Vaccine escape of piliated Streptococcus pneumoniae strains.

INTRODUCTION: Type1-pilus proteins were suggested as targets of future protein-based vaccines. Here we studied the effect of pneumococcal-conjugate vaccine (PCV7) implementation on the prevalence of piliated strains in a unique study setting which controls for typical confounders; the Palestinian-Israeli Collaborative Research (PICR). METHODS: Annual cross-sectional surveys of pneumococcal carriage were performed during 2009-2011 among two closely related population that live under different health policies (a) Palestinian-Authority (PA) (n=1773), where PCV7 was not yet introduced (b) East-Jerusalem (EJ) (n=983) where PCV7 was rapidly implemented. Clinical data were collected, pneumococci identified and characterized and the presence of Type1-pilus genes was determined by rrgC PCR. RESULTS: Following PCV7 implementation in EJ, overall carriage prevalence did not change (∼30%), but VT7 strains decreased from 61.5% to 33.8%. While prevalence of non-piliated-VT7 isolates decreased from 37% to 10%, p<0.001, the prevalence of piliated-VT7 strains persisted ∼25%. Additionally, piliated non-VT13 strains emerged (1-15%, p<0.001). These changes were not observed in PA. These dynamics were independent of the bacteria's resistance pattern. CONCLUSIONS: A differential effect of PCV7 was observed with a relative resistance of piliated strains to the vaccine. This suggests that Type1-pilus confers an intrinsic advantage for colonization and may be an attractive vaccine target.

Varied utilisation of health provision by Arab and Jewish residents in Israel.

INTRODUCTION: Provision of healthcare is considered a basic human right. Delivery and uptake is affected by many complex factors. Routine vaccinations are provided free of charge in Israel to all residents. The Palestinian Israeli Collaborative Research (PICR) group conducted research on vaccine impact at eight primary care facilities in east Jerusalem (EJ) and central Israel (IL) which allowed assessment and comparison of interactions of these Arab and Jewish populations, respectively, with healthcare services. METHODS: Families attending clinic with a child under five years old were invited to participate. Utilisation of healthcare was assessed using data from standardise questionnaires completed after enrolment, using proxies of vaccination status, antibiotic use, primary care physician and hospital visits as well as demographics such as household size. Differences between EJ and IL were assessed using chi squared tests; univariate analyses identified potential confounders which were tested in a multiple logistic regression model for any independent associations between region and outcome. RESULTS: Children in EJ were significantly more likely to live in larger households, with tobacco smokers, to have been breastfed, hospitalised and used antibiotics recently than those in IL, who were significantly more likely to have recently seen a primary care physician (all p < 0.01). Receipt of routine vaccinations, given at well baby clinics, was similar between the regions at above 95% (p = 0.11), except for influenza which was delivered separately at primary physician clinics to 5% (EJ) and 12% (IL). Receipt of pneumococcal vaccine when paid for separately was significantly higher in IL than EJ (3% vs 31%). Multivariate analysis identified the most important independent predictors of these differences as region, age and household size. CONCLUSIONS: Healthcare in Israel is of a very high standard, but it is not uniformly utilised within the community in all geographical areas, though in some key areas, such as uptake of most routine childhood vaccination, equality seems to be achieved. To ensure excellent healthcare is achieved across the population, inequalities must be addressed, for instance in health promotion and other activities, which could improve and normalise health outcomes.

Measuring the effects of pneumococcal conjugate vaccine (PCV7) on Streptococcus pneumoniae carriage and antibiotic resistance: the Palestinian-Israeli Collaborative Research (PICR).

