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Dispatch
Asymptomatic Visceral Leishmaniasis,
Northern Israel
Irit Adini,* Moshe Ephros,† Jacopo Chen,* and Charles L. Jaffe*
*The Hebrew University–Hadassah Medical School, Jerusalem, Israel; and
†Technion-Israel Institute of Technology, Haifa, Israel
Suggested citation for this article: Adini I,
Ephros M, Chen J, Jaffe CL. Asymptomatic visceral leishmaniasis, Northern
Israel. Emerg Infect Dis [serial online] 2003 Mar [date cited].
Available from: URL: http://www.cdc.gov/ncidod/EID/vol9no3/02-0297.htm
Asymptomatic human
visceral leishmaniasis was identified in Israel by using an enzyme-linked
immunosorbent assay. Positive serum samples were more prevalent in visceral
leishmaniasis–endemic (2.97%) compared to nonendemic (1.01%) regions
(p=0.021). Parasite exposure was higher than expected, despite the small
number of clinical cases, suggesting factors other than infection per
se influence clinical outcome.
Human visceral leishmaniasis (HVL), caused by the Leishmania donovani
complex, is lethal if not promptly diagnosed and treated (1).
Yet in the Mediterranean and Middle East, only a small percentage of infections
progress to clinical disease (2,3). HVL in this region
is primarily a disease of young children; however, its epidemiology is
changing. In southern Europe, 50% of new cases are in adults coinfected
with HIV (4).
HVL is endemic in northern Israel; 68 cases, mostly from Arab villages,
were documented from 1960 to 1989 (5). Since 1993, a
drastic reduction in the disease was observed, despite the identification
of nine active sites of canine visceral leishmaniasis (VL) in this region
(G. Baneth and C. L. Jaffe, unpub. data). Recent studies have identified
an emerging focus of human and canine disease near major population centers
in central Israel and the Palestinian Authority (6,7).
In this study, HVL seroprevalence in northern Israel was compared with
that in a region free of clinical disease.
The Study
Prevalence of asymptomatic disease was examined by random cluster sampling
of serum samples from 12 sites (494 serum samples) in a region presumed
to be non–HVL-endemic (i.e., HVL has not been reported) and 11 sites (2,086
serum samples) in the HVL-endemic northern region, where the disease was
previously reported in 8 of 11 sites (Figure). Coded
samples were analyzed blindly by enzyme-linked immunosorbent assay on
L. donovani antigen for anti-leishmanial antibodies (5).
Each plate was read when the positive control serum (1/1,000 dilution)
absorbance λ 405 nm = 1.0–1.2. Most
serum samples were from women ages 18–45. The mean ages for patients in
the non–disease-endemic and HVL-endemic regions were 36 and 30 years,
respectively (range <1 to >75). No symptomatic HVL was diagnosed
during the study.
The mean absorbance for serum samples from HVL-endemic areas (0.0956;
95% confidence interval [CI] 0.0926 to 0.0986) was significantly higher
(p=0.0001; unpaired t test with Welch’s correction) than that for serum
samples from non–disease-endemic areas (0.0832; 95% CI 0.0779 to 0.0885).
The percentage of positive samples (mean of the non–HVL-endemic population
+ 3 standard deviations) was significantly higher (p=0.021, chi-square
test) for the endemic, 2.97% (n=62) than for the non–HVL-endemic region,
1.01% (n=5). Age was directly standardized by examining the percent positive
serum samples in children <14 years of age, who are most likely
to have clinical HVL, and older study participants (>14 years). The
standardized prevalence ratio of positive serum samples in the HVL-endemic
to non–HVL-endemic regions was 2.90. Western blotting was used to confirm
asymptomatic VL (8). Strong reactions were observed to
14- and/or 18-kDa antigens with all positive samples; weak or no bands
were observed with negative samples.
The percentage of positive serum samples for each site is shown (Figure).
