Presented at the Amimmual Meeting, October 1 amud 2, 1955.
l)r. Ilodes is Director, 1)epartmumcmmt of I’ediatrics, Mt. Simmai I lospital amid Clinical Professor of lk’diatrics, Colunmhia University, Nc’ York.
l)r. Steignian is Chairman, Department of Pediatrics, Umuiversity of Louisville, Kentucky.
l)r. Gribetz is Assistant Attending Pediatrician, Mt. Sinai hospital and Instructor in Pediatrics, Co-IuI)uul)ia University, New York.
ADDRESS: (H.L.H.) Fifth Avenue and 100th Street, New York 29, New York.
947
RECENT
DEVELOPMENTS
IN INFECTIOUS
DISEASES
Summary of a Seminar
By Horace 1. Hodes, M.D., Alex J. Steigman, M.D., and Donald Gribetz, M.D.
T
m:N niajor tOI)ics amid several nuinor oneswere discussed during this semimiar.
Time following is a summary of the major
Poimits of the d!isclmssion and! includes some
of the pertinemut questions raised by thie
l)irtidiPa1it5.
POLIOMYELITIS VACCINE
iwo types of vaccine are potentially
aVailah)le to inumumuize a person against a
virus d!iSease. A “killed” \‘inuis vaccine is
OI1( wimichi ind!ulces inimunity d!espite the
fact that it is nuad!e of virus which has been
ren(!ered nouuinfectious h)y I)hiysical or
chuenuical nueans (ultraviolet light,
fornualde-hyd(’, l)lm(’11l, etc.). A “live” virus vaccine contains virus muiutants which I)rodluce only
a IilOd!ifi(’(.l infection amid! yet imiduce
mu-nitmnity against the original virus !iseasc.
The Iuuodifiedi infection may be
accom-P1u(’(l l)y no clinically recognizable
d!i5-ease (yellow fever) or by a recognizable
mild! illuiess ( vaccinia). The fornuor type of
vaccine has the advantage of producing
inumumuity withoumt )rodumcing infection. Its
(!isadvanta (S incltmde difficulties with
“killing” amid! problems concerning the
safe-guardis against muoninfectiouisness. The “live” vaccine has the advantage of producing a
higher diegree of, amid longer lasting
im-niumuity than the “killed” vaccine. Disac!-vamutages are concerned with l)ossil)le viru-lu’iice of the virus muiutants, with production of (lisease in the injected imidividual, and sprca(l of the infection to others. The pres-ently available Salk vaccine for immuniza-tion is of the “killed!” virus vaccine variety,
the virus having been made noninfectious by treatmemut with formaldlehuyd!e.
The need for active immunization of the
I)OPtmlatiomi against pohionuyelitis is empha-sized by the facts that virtually no children ‘3 to 5 years of age have antibody against
all 3 types of pohiomyehitis virus and less than 40 per cent of this age group have
antibody against even 1 type. In fact, only 50 per cent of persomus over 18 years of age have antibody against all 3 typos of virus
( Fig. 1). Furthermore, although there is
some evidence that cross immunity may ex-ist anuong the types, antibody against one
type of virus does not iuusure protection against the others.
Tue initial trials of the Salk vaccine in 1954 indicated that injoctiomu of persons
with no pro-existing antihod!ies produced a mean titer of amitil)odios of 1 : 16 iii 2 weeks.
Following a second injection given 2 weeks
after the first, the mean titer rose to 1 : 128.
No appreciable rise followed a third injec-timi given 4 weeks after the initial inocula-tion (Fig. 2). A small percentage of persons
lacking antibodies failed to develop any rise in titer after immunization. As far as
the booster dose was concerned!, no further aI)preciable rise in titer occurred unless it
was given at least 7 months after the
see-omid! injection. Althoughi thuo most effective intervals for the injections are still prob-lematical, based upon these data, the
pros-ent recommendations are to give 3 injec-tions; the first 2, 4 to 6 weeks apart,
fol-lowed by a third “booster” to be given 7
re-AGE GROUPS
3-5 6-8 9-Il 2-14
PER CENT
15-17
ANTIBODY FOR:
NO TYPES
ONE TYPE
00 90 80 7 60
50 40 30 20
0
0
I
25GROUP
Antibody for one or more types of poliomyelitis virus in (lifferent age groups. Fu. I. Reprinted from PEomATnucs, 12:47:3, 1()5:3#{149}
sumits of the 1954 field! trials are tabulated in
Figure 3.
It is evidlelit froni these data that a!-tluoumgh there was a statistically significant (!iminution in the total number of cases of
pohiomyelitis whuich occurred iii the
vac-cimiated H)t1) in cd)mmtrast to those vho re-ceived a placebo, the most significant
pro-tection was afford!ed against paralytic polio-mylitis, particularly against the bulbar and bulbo-spinal forms of the disease. it is also evident thuat the numuuber of nuajor aiid
GEOMETRIC
MEAN
TITERS
AFTER
EACH
OF THREE
DOSES
OF
REFERENCE
VACCINE
N4II ML., I.M., IN 20 SUBJECTS WITH NO PRE-ANflBODv
10 ANY TYPE
TYPE I TYPE U TYPE Ill
5I
I
948 HODES - RECENT DEVELOPMENTS IN INFECTIOUS DISEASES
i
_
,
_
,;/;/;.70 42
NO OF SUBJECTS IN EACH
TOTAL 308
Two TYPES
THREE TYPES
6-
o
?4WEEKS
Fic. 2. Reprinted from Salk, J. E. : Vaccination Against Paralytic Poliomyelitis : Performance and
Vaccine
Total No.
\tinor reactions
\Iajor reactions
Totul polio (l5CS
Iota! paralytic cases
iota! bull)ar and bulbospinal cases
Total nonparalytic cases
Laboratory positive cases
Total of all nanufacturers
Fa;. 3. Condensedl fron#{236}: Evaluation of 1954 Field Trial of Polionmyclitis \Taccine:
Simmnmmiary Report. Ann Arbor, Michigan, April 12, 1955.
Batches % with Live Virus
809 97 2:34
267
126
im(;. 4. Modified from : Public health Service Technical Reprt on Salk Polioniyelitis Vaccine. June, 1955, p. 48.
Copsrison of reported and expected numbers of pOliOIfly1iti1
cases in children receiving poliomyelitia vacci#{248}e ifl NFIP
eunice from April 15 to ty 7, 1955
AMERICAN ACADEMY OF PEDIATRICS
Manufacturer A
Manufacturer B
NIanufacturer D
\Lanufadurcr E
209,211 0.4% 0.004% 82 (41/100,000) 33 (16/100,000) 5 (3/100,000) 24 (12/100,000) 18 (9/100,000)
Placebo
209,806 0.4% 0.007%
162 (81/100,000)
115 (57/100,000) 41 (21/100,000) 27 (13/100,000) 86 (43/100,000)
11% 21% 19%
5% 2%
Vaccine
manufacturer
Approximate number of
vaccinees (NFII’ clinics only)
Poliomyelitie Cases - with onaet
from April 20 - My 21
-Reported Expected
number number
Total 14,844,000 79 36
Cutter Lilly
Parke D&via
Pitman Moore Wyeth
309,000
2,5l1,000
834,000
,000
776,000
35
29
2
2
11
5
21
3
2
2
!./ Reported cases aged 6-8 years with onset between April 20 and t.y 21.
Includes both paralytic and nonpa1ytic cases since expected numbers for
comparison are based on crude rates which include all cases reported as poliomnyelitia in previous years.
J/ Expected cases if the estimated, age-adjusted, median attack rate for
the previous 5 years had pertained in the vaccinees of 1955.