BACKGROUND: The Palestinian-Israeli Collaborative Research (PICR) cross-conflict setting provided a unique opportunity to study overall and indirect effects of pneumococcal conjugate vaccine (PCV7), in two closely related Palestinian populations governed by two distinct health authorities with distinct vaccination policies. Here, PCV7 effects on pneumococcal carriage, serotype distribution and antibiotic resistance are reported. METHODS: Annual cross-sectional surveys of pneumococcal carriage were performed during 2009-2011 among Palestinian children (≤5 years) (a) under Palestinian-Authority (PA) health policy (Ramallah, Nablus and Bethlehem), where PCV7 was unlicensed (b) under Israeli health policy (East-Jerusalem (EJ)) where PCV7 was rapidly implemented from July 2009. Clinical data were collected, pneumococci identified and characterized for antibiotic susceptibilities and serotype. Analyses included multivariate logistic models with an interaction term for PCV7-effect. RESULTS: Altogether, 2755 children from PA (n=1772) and EJ (n=983) were enrolled, of which ~30% were pneumococcal carriers. While overall carriage was not affected by vaccination policy, carriage of vaccine-type (VT7) strains decreased from 52% to 22% (p<0.001) in EJ, where PCV was implemented, but not in PA. This was accompanied by an increase in non-VT13 strains from 34% to 65% (p<0.001) in EJ, but not in PA. Furthermore, within two years post-PCV7 introduction, proportion of multi-drug resistant strains, which was initially 23% in both populations, decreased significantly in EJ, to 10%, while simultaneously it increased in PA to 33% (p<0.001). Similar trends were observed for resistance to most antibiotic groups. The proportion of resistant isolates among non-VT13 strains did not change during the study period. CONCLUSIONS: The unique study design distinguishes secular and seasonal effects from true vaccine effects. While PCV7 did not affect overall pneumococcal carriage rate, VT7 strains, many of which were antibiotic resistant decreased and were replaced by non-VT13 strains, which were mostly not antibiotic resistant, resulting in a net decrease in antibiotic resistance.

Characterization of novel multiantigenic vaccine candidates with pan-HLA coverage against Mycobacterium tuberculosis.

The low protection by the bacillus Calmette-Guérin (BCG) vaccine and existence of drug-resistant strains require better anti-Mycobacterium tuberculosis vaccines with a broad, long-lasting, antigen-specific response. Using bioinformatics tools, we identified five 19- to 40-mer signal peptide (SP) domain vaccine candidates (VCs) derived from M. tuberculosis antigens. All VCs were predicted to have promiscuous binding to major histocompatibility complex (MHC) class I and II alleles in large geographic territories worldwide. Peripheral mononuclear cells (PBMC) from healthy naïve donors and tuberculosis patients exhibited strong proliferation that correlated positively with Th1 cytokine secretion only in healthy naïve donors. Proliferation to SP VCs was superior to that to antigen-matched control peptides with similar length and various MHC class I and II binding properties. T-cell lines induced to SP VCs from healthy naïve donors had increased CD44(high)/CD62L(+) activation/effector memory markers and gamma interferon (IFN-γ), but not interleukin-4 (IL-4), production in both CD4(+) and CD8(+) T-cell subpopulations. T-cell lines from healthy naïve donors and tuberculosis patients also manifested strong, dose-dependent, antigen-specific cytotoxicity against autologous VC-loaded or M. tuberculosis-infected macrophages. Lysis of M. tuberculosis-infected targets was accompanied by high IFN-γ secretion. Various combinations of these five VCs manifested synergic proliferation of PBMC from selected healthy naïve donors. Immunogenicity of the best three combinations, termed Mix1, Mix2, and Mix3 and consisting of 2 to 5 of the VCs, was then evaluated in mice. Each mixture manifested strong cytotoxicity against M. tuberculosis-infected macrophages, while Mix3 also manifested a VC-specific humoral immune response. Based on these results, we plan to evaluate the protection properties of these combinations as an improved tuberculosis subunit vaccine.

A typical hospital-acquired methicillin-resistant Staphylococcus aureus clone is widespread in the community in the Gaza strip.

