Tuberculosis outbreak in a nursing home involving undocumented migrants and Israeli citizens.

ABSTRACK: OBJECTIVES: Israel has absorbed > 60,000 migrant from the horn of Africa (MHOA) since 2006. No cross-transmission of Mycobacterium tuberculosis from MOHA to Israeli citizens has yet been reported. This study describes the results of contact investigation and laboratory work-out of a unique mixed cluster which included both MOHA and Israeli citizens. METHODS: Description of the results of epidemiological investigation including laboratory confirmation. RESULTS: This unique Mycobacterium tuberculosis strain included 29 patients: 26 were MOHA and three citizens who immigrated to Israel from the former Soviet Union. This is the first mixed cluster described in Israel, which has not been represented in the SITVIT international database of genotyping markers. The transmission from non-citizens to citizens occurred in a nursing institution, when MOHA infected three other contacts- two of whom were retarded residents, one of them died. The index case was screened before employment, and was permitted to return to wok although his chest X-ray demonstrated radiological findings compatible with tuberculosis. Epidemiological links were found in other 12 MOHA members of the cluster. CONCLUSION: This report describes cross-transmission of Mycobacterium tuberculosis from non-citizens MOHA to Israeli citizens who were residents of a nursing home, which may be the first sign for an epidemiological shift. Although cross-ethnical transmission is still rare in Israel, medical settings should employ efficient infection control measures to protect both patients and staff from Mycobacterium tuberculosis.

Cross-border outbreak of extensively drug-resistant tuberculosis linked to a university in Romania.

Extensively drug-resistant (XDR) tuberculosis (TB) poses a threat to public health due to its complicated, expensive and often unsuccessful treatment. A cluster of three XDR TB cases was detected among foreign medical students of a Romanian university. The contact investigations included tuberculin skin testing or interferon gamma release assay, chest X-ray, sputum smear microscopy, culture, drug susceptibility testing, genotyping and whole-genome sequencing (WGS), and were addressed to students, personnel of the university, family members or other close contacts of the cases. These investigations increased the total number of cases to seven. All confirmed cases shared a very similar WGS profile. Two more cases were epidemiologically linked, but no laboratory confirmation exists. Despite all the efforts done, the source of the outbreak was not identified, but the transmission was controlled. The investigation was conducted by a team including epidemiologists and microbiologists from five countries (Finland, Israel, Romania, Sweden and the UK) and from the European Centre for Disease Prevention and Control. Our report shows how countries can collaborate to control the spread of XDR TB by exchanging information about cases and their contacts to enable identification of additional cases and transmission and to perform the source investigation.

Tuberculosis in native Israeli Arabs and Jews: trends and treatment outcomes, 1999-2011.

The incidence of tuberculosis (TB) in native ethnic minorities remains high in developed countries. Arabs, the major ethnic minority in Israel, comprise 21% of its population. This retrospective study compared TB incidence, demographic, clinical, laboratory, genotyping characteristics and treatment outcomes in all Israeli-born citizens diagnosed with TB between 1999 and 2011 by ethnicity, i.e. Israeli-born Arabs (IA) and Jews (IJ). A total of 831 Israeli-born TB patients were reported. Of those, there were 530 (64%) IJ and 301 (36%) IA, with an average annual TB rate of 1·1 and 1·6 cases/100 000 population, respectively, lower than the national average (7·0 cases/100 000 population). TB rates in IA and IJ declined and converged to 1 case/100 000 residents. IA TB patients were more likely to be older, have more pulmonary TB and have lower treatment success rates than IJ. Older age and HIV co-infection, but not ethnicity, were predictive of non-success in TB treatment. Ten mixed IA-IJ clades were detected by spoligotyping and three mixed IA-IJ clusters were identified by MIRU-VNTR typing. Only one IA-IJ couple recalled mutual contact. In conclusion, TB rate in IA was higher than in IJ, but declined and converged in both to 1 case/100 000. Treatment success was high in both groups, and was unrelated to ethnicity.

