ENTEROVI
RUSES
Jerome T. Syverton, M.D.
Department of Bacteriology and Immunology, Unieerrity of ?tlinnesota
The Tenth Annual Don W. Gudaktmnst Lecture presented at the School of Public Heaith, University
of ‘sIichigan, February 9, 1959.
The studies carried out in the laboratory of the author were aided by a grant from the National
Fotmndation.
ADDRESS: Minneapolis 14, Minnesota.
PEDmATBICS, October 1959
REVIEW
ARTICLE
643
I
T IS AN HONOR and responsibility topre-sent this Tenth Annual Don W.
Guda-kunst Lecture. Dr. Gudakunst, as first
Mcdi-cal Director of the National Foundation for Infantile Paralysis, was administrator
and participant in a prodtictive research
program. In 1950, the year Dr. Charles
Armstrong gave the first Annual Lecture,’
the program received new impetus with
re-suits now familiar to us all. The list of dis-tinguished lecturers of sticceeding years,
including Sabin,2 Bodian,3 Paul, Salk,5
En-ders,6 Francis,7 Horstmann5 and Huebner,9 is a record of workers and achievement that opened the way to control of poliomyelitis,
and vastly expanded otir understanding of
viruses, nucleic acids, cells, and their inter-action to produce cellular infection. Dr. Gudakunst would be proud of his early
association with and contribution to the re-search program which continues under gen-erotis support of The National Foundation. Apart from its record of outstanding con-tributions to prevention of poliomyclitis,
this annual series of lectures is evidence
that the distinction between pure and ap-plied research has less and less meaning.
With this example before me, in discussing
enteroviruses I shall proceed freely from
epidemiologic to basic research. Work done at Minnesota represents contributions of a group of associated investigators.
THE ENTEROVIRUS TRIBE
In the days when our virologic tools were limited, we used to speculate that the human environment might include many
viral nonpathogens or opportunist patho-gens, as well as the viruses of known dis-eases. Study of the enteroviruses illustrates technologic advances achieved since 1950,
to uncover more than 100 viruses now char-acterized, and many others unidentified but distinguished from known types.’” Our speculations have been substantiated in full
measure. Aside from other tissties, the
htinian gtit (in tropical, temperate or arctic zones) can harbor at least 50 of the new
viruses, making up the enterovirus tribe of Coxsackie, ECHO and poliomyelitis viruses (Table I). The relationships of viruses
with-in the tribe will be considered later. A group relationship is indicatedm2 by their transient inclusion in the microbial flora of the human orointestinal tract’2 and the microflora of monkeys,’3” cattle,17 and
swine,18 as well as by the size of
entero-viruses, their resistance to ether, their cyto-pathogenic effect, seasonal incidence, epi-demiologic pattems and modal disease
spectra. This host-specific, pathogenic group includes the ECHO,’#{176} Coxsackie and poliomyelitis virus subgroups infectious for man.” 20 Such grouping may be artificial as
well as informative, but most of us would agree that viruses represent a unique taxo-nomic problem presently without solution,
and there is no indication of what
signifi-cance a “solution” might have. Without fos-sils, study of viral evolution may be denied
t15. One wonders whether mammoths frozen
in Arctic ice might yield prehistoric
entero-viruses!
