICE, FLORIDA
breaks, observed a pecuIiar fact that in a11 of these pIaces at the time of the typhoid visitation, a Mary MaIIon, competent and cIean Iooking, had been empIoyed as cook. In 1907, Dr. S. Josephine Baker, of the ChiId Hygiene Bureau of the Heaith Department of New York City, had to forcibIy remove Mary MaIIon to the WiIIard Parker Hospital, from a home where she was very popular with her empIoyer as we11 as her feIIow servants. Tests showed that there were many typhoid baciIIi about her, and that any food she might prepare wouId be IikeIy to be contaminated. The gaI1 bladder was found to be badIy infected, but a11attempts at persuasion faiIed to induce the dangerous, stubborn cook to have her gaI1 bIadder removed. She was sent to North Brother IsIand, where she was committed, virtuaIIy a prisoner. In 1909, she appeared before the State Supreme Court demanding reIease from her forced confinement, which she cIaimed was that of a Ieper. The court decided against Mary and she was sent back to the IsIand. FinaIIy, after three years of constant fighting, on February 19, 1910, Mary was freed with the promise on her part that she wouId never handle food as a servant. For a time she apparentIy compIied, but in 1914, four years after her release, typhoid broke out in a sanitarium in NewfoundIand, New Jersey, where it was found that Mary had worked as a cook, but she escaped before she couId be caught. A severe outbreak then occurred at the SIoane Maternity HospitaI in New York where of 285 patients, 25 were infected, 2 dying of typica typhoid fever. Mary, under the name of Mrs. Brown, was found serving as cook. 317
318 American
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On March 27, 1915, the New York HeaIth Department sent Mary back to North Brother IsIand, which proved to be a Iengthy stay, and she became a Iaboratory helper. She Iater had a stroke of apopIexy. She was the first authentic typhoid carrier in this country, and according to WaIker, has an ofhcia1 record of having caused 51 cases of typhoid fever with 3 deaths but how many others might be attributed to her is unknown. It is not known how many carriers there are at Iarge but WaIker in The New Yorker, January 1935, states that there were at that time, 344 in New York City alone. The remarkabIe persistence of the baciIIi to perpetuate themseIves in such cases is iIIustrated by Mary. She was first observed in 1904, ten years later caused an outbreak and, as far as is known, may be a carrier today, twenty-one years after being delinitely proved to be one. Mr. E. F., aged twenty-eight years, was admitted to the FIorida MedicaI Center, on December 29, 1934, complaining of pain over the middle third of the Ieft tibia of two weeks’ duration and some swehing and IocaI eIevation of temperature. Ten days prior to his admission, the pain had increased, was constant and seemed worse whiIe waIking. For three or four days before hospitalization, the pain had been so intense, that he was unabIe to rest at night. Examination reveaIed a dehnite point of tenderness and pain over the middIe third of the Ieft tibia, which on x-ray examination was diagnosed as a smaI1 subperiostea1 abscess. He had been admitted to the Harper HospitaI on JuIy 24, 1934, with a history of headache, malaise, diarrhea, fever, pains in back, arms and in the epigastrum, of tweIve days’ duration and an admission temperature of I 03’, puIse 86, respiration 20. PhysicaI examination reveaIed the tip of the spIeen to be paIpabIe and a miId abdomina1 distention. For twenty-one days the patient ran a persistent temperature of 1o3~--1o4~ and a puIse rate between 80 and IOO. The temperature then dropped to IOO’, onIy to have a reIapse, reaching 104’ two days Iater, and remained high for eIeven days more, then unduIating with a spiking temperature ranging from 100’ to 103” and puIse from go to 126
Bone
Abscess
Aucusr.