Tuberculosis Beijing strain outbreak in an Israeli Arab rural community linked to an incarcerated immigrant.

A tuberculosis (TB) outbreak with six definite and four probable cases, caused by a Beijing strain isolate, occurred in an Arab rural community in north Israel. Using epidemiological investigation and strain genotyping, we identified the source case as an incarcerated immigrant. This outbreak illustrates how a systematic breakdown in TB prevention and control measures at multiple levels, within prisons and upon exiting prison, can result in rapid, cross-ethnic transmission of TB to a low-risk population. The close social bonds in this rural community and downsizing of the regional TB clinic staff may also have contributed to the magnitude of this outbreak.

Molecular epidemiology and mapping of tuberculosis in Israel: do migrants transmit the disease to locals?

SETTING: Israel receives migrants from various countries, some of which have high tuberculosis (TB) prevalence. OBJECTIVE: To assess the predominant Mycobacterium tuberculosis strains in Israel isolated during 2008-2010 among Israeli-born and migrant patients, and to investigate possible transmission of TB from migrants to the local population. METHODS: Molecular characterisation employed 43-spacer spoligotyping and 16-loci mycobacterial interspersed repetitive units-variable number of tandem repeats typing. All patients were classified according to those who were members of a cluster and those who were not. RESULTS: Among 684 M. tuberculosis strains isolated from new patients genotyped and assigned to their specific cohort populations during the study period, major spoligotype families were Central Asian (CAS) (n = 140, 20%), Beijing (n = 101, 15%) and T (n = 160, 23%). Most Beijing strains (66%) were isolated from patients from the former Soviet Union (FSU), while CAS strains were mainly (74%) from Ethiopia, Eritrea and Sudan (EES). For the heterogeneous T-clade, patient countries of origin were 38% EES and 33% FSU. CONCLUSIONS: Predominant M. tuberculosis genotypes in Israel in 2008-2010 were similar to genotypes endemic to the migrants' countries of origin. Epidemiological investigations did not demonstrate transmission between migrants and Israeli-born patients sharing the same cluster.

Drug-resistant tuberculosis in Israel: risk factors and treatment outcomes.

SETTING: All culture-positive tuberculosis (TB) isolates in Israel. OBJECTIVES: To outline the magnitude of drug-resistant TB in Israel, describe treatment outcomes and identify risk factors. DESIGN: Retrospective study of laboratory data of all strains of adult TB patients tested for resistance to first- and second-line anti-tuberculosis drugs between 1999 and 2010. RESULTS: Of 4652 reported TB cases, 3552 (76.3%) underwent culture (annual range 73-81%); 445 (12.5%) were resistant to one or more first-line drugs, while 207 (5.8%) had multidrug-resistant TB (MDR-TB). Risk factors for MDR-TB included being male, age 30-59 years, migrants (mainly from the former Soviet Union [FSU]) who had stayed in Israel >2 years, and having pulmonary TB, human immunodeficiency virus (HIV) infection and sputum smear positivity. Of all MDR-TB patients, 71.0% achieved treatment success, while 19.8% died. Twelve Israeli citizens had extensively drug-resistant TB (5.8% of MDR-TB cases). All had emigrated from the FSU and had pulmonary TB; 1 was HIV-infected. Seven (58.4%) achieved treatment success and 5 (41.6%) died. CONCLUSIONS: Drug-resistant TB in Israel is influenced by migration, especially from the FSU, where the patients were probably infected. Rapid sputum sampling performed in the early stages of the disease, patient isolation and drug susceptibility testing should be the standard of care to avoid further transmission and improve TB control.

Rapid identification of Enterobacter hormaechei and Enterobacter cloacae genetic cluster III.