‘I’ABLE I
I’,Ni’Mmovmmmm.a
SI immunotypes
ckie
Polio
_________
types -3 Subgroup A
t\ types 1-19
\
\
*
types -8
I
11-24type 9
type 0
‘l’.J4IE II
(‘m.msmetm F’:.t’rI’mF:s OF Esi’:imovmmu. IxmF:ui’moN
(‘on, moo
immappml remit i mmfe(’t inmi
muild immdetermmmimmammt or febrile (lisease jt Iior it liout gastroimitest immal (Iisturl)amm(’e a mi(I/or less (‘ommimilomily
symptonis refermi hl’ to t he respira tory I met
E.rtraordinary
examitlmmiia (EC’llO-’2, 4, 6, 9, 14, 16; (‘oxsaekie A-, 4, 9, 16 aml(l B-4
emmamithemna
emiteritis
Imematuria
pleuro(IymmiIl
herl)a mmgimma
aseptic miiemmimmgitis (ECllO-2, 4, 6, 9, 1. I6:
Cox-sackie A-2, 4, 9 011(1 B-i)
Seriowi
paralysis
encephalommmyoearditis
cardit is
644 ENTERO VIRUSES
Subgroup B
types -5
PATHOGENESIS AND CLINICAL FEATU RES
--
::---
The pathogenesis of enterovimus infectionpresents an interesting I)icttire of synd!romes
rather than specific diseases such as are
in-duced by the classic viruses. The human ECHO host receives the enterovirus through the
oropharynx, incubates and niultil)lies the invader in the intestine, and d!iSseminates
it in the feces. Association with his transiemit
gtiest can affect the host ina))arently
(Table II), makes him mildily ill withi fever
or exceptionally with respiratory
discom-fort, or cause him abdlomilinal pain dfldl loss
of appetite and, less commonly, vomiting
and/or
diarrhea.-These manifestations of d!iseaSe can 1)e
attributed to disturbance of the enteric
tract; the emiterovirus can, however, pass
from its primary residence through the
blood to secondary targets, to produce other
varied clinical conditions. Rash and
transi-tory hematuria, for exaniple, are seen with
ECHO virus infections, 1)letirdlYm1it with
Coxsackie B virus infections, amid
herpan-gina and vesictilar exanthemmi with
Cox-sackie A infection.
viruses followed the inadvertent discovery
of the enteric cytopathogenic human orphan (ECHO) virus family, which in tum
stemmed! from the development of cell ciii-hire technic, spurred by the cultivation of
pohomyclitis virus in human cells of
non-nervous origin by Enders et al.,21 and the
demonstration by several research groups that three distinct immunotypes of
polio-myclitis virus were responsible for clinical
poliomyelitis.2 The observations initiated
l)y Dalldorf and associates23’ 24 added the
Coxsackie family to the enterovirus tribe,
by use of stickling mice for isolation. Within
this family, the grotip A viruses induce
flac-cid paralysis, myositis and muscle degenera-tioii, while the group B viruses cause
en-cephalomelitis, I)ctncreatitis, focal myositis
and!/or fat necrosis. The stickling mouse still is best for isolation of types A-i to 8, but ccli cultures can be employed
altema-tively for stud!y of types B-i to 5 and A-9.
In our laboratory, human amnion primary
cultures now are used for study of
Cox-sackie types A-6, 9, ii, 13-15 and 18 and
for types B-i to 5. Cell cultures are
em-ployed rotitinely for study of the remaining
family of the enterovirus tribe, the ECHO,
which incltides at least 24 antigenically
dis-tinct 22#{176},25 ECHO-iO virus is
some-what an outsider in this group;12 its size is
different from that of other ECHO
immuno-types, it can produce respiratory disease in
(‘oxsaekie
\irimses
(‘roimp B
l’YPeS 1 .5
ECho
\irlmses
l’})(’S
1 4
On the average, the family and
immuno-type of the parasite is suggested by the
syndrome, btit in any group of patients
affected with any one enterovirus, responses
may range from paralysis or aseptic
menin-gitis or carditis and/or maculopapular
ru-l)clliform rash (Table III). Individtial
diag-noses thus require laboratory work.
Although paralysis with fever acceptably
indicates poliomyeiitis viriis infection,
oc-currence d!uring 10 years of 15 cases of
clinical and pathologic acute anterior
polio-mychitis from infection by other
entero-virtises2 testifies that damage to the
cen-tral nervous system is not singular to
polio-myelitis virus.
