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Clinical Studies: Arthropod-Borne Virus Disease in Florida
Clinical Studies: Arthropod-Borne Virus Disease in Florida
Clinical Studies: Arthropod-Borne Virus Disease in Florida
T
ifk. small outbreak in man of arthropocl- tients hospitalized \vith \+us meningitis or
t)ornc virus meningitis and encephalitis vllcephalitis betwecu February and September
th.:~t occurred in Miami during the last four lO.i8 were tested for hemag$utination-inhibi-
irwnths of 1958 is noteworthy since it is the first tion antibodies to \-arious group R arl )o viruses,
su~:h outbreak to bc recognized in Florida. Prior and serum samples collected in 1957 and 1958
to this only occasional cases of arthropod-borne from sixty-four Miami residents \\ithout signs of
(ariw) virus infection in man had bcrn detected central nervous system infection \\‘err trs ted for
in the state: only t\vo cases of St. Louis cncepha- iiwtraliziny antihotlics to se\ eraI group .-A and
litis \vcre reported before 1958, and cases of R arho viruses.
Eastern equine encephalomyelitis ancl \l-estern
rquinc enccp halomyclitis \vcrc equalI!! rare
[I:,?]. Similar arbo virus infection occurrccl in L’lit~ictrlC&r irr ‘l’he diagnosis of’ virlus cnccpha-
1958 ill ac\-vral (:aribbean Islancls and on the litis ~vas made in patients with acute OIXCI ol a f’ehrilc
Spanish Main: in Fctxuar)-, St. Louis cncepha- disease associated with impaired intellectual function
or altered consciousness or other objcctikc widenct
litis infection \vas seen in Panama: in August, it
of neurologic abnormality above the filth I:cwical
occurred in Jamaica; and in Scptembrr, it was
segment of the spinal cord. In these t)atit.nts. leuko-
prcscnt in Trinidad and reappeared in Panama. cytes \wre almost alxvays prcsrnt in thr- spillal lluid.
St. T.ouis encephalitis virus was isolatccl from \Yrus mrningitis was considerc.d to 1)~ ;I*, acute’
tllv ))lood of three patients in Trinidad and leebrilc disease characterized l+ the findings of ar
Panama whose onI!- s)-mptoms \vcrc severe lcast 30 \vhitc blood cells per cu. mm. in the spinal
h~aclache and fr\.er; the o\wt encephalitis of fluid, normal sugar levels in the spinal fluid and none
thus Jamaican patients was found to tx St. Louis of the signs of rncephalitis. In both illnesses, headache
ellccphalitis t))- serologic test L&5]. Thus the \vas usually a prominent syin~)torn. Patients with
fwain tumors or abscesses. bacterial or liingal menin-
cases in Miami that year may well liave been
gitis, syphilis, cerebral vascular accidtnts. bacterial
part of the outbreak of arbo virus infection that
cndocarditis and ljoisoning overt’ cuclud~l from the
ws tlwn occurring iii the Caribbean area.
rtudv.
III ;I search for othrr overt and for inapparent In addition to the studies l’or arbo viruses 10 bc
art)0 1 irus infections in South Florida. serologic listed. serologic studies for leptospirosis and lympho-
stuclics were carried out on specimens collected cytic choriomeningitis, influenza .2. aclcnc~~iruses and
from Miami residents prior to October 1’958. C:oxsackie B viruses were performed on IIIOS~ of tllesc~
Serum specimens obtained from eighteen pa- patients at rcfcwnce laboratories.
* l’roin the Department of Medicine, Liniversity of Miami School of Medicine and ‘l‘he Jackson Rl~morial HOS-
pital, htiami, Florida, and the Laboratory of Tropical Virology, National Institute of Allergy and Infectious Diseases,
National Institutes of Isealth, U. S. Public 1Health Service, Bethesda, Maryland. This study was supportctl in part by
U. S. Public Health Service Research Grant No. E-4084 from thr National Institutes of r\llergy and lnfrctiow ‘I)iseases,
Public I Iealth Service, Bethesda, Maryland.
t Markle Scholar in Medical Scienrr.
-r I&stern
employed those contained
from high speed centrifugation
in the supernatant fluid
of a borate-saline
Equine (pH 9.0) suspension of infected brains from suckling
it. Louis Enceph- Ilheus
Enceph- mice. Naturally occurring hemagglutination in-
alitis Virus Virus
alitis hibitors were removed from the serum by acetone
Virus extraction [ 701. Erythrocytes were obtained from
Day
Case Of chickens less than four days of age.
NO. Dis- All serum specimens were stored at minus 20’~.
case * Lo,g IHemag- -femag- 14 until tested.