These rates are specific for geographic areas where the various polio-myelitis vaccines were used.
Inactivation of Poliomyelitis Virus
Theoreticml Curve (after Salk)
1.0 i mo6
m.o mo3 I
.
.i
C
I
m.o mo#{176}
1.0 i
1.0 i
1 1 iO6
! 1 i 1o
1
i.
mio0ii.
1110_iii
1 zA aeries of curves calculated on the assumption
that differe#{252}tportions of the virus mass inactivate at differing rates. The curve
de-scribing the summation of the three curves
fol-lows curve A thtougli dotted line to curve C.
(A small component of a very rapidly
inactivat-ing virus would not be apparent in the system
as described)
0 5.0 6.0
Days of iftectivalios
9.0
As conventionally drawn the ordinate is taken as
the dilution of the viral suspension at which 5
of 10 tissue culture units will demonstrate in-fection when each is inoculated with 1.0 ml. of viral suspension. This figure shows these rela-tion.ehips expressed in tissue culture infective
mnita.
Da of iit*CIIVSIIOO
Fic. 6. Reprinted from: Public Health Service Technical Report on Salk Poliomyehitis Vaccine. June, 1955, pp. 36 and 39.
950 HODES - RECENT DEVELOPMENTS IN INFECTIOUS DISEASES
mimuor reactions was approximately equal in the 2 groups. So far as can be
deter-mimued!, vacciiuation itself d!id not cause po-hiomyelitis in the 1954 field trials.
Pertaining to the 1955 trials, the first
questiomi coiucerns the safety of the vaccine which was used in the spring of 1955 ( Fig.
4).
These data demonstrate thuat 1 out of 5
batches of mamiufacturer A’s vaccine
con-tamed live virus as tested by the procedures set up in April, 1955, by the Public Health Service. It is evident, however, that live virus was present in some of the batches
made by all manufacturers. Further
statis-tics reveal that vaccination of children
dur-ing the spring of 1955 was followed by a
higher imucidence of paralytic pohiomyelitis
in those vaccinated with the products of
one and perhaps that of a second manufac-tuner than was expected ( Fig. 5). It cannot
how l)e doubted! that some cases of polio-nuyehitis were caused! by vaccimuation amid it
is probable that some secondary cases arose
from these. It beconues apparent thuat one
of the reasomus for these “accid!emuts” is that the postulated straighit-limie curve of mac-tivation of the virums by fonluuald!ehvdle treat-nuemut was only theoretical and that the
actual curve is probably muot straight ( Fig.
6). This is probably due to differences in
the rate of inactivation by fornualdehyde of
1)articumlar particles iii the same solution. Therefore, it is now evid!emut that one
can-not depend upon the duration of time of
imuactivatiomu bumt rather must rely on safety tests.
Accordimugly, the following safety tests
are now being used:
1. One thousand ml. froni each 1)atch of
single strain virus vaccimue are tested for
presence of live virus by nueamis of tissue culture.
2. The 3 ty)es of virus vaccimie batches are then Pooled! auid! 1500 mu!. of this triva-lemut pool arc also tested! in tisstmc culture.
a Available from Mr. William Cohen, 3045 San Anselimw, Lomug Beach, California.
3. Random saniples of vaccine from the final containers (vials) of each lot are then
tested! in tissue culture amid! by intracerebral and imutraspinal injection of monkeys ron-dered I)articul1rly susceptible to
poliomyo-hitis virus by treatnuent with large closes of cortisone and whole-body irnad!iation.
It is I)resemitly concluded that if the
above tests are negative, omu a statistical i)asis “final vaccine would be expected to
contain 5 or more live virus particulates per liter less thamu 1 in 100,000 times.”
Amongst the comments made on therapy
of poliomyehitis was the fact that furme-thuide is no longer recommended fcr the
treatment of the complication of bladder
paralysis because of its serious side effects.
Plastic plugs are now available for the
purpose of keeping a tracheotomy stoma
patent for long periods of time.#{176} These are
advantageous because they cause less pain
and local reactiomu. It was also reported that
atteflul)ts are being made on an
experi-mental basis at the Mount Sinai Hospital
Respirator Center to lessen the
hypercal-cemia and hypercalcuria, secondary to
pro-longed! immobilization in paralytic pohiomy-ehitis, by the administration of anabolic
steroids so cli as testosterone.
Discussion
c_
)ucstion: Is protection as good if a 7-month recall imujection is given after an initial single injection rather than after 2 original injections?Answer: Probably secomid injection in 2
weeks did not add! too much to antibody
titer. Therefore, 7-month recall injection
may i)e as good! if only 1 original injection
had! beemi given. Incidentally, at this point,
ho one is certain whether 7, 10 or 14 months
is the best time interval for the recall in-jection.
c_
)ucstion: \\That were the chief reasons for the Academy of Pediatrics recommendation not to imse the vaccine durimug the summer?Answer: It was the umianimous opinion of
the commumittee asked to give advice on this question that the Cutter incident revealed that the safety tests which were first set ump l)y the Public Health Service were
in-adlequate to guaramutee that the prod!uct was safe. It was felt by all of the committee that the possible benefits of vaccination under
these circumstances were outweighed 1w the risk involved. Later, on June 22 and!
June 23, in Washington, D.C., as the
repre-sentatives of the American Academy of
Pediatrics, Dr. Hodes attemided Congress-man Priest’s committee meeting regarding
the pohiomvehitis vaccine. It became ap-parent at this meeting that the testing of the vaccine was of paramount importance
in establishing its safety. It also became clear that the tests for safety which had
been instituted following the Cutter
mci-d!elit were far superior to those previously
re(1tmired. It also developed at the Priest
committee meeting that everyone believed! that the Mahoney strain of Type 1 virus
was a dangerous strain to use and! that it
should be removed from thie vaccine. How-ever, the replacement of the Mahoney strain
by some other Type 1 poliomyehitis virus
strain would have meant that vaccinatiomi
on a large scale would be postponed for a
year. In view of these developments, along
with a majority of the committee, Dr. Hodes felt that it was better to continue the
im-munization and to take the greatly
no-duced risk, rather than to lose the benefit of vaccination for 1955. This view was, of
course, an opinion based! on what was
believed to be the better course, but as is
well known, 2 eminent virologists, namely, Dr. John Enders and Dr. Albert B. Sabin,
wore of the opposite opinion. On the other hand, Dr. Thomas Rivers, Dr. Framik
Hors-fall, Dr. Cohn McLeod and Dr. Thomas Framucis, were in favor of carrying out the
vaccination program (luiring the sumnuer of
1955.
Q
nestion: \Vhat should one d!O abotmt the 7-month recall injection if )oliomuiyehiti5 is still prevalent in the area or is yet to come, as in Florida?Unvaccinated
Taccinated1 ill 1954
\Taccjnated in 1955
to those chuildren who originally received injections 7 months before. I would also start vaccination in children who had!
re-ceived no original injections. This is a
reasonable risk to take since the safety
standards are now far superior and since there is no good evidence as yet to ind!i-cate a provocative effect from the vaccine.
Q
nestion: Are any preliminary results avail-able from the 1955 vaccination program?Answer:
NEW YORK STATE CASES REPoRTED FROM
5/21 to 10/21/55
Total No. Paralytic Rate per Gases 100,000
282,000 59 21
98,000 4 4
:351 ,00()
NEw YORK CITY CASES REPORTEO
6/i to 11/10/55
Vaccinate(l ill 19.55
(6 to 7 vrs. old) Unvaccinated
(6 to 7 ‘rs. (11(1)
lii Iml)state New York, it is evid!ent that
amo)ngst child!ren vaccinated! in 1954 and!