Pletirodynia, epideniic myalgia, acute
myocarditis, aseptic meningitis and/or
niinor febrile illness cami occur alone or
con-currently as e1)idemic infections by
Cox-sackic B viruses. Epidemic pletirodynia,
with its fever and excruciating chest pain
and/or less frequent, abdominal pain, is a
manifestation Of muscle damage. Like
new-born mice, human infamits suffer focal
ne-crosis of various tissues, imicluiding the
myo-cardiumii ; epid!eIflic infant myocarditis with
high niortality has been reported from
van-OtiS parts of the worldl. if;
The fliOst COliliiiOfl fomni of emiterovirus
infection, aseptic menimigitis, fortunately is
short and benign in its cotirse. Almost every
type of enterovirus has been implicated in
aseptic menimigitis, which appears as a
COfliflTIOfl complication of systemic
entero-virus infection whether spOrad!ic, endemic
Or pT Epidemic, enteroviral aseptic
nienimigitis has been distinguished readily
since 1950 l)y 1PPlication of cell culture
technic. A rash may accompany this
epi-d!emic syndrome, and so present a confusing
clinical picture.
Variotis ECHO hid1 Coxsackie viruses
have l)een reported responsible for
out-1)reaks of feverish illness, aseptic meningitis
amid/on exanthiem. In recent years, ECHO 9
‘irtis has been a leading cause of rash and/ or aseptic iiienimigitis in Britain,4’
Westenmi Europe and Canada,52o amid in
North Central and Mididle Westem States
of this cotintry.”’ Although happily not
lethal, these outbreaks must be reckoned! as
TABLE III
As,x’mATIoN OF ENTEmtovm IIUSES wmTIm hUMAN I)msE.s:
bnteroriruses A ssociated J)i,sea.se
Polioviruses
Types 1-S
Summer fehrile ilimiess
Aseptic mnemmingitis
Paralysis (flaccid to mmiuscle veakmmess)
(‘oxsackie
\‘irimses
(;roul) A
‘l’ypes
I-It)
Summner fehrik. illness
Aseptic meningitis (types A-i, I, 9)
Paralysis (?) (A-7, 9
Ilerpa mmgina
Sumimmier febrile illmmess
Aseptic nieningitis
Paralysis (?) (types B-3, 4, .5)
Pleurodynia
Myocarditis or emiceplialomnyocarditis ill
neonatal perio(I 011(1 early cimildhmood
-
----
(types B-, 3, 4,)Summer febrile illness
Aseptic menimigitis (types ‘2-6, 9, 1-1, 16)
Paralysis (?) (types , 4, 6, 16)
I Summimner raslm (types ‘2, 4, 9, 16)
Sumunier diarrlmea of immfants amid
cliii-dren (type IS mimm(l othieFS)
major epidemics : 40,000 people are
be-lieved to have been infected in the
Mi!-vaukce area,61 and last year 220,000 persons
(nearly 20 of the total population
)
in the \‘Iinneapolis-St. Paul area probably wereaffiicted.
In the s’Iinncsota outbreak of ECHO 9 infection, unlike that of Boston5’ ‘ which
gave the name “Boston exanthem” to ECHO-i6 infection, the rash persisted
thin-ing the progress of fever. A somewhat simi-lar exanthematous epidemic near Toronto
was attributed to Coxsackie A virus.7
Asep-tic meningitis from Coxsackie infection likewise may resemble ECHO virus men-ingitis.