1936
daiIy, for a period of twenty-eight days, at which time the temperature was gg”. He remained practicaIIy afebriIe from then, unti1 he was discharged on October 17, twentythree days Iater, after aImost three months. Among the patient’s compIications should be noted a rigidity of the neck and somewhat Iethargic menta1 state appearing on JuIy 27, and persisting for about ten days. There was no Kernig or other neuroIogica1 Iindings. On August 7 the patient manifested twitchings of the hands and muscIes of the face, and the folIowing day, an active delirium, extreme restIessness and vomiting. This neuroIogica1 picture was absent on August 13. At this time, he presented a diffuse rash, with rose spots, over his abdomen. On August 14, bright red bIood was noted in the stools, which continued for approximateIy one week and then traces for three days. During the time of this intestina1 hemorrhage, the patient Iooked acuteIy III with a drawn facies, restIessness and some abdomina1 distention and tenderness across the Iower abdomen. SurprisingIy the pulse remained of fairIy good quaIity, though the patient had deveIoped a profound anemia with a red blood count of 1,770,ooo ceh and hemogIobin of 44 per cent. The white bIood ceI1 count at this time was 2200, and showed a Ieukopenia ranging from 3000 to go00 during this fuI1 period of his first hospitaIization. On August 3 I, he deveIoped a tenderness over the spIeen, which became quite distressing for a few days, the spIeen being paIpabIy enIarged with a questionabIe friction rub over it. A diagnosis of perispIenitis was made. On September 27, he had a IocaIized tenderness and pain over the eighth rib anteriorly, which was beIieved to be a periostitis with possibIe low grade osteomyehtis. There was no associated pain beneath the Costa1 margin or discomfort in breathing. Other incidenta compIications were the deveIopment of an impetigo over the patient’s nose and face, and the presence of a smaI1 acute thrombotic hemorrhoid. The Iatter was excised under IocaI anesthesia. PhysicaI condition was considered very good on discharge from the hospital, with no evidence of any existing or impending compIications. As to the Iaboratory work at the Harper HospitaI, the patient had a secondary anemia
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al1 through his iIIness, the highest recorded count being 3,620,ooo red bIood celIs and 60 per cent hemogIobin, which was taken shortIy after admission, and was exactIy duplicated on discharge, aIthough in the interim, his count averaged 2,000,000 even reaching as low as that previousIy recorded at the time he was showing gross bIood in his stools. The Iowest white bIood ceII count was 2200 with 92 per cent poIymorphonucIear ceIIs and 48 per cent lymphocytes. UrinaIyses were essentiaIIy negative throughout, except for the appearance of 8 to IO Ieukocytes per h.p.f. from September 7 to IO incIusive. Patient had a positive WidaI through a11 diIutions of BaciIIus typhosus, as we11 as positive stoo1 and gaII-bIadder cuhures. There is no record of a positive urine or bIood cuItures. On two occasions a Gram positive baciIIus and StaphyIo6occus aIbus were found in the bIood cultures, though the laboratory considered these as contaminations. The patient’s seroIogy, Wasserman and Kahn, were negative. On December 30, 1934, the patient was operated at the FIorida Medical Center, the subperiostea1 bone abscess being saucerized, drained, scraped thoroughIy and packed with gauze saturated with a compound consisting of parafine go per cent and yeIIow vaseIine IO per cent at I 20“~. A cuIture proved to be typhoid. In view of his previous history of typhoid fever, further investigations were begun immediately. On January I, 1933, a cuIture from the leg wound showed a motiIe baciIIus which was determined cuIturaIIy to be BaciIIus typhosus, ebertheIIa typhi. On January 3, a cuIture from the bIadder urine showed a streptococcus and a motiIe organism, which Iast was determined cuIturaIIy to be BaciIIus typhosus and an agglutination, or WidaI, test made of these cuItures with a known immune serum was positive, as was an aggIutination test made of the cuItures with the patient’s own serum. AIso, on the same date, a WidaI test using the patient’s serum and stock cuItures of BaciIIus typhosus and paratyphoid baciIIus A and B were positive for a11 organisms. On January 7, the examination of a venous bIood culture taken January 3 showed a motiIe baciIIus which was aIso determined cuIturaIIy to be BaciIIus typhosus and the biIe cuIture showed a staphyIococcus and a motiIe baciIIus which were determined cuIturaIIy to be Staphylococcus aureus and BaciIIus typhosus.
Bone
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On January 8, intravenous and IocaI treatments with a Iaboratory bred specific typhoid bacteriophage* were started, using it in asparagin media. The compIete detaiIs of the treatment and time is outIined in the foIIowing: Intravenous
Date
Local Applications to Leg
Bacteriophage
Jndiluted, Cubic Centimeters
1--10
Mution,
Cubic Centimeters
Reaction
I_ I935 Jan. 8. 9:3o A.M..
*:jo P.M..
