Symptom screening rules to identify active pulmonary tuberculosis: Findings from the Zambian South African Tuberculosis and HIV/AIDS Reduction (ZAMSTAR) trial prevalence surveys.

BACKGROUND: High tuberculosis (TB) burden countries should consider systematic screening among adults in the general population. We identified symptom screening rules to be used in addition to cough ≥2 weeks, in a context where X-ray screening is not feasible, aiming to increase the sensitivity of screening while achieving a specificity of ≥85%. METHODS: We used 2010 Zambia South Africa Tuberculosis and HIV/AIDS Reduction (ZAMSTAR) survey data: a South African (SA) training dataset, a SA testing dataset for internal validation and a Zambian dataset for external validation. Regression analyses investigated relationships between symptoms or combinations of symptoms and active disease. Sensitivity and specificity were calculated for candidate rules. RESULTS: Among all participants, the sensitivity of using only cough ≥2 weeks as a screening rule was less than 25% in both SA and Zambia. The addition of any three of six TB symptoms (cough <2 weeks, night sweats, weight loss, fever, chest pain, shortness of breath), or 2 or more of cough <2 weeks, night sweats, and weight loss, increased the sensitivity to ~38%, while reducing specificity from ~95% to ~85% in SA and ~97% to ~92% in Zambia. Among HIV-negative adults, findings were similar in SA, whereas in Zambia the increase in sensitivity was relatively small (15% to 22%). CONCLUSION: High TB burden countries should investigate cost-effective strategies for systematic screening: one such strategy could be to use our rule in addition to cough ≥2 weeks

Bedside testing of CYP2C19 vs. conventional clopidogrel treatment to guide antiplatelet therapy in ST-segment elevation myocardial infarction patients

BACKGROUND: ST-segment elevation myocardial infarction (STEMI) patients are treated with dual antiplatelet therapy comprising aspirin and a P2Y12 inhibitor. Clopidogrel is widely used in these patients in several areas worldwide, such as Middle East, but is associated to sub-optimal platelet inhibition in up to 1/3 of treated patients. We investigated a CYP2C19 genotype-guided strategy to select the optimal P2Y12 inhibitor. METHODS: This prospective randomized clinical trial included STEMI patients. The standard-treatment group received clopidogrel, while the genotype-guided group were genotyped for CYP2C19 loss-of-function alleles and carriers were prescribed ticagrelor and noncarriers were prescribed clopidogrel. Primary outcome was a combined ischemic and bleeding outcome, comprising myocardial infarction, non-fatal stroke, cardiovascular death, or Platelet Inhibition and Patient Outcomes major bleeding one year after STEMI. RESULTS: STEMI patients (755) were randomized into a genotype-guided- (383) and standard-treatment group (372). In the genotype-guided group, 31 patients carrying a loss-of-function allele were treated with ticagrelor, while all other patients in both groups were treated with clopidogrel. Patients in the genotype-guided group had a significantly lower risk of primary outcome (odds ratio (OR) 0.34, 95% confidence interval (CI) 0.20–0.59,), recurrent myocardial infarction (OR 0.25, 95%CI 0.11–0.53), cardiovascular death (OR 0.16, 95%CI0.06–0.42) and major bleeding (OR 0.49, 95%CI 0.32–0.74). There was no significant difference in the rate of stent thrombosis (OR 0.85, 95%CI 0.43–1.71). CONCLUSION: A genotype-guided escalation of P2Y12 inhibitor strategy is feasible in STEMI patients treated with clopidogrel and undergoing PCI and is associated with a reduction of primary outcomes compared to conventional antiplatelet therapy

The epidemiology of tuberculosis in health care workers in South Africa: a systematic review

Background: In South Africa, workplace acquired tuberculosis (TB) is a significant occupational problem among health care workers. In order to manage the problem effectively it is important to know the burden of TB in health care workers. This systematic review describes the epidemiology of TB in South African health care workers. Methods: A comprehensive search of electronic databases [MEDLINE, EMBASE, Web of Science (Social Sciences Citation Index/Science Citation Index), Cochrane Library (including CENTRAL register of Controlled Trials), CINAHL and WHO International Clinical Trials Registry Platform (ICTRP)] was conducted up to April 2015 for studies reporting on any aspect of TB epidemiology in health care workers in South Africa. Results: Of the 16 studies included in the review, ten studies reported on incidence of active TB disease in health care workers, two report on the prevalence of active TB disease, two report on the incidence of latent TB infection, three report on the prevalence of latent TB infection and four studies report on the number of TB cases in health care workers in various health care facilities in South Africa. Five studies provide information on risk factors for TB in health care workers. All of the included studies were conducted in publicly funded health care facilities; predominately located in KwaZulu-Natal and Western Cape provinces. The majority of the studies reflect a higher incidence and prevalence of active TB disease in health care workers, including drug-resistant TB, compared to the surrounding community or general population. Conclusions: There is relatively little research on the epidemiology of TB in health care workers in South Africa, despite the importance of the issue. To determine the true extent of the TB epidemic in health care workers, regular screening for TB disease should be conducted on all health care workers in all health care facilities, but future research is required to investigate the optimal approach to TB screening in health care workers in South Africa. The evidence base shows a high burden of both active and latent TB in health care workers in South Africa necessitating an urgent need to improve existing TB infection, prevention and control measures in South African health care facilities

Effect of Acinetobacter sp on Metalaxyl Degradation and Metabolite Profile of Potato Seedlings (Solanum tuberosum L.) Alpha Variety