1955 ( the latter having been given only 1
injection), the paralytic poliomyehitis rate
was 4 per 100,000 in contrast to an unvac-cinated group in wluich the attack rate was 21 per 100,000. Figures made public
ro-cently for New York City indicate that
chil-d!ren vaccinated during 1955 have thus far
had a significantly lower paralytic
polio-myehitis rate than unvaccinated children. In New York Cits’ in May, 1955, 166,000 children in grad!os 1 and 2 were given 1 dose of Salk vaccine while 87,000 children
in these grades were not vaccinated. Be-tween Jumue 1 and November 10, 1955, 9
paralytic cases of poliomyehitis were
dis-covered among the 166,000 vaccinated chuildren amid 19 amongst the 87,000
unvac-cinated. The paralytic pohiomyelitis rates were 5 per 100,000 amongst the vaccinated
against 22 per 100,000.
Although definite figures from
Massachu-setts are as yet unavailable, it seems that the picture in that state also was much
952 HODES - RECENT DEVELOPMENTS IN iNFECTIOUS DiSEASES
better in the immuutmnized! cluild!remi. This is
even more significant because this particu-lar epidemic was of great severity, a severe
Typo 1 strain being imuvolved. Fragmentary
figures from other parts of the country
in-dicate an appreciable redluctiolu in paralytic pohiomuuyehitis in vaccimuated! children.
Q
uestion: Please give same d!ata concern-ing the major reactions to the vaccine.Answer: a. During the 1954 field trial these consisted of fobnilo reactions, local reac-tions and! allergic manifestations. There also
was 1 case of convulsions aiii 1 case of
nophritis. It shuould be pointed1 out, how-ever, that exactly the same iuumuuber of
re-actions occurred in the vaccinated as in
the placebo group.
14 4 b. The amoumut of penicillin present in
the vaccimue apparently has canse(! little
F)M trouble. Iii fact, after formald!ehvde
die-miaturahization of the vaccine, ‘er’ little
* - penicillin reniains. Patch tests with the
166,000 9 ., vaccine have been negative, aitluomighi
ad-87,00(1 19 22 mittedlly the significance of this fact is not
certain.
c. The question of the kidmmev tissue iii the vaccine is as fohlows: It has been shown
thuat the kidneys of animals injected1 with kid!ney tissue for the prod!uction of
nephiro-sis serum do not suffer themselves.
See-ondly, Mayer tested 100 children vacci-miated with the vaccine for antibod!ies against
monkey kidney. Omuhy 1 child showed! a
f)OSitive reaction. Thuird!hy, dhlilV Addis
counts have beemi d!oIie on vaccinatec! chil-d!ren and no significant findings have suIted. At present there are 0.2 .g. of virus protein per ml. and! 150 ig. of kidney
pro-tom
per ml. in the vaccimie. Metbo(1s areavailable to reverse these quantities aiii it
is hoped that they will be put into misc
shortly.
dl. There huas been no proditictioll of in-compatible Rh and Hr antibod!v in vacci nated people.
Q
nestion: What are the facts concermuimig the provocative effect of vaccination?Answer: Bodian, who has studied thus prob-lem most thoroughly, voted! that the
1955, imudicating that he thought that this
risk was not a very great one. It is apparent
that certain thuings can be provocative if
given during a natural viromia. This may
be true for pemuicilhmn and for pertussis vac-cine. It does riot, however, seem to be true for thie poliomnyehitis vaccine itself so far as is now known.
Q
tiestion: Should patients who have had clinical poliomyelitis or nonparalytic polio-myelitis previously be immunized?AtLswer: It is diefinitely known that second
cases from d!ifferent virus types may occur; therefore, they should be immunized.
Seine 1)rlctical 1)r01)leflls concerning the
t)(lCCifle a(!nhinistration: a. The pH of the
vaccimie is between 7.4 and 7.6; therefore,
it has a 1)ilik color clue to the phenol red in(!icator which it contains.
h. Intrad!ermal adiministration: 0.1 ml.
intrad!ernually is equivalent to 1 ml.
intra-muscularly. Neverthueless, intramuscular in-jections are still advised!.
C. Buttock versus arnu as a site: There
apparently is no c!ifference in provocative effect if different sites are used.
d!. Thue problem of Merthiolate in the
vaccine huas apparently been solved by the
utilization of Versene#{174} which removes the \Ierthiolate”.
e. Vials presemutly produced bear a
5-nuonthu dating period.
Question: Is there any point in adhering to
the age group priorities as originally set up? Answer: It would appear that people
be-tween the ages of 30 and 50 years are the least susceptible. After leaving this group
to the last, the dhfferences are not too groat, and I would not feel that it is important
to adhere to specific age priorities. This
would be negated, however, if a county
muuedica! society has made specific recom-mendations.
HERPES SIMPLEX INFECTIONS
Herpes lesions in the mouth can be dlif-ferentiated from oral spirochetal infections by the fact that herpes involvement causes
hypertrophy of the gums between the teeth,
whereas the spirochetal organisms cause
“eating away” of the gums between the
teeth. It is difficult for herpes lesions to be-come secondarily infected. Although the
lesions may look ugly, necrotic and even
gangrenous, this is due to the primary virus
infection. Recurrences of herpes usually
oc-cur in the same local area, and with the
same general distribution, as the primary infection. The virus can invade the central
nervous system and cause either aseptic
meningitis or deep nuclear lesions. It is
postulated that the virus is probably latent
in the body and that some form of stress,
e.g., infection, allergy, emotional crisis, etc.,
upsets a normal balance and permits the
virus to cause clinical disease.
In relation to treatment, Dr. Steigman
has had experience with cortisone used
locally. He stated that it appears to be of
value in reducing local inflammatory
re-action in recurrent cases. It should never
he used systemically because of the
possi-bihity that it may allow the virus to become generalized and cause central nervous
sys-tom involvement.
Discussion
Q
uestion: Is recurrent smallpox vaccination of value in preventing recurrent herpes?Answer: There is no good evidence to in-dicate that it is efficacious. In fact, it has
been shown that vaccinia and herpes
viruses can be grown in the same cell. Good
results which have been reported may be
due to the psychotherapy resultant from repeated visits to a physician.
Q
uestion: Are antihistaminics or other local anesthetics of use in therapy?Answer: The former may be of some local aid. Pontocaine#{174} or its derivatives are not
advised because of possible sensitization to these compounds.
Q
nestion: Are the lesiomis frequently found on the palates of newborns on the third tosixth day related to herpes?
Answer: This problem has been studied very carefully by Florman. Although these
954 HODES - RECENT DEVELOPMENTS IN INFECTIOUS DISEASES imijurv. They differ from “Epstein’s pearls”
since they occur on the anterior tonsillar
pillars vhuereas the “pearls” are more
fre-quent on the palate. Although the lesions
seem to come in epidemics in nurseries, at this point no etiology has been found. There
may be some relationship to estrogemu trans-ported from the mother since biopsy studies
of thue lesions demonstrate cells which are
similar to vaginal cells.
A.P.C.
(ADENOIDAL-PHARYNGEAL-CONJUNCTIVAL) VIRUSES
The history of the discovery and
classi-fication of this group of viruses was
dis-cussed. Firstly, an epidemic of
conjunctivi-tis was described imu Australia in 1943. In
1951, Cockburn reported an epidemic in
Colorado in whichu the patients had pharyn-gitis, conjumuctivitis, fever and cervical
adenitis. This outbreak was eventually
shown to be due to A.P.C. viruses. In 1952, Huebner, Ward and others recovered
A.P.C. viruses from tissue cultures of ton-sils and adenoids removed during surgery. Other outbreaks were described by Parrot
and Huebner in 1953, by Bell and associates
in 1954 in Virginia, and by Hilleman and
Weiner in \Iissouri.
