A retrospective study on demographic and clinical characteristics of cutaneous leishmaniasis suspected cases in southern Israel, 2013-2016: Comparison between confirmed and negative cases.

BACKGROUND & OBJECTIVES: Clinical diagnosis of cutaneous leishmaniasis (CL) may bear a high rate of false diagnosis. This study assessed CL-suspected episodes, in an attempt to differentiate confirmed CL and non-CL diagnoses. METHODS: In this retrospective, case-control study, medical files of CL-suspected episodes, tested by a biopsy for Leishmania-PCR, from 2013 to 2016, were collected and analysed statistically. RESULTS: Of 324 suspected CL episodes, 48.8% were PCR-confirmed CL (96.2% Leishmania major) and 51.2% were non-CL (57.1% bacterial infections). Overall, 59.3% episodes were in males. Mean (± SD) duration until diagnosis was 3.7 ± 7.2 months. Lesions (mean 2.9 ± 3.8 per episode) were mostly (60.8%) sampled from September through February. Ulcer, pain, itching, purulent discharge and fever were recorded in 55.2, 47, 42.9, 18.2 and 4.7% of episodes, respectively. Univariate analysis showed that male gender, multiple lesions, ulcer, >1-month duration until diagnosis, and seasonality were associated with CL. Empiric CL treatment was recorded in 63.4 and 16% of CL-confirmed and non-CL episodes, respectively (p <0.001); and was observed to be associated with Jewish ethnicity, seasonality, multiple lesions, ulcer, absence of fever and duration of >1-month until diagnosis. In multivariate analysis, seasonality (odds ratio, OR = 2.144), empiric CL treatment (OR = 5.144) and ulcer (OR = 2.459) were associated with CL. Empiric CL treatment was associated with Jewish ethnicity (OR = 2.446) and duration of >1-month until diagnosis (OR = 3.304). INTERPRETATION & CONCLUSION: CL diagnosis should be laboratory confirmed, as clinical appearance is often misleading. Seasonality, ulcer appearance and gender may aid in correct identification and treatment of CL cases.

Cystic echinococcosis in Southern Israel.

The aim of this retrospective, population-based study was to characterize demographically and clinically cystic-echinococcosis (CE) in southern Israel, between 2005 and 2012. Newly-diagnosed (nd-CE) and past-diagnosed (pd-CE, diagnosed before the study) cases were defined. Two populations live in southern-Israel, receiving medical treatment at a single hospital: the Jewish and the Bedouin populations (resembling resource-rich and resource-poor populations, respectively). 126 CE cases were identified; 55 nd-CE and 71 pd-CE. Mean annual nd-CE incidence per 100,000 in the Bedouin and Jewish populations were 2.7 ± 1.2 and 0.4 ± 0.3, respectively (P<0.001). None of the Bedouin and 86.5% of the Jewish patients were born outside Israel. Liver and lung involvement were recorded in 85.7% and 15.1% of overall-CE, respectively. Abdominal pain, cough, fever, eosinophilia and asymptomatic disease were documented in 63.6%, 32.7%, 27.3%, 41.5% and 12.7% of nd-CE, respectively. Serology sensitivity for first test and any positive test were 67.3% and 83.3%, respectively. Computed tomography, ultrasonography and X-ray diagnosis were documented in 79.2%, 58.4% and 17.0% of overall-CE, respectively, with ultrasonography mainly used in liver-CE and X-ray in lung-CE. Treatment included surgery and albendazole in 50.0% and 55.3% of CE, respectively. We conclude that CE is endemic in southern-Israel among the Bedouin population, while disease is probably mainly imported in the Jewish population. Liver involvement and eosinophilia rates were high compared with those of other endemic regions, possibly due to differences in the timing of diagnosis. These findings may help developing treatment and prevention strategies.

Two-dose measles immunization as a strategy to eliminate measles in the Middle East and Israel.

The data presented above show that most countries of the Middle East (Israel and countries of the Eastern Mediterranean Region of the WHO) are progressing towards achieving WHO goals for improving immunization coverage for measles immunization to over 90%, along with the introduction of a two-dose immunization strategy. There has been corresponding progress in the reduction of incidence of measles. However, the goal of the WHO to eliminate measles has not been achieved and is unlikely to be in the near future.

Leishmania major: in vitro and in vivo anti-leishmanial activity of paromomycin ointment (Leshcutan) combined with the immunomodulator Imiquimod.

Paromomycin at 25, 50 and 100 microg/ml, inhibited the growth of Leishmania major amastigotes by 34.5%, 61.2%, 74.9% and 85.4%, 89.9%, 95.7% on the 2nd and the 4th day of treatment in culture, respectively. Methylbenzethonium chloride at 0.1 and 0.5 microg/ml and Imiquimod at 5 and 10 microg/ml, administered separately, inhibited the parasite development by 39.5% and 65.2% and 31.5% and 47.7%, respectively. Imiquimod (5-10 microg/ml) combined with either paromomycin (25, 50 and 100 microg/ml) or methylbenzethonium chloride (0.1 and 0.5 microg/ml) showed an anti-leishmanial additive effect. A 10 day topical treatment, twice daily, with an ointment containing 15% paromomycin and 12% methylbenzethonium chloride (Leshcutan), either undiluted or diluted 1:5 in soft white paraffin combined with 5% Imiquimod cream (Aldara), was as effective as Leshcutan given alone. The present study suggests that a combination of Aldara and Leshcutan is as effective as Leshcutan given alone in the topical treatment of CL caused by L. major.