So we have the picture of these entero-viruses being responsible for a broad range
of
symptoms varying in severity. With aidof
competent laboratory studies, however, one finds that specific infections aredistin-gtiished by frequency (listnihutions of
TABLE IV
PoLmoMYEiTIs Vmmsus ISOLATIONS FROM STooms OF CASES OCCURRING BETWEEN APRIL 1, 1955 AND
AND DEC. 31, 1955 AND DISTRmBUTED AccoRDmNo TO CLINICAL TYPE OF DISEASE-MmNNESOTA 1955
Clinical Type
Number of Patients
Poliovirits TYpe* Positive
I S Total %
Spinal paralytic
Bulhar
Bulhospinal
Totalparalytic
Nonparalytic
I6 58
19 9
33 13
178 80
63 17
8
3
2
13
8
13
4
4
1
6
79
16
19
114
31
6.7
84.’2
57.6
64,0
11.8
Total
(%hytype)
441 97 1 7 145 3,9
100.0
66,9 14,5 18.6
\IRUS IS0LATm0NS mx MINNESOTA 1955-1958
195.5 1956 1957 1958
Pohiovirus
(all types) 175
Coxsackie
A9
B
3
4
5
ECHO
6 9
47 9 1
0 ! .1
(1 0 2 0
(I 6 1
(I 0 1
0 60 18 109
U 0 18 109
(I I
0 149 5
Virus i(lemltification vimade in laboratories of time
I)ept. of Bact., JTj1jy of Mim,m. amid/or Mimmnesota I)ept.
of health.
646 ENTERO VIRUSES
* In(luphicated.
Prepared by L. I%I. Schumnan, M.D.
DIAGNOSTIC AND EPIDEMIOLOGIC
STUDIES
Like other groups, at Minnesota we have been interested in laboratory study of polio-myelitis and associated conditions since 1946. As data accumulated from mass use
of cell cultures for virus 626870 we were intrigued by our failure to recover
poliomyelitis virus from 20 to 40% of pa-tients supposedly poliomyelitic. These fail-ures proved to be related to disease
cate-gory; 64% of paralyzed patients yielded
virus compared to 12% in the nonparalytic category (Table IV). Review of our virus
isolations from 1955 through October 1958 (Table V) shed light on the situation. A
directed effort to identify cytopathogenic
viruses isolated from clinical cases of polio-myclitis or aseptic meningitis revealed that an epidemic of aseptic meningitis in 1956 was in fact an epidemic of Coxsackie B-5
infection.70 The virus was isolated from 60
of 115 patients studied. Epidemic Coxsackie B-5 infection also was seen in Iowa in
1956,’ and has recurred there and in
Mm-nesota in successive summers.
This series of outbreaks is interesting
be-cause Coxsackie B-5 virus had not
previous-ly been found responsible for human illness
since its discovery by Steigman et in 1952. Our program for laboratory study of
epidemic aseptic meningitis in 1957
identi-fled ECHO-9 virus as the principal agent, but in 1958 showed that Coxsackie B-5
virus was with us again.
Table VI summarizes virus isolations in relation to diagnoses during the period
1955-1958. The data indicate replacement in
Minnesota of poiiomyeiitis virus as the
principal agent responsible for viral dis-ease of the central nervous system, in favor of aseptic meningitis from infection
‘If,”
‘it/ark Rates Per 100,000
9
(m/)ara-lijticPolio
1956
6
,
5,0
.5 3
3.5
0,3
0- 4
5- 9
10-14
15-IS)
30-39 >40
(ox.oek,e 115
1956
2,7
9 .9 1
,
94
‘
S1,1
0.3
E(’II()
1957
11,1
3 ‘
43.5
36,9 3 .1
i4
,
5 4.567 31 io
S’l 33
7.5 23 109
S 5
5;
11
78 401
REVIEW ARTICLE
by Coxsaekie B-5 and ECHO 9 ‘irmises, amid
by meningoencephahitic manifestation of mumps virus. A minor number of cases
were attributed to viruses of lymphocytic
ehioniomeningitis, Western and St. Louis
en-cephalitis and the enteroviruses, Coxsackie B-2, 3 and 4 and ECHO I and 6. The
corn-parative age distribution of aseptic menin-gitis induced! by poliomyelitis, Coxsackie
B-5 and ECHO 9 viruses indicates that ECHO 9 infection was new to Minnesota.