Thus far, 6 types of viruses have beemu iso-lated. Only types 3 and 4 have been impli-cated in the causation of clinical disease. Type 3 causes a clinical picture consisting of conjunctivitis, pharyngitis, with
occa-sional vesicles and exudate, fever and
oc-casionally a rash. The conjumuctivitis can be either unilateral or bilateral; it d!oes not
involve the cornea amid does not produce a
i)tmrtmlemut discharge. Type 4 A.P.C. virus
1)rOduces a syncironue characterized by
hoarseness, sore throat, bronchitis, and
oc-casionally an atypical pneumonia,
unac-companied by a rise in cold agglutinimis or
streptococcus MG antibodies. Although
Types 1 amid 2 have thus far not beemu
re-sponsible for climuical disease they have
pro-duced neutralizing antibodies in a large
percemutage of children under 2 years of
age. This suggests that perhaps some mild
respiratory disease in this age group has beemu caused by these viruses.
The highest age imucid!ence of infection with these viruses is 5 to 9 ears. Disease
d!ue to these agemuts is uncomnuomi over the age of 40 years. If infected tvithi one type of A.P. C. virus, cornplememut-fixing antibod!ies are developed against all the other types;
neutralizing antibodies are developed
against only the imifectimug type. People with
other re5)iratory d!iseases have muot
c!uced cOm)lenuemut-fiximug amutibodi es to
A.P.C. viruses. Antibiotics have thus far Provemu to be of no value imu thus dliseas’.
Discussion
Q
uestion: Do recurrences occur with these viruses?Answer: No; probably good! immunity is
conferred by amu imuitial attack.
Q nestion: Are secoiidary in fections with bacteria comnuon in these infections?
Answer: There is a strikimug lack of this l)tmt muuany of the patiemuts were given antibiotics. Thins far, there have beemu no serid)us corn-phications, amidl no deaths.
Q
uestion: Has a vaccine been p1(’p(11(’(l vet for this group of viruses?Answer: One has just been reported. Its
place imu immunization cannot yet be evaltm-ated.
Question: \Vhiat is the relatiomushuip of this group of viruses to Coxsackie virus?
Answer: These are definitely different agemuts.
c_
)nestion: \Vhat is the supposed imicid!ence of these diseases?Answer: Probably these are very comnuomi
dhseases. Large percemitage of adults show
antibodies against these viruses; we
con-dude occurrence of imifection during
“growing up” is common.
Q
tiestion: Amuy chiaracteristics to the blood coumit?Answer: There are no characteristic cells in the blood snuear.
Q
tiestion: Any seasomual incidemice?relationship to swimming pools. However,
the virus has never been isolated from
water of a pool. Chlorine probably kills the
virus. Certainly direct person to person transmission of the agent is of importance.
MENINGITIS
It was repeatedly emphasized that thue
ra1)idity with whuich thue diagnosis is
estab-lishec! amid! the promptmuess with whichu
jroper therapy is instituted are definitely
correlated with the enc!-rosult imi meningi-tis. If after careful search of mamuy smears of centrifuged sediment no organisms are
fotmnd!, treatment must be directed towards both the worst typo as well as the most
comnion type of meningitis. This means
that therapy must be adequate for
pneu-mococcus and H. influenzae meningitis. Parenthetically, it may be stated that while awaitimug results of search for organisms,
sulfadiazine may be administered since it
would be indicated in most types of
men-ingitis.
The treatmemit currently recommended for H. influenzae meningitis is as follows:
1. Chuloramphenicol. 50 mg./kg., diluted in normal saline solution are given in 80
minutes intravenously or by intramuscular injection stat. In 4 to 6 hours, 100 mg./kg./
clay are started in divided doses as mainte-namuce therapy. This is either givemi parenter-ally or orally. Do not use chloramphenicol
palmitate because of somewhat irregular
absorption withi thus preparation.
2. Sulfadiazimie. 40 mg./kg. are given stat in a 5 per cent solution in 15 to 20 minutes,
intraveiuoimsly by drip. This is followed by
100 nug./kg./day parenterally or 200 mg./
kg./day orally in divided doses.
3. Penicillin. Since many strains of H.
imufluenzae are sensitive to penicilhimi in time test tube, 600,000 to 1,200,000 units per day
in 2 doses are given.
Rabbit antiserum may be of value in
smuuahl infants and imu severe cases; it should l)e given only intramuscularly and not in-travemiously or intrathecally. Sulfomiamid
levels by micromethods should be done
frequently midway between 2 doses;
at-tempts should be directed toward main-taimuing a sulfonamid level of 12 to 15
mg./100 ml. Fluid intake, either parenter-all’ or orally, must be maintained.
The above regimen should be maintained
for at least 7 days. Lumbar puncture may
1)0 repeated in 48 hours as a guide to the
patient’s response if it is deemed necessary. Omu time seventhi day, the lumbar iunchmre
should be repeated and! if no organisms are present, pleocytosis has diminished anc!
spinal fluid sugar is normal, therapy may
be stopped. An altermiate method is to ohm-mate the lumbar puncture on the seventh
day and maintain the chloramphenicol
therapy for 10 days.
If symptoms such as vomiting, irritability,
amuorexia, persistence of fever, slow
im-provement or convulsions occur during thue
course of therapy, the presence of a
sub-dural collection of fluid may be suspected. Subdural taps are indicated only in the presence of the above symptoms and are
not advised as a routine. It is felt that sub-dural collections which produce no symp-toms are probably not responsible for
un-toward sequelae. It was also pointed out that the temperature may remain elevated for 4 to 5 days in a patient with meningitis
who is responding satisfactorily and in such a patient subdural taps may not be imudicated. An elevated cell count may per-sist in the spinal fluid for several weeks. This does not indicate that thie child is not recovering in a satisfactory manner.
The treatment currently in use for piieti-mococcal meningitis is as follows:
A combination of sulfadiazine an! peni-cilhin is used. Sulfadiazine should be given
in a quantity sufficient to give blood con-centrations of 10 to 15 mg./100 ml. During the first 24 hours of treatmemut, sodium sul-fadiazine should be given intravenously or subcutaneously. Give 50 mg./kg. at
12-hour intervals for 2 doses. After the first
day of treatment, sulfadiazine may be given
by mouth. Use a dosage of 200 mg/kg.!
956 1IOl)ES - RECENT l)EVELOPNIEN1’S IN I N FECTR)VS I)ISEASES
crystalline pemiicillin should be given intra-venously daily for the first 3 days of ther-apy. After this, 1,000,000 units of procaine penicillin should be given intramuscularly twice d!aily. All therapy may be discon-tinned after 7 days of treatment provided that : clinical course is satisfactory; spinal
fink! obtained 24 or 48 hours after begin-nimig of therapy is sterile; spinal fluk!
ob-tamed on seventh day of treatment
sup-ports clinical impression of improvement
as regards sugar concentration, cell con-tent, and bacterial examination by smear
amid culture. Subdural taps should be
per-formed when clinical findings indicate that a subdural effusion may be present.
