The population impact of MRSA in a country: the national survey of MRSA in Wales, 1997

Continuous data collection on all new isolates of MRSA via CoSurv has taken place in Wales since January 1996. In order to audit this data collection, and to address some of the issues that it does not include, a survey of MRSA was carried out. Questionnaires were completed by infection control teams. Rates were calculated using hospital throughput denominators. Results from the one-day prevalence survey, the two-week incidence survey, and the follow-up survey carried out on new MRSA patients identified in the incidence survey, are presented. Results were found to be broadly similar to those collected via routine surveillance. MRSA was found frequently and disproportionately in the elderly, with higher rates in male than female patients. The highest incidence of total and invasive MRSA was in males aged 75 and over (total: 12.5/1000 finished consultant episodes; invasive: 2.8/1000). Although there was a large community reservoir of MRSA, most appeared to have been acquired in hospital, since most patients had a history of hospitalization, often with multiple hospital admissions. Community-based isolates from cases with no hospital history tended to have been from ulcers. Prevalence and incidence of MRSA was relatively low compared with hospital throughput (mean prevalence: 2.4/100 occupied beds; mean incidence: 3.6/1000 finished consultant episodes), there was also quite large variation between sites, even when screening samples were removed. Patients with MRSA had strikingly long stays before isolation of the organism (prevalence survey: 39 days; incidence survey: 31 days) and highest incidence occurred in elderly care wards. The outcome survey showed that approximately half of the patients were treated with some type of antimicrobial therapy for MRSA. Decontamination therapy was associated with clearance of MRSA only when controlling for sex of the patient. The majority of patients were discharged still with MRSA, mostly to their own homes. The survey emphasizes the need to continue surveillance to detect any changes, to allow guidelines based on evidence to be developed and to monitor the effectiveness of such guidelines.     

Immunological factors in milk from Brazilian mothers delivering small-for-date term neonates

Breast milk samples from three groups of Brazilian women were evaluated: G1, mothers delivering term babies of low birth weight (n=16); G2, mothers delivering preterm babies of appropriate birth weight (n = 20); G3, mothers delivering term babies of appropriate birth weight ( n = 30). Milk samples were obtained at 48 h and on the 7th, 15th, 30th and 60th days after delivery and they were analyzed for lysozyme and total IgA levels and for the presence of specific antibodies against Poliovirus types I, II, III, Rotavirus, Herpes simplex virus, Varicella zoster and Cytomegalovirus. The groups were not statistically different in relation to mother's age, parity, type of delivery or socio-economic levels. IgA levels were higher in both low-birth-weight groups (G1 & G2) compared to the control group (G3) throughout the study period. Lysozyme levels decreased up to the 15th day, increasing thereafter up to the 60th day in all groups. Specific antibodies were detected throughout the study period, with no differences among groups. We conclude that breast milk composition of mothers delivering low-birth-weight babies (G1 & G2) was similar despite the different gestational ages.     

Early pregnancy complications: endovaginal sonographic findings correlated with human chorionic gonadotropin levels

Endovaginal sonography results were compared with quantitatively determined human chorionic gonadotropin (hCG) levels in 84 women referred for early pregnancy complications. Of the 27 with normal intrauterine pregnancies, an intrauterine gestational sac was prospectively identified in one of five cases (20%) in which hCG levels were below 500 IU/L (Second International Standard), four of five (80%) with hCG levels of 500-1,000 IU/L, and all 17 with hCG levels above 1,000 IU/L. In comparison, 17 of the 26 women with ectopic pregnancies (65%) had hCG levels greater than 1,000 IU/L, and none of the 26 had an intrauterine gestational sac. Endovaginal sonography demonstrated an adnexal mass and/or a gestational sac-like structure in 16 of the 17 cases (94%) in which hCG levels were above 1,000 IU/L, compared with only three of the nine (33%) with lower hCG levels (P less than .01). These findings indicate that an intrauterine gestational sac should be normally visualized with endovaginal sonography when the hCG level exceeds 1,000 IU/L, and that visualization of an extrauterine gestational sac and/or adnexal mass is significantly more likely in ectopic pregnancies when the hCG level exceeds 1,000 IU/L.     

Extrapulmonary Tuberculosis in Human Immunodificiency Virus Infection

Background

In view of increase in incidence of exptrapulmonary tuberculosis after the epidemic of human immunodeficiency virus infection, the clinical profile of extrapulmonary tuberculosis in patients with HIV infection was studied.

Method

The study population comprised patients of HIV infection with extrapulmonary tuberculosis. Work up included history, clinical examination, sputum for acid fast bacilli, chext X-ray, ultrasonography (USG) abdomen, fine needle aspiration cytology(FNAC), transbronchial needle aspiration (TBNA) and computed tomography of chest.

