Israel Medical Association Journal

Background: Visceral leishmaniasis was first reported in Israel (then Palestine) in 1929. In the 1960s and 1970s, it was endemic to northern Israel, but only partial data about the disease have been gathered since then.

Objective: To investigate the epidemiologic trends of visceral leishmaniasis in Israel from 1960 to 2000, and to delineate some clinical features of the infection.

Methods: Data were collected from hospital charts, scientific publications, and reports of the Ministry of Health and the Kuvin Center for the Study of Infectious and Tropical Diseases.

Results: During the last four decades, 87 cases of visceral leishmaniasis were diagnosed in Israel, 76 of them (87%) in children. All 54 patients diagnosed in the 1960s occurred in the northern part of the country. The rate of infection declined significantly in the 1970s (5 cases) and then increased slightly in the 1980s (11 cases) and 1990s (17 cases). More than 50% of the cases in the 1990s were in central Israel. Children accounted for 100% of cases in the 1960s but only 58% in the 1990s. The main clinical features of the patients diagnosed in the last decade were fever, weight loss, hepatosplenomegaly and pancytopenia. Three of the adults were co-infected with human immunodeficiency virus.

Discussion: The decline in the incidence of visceral leishmaniasis in the 1970s and the slight increase in the 1980s and 1990s can be attributed to changes in the animal reservoir and vectors, and in the immunity status of part of the population exposed to Leishmania.

Conclusions: Visceral leishmaniasis has reemerged in Israel. This mandates better control of the animal reservoir and vectors and increased awareness of this infection.

Background: Iodine intake is necessary to maintain normal thyroid function and prevent iodine deficiency disorders. In 1990, a resolution calling for universal salt iodination to eliminate iodine deficiency worldwide was taken by the World Health Organization and endorsed by some 130 countries. As of today, very little is known about iodine intake and the prevalence of iodine deficiency disorders in Israel, and iodine enrichment of regular salt has not been authorized.

Objectives: To assess the current level of iodine intake in an unselected group of residents from the Israeli costal area.

Methods: Spot urine samples were collected from three groups: Group A comprising 51 pregnant women attending the Women s Health Clinic at our institution, with a mean age of 32 years and at gestational week 28; group B consisting of 35 healthy subjects, mean age 38; and group C consisting of 16 euthyroid subjects harboring nodular goiters. Tap drinking and mineral water were also analyzed for iodine content. Iodine concentration was measured using the catalytic reduction of ceric ammonium sulfate method.

Results: When considering all groups together the median urinary iodine concentration was 143 µg/L, with 27% of the study population having concentrations under 100 µg/L and 7.8% under 50 µg/L. Values were distributed similarly between sites of residency, and no significant differences were seen between groups. The mean iodine concentration for tap drinking water was 22.8 µg/L (range 0.5–53.5 µg/L) and for mineral water 7 µg/L (range 0–15 µg/L).

Conclusions: Overall, iodine intake appeared to be satisfactory in our study population, however mild deficiency may exist in up to 26% of this group. A nationwide survey is needed to better determine the status of iodine intake in Israel, allowing for recommendations on salt-iodine enrichment in the future.

Background: The humanized SCID mouse model is an attractive tool for testing gene therapy to combat human immunodeficiency virus infection in vivo.

Objectives: To devise a more specific gene therapy directed against HIV, replacing the formerly used interferon with either soluble CD4 molecule immunoadhesin (sCD4-IgG) and/or anti-gp41 monoclonal antibody (2F5), or negative transdominants (Tat, Rev).

Methods: Human monocytoid cell line (U937) was transfected with IFNa[1], b or g genes. 3T3 murine fibroblastic cell line was transfected with sCD4-IgG or 2F5, or both genes, and a human T4 cell line (CEM) was grafted to SCID mice. Negative transdominant genes (Tat, Rev or both) were also transduced in CEM T cell line. Animals were then challenged with HIV-1[2]. Viral load was followed.

