A systematic review and meta-analysis of the diagnostic accuracy of nucleic acid amplification tests in cerebrospinal fluid for tuberculous meningitis

Introduction: Diagnosis of tuberculous meningitis (TBM) is difficult and poses a significant challenge to physicians worldwide. Recently, nucleic acid amplification (NAA) tests have shown promise for diagnosis of TBM, although performance has been variable. We undertook a systematic review and meta-analysis to evaluate the diagnostic accuracy of NAA tests in cerebrospinal fluid (CSF) samples against culture as the reference standard or a combined reference standard (CRS) for TBM.Methods: We searched Embase, PubMed, Web of Science and the Cochrane library for the relevant records. QUADS-2 tool was used to assess the quality assessment of the studies. Diagnostic accuracy measures (i.e. sensitivity and specificity) were pooled with a random effects model. All Statistical analyses were performed with STATA version 14 (Stata Corporation, College Station, TX, USA), Meta-DiSc version 1.4 (Cochrane Colloquium, Barcelona, Spain) and RveMan version 5.3 (Copenhagen: The Nordic Cochrane Centre, the Cochrane Collaboration).Results: Sixty-three studies were included in final analysis, comprising 1381cases of confirmed TBM and 5712 non-TBM controls. These 63 studies were divided into two groups comprising 71 datasets (43 in-house tests and 28 commercial tests) that used culture as the reference standard and 24 datasets (21 in-house tests and 3 commercial tests) that used a CRS. Studies which used a culture reference standard had better pooled summary estimates compared to studies which used CRS. The overall pooled estimates of sensitivity, specificity, positive likelihood ratio (PLR) and negative likelihood ratio (NLR) of NAA tests against culture were 82% (95% CI: 75-87), 99% (95% CI: 98-99), 58.6 (35.3-97.3) and 0.19 (0.14-0.25), respectively. The pooled sensitivity, specificity, PLR and NLR of NAA tests against CRS were 68% (95% CI: 41-87), 98% (95% CI: 95-99), 36.5 (15.6-85.3) and 0.32 (0.15-0.70), respectively.Conclusion: The analysis has demonstrated that the diagnostic accuracy of NAA tests is currently insufficient to replace culture as a lone diagnostic test. NAA tests may be used in combination with culture due to the advantage of time to result and in scenarios where culture tests are not feasible. Further work to improve NAA tests would benefit from standardized reference standards and the methodology

Patients' perceptions of the potential of breathing training for asthma: a qualitative study.

Poor symptom control is common in asthma. Breathing training exercises may be an effective adjunct to medication; it is therefore important to understand facilitators and barriers to uptake of breathing training exercises

Carriage of extended-spectrum beta-lactamase-producing Enterobacteriaceae in HIV-infected children in Zimbabwe.

BACKGROUND: Antimicrobial resistance is an emerging global health issue. Data on the epidemiology of multidrug-resistant organisms are scarce for Africa, especially in HIV-infected individuals who often have frequent contact with healthcare. We investigated the prevalence of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) carriage in stool among HIV-infected children attending an HIV outpatient department in Harare, Zimbabwe. METHODS: We recruited children who were stable on antiretroviral therapy (ART) attending a HIV clinic from August 2014 to June 2015. Information was collected on antibiotic use and hospitalization. Stool was tested for ESBL-E through combination disc diffusion. API20E identification and antimicrobial susceptibility was performed on the positive samples followed by whole genome sequencing. RESULTS: Stool was collected from 175/202 (86.6 %) children. Median age was 11 [inter-quartile range (IQR) 9-12] years. Median time on ART was 4.6 years (IQR 2.4-6.4). ESBL-Es were found in 24/175 samples (13.7 %); 50 % of all ESBL-Es were resistant to amoxicillin-clavulanate, 100 % to co-trimoxazole, 45.8 % to chloramphenicol, 91.6 % to ceftriaxone, 20.8 % to gentamicin and 62.5 % to ciprofloxacin. ESBL-Es variously encoded CTX-M, OXA, TEM and SHV enzymes. The odds of ESBL-E carriage were 8.5 times (95 % CI 2.2-32.3) higher in those on ART for less than one year (versus longer) and 8.5 times (95 % CI 1.1-32.3) higher in those recently hospitalized for a chest infection. CONCLUSION: We found a 13.7 % prevalence of ESBL-E carriage in a population where ESBL-E carriage has not been described previously. Antimicrobial resistance (AMR) in Africa merits further study, particularly given the high HIV prevalence and limited diagnostic and therapeutic options available

