Asymptomatic visceral leishmaniasis, northern Israel. (Dispatches).Asymptomatic human visceral leishmaniasis visceral leishmaniasis
A chronic, often fatal disease occurring chiefly in Asia, caused by a protozoan parasite (Leishmania donovani) and characterized by irregular fever, enlargement of the spleen and liver, and emaciation. was identified in Israel by using an enzyme-linked immunosorbent assay enzyme-linked immunosorbent assay
Enzyme-linked immunosorbent assay (ELISA)
A diagnostic blood test used to screen patients for AIDS or other viruses. . 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 HVL,
n See half-value layer.
half-value layer. ), caused by the Leishmania donovani Leishmania don·o·van·i
The protozoan that includes subspecies that cause visceral leishmaniasis. 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 Southern Europe or sometimes Mediterranean Europe is a region of the European continent. There is no clear definition of the term which can vary depending on whether geographic, cultural, linguistic or historical factors are taken into account. , 50% of new cases are in adults coinfected with HIV HIV (Human Immunodeficiency Virus), either of two closely related retroviruses that invade T-helper lymphocytes and are responsible for AIDS. There are two types of HIV: HIV-1 and HIV-2. HIV-1 is responsible for the vast majority of AIDS in the United States. (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 seroprevalence Immunology The proportion of a population that is seropositive–ie, has been exposed to a particular pathogen or immunogen; the seropositivity of a population is calculated as the number of individuals who produce a particular antibody divided in northern Israel was compared with that in a region free of clinical disease.
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 absorbance /ab·sor·bance/ (-sor´bans)
1. in analytical chemistry, a measure of the light that a solution does not transmit compared to a pure solution. Symbol .
2. .sub.[lambda]405nm] = 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 confidence interval,
n a statistical device used to determine the range within which an acceptable datum would fall. Confidence intervals are usually expressed in percentages, typically 95% or 99%. [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 chi-square test: see statistics. ) 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 [less than or equal to] 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 Galilee (găl`ĭlē), region, N Israel, roughly the portion north of the plain of Esdraelon. Galilee was the chief scene of the ministry of Jesus. ; 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 multifactorial /mul·ti·fac·to·ri·al/ (mul?te-fak-tor´e-al)
1. of or pertaining to, or arising through the action of many factors.
2. . Studies in Brazil on risk factors associated with asymptomatic infection concluded that infection is associated with age ([greater than or equal to] 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 seropositive /se·ro·pos·i·tive/ (-poz´i-tiv) showing positive results on serological examination; showing a high level of antibody.
adj. 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 people 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 blood transfusion, transfer of blood from one person to another, or from one animal to another of the same species. Transfusions are performed to replace a substantial loss of blood and as supportive treatment in certain diseases and blood disorders. , and the potential risk for VL/HIV coinfection.
This research was supported in part by the U.S. Middle East Regional Cooperation (MERC See Maximum expected return criterion.
See Chicago Mercantile Exchange (CME). ) program, Project NIH-NIAID contract number AO1-AI-45186, and the Center for the Study of Emerging Diseases.
(1.) Pearson R, Sousa AdQ. Clinical spectrum of leishmaniasis leishmaniasis (lēsh'mənī`əsĭs), any of a group of tropical diseases caused by parasitic protozoans of the genus Leishmania. . Clin Infect Dis 1996;22:1-13.
(2.) Badaro R, Jones TC, Carvalho EM, Sampaio D, Reed SG, Barral A, et al. New perspectives on a subclinical subclinical /sub·clin·i·cal/ (sub-klin´i-k'l) without clinical manifestations.
Not manifesting characteristic clinical symptoms. Used of a disease or condition. form of visceral leishmaniasis. J Infect Dis 1986;154:1003-11.
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Human immunodeficiency virus (HIV)
A transmissible retrovirus that causes AIDS in humans. coinfection: the first 10 years. Clin Microbiol Rev 1997;10:298-319.
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(8.) le Fichoux Y, Quaranta JF, Aufeuvre JP, Lelievre A, Marty P, Suffia I, et al. Occurrence of Leishmania infantum parasitemia parasitemia /par·a·si·te·mia/ (par?ah-si-te´me-ah) the presence of parasites, especially malarial forms, in the blood.
The presence of parasites in the blood. in asymptomatic blood donors living in an area of endemicity in southern France. J Clin Microbiol 1999;37:1953-7.
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Address for correspondence: Charles L. Jaffe, Department of Parasitology Parasitology
The scientific study of parasites and of parasitism. Parasitism is a subdivision of symbiosis and is defined as an intimate association between an organism (parasite) and another, larger species of organism (host) upon which the parasite is , Hebrew University-Hadassah Medical School, P.O. Box 12272, Jerusalem 91120, Israel; fax: 972-2-6757425; e-mail: firstname.lastname@example.org
Irit Adini, * Moshe Ephros, ([dagger]) Jacopo Chen, * and Charles L. Jaffe *
* The Hebrew University-Hadassah Medical School, Jerusalem, Israel; and ([dagger]) Technion-Israel Institute of Technology, Haifa, Israel
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 Both an international and regional referral center, Beth Israel Deaconess Medical Center (BIDMC) in Boston, Massachusetts is a major teaching hospital of Harvard Medical School. It was formed out of the 1996 merger of Beth Israel Hospital (founded in 1916) and , Harvard Medical School Harvard Medical School (HMS) is one of the graduate schools of Harvard University. It is a prestigious American medical school located in the Longwood Medical Area of the Mission Hill neighborhood of Boston, Massachusetts. , Boston, Massachusetts. She is currently working in the field of angiogenesis angiogenesis /an·gio·gen·e·sis/ (-jen´e-sis) vasculogenesis; development of blood vessels either in the embryo or in the form of neovascularization or revascularization.