Results: IFNa or b were potent anti-HIV, reducing viral load in vivo and inhibiting reverse transcriptase activity in human-removed cells from animals. sCD4-IgG immunoadhesin and gp41 monoclonal antibody resulted in a dramatic reduction of HIV-1 cellular and plasmatic viral load in humanized SCID mice. The simultaneous introduction of negative Tat and Rev genes resulted in a synergistic inhibition of HIV-1 replication in vivo.

Conclusions: Despite the marked reduction of HIV-1 propagation by IFN genes or by negative Tat and Rev transdominants, the gene therapy using soluble CD4 immunoadhesin or anti-gp41 was a more efficient preventive treatment against HIV infection.

Background: Transcobalamin II is a serum transport protein for vitamin B₁₂. Small variations in TC-II[1] affinity were recently linked to a high homocysteine level and increased frequency of neural tube defects. Complete absence of TC-II or total functional abnormality causes tissue vitamin B₁₂ deficiency resulting in a severe disease with megaloblastic anemia and immunologic and intestinal abnormalities in the first months of life. This condition was described in hereditary autosomal-recessive form. Low serum TC-II without any symptoms or clinical significance was noted in relatives of affected homozygotes.

Objectives: To study 23 members of a four-generation family with hereditary vitamin B₁₂ deficiency and neurologic disorders.

Methods: Thorough neurologic, hematologic and family studies were supplemented by transcobalamin studies in 20 family members.

Results: Partial TC-II deficiency was found in 19 subjects. Apo TC- II (free TC-II unbound to vitamin B₁₂) and total unsaturated B₁₂ binding capacity were low in all tested individuals but one, and holo TC-II (TC-II bound by vitamin B₁₂) was low in all family members. The presentation of the disease was chronic rather than acute. Early signs in children and young adults were dyslexia, decreased IQ, vertigo, plantar clonus and personality disorders. Interestingly, affected children and young adults had normal or slightly decreased serum vitamin B₁₂ levels but were not anemic. Low serum B₁₂ levels were measured in early adulthood. In mid-late adulthood megaloblastic anemia and subacute combined degeneration of the spinal cord were diagnosed. Treatment with B₁₂ injections resulted in a significant improvement. The pedigree is compatible with an autosomal-dominant transmission. This family study suggests a genetic heterogeneity of TC-II deficiency.

Conclusions: We report the first family with a hereditary transmitted condition of low serum TC-II (partial TC-II deficiency) associated with neurologic and mental manifestations in childhood. Partial TC-II deficiency may decrease the amount of stored cobalamin, resulting in increased susceptibility to impaired intestinal delivery of cobalamin and predisposing to clinically expressed megaloblastic anemia at a later age. Partial TC-II deficiency should be suspected in families with megaloblastic anemia and in individuals with neurologic and mental disturbances – despite normal serum vitamin B₁₂ levels. Low serum UBBC[2] and apo TC-II should confirm the diagnosis. Early vitamin B₁₂ therapy may prevent irreversible neurologic damage.

Micronutrient deficiencies have reoccupied the center stage of public health policy with the realization that folic acid deficiency results in neural tube defects and possibly other birth defects as well as ischemic heart disease. These, in turn, have raised an older debate on food fortification policy for the elimination of iodine, iron and vitamin D deficiencies. Data from the First Israeli National Health and Nutrition Survey (MABAT 2000) provided an impetus to develop an active national nutrition policy aimed to improve the nutritional status of iodine, iron, vitamins A and D and B-vitamins, including folate. In this paper we examine some of the MND[1] issues in Israel and their implications for public health, and suggest options for the formulation of policy.

Hemophagocytic lymphohistiocytosis is thought to occur as a primary (familial) form or secondary to infection or malignancy. Recently, several defects in genes important for immune functions were identified in patients with HLH[1]. These include mutations in perforin, the gamma common chain, the receptor for interleukin-2, Slap and purine nucleoside phosphorylase. Since abnormal function of these genes is associated with a wide clinical spectrum, HLH is probably another manifestation of immune deficiency and a thorough immune evaluation should be done in all such patients.