Vol. 88, No. 1
A X I S K U H JouEMii. or EPTDHOOLOOT
Pnnltd tn U.S.A.
Copyright O 19*7 by The Johns Hopkim Univetifty
DENGUE FEVER IN A PUERTO RICAN COMMUNITY1
JOHN M. NEFF*, LEO MORRIS', RAFAEL GONZALEZ-ALCOVER4, PHILIP H.
COLEMAN1, STANLEY B. LYSS* AND HENRY NEGRON 1
(Received for publication September 27,1966)
INTEODTJCTION
1
From the Communicable Disease Center
(CDC), Public Health Service, UJ3. Department of Health, Education and Welfare,
Atlanta, Georgia and the University of Puerto
Rico School of Medicine, Rio Piedras,
Puerto Rico.
Grateful acknowledgement is made to the
Puerto Rico Department of Health. Without
their cooperation and active support, this
study would not have been possible: Dr.
Guillermo Arbona, Secretary of Health; Dr.
Francisco Berio, Deputy Secretary of Health;
Dr. Victor A. Gomalee, Director, Bureau of
Health; Dr. Rafael A. Timothee, Director,
Division of Preventive Medical Services; Dr.
0 . Costa Mandry, Director, Division of
Health Laboratories; Dr. Jose Nine Curt,
Regional Director, NE Region, Dean of the
School of Public Health; Dr. Paul Weinbren,
Virologist, Nuclear Center, University Medical
Center; Dr. Agustin Cajigas, Assistant to the
Director, Division of Health Laboratories;
Dr. Francisco Suarei, Director, Guaynabo
Health Center; Mr. Raul A Munoi, Office
of Research Planning, University Medical
Center.
Participants from the Communicable Disease
Center:
Mr. Leslie Beadle, Entomologist, Technology Branch; Dr. Donald Quick, Medical
Epidemiologist, Epidemiology Branch; Mr.
Kent Simmons, Statistician, Epidemiology
Branch; Dr. Milton Tinker, Entomologist,
Technology Branch; Dr. Telford H. Work,
Chief, Virology Section, Laboratory Branch;
Misa Elizabeth Zacha, Nurse Epidemiologist,
Epidemiology Branch.
The authors are greatly indebted to Dr.
D. A. Henderson, former Chief, Surveillance
Section; and Dr. A. D. Langmuir, Chief,
Epidemiology Branch, for their critical review
of the manuscript.
'Formerly Epidemic Intelligence Service
Officer, Epidemiology Branch, C D . C ; Present
address: Children's Hospital Medical Center,
Boston, Mass. 02115.
•Formerly Assistant Chief, Surveillance
Section, Epidemiology Branch, CJD.C; Presently Assistant Chief, Smallpox Eradication
Program, CD.C.
'Department of Medicine, University of
Puerto Rico School of Medicine.
"Formerly Virology Section, Laboratory
Branch, CJD.C; Presently Assistant Chief, Biological Reagents Section, Laboratory Branch,
CD.C.
'Formerly Epidemic Intelligence Service
Officer, Epidemiology Branch, C D . C ; Present
address: Senior Pediatric Resident, Albert
Einstein College of Medicine, New York City.
1
Medical
Epidemiologist,
Technology
Branch, CD.C.
162
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Throughout 1963 and 1964, an illness
serologically documented as a group B
arbovirus infection and clinically resembling dengue fever was present in epidemic proportions in the Caribbean area.
This epidemic was first recognized in
Jamaica in the spring of 1963 and then
in Puerto Rico in August of that same
year. During the latter part of 1963 and
early 1964, outbreaks were also reported
in Venezuela, Antigua, Dominica, St.
Kitts-Nevis and Auguilla, Dominican
Republic, Martinique and the Netherlands Antilles (island of Curacao) (1).
In the United States, a total of 29 imported cases of dengue fever was reported in individuals who acquired the
disease while in the Caribbean. (2)
In Puerto Rico, cases were first reported along the North Central coast in
the municipality of Manati in late August 1963 (figure 1). The epidemic subsequently spread to the San Juan-Rio
FIGURE I
REPORTED OUTBREAKS* OF DENGUE FEVER
PUERTO RICO
August 1-31,1963
August 1963-January
1964
PUERTO RICO
MUNICIPALITIES
• A l Uo*» 100
Pwrto Rico
ID
**.
163
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August I-September 3 0 , 1963
164
NEFF ET AL.
Preliminary mosquito surveys demonstrated the presence of the A. aegypti
mosquito in more than half the dwellings. Guaynabo had reported no dengue-like illnesses before September 1, the
date on which studies were inititated.
This paper will deal with the clinical
and epidemiologic aspects of the disease
as it occurred in the community. Studies
relating to virus identification and more
complete data on serologic response to
infection are reported in other papers
(5,6).
METHODS
At the beginning of the investigation,
a census was taken in the community to
establish accurate geographic and population descriptions. Following this, three
principal and separate studies were developed: 1) a morbidity survey of the
entire community; 2) a pre- and postepidemic serologic survey; and 3) houseto-house surveillance where there was
detailed clinical, serologic and epidemiologic observation of the disease in two
selected areas of town, Barriada Frailes
Llanos and Barriada Marrero.
Census and description of the community. During the first week in September, the boundaries of the community were delineated, as indicated in the
map in figure 2, and a census taken.