One of the most serious diseases in potato cultivars is caused by the pathogen Phytophthora infestans, which affects leaves, stems and tubers. Metalaxyl is a fungicide that protects potato plants from Phytophthora infestans. In Mexico, farmers apply metalaxyl 35 times during the cycle of potato production and the last application is typically 15 days before harvest. There are no records related to the presence of metalaxyl in potato tubers in Mexico. In the present study, we evaluated the effect of Acinetobacter sp on metalaxyl degradation in potato seedlings. The effect of bacteria and metalaxyl on the growth of potato seedlings was also evaluated. A metabolite profile analysis was conducted to determine potential molecular biomarkers produced by potato seedlings in the presence of Acinetobacter sp and metalaxyl. Metalaxyl did not affect the growth of potato seedlings. However, Acinetobacter sp strongly affected the growth of inoculated seedlings, as confirmed by plant length and plant fresh weights which were lower in inoculated potato seedlings (40% and 27%, respectively) compared to the controls. Acinetobacter sp also affected root formation. Inoculated potato seedlings showed a decrease in root formation compared to the controls. LC-MS/MS analysis of metalaxyl residues in potato seedlings suggests that Acinetobacter sp did not degrade metalaxyl. GC–TOF–MS platform was used in metabolic profiling studies. Statistical data analysis and metabolic pathway analysis allowed suggesting the alteration of metabolic pathways by both Acinetobacter sp infection and metalaxyl treatment. Several hundred metabolites were detected, 137 metabolites were identified and 15 metabolic markers were suggested based on statistical change significance found with PLS-DA analysis. These results are important for better understanding the interactions of putative endophytic bacteria and pesticides on plants and their possible effects on plant metabolism

A survey of tuberculosis infection control practices at the NIH/NIAID/DAIDS-supported clinical trial sites in low and middle income countries

BACKGROUND: Health care associated transmission of Mycobacterium tuberculosis (TB) is well described. A previous survey of infection control (IC) practices at clinical research sites in low and middle income countries (LMIC) funded by the National Institute of Allergy and Infectious Diseases (NIAID) conducting HIV research identified issues with respiratory IC practices. A guideline for TB IC based on international recommendations was developed and promulgated. This paper reports on adherence to the guideline at sites conducting or planning to conduct TB studies with the intention of supporting improvement. METHODS: A survey was developed that assessed IC activities in three domains: facility level measures, administrative control measures and environmental measures. An external site monitor visited each site in 2013–2014, to complete the audit. A central review committee evaluated the site-level survey and results were tabulated. Fisher’s exact test was performed to determine whether there were significant differences in practices at sites that had IC officers versus sites that did not have IC officers. Significance was assessed at p</=.05 RESULTS: Seven of thirty-three sites surveyed (22 %) had all the evaluated tuberculosis IC (TB IC) elements in place. Sixty-one percent of sites had an IC officer tasked with developing and maintaining TB IC standard operating procedures. Twenty-two (71 %) sites promptly identified and segregated individuals with TB symptoms. Thirty (93 %) sites had a separate waiting area for patients, and 26 (81 %) collected sputum within a specific well-ventilated area that was separate from the general waiting area. Sites with an IC officer were more likely to have standard operating procedures covering TB IC practices (p = 0.02) and monitor those policies (p = 0.02) and perform regular surveillance of healthcare workers (p = 0.02). The presence of an IC officer had a positive impact on performance in most of the TB IC domains surveyed including having adequate ventilation (p = 0.02) and a separate area for sputum collection (p = 0.02) CONCLUSIONS: Specific and targeted support of TB IC activities in the clinical research environment is needed and is likely to have a positive and sustained impact on preventing the transmission of TB to both health care workers and vulnerable HIV-infected research participants. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-016-1579-y) contains supplementary material, which is available to authorized users

Effects of introducing Xpert MTB/RIF test on multi-drug resistant tuberculosis diagnosis in KwaZulu-Natal South Africa.

CAPRISA, 2014.Abstract available in pdf

Rapid diagnosis of new and relapse tuberculosis by quantification of a circulating antigen in HIV-infected adults in the Greater Houston metropolitan area

Abstract Background HIV-associated immune defects inhibit tuberculosis (TB) diagnosis, promote development of extrapulmonary TB and paucibacillary pulmonary TB cases with atypical radiographic features, and increase TB relapse rates. We therefore assessed the diagnostic performance of a novel assay that directly quantitates serum levels of the Mycobacterium tuberculosis (Mtb) virulence factor 10-kDa culture filtrate protein (CFP-10) to overcome limitations associated with detecting Mtb bacilli in sputum or tissue biopsies. Methods This study analyzed HIV-positive adults enrolled in a large, population-based TB screening and surveillance project, the Houston Tuberculosis Initiative, between October 1995 and September 2004, and assigned case designations using standardized criteria. Serum samples were trypsin-digested and immunoprecipitated for an Mtb-specific peptide of CFP-10 that was quantified by liquid chromatography-mass spectrometry for rapid and sensitive TB diagnosis. Results Among the 1053 enrolled patients, 110 met all inclusion criteria; they included 60 tuberculosis cases (12 culture-negative TB), including 9 relapse TB cases, and 50 non-TB controls, including 15 cases with history of TB. Serum CFP-10 levels diagnosed 89.6% (77.3–96.5) and 66.7% (34.9–90.1) of culture-positive and culture-negative TB cases, respectively, and exhibited 88% (75.7–95.5) diagnostic specificity in all non-TB controls. Serum antigen detection and culture, respectively, identified 85% (73.4–92.9) and 80.0% (67.3–88.8) of all 60 TB cases. Conclusions Quantitation of the Mtb virulence factor CFP-10 in serum samples of HIV-infected subjects diagnosed active TB cases with high sensitivity and specificity and detected cases missed by the gold standard of Mtb culture. These results suggest that serum CFP-10 quantitation holds great promise for the rapid diagnosis of suspected TB cases in patients who are HIV-infected