Effects of different antibiotic classes on airway bacteria in stable COPD using culture and molecular techniques: a randomised controlled trial

Long-term antibiotic therapy is used to prevent exacerbations of COPD but there is uncertainty over whether this reduces airway bacteria. The optimum antibiotic choice remains unknown. We conducted an exploratory trial in stable patients with COPD comparing three antibiotic regimens against placebo

Application of Nitrogen and Carbon Stable Isotopes (δ15Ν and δ13C) to Quantify Food Chain Length and Trophic Structure

Increasingly, stable isotope ratios of nitrogen (delta N-15) and carbon (delta C-13) are used to quantify trophic structure, though relatively few studies have tested accuracy of isotopic structural measures. For laboratory-raised and wild-collected plant-invertebrate food chains spanning four trophic levels we estimated nitrogen range (NR) using delta N-15, and carbon range (CR) using delta C-13, which are used to quantify food chain length and breadth of trophic resources respectively. Across a range of known food chain lengths we examined how NR and CR changed within and between food chains. Our isotopic estimates of structure are robust because they were calculated using resampling procedures that propagate variance in sample means through to quantified uncertainty in final estimates. To identify origins of uncertainty in estimates of NR and CR, we additionally examined variation in discrimination (which is change in delta N-15 ordelta C-13 from source to consumer) between trophic levels and among food chains. delta N-15 discrimination showed significant enrichment, while variation in enrichment was species and system specific, ranged broadly (1.4‰ to 3.3‰), and importantly, propagated variation to subsequent estimates of NR. However, NR proved robust to such variation and distinguished food chain length well, though some overlap between longer food chains infers a need for awareness of such limitations. delta C-13 discrimination was inconsistent; generally no change or small significant enrichment was observed. Consequently, estimates of CR changed little with increasing food chain length, showing the potential utility of delta C-13 as a tracer of energy pathways. This study serves as a robust test of isotopic quantification of food chain structure, and given global estimates of aquatic food chains approximate four trophic levels while many food chains include invertebrates, our use of four trophic level plant-invertebrate food chains makes our findings relevant for a majority of ecological systems

COVID-19—Zoonosis or Emerging Infectious Disease?

The World Health Organization defines a zoonosis as any infection naturally transmissible from vertebrate animals to humans. The pandemic of Coronavirus disease (COVID-19) caused by SARS-CoV-2 has been classified as a zoonotic disease, however, no animal reservoir has yet been found, so this classification is premature. We propose that COVID-19 should instead be classified an “emerging infectious disease (EID) of probable animal origin.” To explore if COVID-19 infection fits our proposed re-categorization vs. the contemporary definitions of zoonoses, we reviewed current evidence of infection origin and transmission routes of SARS-CoV-2 virus and described this in the context of known zoonoses, EIDs and “spill-over” events. Although the initial one hundred COVID-19 patients were presumably exposed to the virus at a seafood Market in China, and despite the fact that 33 of 585 swab samples collected from surfaces and cages in the market tested positive for SARS-CoV-2, no virus was isolated directly from animals and no animal reservoir was detected. Elsewhere, SARS-CoV-2 has been detected in animals including domesticated cats, dogs, and ferrets, as well as captive-managed mink, lions, tigers, deer, and mice confirming zooanthroponosis. Other than circumstantial evidence of zoonotic cases in mink farms in the Netherlands, no cases of natural transmission from wild or domesticated animals have been confirmed. More than 40 million human COVID-19 infections reported appear to be exclusively through human-human transmission. SARS-CoV-2 virus and COVID-19 do not meet the WHO definition of zoonoses. We suggest SARS-CoV-2 should be re-classified as an EID of probable animal origin