Jeutral- Iclutina- Tlutina- VlWral-
ization tion tion ization
CASE REPORTS
Index Inhibi- Inhibi- Index
(log- tion tion ilog- Details of the arbo virus serology in Cases I,
.rithms) Titer 1 Titer t 3rithms) II, III and v are given in Table I.
tliscase point to the recent occurrence of infec- guished in the absence of recovery of the virus.
tioii with this or a closely related agent. In This serologic pattern of high antibocl) titers to
C:ai;c II the marked rise in titer of hemagglutina- antigenically related viruses is similar to that
tion inhibition antibody to St. Louis cncepha- seen in residents of known endemic areas of
litis virus between day 3 and da)- 100 of disease group B arbo virus infection [ 7 jr, I_‘].
clearly associates the time of St. 120uis cncepha- ‘T’herc was no serologic eviclence of infection
litis virus infection with the signs of encephalitis; with Eastern cquinc encephalitis, lvmphocvtic
the low titers of hema gglutination inhibition choriomcningitis, mumps, influenza A, adeno-
and neutralizing antibodies in the specimen viruses, C:ossackie B or leptospirosis in these
taken two years and eight months later are in patients. Attempts to isolate viruses from spinal
keeping with infection by St. Louis encephalitis fluid anct blood in Casr III were unsuccessful.
virus in 1058.
In Chase<III and v a significant rise in the level
of St. I,ouis encephalitis virus neutralizing So hemagglutination inhibition antibody to
anti body was demonstrated at three and one St. Louis cnccphatitis, Ilheus or .Japanesc B
months, respectively, after the beginning of the encephalitis viruses was found in the serum
illrlrsses. The high St. T,ouis encephalitis virus specimens obtained during the acute and con-
hemagglutination inhibition antibody titers in \.alescent phases of disease from fourteen pa-
both confirm the recent occurrence of group B ticnts II-it11 \ irus meningitis and four with
arbo virus infection. In case III, as in Chases I and cnccphalitis accluired in Miami bet~~rcn Frh-
II, the infection was likely due to St. Louis ruary and September 1958.
enccplialitis virus. as the lo\v Ilheus virus In order to investigate inapparent arlx) virus
hemagglutination inhibition antibody titers are infection in h4iami residents, single serum
beet attributed to a response to antigens common specimens obtainect from sixty-one adults and
to I)otli viruses. BJ- contrast, the serologic find- three children in 1937 and early 1058 tvere
ing< in Cast v \rere distinctly different from examined for neutralizing antibodies to group
thc)se in the other casts since this patient’s A and group B viruses. (Table II.) At the time
hrmagglutination inhibition antibod>- titers to of bleeding, the adults had been rcsidcnts of the
Ilheus and St. Louis encephalitis viruses were .Uiami area from three to forty-three years and
equally high. Prior to this illness this patient were under treatment at the Jackson Memorial
(C:asc v) had been a resident of XZiami for Jlospital or Clinics for a variety nf illnesses
t\<‘elve !.ears: ho\Vcver, she was born in Puerto unrelated to those known to be caused by arbo
Rico and earlier infection mitll arl)o viruses viruses. Of serum tested for antibodies to group
ma” ha\v: occurred there. The serologic results A agents (Eastern and LYestern equine cncepha-
in this instance can be attributed to infection litis), one of forty-five neutralized Eastern cquinc
wi.th either Ilheus or St. I,ouis encephalitis encephalitis virus and none of sixty-two neu-
virtls. The infecting agent cannot be. distin- tralized Western equine encephalitis virus. B\
“r,l.. 15, NOVEMRER 1963
678 Arthropod-Borne Virus Disease--Ehrenkranz et al.
TABLE III
T
-
A 27 3 Georgia + - - - -
B 24 3 Bahamas _ - + - T +
C 35 35 Florida - _ _ _ + NT
D 58 8 Tennessee - -
_
-
_
- +
_ NT
E 72 43 Bahamas NT NT +
F 20 20 Florida _ _ _ _ _ +
- - - -I - !-
* f Designates antibody present; - designates antibody not detected; NT designates not tested.
contrast, neutralizing antibodies to four group B litis infection, ncurologic manifestations similarly
agents (St. Louis encephalitis, yellow fever, varied from severe headache alone to frank
Ilheus and West Nile viruses) were detected in encephalitis.
five of sixty-two serum samples. Xeutralizing The concurrence of eight and perhaps ten
antibodies to more than one arbo virus were cases of St. Louis encephalitis in Panama,
found in the serum of only one person, Miami Jamaica, Trinidad and Miami in 1958 points
resident B (Table III); in this instance anti- to trans-Caribbean spread of St. Louis encepha-
bodies to St. Louis encephalitis, Ilheus and litis virus. (Fig. 2.) Since large epidemics of St.