AIM: Enterobacter cloacae complex bacteria are of both clinical and environmental importance. Phenotypic methods are unable to distinguish between some of the species in this complex, which often renders their identification incomplete. The goal of this study was to develop molecular assays to identify Enterobacter hormaechei and Ent. cloacae genetic cluster III which are relatively frequently encountered in clinical material. METHODS AND RESULTS: The molecular assays developed in this study are qPCR technology based and served to identify both Ent. hormaechei and Ent. cloacae genetic cluster III. qPCR results were compared to hsp60 sequence analysis. Most clinical isolates were assigned to Ent. hormaechei subsp. steigerwaltii and Ent. cloacae genetic cluster III. The latter was proportionately more frequently isolated from bloodstream infections than from other material (P < 0·05). CONCLUSION: The qPCR assays detecting Ent. hormaechei and Ent. cloacae genetic cluster III demonstrated high sensitivity and specificity. SIGNIFICANCE AND IMPACT OF THE STUDY: The presented qPCR assays allow accurate and rapid identification of clinical isolates of the Ent. cloacae complex. The improved identifications obtained can specifically assist analysis of Ent. hormaechei and Ent. cloacae genetic cluster III in nosocomial outbreaks and can promote rapid environmental monitoring. An association was observed between Ent. cloacae cluster III and systemic infection that deserves further attention.

Seroepidemiology of Toxoplasma gondii infection in the Israeli population.

Toxoplasmosis seroprevalence varies considerably between countries. We studied the seroprevalence of Toxoplasma gondii IgG antibodies in a national sample of the Israeli population; 2794 sera were tested. The highest age-adjusted seroprevalence rate was in Arabs (non-Bedouins) (60.4%), significantly higher compared to the rate in Jews (19.9%) and Bedouins (27.5%) (P < 0.01). There were no significant gender differences. Seropositivity increased with age in all population groups. For Jews, seropositivity was associated with place of birth and socioeconomic status. A finding of low seroprevalence rate in Bedouins despite their poor living conditions and close contact with livestock is surprising, and might be attributed to the dry and hot climate conditions in their area of residence. In women of reproductive age the seroprevalence was 15.1% in Jews, 25.4% in Bedouins and 72.3% in Arabs (non-Bedouins). Thus, the majority of pregnant women are susceptible to primary infection with T. gondii, and the risk for congenital toxoplasmosis remains high.

Differential expression of intracisternal A-particle transcripts in immunogenic versus tumorigenic S49 murine lymphoma cells.

Tumorigenic S49 mouse lymphoma cells (T-25) were compared to their nontumorigenic (immunogenic) substrate-adherent descendants (T-25-Adh), using the differential display technique. A 784-bp fragment with 92% sequence homology to the intracisternal A-particle (IAP) element family was isolated from the latter cells. IAP sequences are endogenous, noninfectious retroviral elements that can undergo transpositions and act as mutagens. Expression of IAP transcripts (as detected by the isolated fragment) was 5- to 10-fold higher in T-25-Adh cells than in T-25 cells. IAP RT-PCR cDNA clones derived from the immunogenic T-25-Adh cells, but not from T-25 cells, contain two distinctive motifs: (i) a motif characteristic of IAP elements expressed in lymphoid cells (lymphocyte specific, LS); (ii) a nonapeptide sequence known to stimulate cytotoxic T lymphocytes in a leukemia cell line expressing IAP sequences. In addition, expression of transcripts containing these motifs is enhanced in the immunogenic cells as opposed to the tumorigenic cells. Furthermore, one of the IAP elements (belonging to the LS1 subfamily) is specifically hypomethylated in the DNA of the immunogenic cells. The above-mentioned relationship was strengthened when tumorigenic revertants derived from T-25-Adh cells, as well as independently selected tumorigenic and immunogenic S49 sublines, were studied. In all cases, enhanced immunogenicity was linked to the up-regulation of specific IAP elements. No transpositions of LS1 elements were observed among the different sublines studied. These findings suggest that, in the S49 lymphoma, selectively expressed IAP retroviral elements may function in a tumor suppressive capacity by affecting the immunogenic potential of these cells.

Nucleolar localization of mouse mammary tumor virus proteins in T-cell lymphomas.