Epidemiological data on community acquired methicillin-resistant-Staphylococcus aureus (CA-MRSA) carriage and infection in the Middle-East region is scarce with only few reports in the Israeli and Palestinian populations. As part of a Palestinian-Israeli collaborative research, we have conducted a cross-sectional survey of nasal S. aureus carriage in healthy children and their parents throughout the Gaza strip. Isolates were characterized for antibiotic susceptibility, mec gene presence, PFGE, spa type, SCCmec-type, presence of PVL genes and multi-locus-sequence-type (MLST). S. aureus was carried by 28.4% of the 379 screened children-parents pairs. MRSA was detected in 45% of S. aureus isolates, that is, in 12% of the study population. A single ST22-MRSA-IVa, spa t223, PVL-gene negative strain was detected in 64% of MRSA isolates. This strain is typically susceptible to all non-ß-lactam antibiotics tested. The only predictor for MRSA carriage in children was having an MRSA carrier-parent (OR=25.5, P=0.0004). Carriage of the Gaza strain was not associated with prior hospitalization. The Gaza strain was closely related genetically to a local MSSA spa t223 strain and less so to EMRSA15, one of the pandemic hospital-acquired-MRSA clones, scarcely reported in the community. The rapid spread in the community may be due to population determinants or due to yet unknown advantageous features of this particular strain.

[Incidence of venous thromboembolism in 700 patients with acute tuberculosis].

BACKGROUND: Studies have demonstrated a link between pulmonary tuberculosis and hypercoagulable state, with reported rates of 3-10% venous thromboembolism (VTE) in all adults with tuberculosis. However, the latest research was conducted almost 18 years ago. AIM: The present study aims to evaluate the current incidence and characteristics of VTE in a large sample of patients with acute tubercuLosis. METHODS: The study included 700 adults treated for tuberculosis from 1999 to 2007.The files were reviewed for Length of hospital stay, occurrence of VTE, site of VTE, interval from onset of tuberculosis/treatment to VTE, and outcome. To exclude primary hypercoagulable state, all patients with VTE underwent a complete hypercoagulation profile. RESULTS: VTE was noted in 5 of the 700 patients (0.7%). Ages ranged from 19 to 70 years (median 53). All had pulmonary tuberculosis; median hospital stay was 28 days (range, 26-44 days). All cases of VTE occurred within the first month of treatment. All 5 patients had deep vein thrombosis, and one also subsequently developed a pulmonary embolism. All patients responded to anticoagulation treatment. CONCLUSION: VTE occurs in 1 out of every 140 patients with acute tuberculosis. It seems to deveLop mainly in the first month of treatment, especially in those with a prolonged hospital stay. Outcome is good.

Streptococcus pneumoniae carriage in the Gaza strip.

BACKGROUND: Pneumococcal infections cause major morbidity and mortality in developing countries. We report the epidemiology of S. pneumoniae carriage in a developing region, the Gaza strip, and evaluate the theoretical coverage of carriage strains by pneumococcal conjugate vaccines (PCVs). METHODOLOGY: In 2009 we conducted a cross-sectional survey of S. pneumoniae carriage in healthy children and their parents, living throughout the Gaza strip. Data were collected and nasopharyngeal swabs were obtained. Antibiotic susceptibilities were determined by Vitek-2 and serotypes by the Quellung reaction. PRINCIPAL FINDINGS: S. pneumoniae carriage was detected in 189/379 (50%) of children and 30/376 (8%) of parents. Carriage prevalence was highest in children <6 months of age (63%). Significant predictors for child carriage were number of household members and DCC attendance. The proportion of pediatric and adults isolates with serotypes included in PCV7 were 32% and 20% respectively, and 46% and 33% in PCV13 respectively. The most prominent non-vaccine serotypes (NVT) were 35B, 15B/C and 23B. Penicillin-nonsusceptible strains were carried by 70% of carriers, penicillin-resistant strains (PRSP) by 13% and Multi-drug-resistant (MDR) by 30%. Of all PRSP isolates 54% belonged to serotypes included in PCV7 and 71% in the PCV13. Similarly, 59% and 73% of MDR-SP isolates, would theoretically be covered by PCV7 and PCV13, respectively. CONCLUSIONS: This study demonstrates that, PCV13-included strains were carried by 46% and 33% of pediatric and adult subjects respectively. In the absence of definitive data regarding the virulence of the NVT strains, it is difficult to predict the effect of PCVs on IPD in this region.