Influence of homogenization conditions on physical properties and antioxidant activity of fully biodegradable pea protein-alpha-tocopherol films

In this study, antioxidant biodegradable films based on pea protein and alpha-tocopherol were successfully developed by solution casting. The effect of both the homogenization conditions (rotor stator and microfluidizer) and the relative humidity (RH) on the microstructure and physical properties (transparency, tensile, oxygen and water vapour barrier properties) of pea protein/alpha-tocopherol-based films was evaluated. The addition of alpha-tocopherol produced minimal changes in the films transparency, while providing them with antioxidant properties and improved water vapour and oxygen barrier properties (up to 30 % in both water vapour and oxygen permeability) when films were at low and intermediate RH. The addition of alpha-tocopherol in microfluidized films gave rise to an increase in their resistance to break and extensibility (up to 27 % in E values) at intermediate and high RH. These results add a new insight into the potential of employing pea protein and alpha-tocopherol in the development of fully biodegradable antioxidant films which are of interest in food packagingThe authors acknowledge the financial support from the Spanish Ministerio de Educacion y Ciencia throughout the project AGL2010-20694, co-funded by FEDER. Author M.J.Fabra is a recipient of a Juan de la Cierva contract from the Spanish Ministerio de Economia y Competitividad.Fabra, MJ.; Jiménez, A.; Talens Oliag, P.; Chiralt, A. (2014). Influence of homogenization conditions on physical properties and antioxidant activity of fully biodegradable pea protein-alpha-tocopherol films. Food and Bioprocess Technology. 7(12):3569-3578. https://doi.org/10.1007/s11947-014-1372-0S35693578712ASTM (1995). Standard test methods for water vapor transmission of materials. Standards Desingnations: E96-95. In: Annual Book of ASTM Standards (pp. 406-413); American Society for Testing and Materials: Philadelphia, PA.ASTM (2001). Standard test method for tensile properties of thin plastic sheeting. Standard D882. In: Annual book of American Standard Testing Methods (pp 162-170). D882. Philadelphia:ASTM.Bertan, L. C., Tanada-Palmu, P. S., Siani, A. C., & Grosso, C. R. F. (2005). Effect of fatty acids and “Brazilian elemi” on composite films based on gelatin. Food Hydrocolloids, 19(1), 73–82.Byun, Y., Kim, Y. T., & Whiteside, S. (2010). Characterization of an antioxidant polylactic acid (PLA) film prepared with alpha-tocopherol, BHT and polyethylene glycol using film cast extruder. Journal of Food Engineering, 100, 239–244.Cerqueira, M. A., Costa, M. J., Fuciños, C., Pastrana, L. M., & Vicente, A. A. (2014). Development of active and nanotechnology-based smart edible packaging systems: physical-chemical characterization. Food and Bioprocess Technology, 7(5), 1472–1482.Choi, W. S., & Han, J. H. (2001). Physical and mechanical properties of pea–protein-based edible films. Journal of Food Science, 66, 319–322.Choi, W. S., & Han, J. H. (2002). Film-forming mechanism and heat denaturation effects on the physical and chemical properties of pea-protein-isolate edible films. Journal of Food Science, 67, 1399–1406.Fabra, M. J., Talens, P., & Chiralt, A. (2009). Microstructure and optical properties of sodium caseinate films containing oleic acidebeeswax mixtures. Food Hydrocolloids, 23, 676–683.Fabra, M. J., Talens, P., & Chiralt, A. (2010). Water sorption isotherms and phase transitions of sodium caseinate–lipid films as affected by lipid interactions. Food Hydrocolloids, 24, 384–391.Fabra, M. J., Hambleton, A., Talens, P., Debeaufort, F., & Chiralt, A. (2011). Effect of ferulic acid and α-tocopherol antioxidants on properties of sodium caseinate edible films. Food Hydrocolloids, 25, 1441–1447.Fabra, M. J., Talens, P., Gavara, R., & Chiralt, A. (2012). Barrier properties of sodium caseinate films as affected by lipid composition and moisture content. Journal of Food Engineering, 109, 372–379.Frankel, E. N., Huang, S. W., Kanner, J., & German, J. B. (1994). Interfacial phenomena in the evaluation of antioxidants: bulk oils vs emulsions. Journal of Agriculture and Food Chemistry, 42(5), 1054–1059.Gómez-Estaca, J., Giménez, B., Montero, P., & Gómez-Guillén, M. C. (2009). Incorporation of antioxidant borage extract into edible films based on sole skin gelatin or a commercial fish gelatin. Journal of Food Engineering, 92, 78–85.Huang, S. W., Frankel, E. N., & German, J. B. (1994). Antioxidant activity of alpha.