Trained interviewers from the University of Puerto Rico Office of Research
Planning and the Division of Preventive Medical Services, Puerto Rico Department of Health, visited the 591
households within the census area. Interviews were completed in 553 of 556 occupied households, which included a total
of 2,777 persons, an average of five persons per household. Two households
were on vacation, and a third household refused to be interviewed.
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Piedras area, Ponce and the eastern end
of the island during the month of September. By January 1964, most of the
populated municipalities along the coast
had been infected, leaving the central,
sparsely populated mountain regions relatively unaffected. The Puerto Rico epidemic reached its peak during the latter
part of 1963 and subsided rapidly during
the early months of 1964. Although
greatly under-reported, there were more
than 27,000 cases officially recorded by
the Puerto Rico Department of Health
during the course of the epidemic. There
were essentially no hemorrhagic manifestations, no mortality, and only a
small proportion of cases sought medical attention.
Although many epidemics of dengue
have been reported in the past and dengue fever as a disease entity was recognized as early as 1779 (3), it was not
until the work of Sabin and his associates during World War II (4) that its
definition through virologic and serologic techniques became feasible. The
occurrence of the recent epidemic in
Puerto Rico offered a unique opportunity to study this disease epidemiologically in more detail than had previously
been possible. Because of early recognition of the disease and the demonstration that the vector Aedes aegypti
was prevalent in many communities
throughout the island, it was possible to
initiate a prospective epidemiologic study
by choosing a community to which the
disease would most probably spread.
The town chosen for this study was
the small, semi-rural community of
Guaynabo situated along the Northern
coastal plain of Puerto Rico, 35 miles
east of Manati and 10 miles south of San
Juan. The altitude of this community is
not over 500 feet; the seasonal variation
of temperature and rainfall is slight.
DENGUE PEVEB IN A PUEBTO BICAN COMMUNITT
165
Figure 2.
GUAYNABO,
PUERTO RICO
Of the 563 households interviewed, 45
per cent of the dwellings had open cement
foundations, and 94 per cent had no
window screens. The houses were generally closely clustered, and in many instances open cans, tires and other possible mosquito-breeding sites were found
in the immediate surrounding areas. Approximately one-third of the households
used plumbing facilities for sewage disposal, one-third, septic tanks and onethird, open privies. Over 90 per cent of
the population had always resided in
Puerto Rico. The majority of those who
had not always resided in Guaynabo
had moved there from the San Juan
metropolitan area.
In general, the heads of the households reported limited educational experience. Only 2.9 per cent were college
graduates, another 18.2 per cent were
high school graduates, and more than
half had had less than 6 years of schooling. Seventy-six per cent were employed
in a skilled manual, semi-skilled or unskilled capacity.
The 2,777 persons in the 553 households formed the sampling frame from
which random samples could be selected
during the course of the study. Estima-
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N
166
NEFF ET AL.
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tion of sample sizes and variances of the six weeks was excluded from the survey.
sample estimates were computed accord- This left 22 illness-free households coming to methods described by Cochran prising 102 persons. Paired pre- and
post-epidemic sera were obtained from
(7).
Morbidity survey. A household mor- 66 of these 102 persons. The pre-epibidity survey of the community followed demic sample was drawn at the end of
the general course of the epidemic. A the first week in September, and the
simple random sample of 177 house- post-epidemic sample during the last
holds, approximately 30 per cent of the week in November. These 22 housepopulation, was selected. Each house was holds were visited every two weeks for
visited every two weeks during the three- follow-up in the same manner as the 177
month study period, and on each visit households that were included in the
the history and symptomatology of all morbidity survey.
House-to-house surveillance {study
illnesses occurring in the household during the preceding two to three weeks area). In two segments of the commuwere elicited and recorded on a standard nity, Barriada Frailes Llanos and Barriada Marrero, the course of the epidemic
form.
Dengue fever without hemorrhagic was followed by daily house-to-house
manifestation has been classically de- surveillance. These two areas, located in
scribed as an incapacitating illness char- the north and south of the town (figure
acterized by a short. prodromal period 2) included a total of 145 households infollowed by an abrupt onset of fever habited by 738 persons, or 25 per cent
associated with severe headache, sensa- of the entire community. In Barriada
tion of chilliness, opthalmalgia, conjunc- Frailes Llanos 524 individuals lived in
tivitis, severe myalgia and often a rash. 104 houses; in Barriada Marrero 214 inThe duration of illness, while variable, dividuals lived in 41 houses. Both areas
is generally not more than 7 to 10 days. were socially and geographically sepaThere is essentially.no associated mor- rate.
The method of surveillance was as
tality, but severe cases may .be followed
by a prolonged convalescent period, of follows: From the beginning of the secseveral weeks characterized by marked ond week in September and continuing
asthenia (8). Based on this description, to the first week in November, each
any illness with fever or chilliness in household was visited every morning
combination with headache, muscle pain by one of four trained interviewers from
or rash was initially considered to be a the University of Puerto Rico. The occurrence of any type of illness during
dengue-like illness.
Pre- and post-epidemic serologic sur- the preceding 24 hours was ascertained.
vey. A serologic survey characterized the In the afternoon, a physician and an
population and measured the rate of interviewer revisited the area and obantibody conversion during the epidemic. tained a clinical history and conducted
Fifty households reported to be illness- a limited physical examination on infree at the time of the census were ran- dividuals reporting an illness. When posdomly selected. Each of the 50 houses sible, acute and convalescent sera were
was visited by a physician, and those obtained, and the patient was followed
in which any member of the household daily for the duration of his or her illreported an illness during the preceding ness. Acute sera were obtained within
DENGUE FEVEE IN A PUEBTO HICAN COMMUNITY
of infection. Paired specimens were collected at least two weeks apart.