The treatment for meningococcic
nuen-imugitis is as follows:
A comnbimuation of sulfadiazine amid! peiui-cilhin generally is used. Give sodium
stml-fac!iazimue intravenously ( as soon as
possi-ble after admission), 40 mg./kg. Then give
stmlfadiazine by mouth if child is able to
swallow and is not vomiting. Use oral close
of 200 to 250 mg./kg./day for infants and
small childremu, and 100 mg./kg./day for
older children. If oral route is not possible, give sodium sulfadiazine subcutaneously 1()0 nug./kg. every 12 hours for infants and
small children, and 50 mg./kg. for older
children and adults. A concentration in the
blood of 8 to 10 mg./100 ml. should be
iuiaintained for 5 days.
Penicillimu is recommende! for severe
cases imu ac!c!itiomi to sulfadiazine. Sonue use 1)0th drugs in all cases. Procaine penicihhimi
iii dosage of 6(X),00() to 1,000,0()0 units
twice daily is used generally.
Iii connection with meningococcic men-imigitis, it was pointed out that circulatory failure amid toxemia (
Waterhouse-Frider-ichsen symudrome) may occur. This may
re-stilt during the course of burns and other
overwhelming bacterial infections and ad-remial pathology need not necessarily be
OflO of hemorrhage; it may consist of
necro-sis of cells only. The eosinophih count may 1)0 of aid in imid!icating whether injury to
the adrenals of severe extent has occurred. When the adremuals are responding
nor-mally to imufoction, the eosimuophil coumut is zero. When the adrenahs have lost thue
abil-ity to respond, counts above 50 to 75/rem. are found. Cortisone or one of its analogs
may be indicated for the treatnuent of this complication; these compounds are
rela-tively safe in the presemuce of memuingococ-cic infection umuder adequate chemuuotherapv, since the organisms are rarely resistant.
Cortisone is administered in a dose of 1(X)
mg. intravenously and 100 mg. imutramus-cularhy immediately. The dose is then duced on successive days, utihizimug eosnio-phil counts and the blood pressure as
guides. It was emphasized that cortisone should not be employed in every case of meningococcic infection l)tmt should be
re-served for the severely ill. It is probable also that patients with adremual shiock may have as mtmch medullary disturbance as
cortical in the adrenals. Nor-epinephnine may, therefore, be added to the therapeutic
regimen for this roasomu. It is admninisteredl intravenously in a concentratiomi of 5 mg./l., the speed! of imijectiomi beimig regulated! ac-cordimug to the patient’s blood! pressure.
For purulent meningitis in the miewbormu which is most frequently caused by E. cohi, neomycin and polymyximi are recom-mended. The former is givemi imi a chose of
2.5 to 5.0 mg/kg/day mntranuuscuharly, amid
the latter in a c!ose of 10 to 20 mg./kg./!av intramuscularly.
Because the pleasure of witnessimig i-tients recover from tuberculous nuemuimugitis
is now at hand, the management of patiemuts with this heretofore fatal disease has to 1)e revised. The antibacterial therapy currently recommended is as follows:
a. Streptomycin, intramuscularly, 0.5 to
1.0 gm./day in 2 closes is given for 2 weeks. This is followed by the same dose :3 times a week for another 2 weeks; then the sanue
dose twice weekly for 3 months. 50 mu.,
intrathecally, are givemu daily for 10 to 14
days. Lately, some have been eliminatimug intrathecal therapy.
b. Para-ammno-sahicyhic acid ( PAS): 6
gm./!ay in small children; ump to 12 gun.!
is Rezi-Pas. This is PAS combined with amu ion-exchuange resin. It can be used in
mumch larger doses without gastric
irrita-tion.
C. Isoniazid (INH): 10 to 15 mg.!kg.!
day. These are larger than doses
recom-mended by some. It has been found that
they do not produce pyridoxmne deficiency
OF peripheral neuropathuies. They may
pro-(bce dirunkeluliess or hives.
Other measures which may he included!
iii the therapy of tubercumlous meningitis
are barbiturates and, if necessary, inhala-tion amuesthesia for thue immediate control of convulsions. Barbiturates or Dilantin#{174} for :3 to 4 months are recommended by
some in all patients to prevent clinical and “electrical” seizures. Cortisone is another agent now comusidered useful in this disease. It is indicated because of its lytic effect omu
exudate and adhesions, with the hope that
it niay prevent the situatiomu iii which chil-dreii are mache bacteriohogically sterile bumt
remain with hydrocephalus and other
ccii-trah nervous system complications. Thus far
30 chuildren have beemu treated by Dr.
Steig-mamu with cortisone. His regimen is as
fol-lows: 250 to 300 mg. are given the first day; the dose is then gradually reduced so that
h)y the end of the first week the dose is
100 nug. daily; this dosage is then
main-tamed for 6 to 7 weeks. Cortisomie can now
be eiui)lOyed in the presence of tubercumlous imufection because of the presently available
excellent chemotherapy. Thus far, it was
reported that results with the above
regi-memTl have been emicouraging.
As for prevention of tuberculous
menin-gitis, there is now tmnderway a co-operative
study involving 25 centers in the United
States, Canada and Puerto Rico. The plan
of this study is to discover children who
have I)Ositive tuberculin tests but are
clinically well. Among such children,
alter-muate cases are treated with isoniazid or a
placebo. If clinical symptoms occur, the
child! is takemi out of the study and given
conuplete anti-tuberculous therapy. In addi-tion, routine measures are undertaken to
find the source of the infection in the
house-hold. The aim of this venture is to
deter-mine whether isoniazid given to clinically well but tuberculin positive children will prevent the dreac! complication of monin-gitis.
Discussion
Q
uestion: Does sulfonamid impede thueaction of penicillin in pnounuococcal monimu-gitis?
Answer: The original data suggestimig this huas been questioned by many. The
labora-tory work which demonstrated antagonism between amutil)iotics was carried out under highly artificial and suboptimal conditions. We believe this work has no practical
hear-ing on clinical use of combimuations of amuti-biotics.
Q
uestion: Comment on the toxicity of strep-tomycin and dihydrostreptomycimu.Answer: Dihydrostreptomycin is not reconu-mended at present since it produces
deaf-ness. Streptomycin on thue other baud pro-c!uces vestibular damage which is less serious. Chiklremu will compemusate for the latter although they are not cured from it.
For study purposes, children have been
treated for tubercumlous menimugitis without streptomycin at all. Good results luave been
obtained.
Q
uestion: Is Aureomycin as effective for H. influenzae menimigitis as chloramphieni-col?Answer: Chloramphemuicol has beemi so
effective that it is muot a goodi idea to use other drugs. Aureomycin#{174} has been
effec-tive, but tendency to relapse may be greater than it is with chloramphemuicol.
Q
uestion: What antibiotic would you use in a re5)iratory infection with the k!ea of preventimig meningitis?Answer: If thie infant is umid!er 6 muuonths
old, there is less likelihood of an infection
caused by streptococcus. Therefore, a
broad-spectrum antibiotic is indicated. Would also use chhoramphenicol more fre-quently since it is probably the best drug for H. influenzae, and the best or second
best drug against staphylococcus.
deriva-958 IIODES - RECENT DEVELOPMENTS IN INFECTIOUS DISEASES
tives superior for treatment of adrenal
in-sufficiency or circulatory failure and toxo-mia?
Answer: Apparently hyiirocortisoiue
hem-isumccinate (SolucortefR) has certain
ad-vantages. It is not an alcoholic preparation and! it may be ad!ministored intravenously. There is no rationale for tlue use of large
(loses of vitamimu C in moningococcic
men-ingitis.
c_
)uestion: Does old tuberculin (O.T.) have amuy place in the therapy of tuberculous iuuemuimugitis?Answer: It has been discontinued because
of the good results withu the 3 presently available drugs. It is questionable whether it ever was of any value. Dr. Worden of
Momutreal commented that 60 to 70 patients have been treated with purified tuberculin protein derivitive (PPD) and have recovered
tIid! time follow-up stuc!ies of these patients have l)een excellent. It is the impression of the Montreal workers that this technique has been of defimuite aid!.