- and.gamma.-tocopherols in bulk oils and in oil-in-water emulsions. Journal of Agriculture and Food Chemistry, 42(10), 2108–2114.Hutchings, J. B. (1999). Food and colour appearance (2nd ed.). Gaithersburg: Chapman and Hall Food Science Book, Aspen Publication.Jiménez, A., Fabra, M. J., Talens, P., & Chiralt, A. (2010). Effect of lipid self-association on the microstructure and physical properties of hydroxypropylmethylcellulose edible films containing fatty acids. Carbohydrate Polymers, 82(3), 585–593.Jiménez, A., Fabra, M. J., Talens, P., & Chiralt, A. (2013). Physical properties and antioxidant capacity of starch-sodium caseinate films containing lipids. Journal of Food Engineering, 116(3), 695–702.Jung, M. Y., & Min, D. B. (1990). Effects of alpha-. γ-, and δ-tocopherols on oxidative stability of soybean oil. Journal of Food Science, 55(5), 1464–1465.López-de-Dicastillo, C., Alonso, J. M., Catalá, R., Gavara, R., & Hernández-Muñoz, P. (2010). Improving the antioxidant protection of packaged food by incorporating natural flavonoids into ethylene-vinyl alcohol copolymer (EVOH) films. Journal of Agricultural and Food Chemistry, 58, 10958–10964.Ma, W., Tang, C.-H., Yin, S.-W., Yang, X. Q., Qi, J. R., & Xia, N. (2012). Effect of homogenization conditions on properties of gelatin-olive oil composite films. Journal of Food Engineering, 113(1), 136–142.Mauer, L. J., Smith, D. E., & Labuza, T. P. (2000). Water vapor permeability, mechanical, and structural properties of edible β-casein films. International Dairy Journal, 10(5–6), 353–358.Mc Hugh, T. H., Avena-Bustillos, R., & Krochta, J. M. (1993). Hydrophobic edible films:modified procedure for water vapor permeability and explanation of thickness effects. Journal of Food Science, 58(4), 899–903.McHugh, T. H., & Krochta, J. M. (1994). Dispersed phase particle size effects on water vapour permeability of whey protein–beeswax emulsion films. Journal of Food Processing and Preservation, 18, 173–188.Ozkan, G., Simsek, B., & Kuleasan, H. (2007). Antioxidant activities of Satureja cilicica essential oil in butter and in vitro. Journal of Food Engineering, 79, 1391–1396.Pereira de Abreu, D. A., Paseiro Losada, P., Maroto, J., & Cruz, J. M. (2011). Natural antioxidant active packaging film and its effect on lipid damage in frozen blue shark (Prionace glauca). Innovative Food Science and Emerging Technologies, 12, 50–55.Re, R., Pellegrini, N., Proteggente, A., Pannala, A., Yang, M., & Rice-Evans, C. (1999). Antioxidant activity applying an improved ABTS radical cation decoloration assay. Free Radical Biology and Medicine, 26, 1231–1237.Roos, Y. H. (1995). Phase transitions in food. San Diego: Academic Press.Salgado, P. R., Molina Ortiz, S. E., Petruccelli, S., & Mauri, A. N. (2010). Biodegradable sunflower protein films naturally activated with antioxidant compounds. Food Hydrocolloids, 24(5), 525–533.Salgado, P. R., Fernández, G. B., Drago, S. R., & Mauri, A. N. (2011). Addition of bovine plasma hydrolysates improves the antioxidant properties of soybean and sunflower protein-based films. Food Hydrocolloids, 25, 1433–1440.Samaranayaka, A. G. P., & Li-Chan, E. C. Y. (2008). Autolysis-assisted production of fish protein hydrolysates with antioxidant properties form Pacific hake (Merluccius productus). Food Chemistry, 107, 768–776.Souza, B. W. S., Cerqueira, A., Casariego, A., Lima, A. M. P., Teixeira, J. A., & Vicente, A. A. (2009). Effect of moderate electric fields in the permeation properties of chitosan coatings. Food Hydrocolloids, 23, 2110–2115

