Am. J. Trop. Med. Hyg., 66(1), 2002, pp. 61–70
Copyright ? 2002 by The American Society of Tropical Medicine and Hygiene
LEPTOSPIROSIS IN HAWAII, 1974–1998: EPIDEMIOLOGIC ANALYSIS OF 353
ALAN R. KATZ, VERNON E. ANSDELL, PAUL V. EFFLER, CHARLES R. MIDDLETON, AND DAVID M. SASAKI
Department of Public Health Sciences and Epidemiology, John A. Burns School of Medicine, University of Hawaii, Honolulu,
Hawaii; Kaiser-Permanente Medical Center, Honolulu, Hawaii; Epidemiology Branch, Communicable Disease Division,
Hawaii State Department of Health, Honolulu, Hawaii
associated with both case detection and confirmation. In addition, leptospirosis was eliminated from the list of National
Notifiable Diseases in 1995. From 1974 until the cessation of national surveillance, Hawaii consistently had the
highest reported annual incidence rate in the United States. From 1974 through 1998, 752 leptospirosis cases were
reported in the State of Hawaii. Of these, 353 had exposures within the state and were laboratory confirmed. The
mean annual incidence rate was 1.29 per 100,000. Cases were predominately male. Rates were highest in rural areas.
Occupational exposures diminished over time while recreational exposures increased. This series represents the first
large U.S. leptospirosis surveillance report since 1979. With leptospirosis recently being identified as a re-emerging
zoonosis, continued national surveillance and case reporting should be reconsidered.
The epidemiologic characterization of leptospirosis in the United States has been limited by difficulties
Leptospirosis is an illness with protean manifestations and
world-wide distribution.1It has been classified as a re-emerg-
ing zoonosis by the World Health Organization.2Recently
reported outbreaks in Nicaragua,3Costa Rica,4Brazil,5In-
dia,6the mainland United States,7and among participants in
the EcoChallenge competition in Borneo8,9have refocused
attention on this disease. From 1974 through 1994, Hawaii
consistently had the highest reported annual incidence rate
in the United States.10–30Although leptospirosis was deleted
from the list of nationally notifiable infectious diseases in
1995,31cases remain reportable in the State of Hawaii. This
paper describes the epidemiologic characterization of lepto-
spirosis in the State of Hawaii through a detailed analysis of
confirmed cases related to exposures within the state.
Leptospirosis case investigation reports collected by the
Hawaii State Department of Health (DOH) were reviewed
for the 25-year period from 1974 through 1998. These re-
ports are generated by DOH epidemiologists for all reported
leptospirosis cases in the State, and include demographic,
epidemiologic, clinical, and laboratory information obtained
from patient interviews, medical record reviews, and labo-
ratory reports of serologic, culture, and fluorescent antibody
Cases were classified as either confirmed, probable, or
suspect based on clinical and laboratory findings. A con-
firmed case had a clinically compatible illness with at least
one of the following laboratory criteria for confirmation:
four-fold or greater increase in microscopic agglutination test
(MAT) titer between acute- and convalescent-phase serum
specimens; isolation of Leptospira from a clinical specimen;
or demonstration of Leptospira in a clinical specimen by
immunofluorescence.32,33Cases were classified as probable if
there was a clinically compatible illness with supportive se-
rologic findings (i.e., MAT titer ? 1:200 in one or more
serum specimen without a four-fold increase in titer).34Sus-
pect cases were defined as being clinically compatible with
laboratory evidence of infection including a positive mac-
roscopic slide agglutination test result, reactive IgM enzyme-
linked immunosorbent assay (ELISA), positive indirect hem-
agglutination assay (IHA), MAT titer ? 1:200, or presump-
tive identification of leptospires in blood, body fluids, or
tissue specimens by darkfield microscopy. Only cases clas-
sified as confirmed were included in this analysis. The MAT
and direct fluorescent antibody testing were conducted by
the U.S. Centers for Disease Control and Prevention (CDC)
in Atlanta, Georgia. The DOH laboratory conducted isola-
tion procedures using Ellinghausen-McCullough-Johnson-
Harris semisolid media. Serogrouping and serotyping of cul-
ture isolates were also conducted by the CDC.32Technical
assistance was received from the Royal Tropical Institute
(RTI) in Amsterdam, the Netherlands in 1989 for micro-
scopic agglutination testing and serotyping.