RESULTS
Entomologic survey. During the second week of September, a mosquito survey was conducted in Guaynabo to estimate the prevalence of the A. aegypti
adult mosquito and larvae throughout
the community. A simple random sample
of 60 households, which included 53
premises, was selected to estimate the
adult female index and breeding index,
respectively.
Of the 60 households, 57 were inspected and 33 (58 per cent) were found
to have A. aegypti female adulte present. Of the 53 premises, 50 were inspected and 15 (30 per cent) were found
to have larvae. These indices are well
above the normally accepted threshold
of 5 per cent generally considered necessary for the propagation of an epidemic
of dengue fever or yellow fever (11). In
fact, the lower limit of the. 95 per cent
confidence interval computed for the
estimated adult female index and the
estimated breeding index were 46 per
cent and 19 per cent, respectively.
In the two study areas, Barriada
Frailes Llanos and Barriada Marrero,
a similar survey, which included all 145
households in the two barriadas, was
conducted during the third week of October. In Barriada Frailes Llanos, adult
mosquitos were present in 59 per cent of
the houses and larvae were present on
24 per cent of the premises. In Barriada
Marrero, adults were present in 38 per
cent of the houses and larvae were present on 11 per cent of the premises.
Morbidity survey. The bi-weekry
household morbidity (sample), survey
indicated that dengue-like illness began
to occur in Guaynabo during the first
week in August (figure 3). During the
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48 hours of the onset of symptoms and
convalescent' sera at least two weeks
later. In this manner, each illness was
defined as to its onset, duration, severity
and symptom complex during the months
of September and October. During the
month of November, the households were
visited at two-week intervals. At the
close of the study, during the second
week of December, a final survey was
completed and an attempt was made to
obtain a post-epidemic serum sample
from all 738 residents of the two barriadas; at least one serum sample was
obtained from 464, or 61.5 per cent. Of
the 633 individuals over 4 years of age,
440 blood specimens (69.5 per cent) were
obtained. At least one blood specimen
was obtained from more than 70 per
cent of the 390 individuals who suffered
one or more illnesses during the course
of the study.
The two barriadas are considered the
"study area" for purposes of data presentation in tables 4 through 10 and
figures 4 through 9.
Laboratory studies. Serologic and virologic studies were conducted in the
Nuclear Center Laboratory, University
of Puerto Rico, and in the Laboratory
Branch, Communicable Disease Center,
Atlanta, Georgia. Specimens were tested
for hemagglutination-inhibition (HI)
antibodies according to the technique
described by Clark and Casals (9) and
for complement-fixation (CF) antibodies according to the technique described
by Hammon and Work (10). Antibodies
were tested for eight group B arboviruses; dengue types I, II, III and IV;
St. Louis encephalitis; Ilheus, Murray
Valley encephalitis; and yellow fever. A
fourfold or greater rise in titer in CF
antibodies to any one of the four dengue
viruses tested was considered evidence
167
168
NEFF HT AL.
Figun 3.
GUAYNABO MORBIDITY SURVEY
DENGUE-LIKE ILLNESS
BY WEEK OF ONSET
i, r963-N0V.t6.O63
SEPTEMBER
OCTOBER
NOVEMBER
first part of September, there was an
abrupt increase in cases, with a sharp
Guaynabo morbidity survey*—dengue-like illness peak in the third week of that month.
by age group and sex, August 1The incidence of cases fell off gradually
November 16, 1963
during October and November. By the
Population
week ending November 16, the overall
Cues
Attack rmtet (%)
Age group
attack rate of dengue-like illness had
M F T M F T M
F
reached 36.2 per cent (table 1). All age
143 136 279
0-9
87 25.2137.5 31.2 groups were equally affected. There was
198
10-19 109
75 29.4 48.3 37.9 a higher attack rate reported among fe20-29
68 60 118
56 44.860.0 47.5 males than males, through 49 years of
30-39
48 63101
42 35.447.241.6 age.
4<M9
42 47
TABLE 1
50-69
60+
Unknown
Totals
1
23
30
1
28 23.838.3 31.6
39.1 36.437.8
40.021.930.6
454 442 896142182 324 31.3 41.2 36.2
Sample survey included 177 households.
Pre- and post-epidemic
serologic sur-
vey. A uniform attack rate was also evident among the 66 individuals from
whom pre- and post-epidemic serologic
specimens were obtained (table 2). Of
the 66 persons in the serologic survey 24
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AUGUST
169
DENGUE FBVEE IN A PTJEBTO BICAN COMMUNITY
TABLE 3
Pre-epidemic serologic survey.
Presence of pre-epidemic antibody to group B
arboviruses by age group
Antibody present
Age group
Paired
•era
Total
with
antibody
Percent
positive
HI
CF
HI &
CF
60+
26
27
13
0
4
6
0
1
0
0
10
6
0
16
11
0.0
66.5
84.6
Totals
66
9
1
16
26
39.4
0-24
25-49
The serologic profile of the 66 individuals in the survey revealed that at
the beginning of the epidemic 26 (39.4
per cent) had demonstrable HI or CF
antibodies to one of the eight group B
arboviruses tested (table 3). In sharp
contrast to the uniform age-specific attack rates, however, CF and HI antibodies were present in increasing proportion with age. No pre-epidemic CF
or HI antibodies were present in any of
the 26 individuals younger than 25 years
of age; 26 individuals 25 yeare of age
or older (65.0 per cent) had demonstrable CF or HI antibodies. This difference between those younger than and
older than 25 years of age is statistically
significant (p < .001). The profile sug-
TABLB 2
Pre- and post-epidemic serologic survey
Comparison of serologic responses and clinical illness
Dengue-like ffloess
Afe group
0-24
25-19
60+
Totals
Total
•ample
Paired
•era
No.
