Therapeutic cancer vaccines rely on the immune system to eliminate tumor cells. In contrast to chemotherapy or passive (adoptive) immunotherapies with antibodies or ex vivo-expanded T cells, therapeutic vaccines do not have a direct anti-tumor activity, but aim to reset patients' immune systems to achieve this goal. Recent identification of effective ways of enhancing immunogenicity of tumor-associated antigens, including the use of dendritic cells and other potent vectors of cancer vaccines, provide effective tools to induce high numbers of circulating tumor-specific T cells. However, despite indications that some of the new cancer vaccines may be able to delay tumor recurrence or prolong the survival of cancer patients, their ability to induce cancer regression remains low. Recent reports help to identify and prospectively remove the remaining obstacles towards effective therapeutic vaccination of cancer patients. They indicate that the successful induction of tumor-specific T cells by cancer vaccines is not necessarily associated with the induction of functional cytotoxic T lymphocytes, and that current cancer vaccines may promote undesirable expansion of Treg cells. Furthermore, recent studies also identify the tools to counteract such phenomena, in order to assure the desirable induction of Th1-cytotoxic T lymphocytes, NK-mediated type-1 immunity and appropriate homing of effector cells to tumors. †Author Immune system as a means to fight cancerDespite an overall progress in cancer therapy, substantial groups of cancer patients lack effective treatment options, and even larger groups lack curative therapies. Combined use of surgery, radio-and chemo-therapy is often highly active in eliminating the major tumor mass, but is less effective in eliminating residual cancer cells and in preventing disease recurrence. This particular deficit of the current treatments provides the rationale for the utilization of the immune system, specialized in eliminating such 'rare events' in our bodies as invading bacteria or the individual host's cells hijacked by viruses, in order to identify and destroy cancer cells.The goal of therapeutic cancer vaccines (or active immunotherapy) is to instruct the patient's own immune system to kill cancer cells. Compared with chemotherapy, the theoretical advantages of such an approach are its higher ability to selectively eliminate the transformed cells, resulting in low toxicity, and the ability to recognize and attack multiple target molecules, even the newly arising antigens on rapidly mutating tumor cells (due to the phenomenon of epitope spreading). 1]). Throughout the following century, repeated attempts to utilize the immune system to fight cancer in a systematic approach were met with limited success, prompting a century-long debate on the relevance of the immune system to cancer surveillance and therapy [2,3].At the beginning of the 21st century, it has become evident that the immune system can be utilized to fight cancer, but it is also clear that the spontaneously ...

Considering the emergence of high level aminoglycoside resistance (HLAR) in enterococci this study was undertaken to determine their status in a rural setting. HLAR by disc diffusion and agar dilution, beta lactamase by nitrocefin disc and vancomycin resistance by agar dilution was determined in 150 enterococcal isolates, as per NCCLS guidelines. Only two species, Enterococcus faecalis (85.5%) and Enterococcus faecium (14.7%) were recovered, mostly from blood. Forty six percent showed HLAR. Multi drug resistance and concomitant resistance of HLAR strains to beta lactams were quite high. None showed beta lactamase activity or vancomycin resistance.

IntroductionThere is lack of information on the proportion of new smear—positive pulmonary tuberculosis (PTB) patients treated with a 6-month thrice-weekly regimen under Revised National Tuberculosis Control Programme (RNTCP) who develop recurrent TB after successful treatment outcome.ObjectiveTo estimate TB recurrence among newly diagnosed PTB patients who have successfully completed treatment and to document endogenous reactivation or re-infection. Risk factors for unfavourable outcomes to treatment and TB recurrence were determined.MethodologyAdult (aged ≥ 18 yrs) new smear positive PTB patients initiated on treatment under RNTCP were enrolled from sites in Tamil Nadu, Karnataka, Delhi, Maharashtra, Madhya Pradesh and Kerala. Those declared “treatment success” at the end of treatment were followed up with 2 sputum examinations each at 3, 6 and 12 months after treatment completion. MIRU-VNTR genotyping was done to identify endogenous re-activation or exogenous re-infection at TB recurrence. TB recurrence was expressed as rate per 100 person-years (with 95% confidence interval [95%CI]). Regression models were used to identify the risk factors for unfavourable response to treatment and TB recurrence.ResultsOf the1577 new smear positive PTB patients enrolled, 1565 were analysed. The overall cure rate was 77% (1207/1565) and treatment success was 77% (1210 /1565). The cure rate varied from 65% to 86%. There were 158 of 1210 patients who had TB recurrence after treatment success. The pooled TB recurrence estimate was 10.9% [95%CI: 0.2–21.6] and TB recurrence rate per 100 person–years was 12.7 [95% CI: 0.4–25]. TB recurrence per 100 person–years varied from 5.4 to 30.5. Endogenous reactivation was observed in 56 (93%) of 60 patients for whom genotyping was done. Male gender was associated with TB recurrence.ConclusionA substantial proportion of new smear positive PTB patients successfully treated with 6 –month thrice-weekly regimen have TB recurrence under program settings.