Reduction in antibiotic use following a cluster randomized controlled multifaceted intervention: the Israeli judicious antibiotic prescription study.

BACKGROUND: Antibiotic overuse is of great public health concern. This study assessed whether intervention among physicians and their treated population could achieve a sustained reduction in antibiotic use, specifically in classes known to promote antibiotic resistance among children in a community setting. METHODS: We performed a cluster randomized controlled multifaceted trial among 52 primary care pediatricians and the 88,000 children registered in their practices. The intervention was led by local leaders and engaged the participating physicians. It included physician focus group meetings, workshops, seminars, and practice campaigns. These activities focused on self-developed guidelines, improving parent and physician knowledge, diagnostic skills, and parent-physician communication skills that promoted awareness of antibiotic resistance. The main outcome measure was the change in annual antibiotic prescription rates (APRs) of children treated by the intervention group physicians as compared with rates among those treated by control group physicians. The study comprised a 2-year pre-intervention period, a 3-year intervention period, and a 1-year follow-up period. Mixed-effect models were used to assess risk ratios to account for the clustered study design. RESULTS: A decrease in the total APR among children treated by the intervention physicians compared with those treated by the control physicians was observed in the first intervention year (APR decrease among control physicians, 40%; APR decrease among intervention physicians, 22%; relative risk [RR], .76; 95% confidence interval [CI], .75-.78). This reduction crossed over all antibiotic classes but was most prominent for macrolides (macrolide prescription rate among control physicians, 58%; macrolide prescription rate among intervention physicians, 27%; RR, .58; 95% CI, .55-.62). The effect was sustained during the 4 following years. CONCLUSIONS. Multifaceted intervention that engages the physicians in an educational process is effective in reducing APRs and can be sustained. CLINICAL TRIALS REGISTRATION: NCT01187758.

Changing parents' opinions regarding antibiotic use in primary care.

Parents' wish for antibiotics is a significant determinant of antibiotic prescription for their children. The objective of the study was to assess the effect of an educational intervention on parents' attitudes towards antibiotic use. Parents accompanying their children to primary pediatric clinics of Jerusalem-Hashfela District of Maccabi Healthcare Services responded to a survey regarding their wish for antibiotic treatment. Two groups of parents were surveyed: A (control) in a pre-intervention period and B (intervention) during the intervention period. The intervention included posters, pamphlets, and drawing booklets for children in the waiting rooms. A per-protocol analysis that included from group B only parents that stated they noticed the educational material (B1) was also performed. Eight hundred and sixty-eight parents were surveyed during the pre-intervention period and 688 parents during the intervention period. Children's median age was 4 years (8 days-16 years). Most (86%) of the parents were mothers. Groups were similar in socio-demographic characteristics and children's medical complaints. Factors associated with parent's low expectation for antibiotics were a general negative attitude to antibiotics (OR 1.66, 95% CI 1.20-2.30), current upper respiratory tract symptoms (OR 0.29, 95% CI 0.21-0.39), advanced knowledge regarding antibiotics (OR 1.72, 95% CI 1.26-2.34), and being in group B (intervention) (OR 1.47, 95% CI 1.08-2.00). The effect of the intervention was greater in the per-protocol analysis (OR 1.75, 95% CI 1.20-2.55). A simple educational intervention was effective in reducing parents' expectation for antibiotics but was significantly more effective when parents reported they noticed the campaign. Improving parents' knowledge regarding antibiotics can reduce parents' wish for antibiotic treatment.