Table VII shows that the incidence of
nonparalytic poliomyelitis and Coxsackie B-5 meningitis was highest in the earlier years of life, as commonly is the incidence
of childhood virus infections that produce relatively immune adult populations. Con-traniwise, attack rates for ECHO 9 aseptic
meningitis formed a plateau through the
age range of from 5 to 40 years to indicate
a population without residual immunity
(
lower rates under 5 and over 40 years asexpected reflect differences in exposure po-tential).
These and other epidemiologic studies of enteroviruses carried on in a number of in-stitutions allow virohogists to examine
vane-ties of human viral diseases in relatively pure fomni . Cell-culture diagnostic methods
for the first time make it possible to detect
epidemics according to etiology before their
‘I’,BLl: VI
\IUAI. l)ms:.&ss om” TIlE (:x’mutm, Nm:mmvo;’s
Si’STE\I, MmNNF:so’m’.
I)iugnosis 1955 i95f 19:57 1958*
Paralytic 1)liommmYehitis 1IS
Nonparalytie poliomyelitis i9
Coxsackie B5 aseptic meningitis ECHo 9 aseptic meningitis W’estern equimme eimcephalitis
St. IMImis encephalitis
IyI1i)lI(XIytiC choriomemiimmgitis 10
MumI)s muemmimigoencephalitis 5
Aseptic mmmemmimmgitis, etiology
lmmm(leterlmiimied 1.7
* I)ata current as of oct. ‘10,19.55,
Data prvi(lNl l)%’courtesy of Dr. llermmmamm Kleimm,mmatm,
Chief, Section of Chrommic 1)iseases, I)iv. of I)isease
I’re-vention & Commtroi, Minnesota Dept. of Health,
‘i’,\BLE \‘hl
647
( #{176}MPARATIVE AGE DIsTRIBuTIoN on THREE TYPES
OF ASEPTIC MENmNGITIS IN MINNESOTA
I)ata provided by I)r. II. Kleimim,ummm,IiIImm(’sota
l)e-partment of Health.
pathologic characterization. Many
interest-ing questions have been raised thereby:
what factors other than humoral antibody
may be involved in the variable manifesta-tions of enterovirus infection, and what
fac-tons are responsible for the apparently
sud-den introduction of a particular enterovintis
infection into a population?
EXPERIMENTAL STUDIES
The epidemiology of virus infection of man or animals is the practical side of
virology, while the biology of virus
infec-tion is the academic side. Both of these
aspects of virology also are aspects of
mam-Inahan cell biology. One of our group72
re-cently completed a study of the stability of
ECHO virus immtinotypes and type 1 polio-myclitis virus in media and under
environ-mental conditions appropriate to cell
cul-ttmne, primarily to aid assessment of
labora-tory findings. ECHO viruses exhibited a
wide range of stability, half-life varying
from about 40 hours for ECHO-6 to about
‘ 2 hours for ECHO 20 and about 48 hotmrs
::
. - fortion typein biologic1 poliomnyclitisproperties virus.of entero-virusesSuchvania-357 may he of epidemiologic interest, in view
of the wide range of disease manifesta-tions which appears related to the
trans-portation of these agents from the
else-ENTEROVIRUSES
‘here iii tlu’ hR)dlt’ 111tlic sanic \‘VlIi of
con-sideration, one may wonder abotit the
ca-1acit’ of cells other than gastrointestinal to
suffer infection. The varying clinical
mani-festations of enterovirus infections suggest
that many cell types are stisceptible, but
thiat this potentiality is realized to a widely
varying d!egrce in particular persons at
par-ticular times,
Further teclimiical advances in cell-culture
methods arc required to translate such
qtiestions into laboratory investigatiomi. For example, one would like to dissociate
se-lected mammalian tissues into suspensions
of constituent cells, amid propagate these
from primary clonal origin. As an approach
to this objective, ne of ur group,7 :‘ fl
lowing 4 ‘ work with mouse
mammary gland, has used collagenase
suc-cessfully to disperse mammalian Iting
tis-sue. Such tissue, probably by reason of its
fibrous content, is poorly dissociated by
tryptic digestion. Primary and continuotis
ctiltures of cells, morphologically resem-bhing mesothelitim, were readily produced from the lung of adult or fetal human, swine
Oi rabbit. Human lung cultures, although minimally affected pathologically,
propa-gated egg-infectious influenza A and B
viruses through many passages. Human
lung cells d!id! not propagate swine vintis.