Currently available nucleic acid amplification platforms for tuberculosis (TB) detection are not designed to be simple or inexpensive enough to implement in decentralized settings in countries with a high burden of disease. The loop-mediated isothermal amplification platform (LAMP) may change this. We conducted a study in adults with symptoms suggestive of TB in India, Uganda, and Peru to establish the feasibility of using TB-LAMP (Eiken Chemical Co.) in microscopy laboratories compared with using smear microscopy against a reference standard of solid and liquid cultures. Operational characteristics were evaluated as well. A total of 1,777 participants met the eligibility criteria and were included for analysis. A pproximately 9 million people developed tuberculosis (TB), and 1.5 million people died from the disease in 2013 (1). Substantial progress has been made in increasing treatment success, but 2.9 million of these cases were not diagnosed or diagnosis was not reported due to limited access to diagnostic tests, insufficient sensitivity, or long turnaround time. More rapid and accurate detection at lower levels of care is necessary to reach these lost and missed cases (2). Nucleic acid amplification tests (NAATs) offer speed and sensitivity for pathogen detection, but until recently, no commercial systems had been designed to be simple or inexpensive enough for decentralized settings (3).Xpert MTB/RIF (Cepheid Inc., Sunnyvale, CA), a rapid automated molecular test, has been a major step in the right direction, but initial investment in the equipment and subsequent maintenance remain quite expensive. The development of a less costly approach through the use of manual techniques may expand the application of NAATs.TB-LAMP is a manual TB detection method that is based on the novel loop-mediated isothermal amplification platform (LAMP) from Eiken Chemical Co. in Japan. LAMP has several features that make it attractive as a diagnostics platform for resource-poor settings. It takes less than 2 h (Ͻ60 min of hands-on time), it is less complex than traditional molecular methods, and it generates a fluorescent result that can be detected with the naked eye (4). In a recent study in peripheral laboratories in China using the TB-LAMP assay, the sensitivities in smear-positive, culturepositive sputum specimens and smear-negative, culture-positive sputum specimens were 92.1% (152/165; 95% confidence interval [CI], 86.9% to 95.3%) and 53.8% (113/210; 95% CI, 47.1% to 60.4%), respectively, using solid culture as a reference. The specificity in culture-negative samples was 98.3% (938/954; 95% CI, 97.3% to 99.0%) (5).In this study, we aimed to evaluate the feasibility and operational characteristics of LAMP in microscopy centers, including Citation Gray CM, Katamba A, Narang P, Giraldo J, Zamudio C, Joloba M, Narang R, Paramasivan CN, Hillemann D, Nabeta P, Amisano D, Alland D, Cobelens F, Boehme CC. 2016. Feasibility and operational performance of tuberculosis detection by loop-mediated isothermal amplification platform in ...

A house based survey was conducted during 2007-2009 in a representative sample of population in Wardha district implementing Directly Observed Treatment Short Course strategy for tuberculosis (TB) control since 2001. The objective was to estimate prevalence of bacillary pulmonary TB (PTB) in individuals aged 15 years or above, and to estimate trends in prevalence when compared to a previous survey carried out in mid 1980's. Two sputum samples (one spot, one early morning) collected from individuals having symptoms suggestive of PTB, history of previous anti-TB treatment (ATT) or abnormal pulmonary shadow on Mass Miniature Radiography (MMR) consistent with possibly or probably active tuberculosis were subjected to Ziehl-Neelsen microscopy and culture on Lowenstein-Jensen medium. Of 55,096 individuals registered into the survey, 50,332 (91.4%) were screened by interview for symptoms and history of ATT and/or by MMR. Of them, 4805 were eligible for sputum collection; both specimens were collected in 4285 (89.2%) and only one specimen in 27 (0.6%). A total of 86 bacillary cases were detected during the survey. Prevalence of bacillary PTB was estimated at 188.7 (140.3-236.9) per 100,000 populations. There was a decline of 61% in the prevalence of PTB over a period of 22 years.