Antimicrobial resistance preparedness in sub-Saharan African countries

Background: Antimicrobial resistance (AMR) is of growing concern globally and AMR status in sub-Saharan Africa (SSA) is undefined due to a lack of real-time data recording, surveillance and regulation. World Health Organization (WHO) Joint External Evaluation (JEE) reports are voluntary, collaborative processes to assess country capacities and preparedness to prevent, detect and rapidly respond to public health risks, including AMR. The data from SSA JEE reports were analysed to gain an overview of how SSA is working towards AMR preparedness and where strengths and weaknesses lie. Methods: SSA country JEE AMR preparedness scores were analysed. A cumulative mean of all the SSA country AMR preparedness scores was calculated and compared to the overall mean SSA JEE score. AMR preparedness indicators were analysed, and data were weighted by region. Findings: The mean SSA AMR preparedness score was 53% less than the overall mean SSA JEE score. East Africa had the highest percentage of countries reporting having AMR National Action Plans in place, as well as human and animal pathogen AMR surveillance programmes. Southern Africa reported the highest percentage of countries with training programmes and antimicrobial stewardship. Conclusions: The low mean AMR preparedness score compared to overall JEE score, along with the majority of countries lacking implemented National Action Plans, suggests that until now AMR has not been a priority for most SSA countries. By identifying regional and One Health strengths, AMR preparedness can be fortified across SSA with a multisectoral approach

Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies

Tuberculosis remains the world's leading cause of death from an infectious disease, responsible for an estimated 1 674 000 deaths annually. WHO estimated 600 000 cases of rifampicin-resistant tuberculosis in 2016-of which 490 000 were multidrug resistant (MDR), with less than 50% survival after receiving recommended treatment regimens. Concerted efforts of stakeholders, advocates, and researchers are advancing further development of shorter course, more effective, safer, and better tolerated treatment regimens. We review the developmental pipeline and landscape of new and repurposed tuberculosis drugs, treatment regimens, and host-directed therapies (HDTs) for drug-sensitive and drug-resistant tuberculosis. 14 candidate drugs for drug-susceptible, drug-resistant, and latent tuberculosis are in clinical stages of drug development; nine are novel in phase 1 and 2 trials, and three new drugs are in advanced stages of development for MDR tuberculosis. Specific updates are provided on clinical trials of bedaquiline, delamanid, pretomanid, and other licensed or repurposed drugs that are undergoing investigation, including trials aimed at shortening duration of tuberculosis treatment, improving treatment outcomes and patient adherence, and reducing toxic effects. Ongoing clinical trials for shortening tuberculosis treatment duration, improving treatment outcomes in MDR tuberculosis, and preventing disease in people with latent tuberculosis infection are reviewed. A range of HDTs and immune-based treatments are under investigation as adjunctive therapy for shortening duration of therapy, preventing permanent lung injury, and improving treatment outcomes of MDR tuberculosis. We discuss the HDT development pipeline, ongoing clinical trials, and translational research efforts for adjunct tuberculosis treatment