MONILIA INFECTIONS OF THE SKIN
The following discussion was presented
l)y Dr. B. Dobias of Jersey City, New
Jersey. He pointed out that monilia infec-tiomi of the skin is not as rare as was
previ-ously thoughut. It is frequently misdiagnosed as diaper rash, eczema or Leiner’s disease. A series of 70 patients with this disease, 50 per cemut of whom were under 3 years of age, was described. In most, the white
glistening scaly lesions were below the
umbilicus; in some of the children there
was loss of hair and depigmontation of the skin. Precedimug oral thrush was noted in 75 per cemut of the patients, and there was a
definite correlation with maternal vaginitis. Only a small percentage of the children hac! been umuc!er therapy with antibiotics for other comiditions. Other organs occasionally
affected by Candida albicans in this series
were: lungs, vagina, conjunctivae and
gas-trointestimual tract. A generalized form of
the disease also occurs in which there is
vomitimug, dehydration, fever, hepatospleno-megaly and lymphocytopenia.
Treatment consisted of the use of a newly
available amitifungus agent, Mycostatin . It
is prepared from Streptomuuvces noursei and
is available in 500,000 unit tablets. The
children received 100,000 units, prepared
as a flavored po\\’d!er, “3 to 5 tinues daily for 2 to 5 c!ays (an oral sumspemusion ‘ill be available containing 100,000 units/mI.).
Topical therapy with an oimutmuuemut
comutaimu-ing 100,000 units/gm. was added! iii some
chuildremu. Results thins far have beemu excel-lent, especially with local therapy for
cutaneous lesions. N’Iycostatimi “ appears to
be the first pronuising agent available for treatmuuent of monihia infectiomu.
PENICILLIN V
The following d!escriptiomi vas given by
Dr. \Valter Voodl of the University of Ilhi-iiois. This is a newly prepared I)enicihlill nuade from a muuold, Pemuicilhiummu chryso-genunu. Pemuicilhin V ( phiemioxyniethvl
peni-cilhimu) is an acid amid is therefore stdl)le in
stomach secretions. It is absorbed iii the small intestine, destroyed imi the large I)owel and excreted by the kidney, similar to othuer
penicilhins. Organisiuus generally exhibit the
same sensitivity to penicihlimu V as to time
previoumsly available penicilhins, aiuc! allergic reactions to the drug are also simuuilar.
Because of its stability iii acid nuedia, it is muiore suitable for oral adnuinistratiomi. Clinical trials thus far have shown that it is at least as effective, if not nuore so, as
penicillin G when bothi are administered orally. It has been suggested that it may
be as effective orally as penicillin C is
parenterally, but proof of this is as yet
lack-ing. Studies performed on patients vithi a
variety of infections have yiek!ed excellent results. Penicillin V possesses a distinct ad-vantage since its oral ad!ministration
p’s-d!uces higher and more prolonged! blood
levels than do other pemuicillimis when given by the same route.
EPIDEMIC DIARRHEA OF THE NEWBORN
“Epid!enuic diarrhea of the newborn” cami
ho lomiger be consid!ered a single entity.
Tic. 7. Modified frommi Ewing et al. : Pul). 1Iealth Rep., 70: 107, 1955. datIse(l l)V iiiaiiy agents amnomigst vhich are
viruses, E. cohi organisnus, nuembers of the Salnionella fanuily, and occasionally Shuigella
organisms. Most of the discussion was
con-cerne(i with E. cohi as causative agents.
Simuce 1890, it has been suspected! that
dOlOll bacilli might caumse infantile d!iarrhea, but the first diefimuitive studlies were
per-formuied in 1912 when it was shown that E.
(Oh strains fronu calves and infants, with
(!iarrllea, had certain cOIiiIIiO)I1
character-istics. Further important studies were
huer-fornied liv A!ani in 1921, amid! by Theobald!
Smith iii 1925 to 1927. Kauffnuanii and
\Vlmite l)egan the laborious task of typing dOli orgamlisms in the late 1920’s, and! they denionstratec! that there were 1 28 different
tVI)eS of E. cohi, as (lifferemitiated by the 0
(soniatic) antigen; there are also 3 different K (surface) antigens. Renewed! interest in
F. coli as a cause of infamitihe dliarrhea was stiniulated 1)\’ Bray and co-workers in 1944, when they dleliiOnstrated that a simugle sero-logic type of E. coli was Present iii large nuIlil)ers in the stools of infants suffering from (l)i(iemiuic diarrhea in a hospital. This
tYpe was sul)sequently shiovii liv Kaimffniamni and DuPont to be 0111:B4.
At the present time, it is felt by most workers in the fielc! that certain types of E. coli (enteropathogemuic coli) camu be garded as etiohogic agents iii infantile d!iar-rhea for time followimug reasoms (Fig. 7):
1. A number of sj)ecific types of E. cohi
have been isolatec! imi large muumbers froni the stools of imufants suffering froni
epi-demnic diarrhea. Such epk!enuics have
oc-curred in 4 continents. These saiuie types are very rarely encoummutered aniong normal infants. The epi(!enuiologic evidence is very strongly in favor of the etiologic significance of 10 types of E. coli. These incha!e 01 1 1 : B4,
055:B5, 026:B6 amid 0127:B8 (see Fig. 7).
2. Feed!imig of a relatively small nuinber
of E. cohi 0111:B4 orgamuisms to 1 infant
has been followed! by the production of dbarrhea, and feed!ing a large nimmuuber of thiese organisms has produced d!iarrhiea in several adults.
3. Ordlimuary techuniqtmes have imi general
failed! to show the c!evelopnuent of specific
antibodies in thie blood of babies considere(i
ESCHERICHIA COLI SEROTYPES ASSOCIATED WITH INFANTILE DIARRHEA
*NTIGENS
SYNONYMS AUTHORS REPORTiNG ISOLATiON
0 K H
I I I
55
26 B4
B5
B6
2, 2, 21, OR
NON-MOTiLE (-).
2, 6,7, OR (-).
II OR (-).
BACTERIUM COU NEAPOLI-TANUM
TYPE D433
B. COLI BETA TYPE
E. COLI 026
E. COLI 026B6
TYPE E893
BRAY, BRAY AND BEVAN
TAYLOR, POWELL AND WRISHT GILES, SANOSTER AND SMITH
ORSKOV
CHARTER AND TAYLOR, TAYLOR AND CHARTER
IIZa)
I I2b)
B13 8 1411-50 EWING AND KAUFFMANN
I12o)
II2c)
BII (-) SHIGELLA GUANABARA DE ASSIS
No B? 8,9,10, II
OR C-).
TYPE E990 CHARTER AND TAYLOR
IlS BI4 6 ABERDEEN 53T52 SMITH
125 BIS IS CANIONI, VINCENT CHARTER AND TAYLOR
126 BIB 2 E6II CHARTER AND TAYLOR
960 IIODES - RECENT DEVELOPMENTS IN INFECTIOUS DISEASES
to I)e suffering from E. cohi diarrhea. More
recently, however, it has been found by
Neter that agglutinins can he demonstrated
against specific “0” antigen absorbed on
ervthrocytes. Using a similar technique. \Vheeler has shown a transient, but signifi-cant, rise in anti-B antibody among infants
who have hiac! au attack of E. cohi diarrhea. Ve huave lately shown time development of a high titer against B antigens under similar
circumstances.