West Nile viruses were all present. The amounts Louis encephalitis are infrequent and the ratio
of serum available from two persons with Ilheus of inapparent to apparent infection in such
antibody were insufficient to test for presence outbreaks ranges from 16: 1 to 500: 1 ]13], it is
of West Nile virus neutralizing antibodies. The likely that undetected cases of St. Louis encepha-
three serum specimens reactive with Ilheus litis virus infection occurred elsewhere in South
virus in the screening virus neutralization test Florida and Caribbean Islands in 1958 and
were tested further and log neutralization that this outbreak may have been considcrabl)
indices of Ilheus virus were 1.8, 2.0 and 1.2. more extensive than these cases suggest. Indeed,
a major factor making possible the intensive
COMMENTS
study of these cases in Panama, Jamaica,
St. Louis encephalitis in three Miami patients Trinidad and Miami was their occurrence in
(Cases I, II and III) was characterized by severe relative proximity to laboratories engaged in
headache, fever and impaired intellectual func- arbo virus research.
tion or coma. Two additional patients may have Above and beyond these cases of St. Louis
had St. Louis encephalitis virus infection as encephalitis, the serologic survey of specimens
well: in Case IV the diagnosis of virus encepha- obtained prior to the autumn of 1958 reveals
litis was made solely on the pathologic findings, that South Florida, together with various
and in Case v serologic studies did not distin- Caribbean areas, is a region of considerable
guish between St. Louis encephalitis and Ilheus arbo virus activity. Six of sixty-four serum
virus infection. In the latter two patients, samples from Miami residents neutralized arbo
encephalitis was not clinically apparent and viruses and five of the six had antibodies to
their illnesses consisted of headache, fever and group B arbo viruses (St. Louis encephalitis,
meningitis. In the patients from Jamaica, Ilheus and !Vest Nile viruses). This proportion
Trinidad and Panama with St. Louis encepha- is similar to that of another 1957-1958 study of
AMERICAN JOURNAL OF MEDICINE
Arthropod-Borne Virus Disease-Ehrenkranz et al. 679
1958 TRANS-CARIBBEAN
OUTBREAK OF
ARTHROPOD- BORNE VIRUS
INFECTION
REPUBLIC
OF
FIG. 2. Sites of group B arbo virus casvs occurring in Ck~ribbean Islands and adjacent arras in 19Sb.
serum samples from Miami residents in which to Ilheus and other group B arbo viruses j 171.
9 per cent of the adults were found to have “Dengue-like” disease has occurred in Miami,
group B arbo virus antibodies as manifested by hut attempts to isolate an infecting agent have
the results of an hemagglutination inhibition not been successful [74,78]. Dengue virus has
test with a. dengue virus [ 741. Serologic reactions I xen present in Jamaica, Trinidad and British
to arbo virus infection are not limited to the (Guiana in recent years [77,77,7Q]. Ilheus virus
infecting agent but are apt to occur bvith anti- infection may well occur in Florida as Ilheus
genitally related viruses as well [ 7 1,751; thus the virus infwtion of birds, mosquitos and man does
occurrence of antibodies to St. Louis enccpha- occur on both sides of the (:aribhean Sea in
litis, Ilheus, \2:est Nile and dengur viruses in Honduras, Guatemala, Trinidad and British
South Florida’:residrnts does not imply, neces- Guiana [_)1)_-221;too little is currently known of
sarily, infection with each iof thcw viruses. the natural clisease to recognize it clinically
However, the presence in Florida of a group B [Xl. While antibodies to St. I.ouis encephalitis,
arbo virus other than St. Louis encephalitis is Ilheus, IVest Nile and dengue viruses are found
suspect due to the absence of antibody to St. in populaces of South Florida as well as of some
Louis encephalitis virus in some serum samples Caribbean Islands, serologic cvidencc of infec-
from Miami residents neutralizing Ilheus or tion with yellow fever (another group II arbo
\Vest Nile viruses. (Tahlc III.) Since 1Vest Nile virus) is confined to residents of the more
virus has not yet been encountered in the Yew southern Caribbean areas [ 7 7,771. Ar bo l;irusrs
World, it is unlikely that infection with this thus far isolated in the Caribbean Islands and
virus has been occurring in Miami.* ‘IVest Nile North America are listed in Table IV.
virus neutralizing antibodies have also been The possible relation of bird migration to
detected in the serum of Trinidad residents but trans-Carihbcan arbo virus infection is at
only in association with neutralizing antibodies present a sub.ject for further investigation since
insufficient data arc at hand to support or reject
* Because of the mig-ration of cattle rgrets from .4frica
this hypothesis. Suffice it to say that birds using
to South and North America [7ril thrrc is a remote
possibility t.hat IVest Nile virus map have bwn recently the Mississippi and Atlantic fly-ways of North
introduced into the Ll’estern Hemisphere. -America traverse the Florida peninsula on their
vol.. 35, NOVEMBER 1963
680 Arthropod-Borne Virus Disease-E/zrenkranz et al.
TABLE IV presented. These findings suggest that Florida,
ARTHROPOD-BORNE VIRUSES OF NOR?‘H AMERICA
together with the Caribbean Islands and the
AND TIIE CARIBBEAN ISLANDS [75]
Spanish Main, is an endemic area of arthropod-
borne virus disease.