The burden and cost of ambulatory cases of rotavirus gastroenteritis in central Israel.

BACKGROUND: While the burden of rotavirus infection with regard to hospitalizations has been extensively investigated, there are sparse data on the cost and impact of this infection on the ambulatory part of the health system in Israel. OBJECTIVES: To investigate the burden of rotavirus infection on the ambulatory system in Israel. METHODS: Infants younger than 3 years examined for acute gastrointestinal symptoms in four pediatric clinics had their stool tested for rotavirus. The parents were contacted 7-10 days later and questioned about the symptoms of illness, medications given, use of diapers, consumption of formula, and any loss of parents' workdays. RESULTS: Rotavirus was detected in 71 of the 145 stool samples tested (49%). A total of 54 parents responded to the telephonic survey. Patients' mean age was 15.4 months. Three patients were hospitalized due to the illness. The mean duration of fever was 1.7 days. Infants with rotavirus gastroenteritis had on average 2.25 days of vomiting and 7.5 days of diarrhea. The average number of workdays lost was 2.65 days per RVGE case. The cost of the average case of RVGE in Israel is 257 euros; 69.64% of this cost (179 euros) is due to parental work loss. CONCLUSIONS: Our results indicate that the economic impact of the ambulatory cases in Israel is quite significant.

The QuantiFERON-TB-GOLD assay for tuberculosis screening in healthcare workers: a cost-comparison analysis.

The aim of this study was to assess the costs of screening healthcare workers (HCWs) for tuberculosis (TB) using the novel interferon-gamma release assay QuantiFERON((R))-TB Gold In-tube (QFT) versus the tuberculin skin test (TST). We used a prospective observational study with a cost-comparison analysis. The study was conducted at a regional center for ambulatory TB treatment. The study included 100 Israeli HCWs who were referred for routine TB screening. The participants were tested with both TST and QFT. For the TST, induration of 10 mm or more was considered a positive test. For the QFT, a threshold of 0.35 IU/ml interferon-gamma above background levels was a positive test. We developed a computerized model of the present TST-only screening method versus the QFT either alone (instead of the TST) or as a confirmatory test for a positive TST. Of the 100 subjects, 34 had a positive TST result and 17 had a positive QFT result. There was poor agreement between the TST and the QFT (kappa = 0.19). Assuming adherence to treatment of 50%, costs were minimized by using the QFT to confirm a positive TST (4155). The QFT-only model was cheaper than the TST-only model (7280 vs. 8217, respectively). The QFT-only method required the fewest clinic visits (121) compared to the TST (344). Adherence to treatment in the QFT-positive group was 47% compared with 12% for the TST-positive group. Screening HCWs with the QFT test compared to the TST resulted in fewer possible cases being identified, lower costs, and increased adherence to treatment. Costs were minimized by using the QFT to confirm a positive TST. A QFT-based screening program for HCWs is feasible and should be evaluated systematically.

Parental Staphylococcus aureus carriage is associated with staphylococcal carriage in young children.

BACKGROUND: Staphylococcus aureus colonization typically precedes infection but risk factors for colonization in children are not well defined. Our previous study suggested that S. aureus carriage in children is associated with parental carriage. Here we wished to distinguish the different components that play a role in the risk to a child of a S. aureus-carrying parent. METHODS: Between 2002 and 2005, children (0-40 months) and their parents were screened for carriage of S. aureus and Streptococcus pneumoniae during 1 of 6 surveys. Data were collected from the parents and the medical files. Multivariate analysis of possible associated factors and effect modifiers was carried out. Pulse-field gel electrophoresis was performed to determine strain relatedness. RESULTS: A total of 4648 children were screened. S. aureus was isolated from 342 (7.6%) children and 992 (22%) parents. Pairs of parent-child carriers were found in 155 cases, over twice the rate expected by chance (1.66%, P<0.0001). The variable that was most significantly associated with carriage in children was having a parent carrier (OR: 3.35; 95% CI: 2.59-4.33), whereas close contact with peers (as assessed by day care centers attendance or having young siblings) was not associated with carriage. Children<3 months had the highest carriage rate and children aged 6 to 12 months had the lowest (25.4% and 4.3%, respectively, P<0.0001). Breast-feeding was not associated with higher or lower carriage. In 30 of 150 strains studied, >70% parent-child strains were genetically identical. CONCLUSIONS: Parental S. aureus colonization, but not DCC attendance or having young siblings, is an independent predictor for staphylococcal carriage in young children.