Infecting serogroups were definitively identified on cul-
ture isolates but only presumptively identified by MAT, since
definitive identification is not possible with MAT due to
cross-agglutination/cross-reactivity between serovars of dif-
ferent serogroups.35For cases demonstrating a four-fold or
higher increase in MAT titer between acute- and convales-
cent-phase serum specimens, the serogroup showing the
highest titer on the convalescent-phase sera was considered
to be the presumptive infecting serogroup. If there were
more than one serogroup with the same high titers, the pre-
sumptive infecting serogroup for the case was designated
Data analysis. Cases were analyzed individually and cat-
egorized into five five-year intervals from 1974 to 1998 to
assess temporal trends. Frequencies, relative risks, and chi-
square tests for linear trend were calculated using Epi Info
version 6.04 (CDC, Atlanta, GA). Mid-P-corrected 95%
confidence intervals and exact P values for odds ratios and
relative risks, and exact 95% confidence intervals for annual
leptospirosis incidence rates using Clopper-Pearson method
were calculated using StatXact version 4.0.1. (Cytel Soft-
ware Corporation, Cambridge, MA). Reference groups se-
lected for comparisons were those subgroups in each cate-
gory with the largest populace according to the 1990 U.S.
Census (ethnicity: Caucasian; age ? 30–39 years; island:
Oahu).36The independent contribution of age, island of ex-
posure, and ethnicity was assessed in a multivariate analysis
KATZ AND OTHERS
of Hawaii, 1974–1998. 95% confidence intervals are indicated by
Annual confirmed leptospirosis incidence rates, StateFIGURE 2.
State of Hawaii, 1974–1998.
Month of onset for 352 confirmed leptospirosis cases,
Island of exposure for 353 confirmed leptospirosis cases, State of Hawaii, 1974?1998
18.26 (13.83, 24.32)
24.50 (18.00, 33.50)
1.0 (Reference group)
0.68 (0.24, 1.58)
* (Number of cases observed over a 25-year period for a specific island of exposure/25)/island-specific population from 1990 U.S. Census data.36
using logistic regression, where denominators were obtained
from aggregate factor-specific Hawaii State data from the
1990 U.S. Census.36Odds ratios and likelihood ratio 95%
confidence limits were adjusted by a scale factor of 1.149
(based on deviance divided by degrees of freedom) and cal-
culated using the Genmod Procedure of SAS version 8.0.
(SAS Institute, Cary, NC). P values less than or equal to
0.05 were considered statistically significant. All test were
A total of 752 cases were reported to the DOH during the
25-year period, 1974–1998. Seven hundred nine cases were
contracted through exposures within the State of Hawaii,
while 43 cases were related to exposures that occurred out-
side the State. Of the 709 cases of leptospirosis due to ex-
posures within the State, 353 were classified as confirmed;
180 were classified as probable, while 176 were classified
The number of confirmed cases reported to the DOH per
year ranged from zero (1977) to a high of 37 (1998), with
a median of 14 annual case reports, and a mean annual in-
cidence rate of 1.29 per 100,000 population. There was a
significant temporal trend in increasing leptospiral incidence
rates over this 25-year period (?2for linear trend ? 7.89, P
? 0.005) (Figure 1). The month of occurrence was identified
for virtually all cases (352 of 353). Sixty-nine percent (243
of 352) of cases occurred during the late summer, fall, and
early winter months (July through December) while 31%
(109 of 352) occurred during the late winter, spring, and
early summer months (January through June) (Figure 2).
The island of exposure was identified for ? 99% of the
cases (351 of 353). Most cases were exposed on the island
of Hawaii (50%), followed by Kauai (28%), and Oahu
(19%), with very few cases reported from the island of Maui
(1%). A single case was exposed on each of the following
islands: Niihau, Molokai, and Lanai. Cases from the latter
three islands were not included in the island-specific rate
calculations or multivariate statistical analysis. A compari-
son of mean annual incidence rates revealed Kauai with the
highest rate (7.85 per 100,000) followed by Hawaii (5.85
per 100,000), Oahu (0.32 per 100,000), and Maui (0.22 per
100,000). A comparison of incidence rates on the less pop-
ulated neighbor islands using Oahu as the reference popu-
lation, revealed a relative risk of 24.50 for Kauai (95% con-
fidence interval [CI] ? 18.00, 33.50) and 18.26 for the island
of Hawaii (95% CI ? 13.83, 24.32) (P ? 0.0001 respec-
tively), while the relative risk for exposure on Maui was 0.68
(95% CI ? 0.24, 1.58) (P ? 0.55) (Table 1). In addition to
information on island of exposure, an attempt was made to
identify the location of exposure, by census tract and district,
on each island. The most common locations were census
KATZ AND OTHERS
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