Israel Medical Association Journal

Background: Traditionally, medication dosage was based on clinical and demographic parameters, but drug metabolism was recently recognized as an important factor for proper dosing and prediction of side effects. Metabolic considerations are crucial when administering drugs with a narrow therapeutic index, such as those of the thioguanides family (azathioprine and 6-MP). These can cause life-threatening myelosuppression due to low activity of a critical metabolic enzyme, thiopurine S-methyl transferase. A number of single nucleotide substitutions encoding variant enzymes account for most enzyme deficiencies.

Objectives: To determine the frequency of individuals from different Israeli ethnic groups who may be at risk for drug toxicity from drugs of the thioguanide family due to enzymatic variants.

Methods: DNA analysis was performed using polymerase chain reaction methods. We tested TPMT[1] allelic variants TPMT*3A (G460A, A719G), TPMT*3B (G460A) and TPMT*3C (A719G) in five subpopulations in Israel: mixed-origin Israeli Jews, Arabs, Druze, Jews of Kurdish extraction, and Ethiopian Jews.

Results: The Druze (P = 0.0002) and Ethiopian Jewish (P = 0.015) subpopulations had a significantly unique distribution of allelic variants compared to the rest of the Israeli population. The Druze subpopulation showed a high number of TPMT variants with decreased activity, and a homozygote for TPMT*3A/ *3A was detected.  Ethiopian Jews were found to carry mainly the TPMT*3C variant, also observed in other studies of African populations.

Conclusions: It is advisable that Druze patients be tested for the TPMT enzyme before starting treatment with 6-MP or azathioprine. Such testing may also be considered for other Israeli ethnic subgroups.

Background: The incidence of cutaneous leishmaniasis in northern Israel began to rise in 2000, peaking at 41.0 per 100,000 in the Kinneret subdistrict during the first half of 2003.

Objectives: To examine the morbidity rates of CL[1] in northern Israel during the period 1999–2003, which would indicate whether new endemic areas were emerging in this district, and to identify suspicious hosts.

Methods: The demographic and epidemiologic data for the reported cases (n=93) were analyzed using the GIS and SPSS software, including mapping habitats of suspicious hosts and localizing sites of infected sand flies.

Results: The maximal incidence rate in the district was found in the city Tiberias in 2003: 62.5/100,000 compared to 0–1.5/100,000 in other towns. The cases in Tiberias were centered on the peripheral line of two neighborhoods, close to the habitats of the rock hyraxes. Sand flies infected with Leishmania tropica were captured around the residence of those affected. Results of polymerase chain reaction were positive for Leishmania tropica in 14 of 15 tested patients.

Conclusions: A new endemic CL area has emerged in Tiberias. The most suspicious reservoir of the disease is the rock hyrax.