Jan. 9.. Jan. 10.. Jan. II. Jan. 12.. Jan. 14.. Jan. 15._._. Jan. 16.. Jan. I,. Jan. 18.. Jan. 19. Jan.zo..... Jan. 11.. Jan.~.....
2 5
Amount Indiluted, Cubic Centimeters ___~
N0lle NOlie
-I
Slight Very mild NolIe NolIe None None NOIF? Slight NOlIe N0n.Z N0oe Non‘? N0oe
2 2 z 2 5
I
5
It wiI1 be noted from the chart that on January 22 the last of the bacteriophage was given. On January 23, a compIete check of the bile, urine, stool and blood was made and a11 proved to be negative. The patient was discharged from the hospita1 with instructions to return in three weeks for another check. This he did on February 14, 1935, at which time a11 four specimens proved to be negative for the typhoid bacillus. He was asked to return again on March 23, and nearIy one year Iater, nameIy, December 28, 1935, for additional checks and at these times, a11 specimens again proved to be negative. Viz: BIood cuItures made in meat infusion broth, negative for BaciIIus typhosus after 5 days incubation. Urine cuItures made in meat infusion broth, negative for BaciIIus typhosus after 5 days incubation. Urine cuItures made on nutrient agar sIant, negative for BaciIIus typhosus after 5 days incubation. * MCNEAL, WARD J., M.D. “Specific Treatment of Septic Infections, ParticuIarIy with Aid of Bacteriophages.” American Journal of Medical Sciences, V&me 187, May, 1934.
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AIbee et aI.-Typhoid
The Iaboratory work on these examinations of bile, urine, bIood and stool foIIowing the Iast administration of the phage was identicaIIy the same as that which was done on January 1, 3, and 7, 1935.
In reporting this case, it is reaIized that one case does not make a cIinic, yet, at the same time, it is interesting to note that here is a known typhoid carrier with typhoid periostitis and bone abscess who has been bacterioIogicaIIy and cuIturaIIy cIeared entireIy by the use of bacteriophage, appIied intravenousIy and IocaIIy to the Ieg. TYPHOID
FEVER
AND
PARATYPHOIDS*
The therapy by bacteriophage of typhoid and paratyphoid fevers has been the object of many studies and reports since Beckerich and Hauduroy pubIished their first observations. Some have obtained marked success whiIe others have faiIed. As for typhoid fever the therapy is made more diffrcuh by the fact that it entaiIs specia1 Iaboratory tests to find the desired poIyvaIent bacteriophage, obtained by mixing bacteriophages of a Iarge number of variety of races. Much has been accompIished in Italy aIong these Iines. A Iaboratory in Rome prepares a poIyvaIent bacteriophage by isoIating a variety of races of phage from specimens of stooIs from patients in the IocaIity * TransIated from: The Bacteriophage and Its Therapeutic AppIications by F. d’HereIIe. In: La Pratique MedicaIe IIIustree, G. Doin & Co., Paris, P. 23.
Bone
Abscess
AUGUST, 1936
of an epidemic. This bacteriophage is then sent to the various localities where there is an epidemic of typhoid fever with _instructions that it be given both intravenousIy and oraIIy. This method, according to the Iast pubIications of AIessandrini,* has given exceIIent results, and the number of faiIures is decreasing. If the therapy does not meet with success, the Iaboratory at Rome sends a bacterioIogist who isoIates from specimens of stooIs of convalescent patients a new race of bacteriophage, which is added to the stock bacteriophage. Typhoid fever is mostIy a septicemia; therefore, the administration of bacteriophage is indicated not onIy 2 to 5 C.C. every six hours per OS but aIso intravenousIy, in the same way as in staphyIococcic septicemia, i.e., in doses of IO to 20 C.C. diIuted to 500 C.C. in isotonic
saline soIution, and injected sIowIy within a period of at Ieast thirty minutes. Further investigation into the use of intravenous bacteriophage in treating typhoid carriers wiI1 be of great interest. SUMMARY
A case is reported of a typhoid fever carrier with typhoid periostitis and bone abscess having positive cuItures from the abscess, the bIadder urine, the bIood and the biIe, which was compIeteIy cIeared by bacteriophage administered IocaIIy and intravenousIy. *ALESSANDRINI and DORIA. Med. Klin., 1924 and II. Policlinico, 31: Iog, 1924.
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