Titer
rite
No illness
Attack rate
No.
Titer
rise
Dengue-like
ilmfuff
Confirmed
dengue
49
36
17
26
27
13
8
11
5
7
8
4
18
16
8
2
2
0
30.8
40.7
38.5
26.9
29.6
30.8
102
66
24
19
42
4
36.4
28.8
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(36.4 per cent) reported a dengue-like
illness during the course of the epidemic.
There was no statistical difference in the
attack rate by major age groups, and the
overall attack rate of 36.4 per cent was
in close agreement with the attack rate
of 36.2 per cent observed in the morbidity survey of the entire community.
Serologic data generally confirmed the
clinical observation. Nineteen of the 24
individuals (79.2 per cent) who reported
a dengue-like illness had a fourfold rise
in CF antibodies to one of the four dengue viruses, while only 4 of the 42 individuals (9.5 per cent) with no history
of a dengue-like illness had an antibody
conversion. When the attack rates are
computed for serologically confirmed
cases only, there is even less difference
in the attack rate by major age groups;
26.9 per cent of the age group 0-24, 29.6
per cent of the age group 25-49, and 30.8
per cent of the age group 50+ had confirmed dengue illnesses. This uniform attack rate and the close correlation between clinical diagnosis and serologic
evidence of infection suggests that the
study population was uniformly susceptible. Further, it was evident that the
symptomatology of the illness was reasonably distinctive, and that the rate of
inapparent or missed infections was
low.
170
NEFF BT AL.
House-to-house surveillance
(study area)
Clinical description of illnesses with
serologic identification. During the three
months of intensive surveillance, 390 of
the 738 persons in Barriada Frailes
Llanos and Barriada Marrero experienced at least one illness clinically consistent with dengue fever. Conclusive
serologic data were obtained for 167 of
these 390 persons. In adults (10 years
of age or older) serologic confirmation of
dengue was based upon a fourfold increase in CF antibodies to one of the
four dengue types. In children younger
than 10 years of age, .the criterion for
serologic confirmation was a positive
convalescent serum (CF titer > 1:8).
Using these criteria, 72 of the 167 had
a single illness serologically confirmed.
TABLE 4
These were therefore called "confirmed"
Confirmed dengue fever symptomatology of cases of dengue fever. The other 95 inadults and children, Barriadas Frailes
dividuals had either no fourfold rise in
Llanos and Marrero (Study area)
CF antibody titer following illness or
had no antibodies to any of the group B
Per cent with lign
or tymptuui
arboviruses on a single serum sample at
Severity of lignj and lymptoms
the
end of the period of surveillance:
Adults Children
(10+ yn. (<10yn.
the
illnesses
of these 95 individuals were
of age)
of age)
not considered cases, of dengue fever.
Fever at leaat 3 days
71
83
Illnesses in the other 223 individuals
<99.9°
19
20
could not be specifically identified either
80
31
•iooo-ioi.9°
because of multiple illnesses between
>102<<\
50
paired
sera or because of incomplete
Chilliness at least 2 days
60
83
Headache at least 3 days
78
61
serologic evidence of infection.
Myalgia at least 2 days
84
76
The symptomatology of the 72 cases
Ophthalmalgia
60 '
88
of
"confirmed" dengue fever is shown in
88
Conjunctivitis
67
table 4. There were 51 individuals 10
Lymphade nopa thy
85
73
years of age or older and 21 individuals
81
Rash
57
Petechiae i
0
10
younger than 10 years of age. The illNausea. •
72
41
nesses were reasonably similar in chilUpper respiratory symptoms
29
34
dren
and adults; they were marked by
85
Duration of illness at least
81
abrupt onset with sever^ headache and
4 days
orbital pain progressing within a few
Incapacitated at least 2 days
63
85
hours to fever, chilliness, myalgia, ar21
Total patients in group
51
thralgia and conjunctivitis. Fever ob• 1
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gests that this community had been essentially free of group B arbovirus infection for at least two decades preceding
this epidemic and that the pre-existing
antibodies in the older age groups exerted essentially no protective effect. Attack rates in individuals with and without various group B antibodies were also
compared and those with any pre-existing group B antibodies, regardless of
the type, had as high a clinical attack
rate and serologic conversion rate as
those ^ix&t had no pre-existing Group B
antibodies. In addition, the relative severity of the illness, as measured by absence from school or work or stated inability to do housework was the same in
those individuals with and those without pre-existing antibodies.
DENGUE FEVEE IN A PUEBTO EICAN COMMUNITY
171
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served in 83 per cent of the adults and plain of a convalescent period of depres71 per cent of the children lasted at sion or listlessness.