4. Diarrhea huas been produced in calves
h)y feeding E. cohi 026:B6. This disease can
be prevented in the calves if they are fed
colostrurn containing antibodies against the B antigens of this organism.
5. The possibility exists that E. cohi
diar-rhuea may be in part due to unknown
vi-ruses. Several studies, however, carried out with the best available virums techniques, have failed to reveal the presence of such
a virus.
It is conclud!ed! that by means of
epi-c!erniologic evidence, feeding experiments, reproduction of the disease in calves and
the development of antibodies to these or-ganisms, that certain strains of E. coli can be implicated as causative agents in
“epi-demic diarrhea of the newborn.”
The diagnosis of E. cohi diarrhea is de-pendent upon isolation of the organisms from the stools. A slide agglutination test
is available for thue detection of these or-ganisms in the feces. Zepp and Hodes have
recently devised a precipitin test which
may iuuake identification of enteropatho-genie cohi easier. Identification of
anti-bodies is possible as yet in only a few
lab-oratories.
Since nuost infants with this !isease
re-cover spontaneously, it is not certain
whether specific therapy is necessary.
Nevertheless, because it is innocuous when
given orally, and it does seem to aid the
clinical course, mueomycin, in doses of 50
mg./kg.!day orally is recommended.
RABIES
In connection with rabies, at the present time the chief problem is which procedure
to follow after a bite by an aninual whose status as regards rabies cannot be
deter-mined at the time of the bite.
The risk of neuroparalYtid. acci(lelits foh-lowing anti-rabies vaccine is a considerable
one since the vaccimue contains nerve tissue. The risks of such accidents is greatest with vaccine containing d!iluted!, unmodified! liv-ing virus (approximately 1 pr 2300 persons inoculated). The risk is lowest ‘heii ‘ac-cines contaimuing virus killed! 1w ether, plw-muol or heat are used (approximately 1
mien-roparalytic accident per 8500 persons
vac-cinated).
Several attempts huave been nuade to
de-velop a vaccine free of nerve tissue. Promuuis-ing stud!ies have been nuadle with tIme Flurv
vaccine, a live attenuated virus vaccine
grown on hens’ eggs. Thus far, this vaccine
has been successful in protecting dogs
against rabies. Although it has l)eeli tried! experimentally iii a few hunuans, it is not as yet available for clinical use. Another vaccine which will be availahule shortly is made from virus grown on !nck eggs. It is a 1)hienOhized! “killed” vaccine which
stinu-ulatos good antibody 1)rod!uctiolu amic! has prodluced few reactio)ns. It too should prove effective climuically. At present only the
Semnple vaccine is available for routine
clinical use.
A hyperimmune amiti-rabies serummuu malc by imnuuniziiug horses with Flury vaccine is available. It shuould be used regularly as au adjuiuct to active inimunization in persomis bitten on the face, head or neck
by a rabid! c!og, since iii such cases the
incubation period! is short, aiud the risk of rabies after vaccimuation is relatively great. It may also be used while awaiting
the possible development of rabies when the biting dog shows no evidience of the
disease at the time of the bite. Figure 8
gives an outline of recommemided proce-dures in different situations. The serum is
effective only if given within 72 hours after the bite. Thue dose is 0.5 nul.!kg. of badly
weight. The incidemuce of serum sickness
following use of thuis serum is 5 to 8 per
.\(IIure (if l.rposure
‘ 1)uring ()bs. Period
.11Time of !‘xpo.vire
of Jo Days
111(017! rues(le(i irealnieni
None6
111. Bites:
(1) Sinmphe exposure
Start vaccine Rt first signs of rahies
in aiminial
Start vaccine imnme(hiately ; stop
treatnient if aimimnal norimmal on .5th
day after exposmiref
- Start ‘8c(iIme inmnme(liately
INI)ICATION.S FOR SPE(-mFme PosT-ExposuRE ‘I’REATMENT
(‘ondilion of lIlting Animal
I. No lesions; in(lirert
(Olitact only
11. Licks:
( 1 )Fmiahraded skimi ( ‘1 ) 1)rac1ed skiii amid ahra(le(l or
miii-al)ra(le(l nmucosa
() Severe (Xl)t)s(1rV:
(nmmiltiple; or
face, head, or
iIe(k hites)
R.al)i(l
rabid (a) healths (h) E!ealth
((.) Signs suggestive of
rabies
(d) Itah)i(l, esciIpe(l, killed
OI ummknown
(a) healthy (I))Healthy
((.) Signs suggestive (If
ral)ies
(d) RaI)id, (s(ILI)((l,
killed, or unknown:
or any bite iy wolf, jackal, fox, or other vild animal
(a) healthy
(b) healthy
(c) Sigims suggestive of
rabies
(d) Rabid, eS(al)e(l,
killed or imimknoii.
Any bite by wild
ani-mmml
Ilealthy
( linical signs or rahims or iroveim rahmid I lealthy
hlealthmj’
(‘linical signs of ralies
0! proven rabid
healthy
healthy
Clinical signs of rabies
01 proven ral)i(l
healthy
None
None
Start vaccilme first signs of rabies in
11mimmial
Start vaccine inmnme(hately ; stop Ireatnient if animmal norumal on .5t Ii day after exposuref
St rt Va((ilme iIImni((l iately
Ihyperinmnmune serunm inmnmediately;
10 vaccilme as long as aninial re-mains imormnal
hlyperirnniune serurim inmnmediately; start vaccine at first sign (If rabies llYhwrIIIitliuime serum immediately, followed 1)’ vaccine; vaccine niay
be stopped if aninial is norumal on 3th (lay after CXhX)5liC
Ihyperimmummumme seruimi inmnme(hiately. followed l)V vac(nme
* Start vaccine inmnme(hiately in young children 11(1 in I)atiemmts -here a reliable history (-annot he obtained.
f An ahtermmative treatnment vould lie to give hyperinmnmune sertmni 111(1not start vaccine as long as the aninial
relnaine(l norimmal.
NOTE: ‘I’o le effective hyperimnimmuime sertmnm must be given within 7l hours of exposure. 1)ose: (1.5 nil/kg. of
body-weight.
Fic. 8. Modified from \Vorld Health Organization: Expert Committee on Rabies. Second Reprt, WId. HIth. Org. Tech. Rep. Ser. No. 82, p. 12, 1954.
The method of eradicatimug rabies is to
attack the problem in dogs. Vaccination with thue Flury vaccine should be repeated
every 2 years in these animals; stray dogs
should he destroyed, dog licensure and
quarantimue of suspect animals should be
rigidly enforced. The value of vaccination of dogs in preventing dog-rabies and con-sequently human-rabies was shown by
962 HODES - RECENT DEVELOPMENTS IN INFECTIOUS DISEASES
Malaya and Israel. In both of those
coun-tries, this procedure was followed by a
sharp drop in the imicidemuce of dog-rabies.
Discussion
( )uestion: Are repeated doses of serum
as good as vaccimuation?
Answer: Thus is not known but the
incu-batiomi period of rabies may be as bug as 6
nuonthus; therefore, this would be some-what impractical.
c
)iiestion: What should one do if thuere is a repeated exposure in a person who has already had vaccine?Answer: One may give omily 7 doses of vaccine instead of 14.
Q
aestion: Is cortisone of any use for the central nervous system reaction due to theSemple vaccine?
Answer: There is no evidence that it is of any use d!espite the fact that this is not an actual imuvasion with virus, like measles. Question: Local therapy of the bite?