In the non–HVL-endemic region, most serum samples collected (64.6%) came
from Atlit (Jewish, n=146) and Isfiya (Arab, n=173). The remaining serum
samples (n=175) originated from 10 sites, with a maximum of 39 samples
per site. Only 1.1% of these samples (2/175) were positive, a value similar
to that found for the larger towns of Atlit and Isfiya (p=1.0, Fisher
exact test). Essentially no difference in the percentage of positive serum
samples (p=1.0, Fisher exact test) was found between non–leishmaniasis-endemic
Arab (Isfiya, 1.2%) and Jewish (Atlit, 0.7%) towns, even though residents
of Isfiya are more likely to visit villages where the disease occurs.
Large numbers of samples (>140/site) were collected from 9 of 11 HLV-endemic
sites. The percentage of positive samples from Arab areas (3.1%) was not
significantly higher (p=0.46, chi-square test) than for samples from Jewish
areas (1.8%), even though most HVL case-patients in this region are from
Arab villages. However, the percentage of positive serum specimens in
7 of 11 HVL-endemic sites was three- to six-fold the average percentage
found in the non–HVL-endemic region. The number and percentage of positive
HVL-endemic serum samples during the second year were almost twice (3.9%;
p=0.038, unpaired t test) the figures observed for the first year (2.2%).
The opposite trend was found in the non–HVL-endemic region, where the
number and percentage of positive samples decreased from 1.9% to 0.3%
(p=0.044) in the first and second year, respectively. Nine of the 11 HLV-endemic
sites showed increases in the percentage of positive serum samples during
the second year.
During the 1960s, 45 cases of VL were diagnosed in western Galilee; more
than half were from eight sites, all Arab villages, included in this study
(5). Since then, the incidence of HVL in northern Israel
has decreased: only three cases have been diagnosed in the last 7 years.
This finding is not due to the absence of parasite transmission, since
canine VL remains common (G. Baneth and C. L. Jaffe, unpub. data). While
HVL is decreasing in northern Israel, the disease has emerged in central
Israel, where numerous dogs and seven persons have been diagnosed with
VL since the index HVL case in 1994 (6). Villages in
both regions are rural, and stray dogs and jackals are frequently observed.
The conditions contributing to the changes in disease epidemiology in
Israel are unknown but are likely multifactorial. Studies in Brazil on
risk factors associated with asymptomatic infection concluded that infection
is associated with age (>2 years), location of dwellings, and
presence of relatives with acute VL. Malnutrition was not associated with
infection (9). A higher standard of living and health
was also postulated to be involved in decreased VL incidence over the
past 10 years (10). During the last decade, improvements
in the standard of living, health care, and infrastructure of Arab villages
in Israel have taken place. Though data are not available for most study
sites, the percentage of seropositive persons in Yirka, for example, decreased
from 10% in 1989 (5) to 1.5% in the current study (1994–1996),
suggesting that exposure to parasites in Yirka has decreased during the
last decade.
The percentage of seropositive people is significantly greater in the
HVL-endemic northern than the non–HVL-endemic coastal and Carmel Mountain
regions. The presence of positive samples in the non-HVL–endemic region
suggests that parasite transmission occurs, even though HVL has not been
reported. Since persons from this region frequently travel to northern
Israel, we cannot exclude the possibility that they were infected there.
Although the incidence of the disease is lower in Israel than in other
HVL-endemic regions, our results suggest that cumulative exposure to the
parasite and asymptomatic infection in Israel are more frequent than otherwise
predicted, based on the yearly incidence of VL. These data will be important
in understanding the spread of human and canine disease into new regions,
transmission by blood transfusion, and the potential risk for VL/HIV coinfection.
This research was supported in part by the U.S. Middle
East Regional Cooperation (MERC) program, Project NIH-NIAID contract
number AO1-AI-45186, and the Center for the Study of Emerging Diseases.
Dr. Adini received her doctoral degree from the Hebrew
University-Hadassah Medical School in 2002 and is now a postdoctoral
fellow at Beth Israel Deaconess Medical Center, Harvard Medical School,
Boston, Massachusetts. She is currently working in the field of angiogenesis.
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