During the surveillance period, there
least three days and, at its peak, was
over 100 F (oral) in 80 per cent of all were 145 illnesses in 95 individuals that
individuals. In most instances, the fever on the basis of serologic findings were not
and symptoms subsided by the fourth cases of dengue fever. In contrast to the
day, and only rarely was a return of confirmed dengue fever cases, most of
fever noted. ,Two types of rashes were these illnesses were relatively mild and
observed. On the first day of illness, of short duration. The symptoms most
there was frequently a generalized ery- frequently noted were vague complaints
thematous hue that lasted not more than of myalgia, headache and upper-respira24 hours; on'the third or fourth day of tory or gastro-intestinal disturbances.
illness, with the subsidence of symptoms, Few of the illnesses were febrile, and
a faint maculopapular rash often de- in most instances the patient could carry
veloped over the entire body. This lasted out his or her daily activities.
Illnesses defined by clinical criteria.
not more than 48 hours. At least one of
With
a high correlation between clinical
these two rashes was noted in 81 per cent
and
serologic
observations, clinical criof the adults and 57 per cent of the chilteria
were
evolved
so that a clinical
dren. Only rarely were petechiae obevaluation
could
be
made
for the 223 ill
served in the adults and never in the
persons
whose
illnesses
could
not be dechildren. Lymphadenopathy, particufined
serologically.
These
four
criteria
larly in the posterior auricular and posincluded:
1)
an
illness
of
at
least
three
terior cervical nodes, was found in most
days'
duration
characterized
by
2)
feindividuals and often persisted for some
ver and chilliness, S) rash and 4) incatime after the patient's recovery. A senpacitation (absence from school or work
sation of abdominal discomfort manior inability to do housework) for at
fested either as nausea or anorexia ocleast two days. For those younger than
curred in 72 per cent of the adults and
five years of age, incapacitation was not
41 per cent of the children. Upper resappraised. The serologically confirmed
piratory symptoms were uncommon, and excluded illnesses are shown by
mild and generally consisted of only a these clinical criteria in table 5. This
moderate degree of nasal stuffiness. A table includes the 72 illnesses confirmed
not unusual finding was posterior pha- as dengue fever presented in table 4 and
ryngeal erythema accompanied by the 145 illnesses that were identified as
marked coating of the tongue and a not dengue fever.
vague sensation of altered taste.
Among individuals five years of age
The duration of illness was generally and older, 38 (56.7 per cent) of the 69
between four and seven days. Eighty- dengue illnesses and 7 (5.9 per cent) of
five per cent of the adults and 81 per the 138 non-dengue illnesses included all
cent of the children were ill for at least of the clinical criteria; only 4 (6.0 per
four days, to the extent of being unable cent) of the dengue illnesses met fewer
to go to work, school or do routine than two of the criteria compared to 41
housework. Most individuals returned to (34.4 per cent) of the non-dengue illtheir usual occupation by the end of one nesses. Among those younger than five
week, and only rarely did a person com- years of age, 2 (66.7 per cent) of the
172
NBFF ET AL.
TABLE 5
Clinical criteria for all serologically identified
illnetses in study area*
Serologically confirmed
Clinical criteria
Dengue
No.
Per
centf
Not Jengae
No.
Per
centt
A. Individuals > 6 years of age
Four of four
Two or three of four
Less than two of four
Unknown
Totals
38
25
4
2
69
56.7
37.3
6.0
7
71
41
19
6.9
59.7
34.4
100.0 138 100.0
B. Individuals < 5 years of age
Three of three
Two of three
Less than two of three
Unknown
Totals
2
1
0
0
66.7
33.3
0
3
100.0
2
3
2
0
28.6
42.8
28.6
7 100.0
* See text for the four (4) clinical criteria,
t Of those with known clinical criteria.
TABUB 6
Clinical evaluation of individual illnesses not
seroloffically defined, study area
Individ- IndividClinical evaluation*
Dengue
Possible dengue
Not dengue
Unknown
Totals
•O years 5 5 years
of age
of age
Total
24
14
3
8
48
79
26
21
72
93
29
29
49
174
223
• Based on clinical criteria described in text.
criteria was called a case of dengue fever, and any illness meeting fewer than
two of the criteria was "excluded" as a
case. The remaining illnesses, those that
met two or three of the four criteria,
were classified as "possible" dengue
fever. By this classification (table 6),
72 individuals were classified as having
experienced dengue fever. Of these 72,
three individuals, two of whom were under five years of age, had two illnesses
with all of the clinical criteria. In
these three individuals, the illness of
longest duration was classified as dengue
and the other illness excluded. Ninetythree individuals had illnesses that were
classified as "possible" dengue. Eight
of these, only one of whom was under
five, had more than one illness that satisfied the criteria of "possible" dengue.
As in the cases of dengue, the illness of
longest duration was included and the
other excluded. Finally, 29 individuals
had illnesses that met less than two of
the necessary criteria. These 29 individuals, along with 29 for whom there was
insufficient data for classification and/or
who were lost to followup, were excluded
from subsequent analysis.
The final classification of the 390 ill
individuals is shown in table 7; 144
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dengue ilbesses and 2 (28.6 per cent) of
the non-dengue illnesses met all of the
criteria, while none of the dengue illnesses and 2 (28.6 per cent) of the nondengue illnesses met fewer than two of
the criteria.
On the basis of these clinical criteria
it is apparent that, in individuals over
the age of four, very few non-dengue
illnesses are characterized by all of the
clinical criteria, and conversely very few
dengue, illnesses met fewer than two of
the clinical criteria. For those under five,
the numbers are small and the characterization of illness is not as distinct.
In the study area, there were 254 illnesses in 223 individuals for which there
was no conclusive serologic data. Utilizing the clinical criteria established, any
illness characterized by all of the clinical
173
DENGUE FEVEB IN A PUEBTO RICAN COMMUNITY
TABLB 7
Final classification of all tU individuals
study area
B u l l of final
4*l*¥ftfiftJ0D.