To characterize novel proteins expressed in lymphoma cells, monoclonal antibodies (MAbs) were raised against variant S49 mouse lymphoma cells. Immunoperoxidase analysis with a specific MAb, named M-66, revealed nuclear localization with prominent staining in the nucleoli of both tumorigenic (T-63) cells and nontumorigenic, immunogenic (T-25-Adh) cells. Weak signals were also observed in the cytoplasm and plasma membrane of both cells. Western blot analysis with M-66 antibody revealed a 14-kDa protein in nuclear extracts of both T-25-Adh and T-63 cells. An additional nuclear 21-kDa protein was evident only in T-63 cells. M-66 identified several clones from a T-25-Adh cDNA expression library. These clones demonstrated extensive homology (approximately 95% identity throughout their length) to the mouse mammary tumor virus (MMTV) env and LTR regions. Extensive amino acid sequence homology (approximately 90% identity) between the clones and the env protein was observed. M-66 identified the 14-kDa protein in another MMTV bearing T-cell lymphoma, EL-4. Immunoperoxidase analysis of EL-4 cells with M-66 also revealed prominent nucleolar staining. MMTV-negative cells and MMTV-positive cells of nonlymphocytic origin were devoid of both 14- and 21-kDa proteins. Moreover, an anti-MMTV gp52 (env) antibody precipitated the 21-kDa protein in T-63 cells. We thus suggest that MMTV bearing T-cell lymphomas express nucleolar proteins translated from the env region of MMTV.

Structure and evolution of the human prosaposin chromosomal gene.

The gene for prosaposin was characterized by sequence analysis of chromosomal DNA to gain insight into the evolution of this locus that encodes four highly conserved sphingolipid activator proteins or saposins. The 13 exons ranged in size from 57 to 1200 bp, while the introns were from 91 to 3812 bp in length. The regions encoding saposins A, B, and D each had three exons, while that for saposin C had only two. This sequence included the regions that encode the carboxy terminus of the signal peptide, the four mature prosaposin proteins, and the 3' untranslated region. Primer extension studies indicated that over 99% of the coding sequence was contained in these 19,985 bp. Use of PCR and reverse PCR techniques indicated that the most 5' coding approximately 140 bp contained large introns and at least two small exons. Analyses of the intronic positions in the saposin regions indicated that this gene evolved from an ancestral gene by two duplication events and at least one gene rearrangement involving a double crossover after introns had been inserted into the gene.

Molecular cloning of a human co-beta-glucosidase cDNA: evidence that four sphingolipid hydrolase activator proteins are encoded by single genes in humans and rats.

Authentic cDNAs encoding the activator protein for acid beta-glucosidase (EC3.2.1.45), co-beta-glucosidase, were cloned from the pCD and lambda gt11 human cDNA libraries. Initial screening with oligonucleotide mixtures encoding amino acid sequences of co-beta-glucosidase identified partial cDNAs which were used to obtain a potentially full-length cDNA from the lambda gt11 library. This clone (2767 bp), EGTISI, contained 5' (38 bp) and 3' (1157 bp) noncoding sequences, a translation initiation site, and an open reading frame encoding 524 amino acids which included a typical hydrophobic signal sequence (16 amino acids). Computer analyses identified three regions of high similarity to co-beta-glucosidase encoded by tandem sequences in EGTISI. Searches revealed that two of these regions encoded peptides of known function; SAP1 (sphingolipid activator protein 1) and protein C (a new sphingolipid activator protein) were encoded by EGTISI sequences 5' and 3', respectively, to those for co-beta-glucosidase. The third region of similarity, encoding a theoretical peptide (undefined function), was located most 5' in the cDNA. EGTISI and its encoded polypeptide had high similarity (77% nucleotide identity and about 80% amino acid similarity) to a rat Sertoli cell cDNA and its encoded sulfated glycoprotein-1. These results indicate that a single highly conserved gene encodes the precursor for four potential sphingolipid activator proteins in rat and man.