Results

There were 50 cases, all males with mean age of 35 years. 24(48%) were without pulmonary tuberculosis and 26(52%) had pulmonary tuberculosis. 41(82%) had disseminated disease and 9(18%) involve one site. Fever and weight loss were the most frequent symptoms (79% and 58% respectively) in cases without pulmonary tuberculosis. The most frequent extrapulmonary site was lymph node in 46(92%), followed by spleen in 13(26%), pleura 9(18%), miliary 7(14%) and hepatic 1(2%). The diagnosis was confirmed by invasive methods in 30 out of 50(60%) cases [FNAC in 23(88%), TBNA in 2(25%) and pleural biopsy in 5(55%)].

Conclusion

In HIV infected patients, the most common extrapulmonary site is lymph mode followed by spleen.Key Words: Extrapulmonary TB, HIV Infection     

Point-of-care controls for nosocomial legionellosis combined with chlorine dioxide potable water decontamination: a two-year survey at a Welsh teaching hospital

This study reports a two-year programme of attempted eradication of Legionella colonization in the potable water supply of a 1000-bed tertiary care teaching hospital in Wales. There was a simultaneous, point-of-care, sterile-water-only policy for all intensive care units (ICU) and bone marrow and renal transplant units in order to prevent acquisition of nosocomial Legionnaires' disease. The programme was initiated following a case of nosocomial pneumonia caused by Legionella pneumophila serogroup 1-Bellingham-like genotype A on the cardiac ICU. The case occurred 14 days after mitral and aortic valve replacement surgery. Clinical and epidemiological investigations implicated aspiration of hospital potable water as the mechanism of infection. Despite interventions with chlorine dioxide costing over 25000 UK pounds per annum, Legionella has remained persistently present in significant numbers (up to 20000 colony forming units/L) and with little reduction in the number of positive sites. Two further cases of nosocomial disease occurred over the following two-year period; in one case, aspiration of tap water was implicated again, and in the other case, instillation of contaminated water into the right main bronchus via a misplaced nasogastric tube was implicated. These cases arose because of inadvertent non-compliance with the sterile-water-only policy in high-risk locations. Enhanced clinical surveillance over the same two-year period detected no other cases of nosocomial disease. This study suggests that attempts at eradication of Legionella spp. from complex water systems may not be a cost-effective measure for prevention of nosocomial infections, and to the best of our knowledge is the first study from the UK to suggest that the introduction of a sterile-water-only policy for ICUs and other high-risk units may be a more cost-effective approach.     

Apoptotic susceptibility of cancer cells selected for camptothecin resistance: gene expression profiling,functional analysis,and molecular interaction mapping

To study the molecular mechanisms by which drug resistance develops, we compared DU145 humanprostate cancer cells with a subline selected for resistance to camptothecin.Differences in gene expression level were assessed by hybridizing the two cell types against each other using quadruplicate "Oncochip" cDNA microarrays that included 1648 cancer-related genes. Expression levels differing by a factor of >1.5 were detected for 181 of the genes. These differences were judged statistically reliable on the basis of a stratum-adjusted Kruskal-Wallis test, after taking into account a dye-dependent variable. The 181 expression-altered genes included a larger than expected number of the "apoptosis-related" genes (P = 0.04). To assess whether this observation reflected a generalized resistance of RCO.1 to apoptosis, we exposed the cells to a range of stresses (cisplatin, staurosporine, UV, ionizing radiation, and serum starvation) and found greatly reduced apoptotic responses for RC0.1 (relative to DU145) using flow cytometric Annexin V and terminal deoxynucleotidyl transferase-mediated nick end labeling assays. We next examined the apoptosis-related genes in the context of a molecular interaction map and found expression differences in the direction "expected" on the basis of the apoptosis-resistance of RC0.1 for BAD, caspase-6, and genes that signal via the Akt pathway. Exposure of the cells to wortmannin, an inhibitor of the Akt effector phosphatidylinositol 3-kinase, provided functional support for involvement of the Akt pathway. However, closer examination of the molecular interaction map revealed a paradox: many of the expression differences observed for apoptosis-related genes were in the direction "contrary" to that expected given the resistance of RC0.1. The map indicated that most of these unexpected expression differences were associated with genes involved in the nuclear factor kappa B and transforming growth factor beta pathways. Overall, the patterns that emerged suggested a two-step model for the selection process that led to resistance in RC0.1 cells. The first hypothesized step would involve a decrease in apoptotic susceptibility through changes in the apoptosis-control machinery associated with the Bcl-2 and caspase gene families, and also in antiapoptotic pathways operating through Akt/PKB. The second step would involve changes in multifunctional upstream genes (including some genes in the nuclear factor kappa B and transforming growth factor beta pathways) that can facilitate apoptosis but that would also tend to contribute to cell proliferation in the presence of drug. Thus, we propose that a downstream blockade of apoptosis was "permissive" for the selection of upstream pathway changes that would otherwise have induced apoptosis. This model is analogous to one suggested previously for the relationship between oncogene function and apoptosis in carcinogenesis.