Totals
Final cl&uific&tion
Sero logic Clinical
evaluation evaluation
Dengue fever
Possible dengue
Not dengue
Unknown
Totalfl
72
0
95
0
72
93
29
29
144
93
124
29
167
223
390
FIGURE 4
DENGUE AND POSSIBLE DENGUE
BY WEEK OF ONSET, STUDY AREA
DENGUE
POSSIBLE DEN6US
20
BARRIADA
UAKRERO
IS
10
5'
CO
0
80
BARRIADA
FRA1LES LLANOS
25
2015
10
8
WEEK
ENOINQi
3
17 31
AUO
in
14 2 8
SEPT
12 2 6
OCT
9
23
NOV
6
20
DEC
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cases were classified as dengue fever. Of
these, 72 were serologically defined and
72 were clinically defined. Ninety-three
cases were called possible dengue; all
of these were clinically defined. There
were 124 cases considered not to be
cases of dengue; 95 were serologically
defined and 29 clinically defined. These
final classifications are used in the following epidemiologic description of the
dengue outbreak in the study area.
Epidemiologic analysis of the outbreak in the study area. Figure 4 de-
174
NEPF ET AL.
was gradual throughout the month of
November.
In Barriada Marrero there was essentially one major focus of illness around
which other cases developed; in Barriada
Frailes Llanos there were at least three
different foci. Cases tended to occur
within households and spread down the
street from house to house or in concentric circles around the index house.
The remarkably focal nature of this epi-
FIGURE 5
CASES OF DENGUE AND POSSIBLE DENGUE
BARRIADA FRAILES LLANOS
STORE, MECHANIC SHOP OR
HOUSE UNDER CONSTRUCTION
CHURCH
ONSET THIS 6-WEEK INTERVAL
A. CASES WITH ONSET DURING 6-WEEK PERIOD EN0IN8 AU8U8T S I .
Downloaded from http://aje.oxfordjournals.org/ at Pennsylvania State University on February 18, 2016
picts the epidemic curve for Barriada
Frailes Llanos and Barriada Marrero.
In both areas, cases began to occur in
late August, with increasing numbers of
cases occurring in early September. In
Barriada Marrero the epidemic peaked
in late September and then dropped
off sharply, but in Barriada Frailes
Llanos the epidemic developed gradually
throughout September and did not peak
until mid-October. The decline in cases
175
DENGUE FEVEB IN A PUERTO HICAN COMMUNITY
WITH ONSET
DURING
5-WEEK
demic was quite apparent. One focus of
infected households was as close as 30
yards to a clustered area of noninfected households equally populated
and mosquito infected. An example is
Area A in Barriada Frailes Llanos, where
cases occurred as early as the latter part
of August, while in Area B, about 30
yards from Area A, cases did not begin
to occur until early November (figures 5
and 6). By October, cases had spread
concentrically around the three original
foci in Areas A, C and D. At this time,
cases had still not occurred in Area B
PERIOD
ENDING
OCTOBER
5
(figure 5B) It was not until the week
ending November 9 that the first cases
occurred in Area B (figure 5C) 8 Cases
then continued in Area B around this
new focus. The same pattern could be
seen in Barriada Marrero where cases
occurred by the end of August along
the road bordering Block 36 and in an
adjacent house in Block 38 (figure 7A)
Ten additional cases occurred in Block
"In the October mosquito survey, five of
the eight households and the chicken coop
in Area B were found to be infested with
A. aegypli adults and/or larvae.
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B. CASES
176
NEFF BT AL.
WITH ONSET
DURING
5-WEEK
36 and the lower half of Block 38 during the first two weeks of September.
With the exception of one index case,
cases did not begin to occur m Blocks
37 and 39 until late September (figure
7B). In the upper half of Block 38, no
cases occurred until mid-November. The
houses in Blocks 37 and 39 are not more
than 30 to 40 yards from the houses in
Blocks 36 and 38 (figure 8).
Age-specific attack rates for dengue
fever alone, and including possible dengue fever, are presented in table 8 for
the study area. The overall attack rate
PERIOD
ENDING
NOVEMBER
9
for dengue fever and possible dengue
fever is 32.1 per cent, which is comparable to the total attack rate of 36.2 per
cent for dengue-like illness in the township (table 1). The attack rates, as expressed either for cases of dengue fever
alone or for cases of dengue fever plus
the cases of possible dengue fever, are
uniform for all age groups through 49
years of age. There is then a drop in the
rate for persons 50 years of age or older.
There is no ready explanation for the
lower rate in the older age group in the
study area; rates among all age groups
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C. CASES
DENGUE FEVER IN A PUEETO EICAN COMMUNITY
177
FIGURE 6
BARRIADA FRAILES LLANOS*
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•AREA A- FOREGROUND
AREA B - BACKGROUND
in the township were uniform. As was
noted in the township survey, the attack
rate in the female population in the study
area was slightly higher than that in the
male population.
The numbers of cases of dengue fever
and possible dengue fever by household size are shown in table 9. There
were nine households of one person each.
In none of these nine was there either a
case of dengue fever or possible dengue.
There were 57 households with 2 to 4
178
NEFF ET AL.