Swine lung cultures propagated high-titer
swine virus, and yielded some cgg-infec-tiotis human A virus after 15 passages. Such
improvements in cell culture technic are
needed! to permit the epidemiologist to
select indicator cell cultures appropriate for
study of viruses of interest.
Availability of a wider assortment of human and animal cell types for culture
also would facilitate biologic characteniza-tion of virus variation. It has beemi observed in our laboratories7 that adaptation of Cox-sackie viruses to human amnion cultures
has variable effect on diagnostic
pathoge-nicity of the viruses for suckling mice. With
serial passage in human amnion cultures, Coxsackie A and! B viruses became
increas-ingly infective for amnion cells. This
en-hanced infectivity was accompanied by a
loss of iiioimse 1)atlu)geni(’it\’ in 50(11 I111IIi(’I’
as to distingtiish A-13, A-18 and A-li and 15 Coxsackie viruses. The A-iS virus rapidly lost mouse )athiogdnicitv, l)ut only so far;
A-18 virus contimiucd to lose mouse
pathio-genicitv gradually; and! the A-li and 15
viruses simply lost infectivity rapidly and
steadily beyond limits of detection.
These variations of 1)ath( gen icity are
naturally of interest with respect to virus
vaccine productioti, l)ut also are of
epi-demiologic imitenest with respect to the
dy-namics of propagation of inus populations.
Does multiplication of enterovinuses in thie htiman gut under some conditions yield!
pathogenic variants able to attack cells in
tissue beyond the gut, although undiffen-entiated antigenicahly from the ptremit population? This question suggests another
in tum: Is suscc1)tibiiitv of mammalian cells to enteric or other virus infection
constitu-tionally or phsiologicailv dletenmmnedl? At
Minnesota, we have beemi comicernedi with
associating virtis infection and prodtiction
of virus with physiologic activity of cells.
Recent studlies have shown tis that
stiscepti-bility of primate cells and instisccptibihity
of nonpnimate cells to pohiomyelitis virus is determined by presence or absence of
spe-cific receptive structures resl)onsihle for
ad-sorptive and! eclipse phases of pohiomvchtis
virus infection. ‘ The complex iircess of
infection of stlsceptible cells is initiated! by
apparently mechanical attachment,
fol-lowed by a more complex process of trans-portation of virus beyond! the reach of
externally-applied antibody. This transport
and the inactivation of the infectivity of
cell-received virus was not fotind diependent
on metabolic activity on physical integrity of cells. Debris from pohomyclitis
virus-susceptible cells imiactivated virtis in the
same manner as intact cells adsorbed virus. Since the significance of this work
de-1)ends on unequivocal association of
REVIEW ARTICLE 649
gnotip has contributed a hemagglutmnation
technic to distinguish cellular species. Guinea pigs were immunized with cells of
particular species origin and
hypenimmu-nized with cells of the same or different origin. Species origin of the immunizing
cells was indicated by capacity of antisera
to agglutinate erythrocytes of homologous
species. Species identification was con-firmed by responses of the guinea pigs to hypenimmunization; hyperimmunization
with homologous cells produced typical see-ondary responses, while re-injection with hieterologous cells induced another primary
immune response. When this test was ap-plied, we found no exceptions to the
in-susceptil)ihty of nonpnimate cells to
polio-myehitis virtis infection.
During the period when poliomyelitis
virus adsorbed by primate cells was carried
into the eclipse phase, its infectious
poten-tial was not abolished by treatment with
ribonuclease. It is therefore not clear
whether the process of reception involves
separation of viral ribonucleic acid from its coating protein. It is apparent, however, that the vulnerability of these cells, and the invulnerability of nonprimate cells, is not
dependent omi vital cellular activity.