Three years of pulmonary rehabilitation: inhibit the decline in airflow obstruction, improves exercise endurance time, and body-mass index, in chronic obstructive pulmonary disease.

BACKGROUND: Pulmonary rehabilitation is known to be a beneficial treatment for COPD patients. To date, however, there is no agreement for how long a rehabilitation program should be implemented. In addition, current views are that pulmonary rehabilitation does not improve FEV1 or even slow its decline in COPD patients. The aim of the study was to examine the efficacy of a 3 year outpatient pulmonary rehabilitation (PR) program for COPD patients on pulmonary function, exercise capability, and body mass index (BMI). METHODS: A matched controlled trial was performed with outcome assessments evaluated at 6, 12, 18, 24, 30, and 36 months. Eighty patients with moderate to severe COPD (age 63 +/- 7 years; FEV1 48% +/- 14) were recruited. The control group received standard care only, while in addition, the case study group received PR for duration of three years. These groups were matched for age, sex, BMI, FEV1% and number of pack-years smoked. RESULTS: The decline in FEV1 after the three years was significantly lower in the PR group compared to control, 74 ml versus 149 ml, respectively (p < 0.001). Maximal sustained work and endurance time improved after a short period of PR and was maintained throughout the study, in contrast to the control group (p < 0.01). A decreased BMI was noted in the control group after three years, while in the PR group a mild improvement was seen (p < 0.05). CONCLUSION: Three years of outpatient pulmonary rehabilitation resulted in modifying the disease progression of COPD, as well as improving physical performance in these patients.

Effect of N-acetylcysteine on air trapping in COPD: a randomized placebo-controlled study.

BACKGROUND: FEV(1) is used for the classification of disease severity and is a good predictor of COPD mortality. However, it is a poor predictor of clinical symptoms, exercise tolerance, and response to bronchodilators in COPD. Progressive reduction in inspiratory capacity (IC) during exercise reflects dynamic hyperinflation and is a good predictor of decreased exercise ability as well as increased exertional dyspnea. In animal models of COPD, N-acetylcysteine (NAC), an antioxidant/mucous modifier, has been shown to modify small airways, which mainly causes lung hyperinflation. OBJECTIVE: Our goal was to examine the effect of 1,200 mg/d of NAC on lung hyperinflation at rest and after exercise in patients with moderate-to-severe COPD. METHODS: This was a randomized, double-blind, cross-over study that included 24 eligible patients > 40 years of age with a diagnosis of COPD, a FEV(1) < 70% of predicted, FEV(1)/FVC ratio < 0.70, and a functional residual capacity > 120% of predicted normal. Patients were randomized to placebo treatment or NAC treatment twice daily for 6 weeks. This was followed by a 2-week washout period, and then patients were crossed over to alternate therapy for an additional 6 weeks. Evaluation was performed after each 6 weeks of each treatment. RESULTS: IC and FVC were higher especially after exercise after NAC treatment compared with placebo treatment. In addition, the relationship of residual volume to total lung capacity was reduced in a similar pattern. Furthermore, endurance time was longer after NAC treatment compared with placebo treatment. CONCLUSIONS: NAC treatment of patients with stable, moderate-to-severe COPD has a beneficial effect on physical performance, probably due to a reduction in air trapping. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT00476736.