FIGURE
7
CASES OF DENGUE AND POSSIBLE DENGUE,
BARRIADA MARREO
CWȣT
THIS
PREVIOUS
4-WCCK
INTEHVAL
ONSET
A
CASES WITH OHSET
DURING
4 - WEEK PERUX)
ENDING AOOUST
31
persons. Thirty-five of these 57 (614
per cent) accounted for 61 cases of
dengue fever and possible dengue, resulting in an attack rate of 55 5 per
cent in the infected households. For
households of 5 to 9 persons, 53 out of
69 (76 8 per cent) were infected and the
attack rate in the infected households
was 41.0 per cent Of the 10 households
of 10 persons or more, 8 out of 10 (80.0
per cent) were infected, with an attack
rate in the infected houses of 39.2 per
cent It appears that the likelihood of
household infection increases, but the
attack rate in the infected households
decreases, as the household size increases.
In 33 households in the study area
there was an index case of "definite"
or "confirmed" dengue fever (first case
in the household). Two of the 33 house-
CAMS
WITH
ONSET
DURING
4-WEEK
PERIOO EHDIW SCPTEUMR %%
holds had cases with onset on the same
day, of the 35 index cases, 27 were in females compared with only 8 in males.
This high ratio of females to males
among index cases was most pronounced
in Barnada Frailes Llanos, where 17 of
the 18 index cases were females, and the
1 male index case was a child under
four years old.
The interval in days from the onset
of the index case to the onset of subsequent cases in the same household is depicted in figure 9. There were 45 cases of
dengue and 15 cases of possible dengue,
a total of 60 cases subsequently occurring in the 33 index households. Of these
60 cases, 19 (31 7 per cent) occurred in
the first week after the index case, 10
(16.7 per cent) in the second week, 9
(15.0 per cent) in the third week, and
15 (25.0 per cent) in the fourth week.
There was only one case (1.7 per cent)
in the fifth week, and none until after
the sixth week when 6 cases occurred, 5
of whom lived in one house. Thus,
88 3 per cent of the subsequent cases in
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•
DENGUE FEVEH IN A PUERTO HICAN COMMUNITY
170
FIGURE 8
BARRIAOA
MARRERO*
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ROAD OIVIDING
BLOCK 36-FOREGROUND
BLOCKS 38 FROM 37 ANO 3 9 - BACKGROUNO
180
NEFF ET AL.
TABLE 8
Attack rales by age group, study
area
CaBei
Attack rates (%)
Population
Age
group
Fe- ToUl Males FeMiles males
males
98
77
81
68
43
Totals
371'
367
1
Dengue and
possible dengue
Dengue
FeFe- Total Males Fe- Total
Total Males males
Males males Total
males
203
159
142
138
93
25
11
11
10
3
25
21
15
18
5
50
32
26
28
8
34
20
23
18
12
38
27
27
28
10
72
47
50
46
22
23 8
13.4
18.0
14 3
60
25
27
18
26
11
5
3
5
4
6
24 6
20 1
18 3
20 3
86
32 4
24 4
37 7
25.7
24 0
738*
60
84
144
107
130
237
16.2
22 9
19.5
28 8 35 4 32.1
38.8
35 5
33.3
41.1
23 2
35 5
29 6
35 2
33.3
23.7
T o t a l s include 3 males of unknown ages
TABLE 9
Cases of dengue fever and possible
Household size
(No of persons)
1
2-4
5-9
10+
Totals
dengue by household size, study
Number of
households
infected
%of
households
infected
Number of
persons in
infected
households
9
57
69
10
0
35
53
8
0 0
61 4
76.8
80.0
0
110
331
102
0
61
136
40
145
96
66 2
543
237 (144)
Number of
households
Number of
cases*
(0)
(35)
(86)
(23)
area
Attack rate
(%) m
infected
households
0 0
55 5
41 0
39.2
43 6
* Cases of dengue in p a r e n t h e s e s
the 33 households occurred within the
first four weeks following the onset of
the index case.
DISCUSSION
Dengue fever manifests itself in a
population in two different ways. It
may either be endemic and involve predominantly the younger age groups,
as is the pattern in Southeast Asia, or it
may occur in cycles, at times reaching
pandemic proportions (12). When epidemic, the pattern of spread is explosive, affecting all age groups with
equally high attack rates. This recent
epidemic in the Caribbean described
such a pattern. The disease involved has
been serologically documented as caused
by a member of the group B arboviruses, and it clinically and epidemiologically resembled dengue fever. Viruses,
closely related if not identical to dengue
virus type 3, were recovered from the
acute-phase bloods of persons observed
with dengue-like illness m studies conducted in the eastern end of the island
(6).
The symptoms of the illness are indistinguishable from dengue fever illnesses described in the past (4, 13-21).
The onset was sudden, followed by a
high fever and symptoms of myalgia,
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50+
105
82
61
70
50
0-9
10-19
20-29
30-49
Dengue and
possible dengue
Dengue
181
DENGUE FEVEB IN, A PUERTO HICAN COMMUNITY
zo
is
I 6
14
DENGUE
I2
tf)
M
4
O
POSSIBLE
DENGUE
10-
422
4
6
8
10
12
14
16
18
20
INTERVAL
22
IN
24
26
28
30
32
36 +
DAYS
FIGURE 9 Interval from onset of index case to onset of subsequent household cases, study
area.
arthralgia, opthalmalgia and rash. The
rash particularly characteristic of dengue manifested itself in two forms, first
as a general erythematous hue on the
first day of illness and second as a faint
maculopapular rash on the third or
fourth day of illness. Absent, however,
in the Puerto Rican disease were a severe degree of incapacitation, relapses
of symptoms and long periods of convalescence characterized by mental depression and a general lack of energy.