Repeated treatment of cystic echinococcosis in patients with a long-term immunological response after successful surgical cyst removal.

Six cystic echinococcosis patients underwent surgery for the removal of echinococcal cysts. All were treated with albendazole prior to and following treatment. After surgery, no cysts were detected in five of the six patients examined. Both ELISA and immunoblot analysis have been used to determine specific IgG, IgG4 and IgE activities. Total elimination of IgG and IgG4 was not achieved in any of the patients studied. Prior to the first surgery/treatment, specific IgG, IgG4 and IgE antibodies were demonstrated in all patients, except one who did not show any IgE activity. The first treatment was followed by highly elevated IgE in two patients; in one of them it was further combined with an apparent decrease in IgG activity. Repeated treatment with albendazole given 0.8-8.5 years after the first treatment/surgery was followed by either moderate or highly reduced IgE activity in two patients, respectively, and a slight increase in IgG4 in another patient. A third course of treatment, given 2-2.5 years after the second treatment, barely affected the antibody activities. The present study suggests that anti-echinoccocal antibody activity may remain high many years after successful cyst removal. Determination of IgG, IgG4 and IgE responses is preferable for the assessment of treatment results. The presence of anti-echinococcal antibodies after surgery with no cyst detection does not necessarily indicate an active echinococcal infection.

Differential immune responses to primary measles-mumps-rubella vaccination in Israeli children.

Measles remains an important cause of morbidity and mortality worldwide, primarily due to problems associated with delivery of the live attenuated vaccine to susceptible populations. In some developed countries, there is concern about the effects of immunization on the immune system. In this study, we analyzed the responses of 12-month-old Bedouin and Jewish children living in Israel to routine measles-mumps-rubella (MMR) vaccination. Seroconversion to measles was 99% in Bedouin and 79% in Jewish children (P < 0.01), and that to mumps and rubella was 92 to 100% in both groups. Measles neutralizing antibody titers were higher in Bedouin (333 +/- 39 mIU/ml) than Jewish (122 +/- 60 mIU/ml) children (P < 0.002). Immunoglobulin G levels were higher in Bedouin than Jewish children (P = 0.007) and increased after vaccination (P = 0.0009). Leukocyte (P < 0.02) and lymphocyte (P = 0.04) counts were higher and CD4 lymphocyte percentages were lower (P < 0.001) in Bedouin than Jewish children before and after vaccination. Leukocyte counts and natural killer cell numbers did not change after vaccination, but lytic activity increased in Bedouin children (P < 0.005). Spontaneous proliferation of cultured peripheral blood mononuclear cells increased with vaccination, but there were no changes in the proliferative responses to phytohemagglutinin or tetanus toxoid. In summary, no adverse effects of MMR vaccination on immune function were detected. However, there were differences in underlying immunologic parameters and in response to the measles component of the vaccine between Bedouin and Jewish children. It is not known whether genetic differences or environmental exposure accounts for these differences.

The effect of measles-mumps-rubella (MMR) immunization on the immune responses of previously immunized primary school children.

Current policies for measles control call for administration of a second dose of vaccine to immunize those who failed to respond to the initial dose and to boost the responses of those with low levels of antibody. However, there has been concern expressed publicly that reimmunization may have adverse immunologic consequences. To determine the effects of reimmunization on immune responses, primary school children (N=38, mean age=6.14+/-0.35 years) with documented previous measles-mumps-rubella vaccine (MMR) immunization during infancy 4-5 years earlier were studied before and 1 month after receiving MMR as a part of routine reimmunization in Beer-Sheva, Israel. A substantial number of children were seronegative to measles (24%), mumps (34%) and rubella (44%). On reimmunization all seroconverted to mumps and rubella and all but one (92%) seroconverted to measles. The geometric mean titer of measles virus neutralizing antibody increased from 171 to 724 and the greatest increases occurred in those with the lowest pre-immunization titers. Moderate increases in levels of total IgM, IgG and IgE were detected in those with increases in antibody to measles virus. After reimmunization leukocyte counts decreased significantly from (5.8 x 10(6))+/-2.3 to (3.4 x 10(6))+/-0.7 ml(-1) (P=0.0001). The percentages of both CD4(+) and CD8(+) T cells decreased while the CD4:CD8 ratio remained unchanged. The percentage of CD56(+) natural killer (NK) cells increased from 5.2+/-2.7 to 7.2+/-2.8 (P=0.01). Functional assays showed improved lymphoproliferation in response to stimulation with phytohemagglutinin and tetanus toxoid and stable NK lytic activity. Therefore, reimmunization was accompanied by decreased leukocyte counts, but leukocyte function was unchanged or improved.