The pneumococcal pilus predicts the absence of Staphylococcus aureus co-colonization in pneumococcal carriers.

The determinants of the negative association between Streptococcus pneumoniae and Stapylococcus aureus colonization are unknown. In this matched case-control study, the odds of co-colonization with S. aureus were significantly lower for individuals carrying a piliated versus a nonpiliated S. pneumoniae strain, suggesting the pilus may be a determinant of the negative association.

In vitro bactericidal activity of Streptococcus pneumoniae and bactericidal susceptibility of Staphylococcus aureus strains isolated from cocolonized versus noncocolonized children.

Streptococcus pneumoniae is bactericidal to Staphylococcus aureus in vitro. To determine whether this in vitro effect accounts for the inverse relation between S. pneumoniae and S. aureus colonization reported in previous epidemiologic studies, we compared S. pneumoniae and S. aureus strains from cocolonized children to those from noncocolonized children. Cocolonizing pneumococci were less bactericidal and cocolonizing staphylococci less susceptible to this effect; however, the magnitude of the effect was small. Thus, in vitro killing is not the major determinant of the pattern of cocolonization.

Rehabilitation versus drug therapy for urge urinary incontinence: long-term outcomes.

The objective of this study was to compare the residual effect of a 3-month rehabilitation treatment and a standard drug treatment for urge urinary incontinence (UUI) 21 months post intervention. Forty-four women (ages 27-68 years) who were diagnosed with overactive bladder (OAB) were divided into 2 treatment groups over 3 months: 24 women received rehabilitation (REH) and 20 women were treated with medication (MED) (oxybutynin ER). Outcomes measures included frequency of urination, quality of life (QoL), and number of side effects (no/SE), which were measured upon entry into the study (entry), completion of the intervention (3 months), and at follow-up 3 and 21 months after completion of treatment. In the follow-up period, there was a significant group-time interaction effect on freq/day and freq/night (p < 0.01). At the end of follow-up, the mean number of no/SE was significantly greater in the MED group compared to the REH group (3.3 +/- 0.5 vs 2.4 +/- 0.4; p < 0.05). A significant negative association was found between the urinary symptoms and the I-QoL at the 21-month follow-up (r (p) = -0.45 to-0.57, p < 0.05). In the long-term, the REH patients maintained and even improved the achievements of the intervention period while the MED patients deteriorated to baseline values in urinary frequency. The suggestion for future work is to investigate the effect of each REH treatment component on UUI symptoms.

Prevalence of chronic obstructive pulmonary disease among smokers aged 45 and up in Israel.

BACKGROUND: Chronic obstructive pulmonary disease is an increasing cause of chronic morbidity and mortality around the world. The major cause of the disease is smoking. Despite the gravity of the problem there is no knowledge of its rate in the Israeli smoking population. OBJECTIVES: To assess the prevalence of COPD and early lung cancer among smokers. METHODS: People aged 45 up to 75 with a history of at least 20 pack-years cigarette smoking, including quitters, were screened for COPD. They were interviewed and a spirometry was performed. RESULTS: Of the 1150 people recruited 92% underwent and performed acceptable spirometry; 22% of these subjects had airflow limitation and were diagnosed with COPD according to the GOLD classification. Only 4% had been diagnosed as COPD prior to this screening. The majority of those tested were unaware of or unconcerned about developing the disease. There was no correlation between pack-years smoking and development of COPD, but there was a relative correlation of pack-years smoking and severity of COPD, particularly in the older group (r = 0.42). CONCLUSIONS: About one-fifth of the smokers aged 45 and up developed COPD. There is a significant gap between the disease distribution and its awareness in the population at risk. The need for a national screening program and early diagnosis of COPD in people at risk is needed.

Increased Th1 and Th2 type cytokine production in patients with active tuberculosis.