The epidemic in Puerto Rico was explosive, with high attack rates reported
in all age groups, and the pattern of
spread resembled that of a disease carried by a household vector such as the
A. aegypti mosquito. Females, presumably because of their increased exposure
within the household, were more likely
to be infected than males. In a clustered
population where the degree of contact
of all inhabitants was great, the spread
of the disease was consistently multicentric, tending to infect large house-
holds and spreading only to immediately
adjacent households. Within infected
households the attack rate was high, involving up to 55 per cent of the members.
The index case was often a female, the
person observed to be the one most likely
to spend time visiting other households
In any given household, the occurrence
of subsequent cases following the index
case was explosive, with 88 per cent of
the cases occurring within a month after
the index case, and with atl age groups
equally affected.
The involvement of all age groups
suggests that this population was universally susceptible to this particular infectious agent. At the onset of this epidemic there was some question as to
whether dengue fever had been present
in endemic form in Puerto Rico or
whether this was indeed the first appearance of the disease in many years. Although dengue fever had not been officially reported from Puerto Rico for
nearly 50 years, there had been some
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6-
182
NEFF ET AL.
onstrated circulating neutralizing antibodies to dengue-2 virus only in those
residents of Panama City who had been
living in Panama during the epidemic
of 1941-1942, and postulated that dengue-2 was the etiology of the 1941-1942
epidemic. With the large movements
of troops and civilians during the war
years, it is not unlikely that dengue was
present in several Caribbean islands at
that time and may well have been the
cause of the dengue-like illness reported
in Cuba, Martinique and Puerto Rico
in the early 1940s. The finding in this
study of circulating HI and CF antibodies to the group B arboviruses in the preepidemic serology of only those individuals who had lived in Puerto Rico in the
early 1940s further supports this hypothesis. The lack of reports of denguelike illnesses in Puerto Rico since the
early 1940s relates to the absence of antibodies in those under 25 years of age
in Guaynabo.
The recent epidemic in Puerto Rico,
however, involving a large percentage of
the population, regardless of age, seems
to indicate that no protection was provided through prior exposure to a group
B arbovirus Also, analyses of the typespecific, pre-illness HI and CF antibodies do not indicate any degree of
protection. This is not surprising since
infection with a group B arbovirus may
cause a general non-specific rise in the
HI and CF antibodies to several related
members of the group and the non-specific antibodies can persist for many
years (45). Therefore it would seem
most likely that, although this present
epidemic was caused by a virus antigenically related to a virus or viruses
previously present in Puerto Rico, the
type or strain of the virus involved in
this epidemic is one to which the community has not had previous exposure.
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evidence of periodic dengue fever in
neighboring countries. In 1953, Anderson, Downs and Hill isolated a dengue
virus antigenically related to dengue-2
strain from an 18-year-old resident of
Trinidad (22), and in 1956 and 1957
Downs and his associates conducted
serologic surveys in several Caribbean
islands utilizing both hemagglutination
antibody inhibition and neutralizing
tests to several group B arboviruses
and demonstrated that dengue virus had
probably been present at some time in
the populations of these islands (2330). The absence of any overt epidemic
of dengue-like illness at that time, however, indicated that either dengue viruses were present in a relatively silent
endemic form or that the neutralizing
antibodies resulted from infection in the
recent past. On the other hand, despite
this suggestion of endemic dengue in
the Caribbean, the history of dengue in
the Caribbean and in the surrounding
countries has been more in the form of
cyclic, recurrent epidemics. Large epidemics of dengue have been described in
Panama in 1904 and 1912 (31-33), in
the southeastern regions of the United
States in 1922 (34-36) and in 1934 (3739), and several Caribbean islands (including Martinique, Guadeloupe and
Cuba) and Panama in the early 1940s
(40-42). At this time, a clinical syndrome indistinguishable from dengue, although not officially reported as such,
was also observed in Puerto Rico by
Diaz-Rivera (43). Since then, however,
with the single exception of the isolation of dengue virus from an individual
in Trinidad (21), there has been no
documentation of dengue fever illnesses
in either Puerto Rico or in the other
surrounding Caribbean islands.
In 1954, Rosen conducted a serologic
survey in Panama (44), in which he dem-
DENGUE FEVEB IN A PUEBTO HICAN COMMUNITY
Many of the questions concerning the
more specific etiologic definition of both
this present epidemic and past group B
arbovirus activity in Puerto Rico will
be the subject of a second paper on
the virologic and serologic analysis of
the 1963-1964 outbreak of dengue fever
in Puerto Rico (5).
An epidemic was studied in a small
Puerto Rican community; the illness
was clinically similar to dengue fever,
epidemiologically suggestive of a disease carried by a household vector (such
as the Aedes aegypti mosquito), and
serologically documented as caused by
one of the group B arboviruses. The
epidemic was explosive and tended to
spread concentrically from its point of
introduction. All age groups were affected equally, with attack rates of up to
55 per cent in infected households.
The clinical syndrome was characterized by sudden onset, high fever associated with ophthalmalgia, conjunctivitis, myalgia and often a rash. The
illness was moderately incapacitating
for people in all age groups, and the rate
of inapparent infection was low.
Although there was some serologic
evidence of previous group B arbovirus
infection in the older age groups, there
was no indication epidemiologically or
clinically that this prior infection offered any degree of protection to the
population in the present epidemic.
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