Answer: The first 10 minutes after the
bite are crucial. After that time fixation of the virus takes place. During the first 10
minutes the virus may be washed out of the
woumid. Local cleansing with soap or
de-tergent and water is the most important
timing. Fuming nitric acid should not be
used, since many authorities now believe washuimig with detergent is as good, and muitric acid is painful. One can give tetanus
prophylaxis if the bite is deep and pene-trating; also give penicillin.
ENCEPHALITIS
Thiere is ho specific therapy for measles emiceplualitis. Rather, patiemuts shiouk! get careful symptomatic therapy and nursing
care, including tracheotomy and mechanical respiratory aid, if necessary. Gamma globu-hin appears to be of no value in thuerapy.
Many of time patients recover
spontane-ously evemu after weeks of coma.
Recently, hypothermia, pattermued after Dr. Temple Fay of Philadelphia, has been
tried in the therapy of encephalitic coma. In 1 case, dramatic improvement resulted;
other resumlts have been negative or doubtful. The patient’s temperature is lowered! to be-tween 85#{176}and 90#{176}F.by means of ice packs and certain adjuvant drugs, e.g., Thorazine#{174}
and Phenergan#{174}. Time patient nuay be
main-tamed at these temperatures as long as is
requirec! for recovery. Time aid of thue
anes-thietist amuc! carc!iac surgeon may be em-ployed, since they have experience with like proced!ures in cardiac surgery. The
rationale behind suchi therapy is twofold: When a patient’s temuuperature is lowered to these levels, there is an econonuy of
ox-pond!itumre of oxygen; there is also au econ-omiuy of insemisible fluid loss since the
respira-tory rate is reduced.
ORPHAN VIRUSES (ECHO VIRUSES)
The “orpluami viruses” have recently been
renamed ECHO viruses ( enteric,
cvto-pathogenic, hiumami orphan viruses); thus far 13 amitigenicall distinct viruses in this group have been identified. Most of them
have been isolated fronu stools of patients
who have had a disease vhichu resembled nonparalytic polionuyelitis.
Characteristics of thiese viruses include:
1. They have been isolated! fronu the
gastrointestinal tract of man, but thueir sig-nificance as regards the causation of
hiu-man disease is not yet kmuown. These
vi-ruses are neutralized by humuuan gamma
globulin, indicating that they do cause hum-man infection;
2. ECHO viruses are cytopathiogemuic for
monkey and human cells in tissue culture; they do muot affect suckling mice, nuomikeys or other laboratory animals;
3. ECHO viruses are not neutralized by pohiomyelitis or Coxsackie virus antisera;
4. ECHO viruses are not related to those
causing huerpes simplex, imufluenza, niumps or varicella, and they are not related to the APC viruses.
The significance of this group of viruses is revealed by the following facts. In Massa-chusetts in 1954, 17,000 children were
963
In the latter 2 groups there were 43 patients who were thought to have had
poliomye-hitis. Of these, 29 had 1 of the ECHO viruses in their stools, isolated by Enders. In tipper New York State, thuere were 16,000 chihdremu who were vaccimuated, 16,000
re-ceived placebo, and 20,000 were observed. Of the 49 patients reported to develop
polio-nuyehitis, 30 to 35 yielded ECHO viruses
from time stools. Historically, it is interesting
to recall thiat imi 1947, Sabin and Steigman describec! an epidemic in which there was
headache, fever, malaise, amid a stiff neck. One-third of the patients had spinal fluid
)leocytosis. There were 85,000 cases
de-scribed! iii this epidemic in Cleveland. At
first, it was thuought to be caused by a single
agemut l)tlt since themu, with the newer tech-niques, 5 different virtmses have been
iso-hated. These imucludle Coxsackie B type 5,
Coxsackie A type 12, pohiomyehitis virus type 1, poliomyehitis virus type 2, anc! a group of
immuclassifiec! viruses whichu may be k!emutical with or related! to the ECHO viruses.
It is concluded that althoumgh the exact sigmuificamuce of these virumses is not as yet
known, they do appear to have pathogenic potentiality. It is importamit to point out, however, that the fimuding of these viruses in tuatiemuts in various pohiomyohitis epidemics may give false results in relation to vaccine evaluation, unless efforts at exact ic!enti-ficatiomi are ummudertaken.
CAT-SCRATCH FEVER
Ami antigen is available for skin testing for the diagnosis of this disease.#{176} One can
also be made from the secretion of an
in-fected IiOd!e. As yet it is uncertain whether a virus is the cause of this syndrome, nor
is it understood why only certain members of a family become infected. Dr. Steigman has treated 4 cases with cortisone. This therapy reduced the local inflammatory reaction withimi 48 hours. There is little
(hanger of dissemination of the virus umider cortisone treatnuent since by the time local
0 1)r. \Vorth B. Daniels, I 150 Conmiecticnt
Aye-mile, NW., \Vashington, D.C.
disease tppears, infection has been Ir’sent for 3 weeks.
GAMMA GLOBULIN
It is questionable whether gamnua globu-un is of any value in children withu repeated respiratory infections unless the individ!uals have absent or low levels of gamma
globu-hin in the serum. Several physicians attend-ing the seminar indicated thuat thiey have used it empirically with what they thuoughut
to be encouraging results. Perhaps comu-trolled studies may be feasible in the near
future in pohiomyehitis patients in respira-tors or in children withi fibrocystic disease of
the pancreas. In these groumps, it is essemutial to control the rather frequemut respiratory in-fections.
PROPERDIN
Properdimi is au euglobuhimi dliscovered
d!tmring attempts to isolate one of the
coin-plemnent fractious of the blood. It is present in muormal serum in very small quantities.
Levels of properdin fall in conditions which cause loss of certaimu types of immumuity, such as that followimug total body
irradia-tion. This decline is accompanied by in-creased susceptibility to gram-negative or-ganisms. Properdimu has been shown to be
involved in natural immumuity against sal-monellae, shuigehlae and other gram-nega-tive organisms.
It is concluded thiat properc!imi, in a norm-specific manner, plays a role in natural immunity to disease. It differs fronu specific antibody in a miumber of ways.
MUMPS
Although a mumps vaccimie is available, thiere is no evidence that it is effective in
young children, and it is questionable
whether it has any value for exposed adumlts.
A mumps skin test is also available but it is not overly reliable. If positive, the
pa-tient !oes not require vaccine for protection. If negative, the skin test itself may confer immunity to the disease.
964 IIODES - RECENT DEVELOPMENTS IN INFECTIOUS DISEASES
Dr. Steigman has adnuinistered cortisone
imutravemuoumsly to several patients with
mumps orchiitis. It was said to produce
marked symptomatic relief in 8 to 12 hours.
DIPHTHERIA
Imu conmuection with the problem of
im-niumnization of children over 8 years of age, the following was recommended. If the patient is Schick positive, the ensuing
pro-cedure should be carried out before at-tempting immunization (Moloney test): 0.1 nil. of a 1:100 dilution of fluid toxoid should be given intradermally and the skin test read imu 20 to 24 hours. If the Moloney
test is positive, the child! probably possesses
antil)acterial immunity (i.e., agaimist C
diphtheriae) and requires no further diphi-theria toxoid. In fact, an intramuscular or subcutaneous injection of toxoid! may
pro-duce a severe reaction in such a child. On the other hand, if the Moloney test is negative in a Schick positive chuild, 0.25 ml.
of diphtheria toxoid should be given
intra-muscularly. The Moloney test shoumhd be
carried out in all children over the age of
8 years, prior to immunizatiomu, to check
for sensitivity to diphtheria toxoid. A new alcohol-purified toxoid may soon be available. This preparation may obviate all the d!ifficulties of severe sensitivity