Presum-ably, the process of virus replication and
assembly must be so dependent.
We have beemi interested to establish a (jtlantitative basis for association of virus
production with cellular physiologic
ac-tivity. By convenient use of manometry for measurement of oxygen consumption, a
pre-viotis member of otin group was able to
quantitate cellular physiologic capacity.8#{176} HeLa and momikey-kidney cells were found
to produce virus at greatly decreased rates
when incubated anaerobically rather than aerobically. When time amount of virus pro-duced was related to the decreased rate of
metabolism tinder anaerobic conditions, the
data stiggested that rate of virus prodtmction
was a ftinction of metabolic activity. The
findings wene compatible with the assump-tioii that the time required for production of nmaximumn ‘irns yield by cells was a
func-tion of the time required for generation of
a certain amount of energy, under either anaerobic or aerobic conditions. A similar
result was observed for the effect of
tem-perature on virus production.8’
From the work of Alexander and hen asso-ciates,82 we know that mammalian cells can
be infected (that is, induced to manufacture infectiotis poliomyelitis virus) by the ribo-nucleic acid component of pohiomyehitis
virus alone. If we accept the nonvital
na-tune of virus adsorption and reception and
associate cellular vital activity with rate of virus manufacture, are we left with the picture of an infected cell as one wholly
dominated by the commands of the crystal-hized code of the foreign nucleic acid? Are
cells that are immune to infectious viruses immune to their nucleic acids as well? The question is pertinent to the epidemiology of
viral disease as well as to the biology of viruses.
Until we elucidate mechanisms for varia-tion and selection of biologic characters of
viruses, we shall continue to wonder where
all of the enteroviruses came from, how
they are establishing themselves with in-creasing frequency as agents of human dis-ease, and where they go when we do not find them as current agents of infections for which they have been responsible
previ-ously.
CONCLUDING COMMENTS
The evolutionary history of the
entero-viruses is evidence that the rapidly
expand-ing field of cellular biology has applied as well as pure scientific value. It has been
said2#{176}that “human enteroviruses are: a) cos-mopolitan in distribution, being found in all
parts of the world; b) seasonal and
temper-ate, with occurrence limited principally to the summer months, and to tropical and sub-tropical areas and health resorts; c)
demo-cratic in practice, being causative agents of inescapable afflictions of man; d)
common-place in their selection of habitat, persisting under natural conditions as transient occu-pants of the orointestinal tract; e)
hardy,
making easy time problem of transfer to a
650 ENTERO VIRUSES
f) productive only of i1wery and ill health,
as evidenced each year by summer grippe and diarrhea, pleurodynia, paralysis, aseptic
meningitis and myocarditis; and finally, g)
eagerly ambitious, as shown by progressive
displacement of the poliomyelitis viruses as causative agemits of virus disease of the central nervous system.”
Acknowledgment
Tables 1-VI are reproduced with pei’niission
from the American Journal of Tropical
Medi-cine and Hvgiemie, 8: 101, 1959.
REFERENCES
1. Armstrong, C. : Seasonal distribution of
pohiomyehitis. Am.
J.
Pub. Health, 40:1296, 1950.
2. Sabin, A. B. : Paralytic consequences of
pohiomehitis infection in different parts
of the world and in different population
groups. Am.
J.
Pub. Health, 41:1215,1951.
3. Bodian, D. : Pathogenesis of poliomyehitis. Am.
J.
Pub. Health, 42: 1388, 1952. 4. Paul,J.
R. : Historical and geographicalaspects of the epidemiology of
pohiomy-litis. Yale
J.
Biol. & Med., 27: 101, 1954.5. Salk,
J.
E. : Principles of immunization asapplied to poiiomyelitis and influenza.
Am.
J.
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