BACKGROUND: The global spread of tuberculosis necessitates the development of an effective vaccine and new treatment modalities. That requires a better understanding of the differences in regulation of the immune responses to Mycobacterium tuberculosis between individuals who are susceptible or resistant to the infection. Previous immune studies in young Ethiopian immigrants to Israel did not demonstrate anergy to purified protein derivative or a Th2-like cytokine profile. OBJECTIVES: To evaluate the profile of Th1 and Th2 cytokine production in immigrant TB patients, in comparison with asymptomatic control subjects. METHODS: The present study included (part 1): 39 patients with acute TB (group 1), 34 patients with chronic relapsing TB (group 2), 39 Mantoux-positive asymptomatic TB contacts (group 3), and 21 Mantoux-negative asymptomatic controls (group 4). Patients were mainly immigrants from Eastern Europe and Ethiopia. Levels of interferon gamma, interleukin 2 receptor, IL-6 and IL-10 were measured in serum and in non-stimulated and PPD-stimulated peripheral blood mononuclear cell culture supernatants, using commercial ELISA kits. In addition (part 2), levels of IFNgamma and IL-12p40 were evaluated in 31 immigrant Ethiopian patients and 58 contact family members. RESULTS: Patients with acute disease tended to secrete more cytokines than contacts, and contacts more than chronic patients and controls, without a specific bias. None of the patients showed in vitro anergy. Discriminant probability analysis showed that from the total of 12 available parameters, a cluster of 6 (IFNgamma-SER, IFNgamma-PPD, IL-2R-SER, IL-10-SER, IL-10-NS and IL-6-PPD) predicted an 84% probability to become a TB contact upon exposure, 71% a chronic TB patient and 61% an acute TB patient. Family-specific patterns of IFNgamma were demonstrated in the second part of the study. CONCLUSIONS: Firstly, no deficiency in cytokine production was demonstrated in TB patients. Secondly, acute TB patients secreted more cytokines than contacts, and contacts more than unexposed controls. Thus, neither anergy nor a cytokine dysregulation explains susceptibility to acute TB disease in our cohort, although chronic TB patients produced less cytokines than did acute patients and less than asymptomatic contacts. Thirdly, a certain cytokine configuration may predict a trend of susceptibility to acquire, or not acquire, clinical TB. It is presently unclear whether this finding may explain the disease spread in large populations. Finally, the familial association of IFNgamma secretion levels probably points towards a genetic regulation of the immune response to Mycobacterium tuberculosis.

Role of soluble interleukin-2 receptor levels in patients with latent tuberculosis.

Serum soluble interleukin-2 receptor (sIL-2R) serves as a marker of disease activity in patients with tuberculosis (TB). However, little is known about its role in latent TB. The aim of this study was to assess the levels of sIL-2R in patients with latent TB and correlate them with the purified protein derivate (PPD) test results. Patients with a diagnosis of latent TB were divided into three subgroups by induration size: <10 mm, 10-20 mm, >20 mm. Blood was collected for sIL-2R assay. Findings were compared to a healthy control group. The study group consisted of 44 patients (68% male) of mean ( +/- SD) age 20 +/- 10 years, and the control group consisted of 41 subjects (42% male) aged 31 +/- 11 years. Comparison of the two groups yielded a significantly higher serum sIL-2R level in the patients (450 +/- 224 U/ml vs. 374 +/- 30 U/ml, p = 0.03). Mean sIL-2R levels were significantly correlated with the presence of latent TB (p = 0.03), and with purified protein derivative (PPD) subgroups: 387 +/- 177 U/ml for induration size <10 mm, NS; 450 +/- 238 U/ml for 10-20 mm, p = 0.04, and 605 +/- 235 U/ml for >20 mm, p < 0.0001. sIL-2R assay may serve as an additional tool to estimate the extent of the immune response in patients with latent TB.