Israel Medical Association Journal

Polyubiquitylation of cellular proteins has long been recognized as a prelude to a degradative fate in proteasomes. In recent years, however, ubiquitin conjugation has emerged as a regulatory strategy of considerable versatility. Most notably, monoubiquitylation is attributed an intimate role in trafficking of membrane proteins between various cellular compartments. Diverse classes of transmembrane proteins from across the eukaryotic spectrum (e.g., epidermal growth factor-receptor and other receptor tyrosine kinases) become modified with monoubiquitin molecules. Monoubiquitylation of substrates, in turn, regulates both their endocytosis at the plasma membrane and sorting in endosomes for delivery to lysosomes or vacuoles. A mechanistic rationale lies in the identification of a growing list of ubiquitin-binding domains carried by a variety of endocytic adaptor proteins. Thus, ubiquitin-conjugated membrane proteins may form extensive contacts with the endocytic machinery. Further, ubiquitin-binding adaptors and other endocytic components are, likewise, often monoubiquitylated. In this case, ubiquitin conjugation may serve to enhance intermolecular avidity in cargo-bound endocytic complexes, or alternatively, to mediate timely inactivation of ubiquitin-binding adaptors. Interestingly, the ubiquitin/endocytosis interface is appropriated by pathogenic organisms, for instance, during budding of viruses from host-infected cells. Moreover, compromised ubiquitin-mediated transport of certain signaling receptors is associated with disease states, including oncogenic transformation.

Objectives: To characterize the demographic and clinical features of malaria acquired in Kenya, and to assess the adequacy of preventive measures.

Methods: Data were collected from investigation forms at the Ministry of Health. All persons who acquired malaria in Kenya during the years 1999–2001 were contacted by phone and questioned about use of chemoprophylaxis, attitudes towards malaria prevention, and disease course. Further information was extracted from hospital records.

Results: Kenya accounted for 30 of 169 (18%) cases of malaria imported to Israel, and was the leading source of malaria in the study period. Of 30 malaria cases imported from Kenya, 29 occurred after short (1–2 weeks) travel to holiday resorts in Mombassa. Average patient age was 43 ± 12 years, which is older than average for travelers to tropical countries. Only 10% of the patients were fully compliant with malaria chemoprophylaxis. The most common reason for non-compliance was the belief that short travel to a holiday resort carries a negligible risk of malaria. Only 3 of 13 patients (23%) who consulted their primary physician about post-travel fever were correctly diagnosed with malaria. Twenty percent of cases were severe enough to warrant admission to an intensive care unit; one case was fatal.

Conclusions: Measures aimed at preventing malaria and its severe sequelae among travelers should concentrate on increasing awareness of risks and compliance with malaria chemoprophylaxis.

Objective: To describe the epidemiology of ceftazidime-resistant K. pneumoniae in our medical center, as representing the situation in tertiary care hospitals in Israel.

Methods: We vigorously restricted the use of ceftazidime in the ICU and enforced barrier precautions. The susceptibility rate of K. pneumoniae was surveyed in the ICU and throughout the hospital before and after the intervention in the ICU.

Results: Following the intervention, the susceptibility rate of K. pneumoniae increased from 11% (3/28) to 47% (14/30) (P0.01) among ICU isolates, from 55% (154/280) to 62% (175/281) (P=0.08) among total hospital isolates, and from 61% (50/82) to 74% (84/113) (P0.05) among total hospital blood isolates, although no additional control measures were employed outside the ICU.

Conclusions: The epidemiology of ceftazidime-resistant K. pneumoniae in our medical center is similar to that reported from other centers around the world. Early awareness to the emergence of this resistance, identification of the source of the epidemic, and prompt action at the putative source site may reduce the rate of acquisition and spread of such resistance inside and outside of the source unit.