Grouf
A
Eastern equine encephalomyelitis (EEE)
\Yestern equine encephalomyelitis (WEE) dcknowlea&ment: F2:e are grateful to I)r. Joseph
Venezuelan equine encephalornyelitis (VEE) E. Smadel of the National Institutes of Health
Mayaro
and to Dr. Wilbur G. Downs of the Rockefeller
Groufi R
Foundation for their critical and constructive
Bat salivary gland (Rio Bravo)
Ilhcus
reviews of the manuscript. LVe are also grateful
Modoc to Dr. Peritz Scheinberg, Professor of Neurology,
St. Louis encephalitis (SLE) University of Miami, for bringing Cases I and II
Yellow fever to our attention.
Powassan
Dengue viruses
REFERENCES
Runy~n~uern Grou/,
Cache Valley 1. Surveillance of arthropod-borne encephalitis in the
Kairi United States-1956-1957-1958-1959. Reports of
Other Grouj~s the U. S. Department of Health, Education and
California encephalitis Welfare, Public Health Service.
Trivittatus 2. SANDERS, M., BLUMBERG, A. and HAYMAKRR, \V.
Melao Polyradiculopathy in man produced by St. Louis
Bimiti encephalitis virus (SI,E). Southern .2Z. ,J.-, 46: 606,
Oropouche 1953.
Turlock 3. GRANT, I,. Encephalitis in .Jamaica. Presented at the
Fifth I\nnual Meeting of the Standing Advisory
Ungrou@d
Committee for Medical Research in the British
Blue tongue
Caribbean Territories, Kingston, Jamaica, B. W. I.
Colorado tick fever
April 1960.
Hart Park
4. SPENCE, L., DOWNS, LV. G. and Bout, C. Isolation
Manzanilla
of St. Louis encephalitis virus from the blood of a
Other Unnamed Viruses
child in Trinidad, W. I. WestIndian izf. J., 8: 195,
1959.
5. GALINDO~ F., DE RODANICII~, E. and JOIINSON, C. M.
St. T,ouis encephalitis in Panama. I. Isolation of
way to and from the Caribbean and that arbo the virus from forest mosquitoes and human
viruses have been isolated from migratory birds blood. Am. .J. Trofi. Mrd., 8: 557, 1959.
6. PAUL, .J. R. The filterable viruses. In: Laboratory
in various parts of the Caribbean Sea [23].
Methods of the United States Army, p. 579.
Edited by Simmons, J. S. and Gentzkow, C. .J.
SUMMARY
Philadelphia, 1344. Lea & Fcbiger.
.i\rthropod-borne virus infections occurred in 7. SMrrHBcJRx, K. C. Neutralizing antibodies against
arthropod-borne virus in the scra of long-term
a small group of human subjects in Miami,
residents of Malaya and Borneo. ~fm. .I. Hyg., 59:
Florida, in 1958. Serologic studies in four of the 157,1954.
five cases reported herein indicate that St. J,ouis 8. REED, I,. J. and MUENCH, H. A simple method of
encephalitis virus or a closely related agent was estimating 50 per cent end points. Am. .J. ZZvg., 27:
the probable cause. Autopsy specimens in one 493, 1938.
9. CLARKE, D. IT. and CASALS, J. Techniques for
case revealed microscopic evidence of viral
hemagglutination and hemagglutination inhibi-
encephalitis. These cases in Miami were asso- tion with arthropod-borne viruses. .Im. .J. Trap.
ciated in time with similar ones in .Jamaica, Itled., 7: 561, 1958.
Trinidad and the Republic of Panama: this 10. CASAIS, .J. and BROWN, I,. V. Hemagglutination
with arthropod-borne viruses. .I. Eqber. Med., 99:
points to an outbreak involving the Caribbean
429,1954.
and adjacent areas.
11. DOWNS, W. G. Immunity patterns produced by
.4 survey of serum specimens obtained from arthropod-borne viruses in the Caribbean area.
sixty-four Miami residents prior to the outbreak In: Proceedings of the 6th International Con-
revealed that six had neutralizing antibodies to gresses on Tropical Medicine and Malaria, vol. 5,
p. 5. Lisbon, 1958. Imprensa Portuguesa.
one or more arthropod-borne viruses. Serologic
12. POND, W. L., Russ, S. B., LANCASTER, W. E. Ii.,
evidence of infection with a group R arthropod- AUDY, .J. R. and ,SMADEL, J. E. Japanese encepha-
borne virus other than St. Louis encephalitis is litis in Malaya. II. Distribution of neutralizing