The effects of anti-inflammatory agents as host-directed adjunct treatment of tuberculosis in humans: a systematic review and meta-analysis.

BACKGROUND: The potential role of adjunctive anti-inflammatory therapy to enhance tuberculosis (TB) treatment has recently received increasing interest. There is, therefore, a need to broadly examine current host-directed therapies (HDTs) that could accelerate treatment response and improve TB outcomes. METHODS: This systematic review and meta-analysis included randomised controlled trials of vitamin D and other HDT agents in patients receiving antibiotic treatment for pulmonary TB. Sputum smear conversion rate at 4-8 weeks was the primary outcome. Secondary outcomes included blood indices associated with infectivity and inflammation, chest radiology and incidence of adverse events. RESULTS: Fifty-five studies were screened for eligibility after the initial search, which yielded more than 1000 records. Of the 2540 participants in the 15 trials included in the meta-analysis, 1898 (74.7%) were male, and the age at entry ranged from 18 to 70 years. There was a 38% significantly (RR 1.38, 95% CI = 1.03-1.84) increased sputum smear negativity in patients administered with vitamin D in addition to standard TB treatment than those receiving only the TB treatment. Patients treated with other HDT anti-inflammatory agents in addition to TB treatment also had a 29% significantly increased sputum smear conversion rate (RR 1.29, 95% CI = 1.09-1.563). Lymphocyte to monocyte ratio was significantly higher in the vitamin D treatment groups compared to the controls (3.52 vs 2.70, 95% CI for difference 0.16-1.11, p = 0.009) and (adjusted mean difference 0.4, 95% CI 0.2 -- 0.6; p = 0.001); whilst tumour necrosis factor-alpha (TNF-α) showed a trend towards a reduction in prednisolone (p < 0.001) and pentoxifylline (p = 0.27) treatment groups. Vitamin D and N-acetylcysteine also accelerated radiographic resolution in treatment compared to placebo at 8 weeks. No differences were observed in the occurrence of adverse events among all HDT treatments. CONCLUSIONS: Vitamin D and other anti-inflammatory HDT medications used as adjunct TB treatment may be well tolerated and effective. They significantly improved sputum smear conversion rate and chest radiological appearance, and also exhibited an inflammation resolution effect.

Evaluation of the treatment guidelines, practices and outcomes of complicated severe acute malnutrition in children aged 0-59 months in sub-Saharan Africa: a study protocol for the SAMAC study.

INTRODUCTION: in hospitals across Africa, the case fatality rates of severe acute malnutrition (SAM) have remained consistently high (over 20%), despite the existence of the WHO treatment guideline. This has been attributed to inconsistencies in the implementation of the WHO treatment guidelines in sub-Saharan African countries. In spite of this awareness, the SAM treatment guidelines adopted by various sub-Saharan African countries and hospitals are unknown. Knowledge of the exact treatment practices employed in the management of SAM in different hospitals in sub-Saharan Africa is not known. This study aims to investigate the admission criteria, in-patient treatment guidelines and practices and outcomes of complicated SAM in sub-Saharan African children aged 0-59 months. METHODS: this is an observational study which involves the extraction of admission, treatment and discharge data from the medical records of infants and children aged 0-59 months diagnosed and treated for complicated SAM in sub-Saharan Africa. This information is being used to develop a comprehensive database on the treatment of complicated SAM across sub-Saharan Africa. Information on the national and hospital guidelines for the treatment of complicated SAM is also collected. RESULTS: results of this study will serve as a useful resource on the true reflection of the treatment of complicated SAM across sub-Saharan Africa and will provide valuable information for optimising SAM treatment. CONCLUSION: in order to advocate best practice and reduce SAM-related mortality in sub-Saharan Africa, the identification of the different diagnostic and treatment methods and respective outcomes across different hospitals and countries is imperative.

Determinants of undernutrition prevalence in children aged 0-59 months in sub-Saharan Africa between 2000 and 2015. A report from the World Bank database.

OBJECTIVE: To determine undernutrition prevalence in 0-59-month-old children and its determinants during the period 2000-2015 in sub-Saharan Africa. DESIGN: Ecological study of time series prevalence of undernutrition in sub-Saharan Africa assessed from 2000 to 2015. SETTING: Underweight and stunting prevalence from the World Bank database (2000-2015) were analysed. Mixed models were used to estimate prevalence of underweight and stunting. Country-specific undernutrition prevalence variation was estimated and region comparisons were performed. A meta-regression model considering health and socio-economic characteristics at country level was used to explore and estimate the contribution of different undernutrition determinants. PARTICIPANTS: Countries of sub-Saharan Africa. RESULTS: During 2000-2015, underweight prevalence in sub-Saharan Africa was heterogeneous, ranging between 7 and 40 %. On the other hand, stunting prevalence ranged between 20 and 60 %. In general, higher rates of underweight and stunting were estimated in Niger (40 %) and Burundi (58 %), respectively; while lowest rates of underweight and stunting were estimated in Swaziland (7 %) and Gabon (21 %). About 1 % undernutrition prevalence reduction per year was estimated across sub-Saharan Africa, which was not statistically significant for all countries. Health and socio-economic determinants were identified as main determinants of underweight and stunting prevalence variability in sub-Saharan Africa. CONCLUSIONS: Undernutrition represents a major public health threat in sub-Saharan Africa and its prevalence reduction during the period 2000-2015 was inconsistent. Improving water accessibility and number of medical doctors along with reducing HIV prevalence and poverty could significantly reduce undernutrition prevalence in sub-Saharan Africa.

Prevalence of glutamine deficiency in ICU patients: a cross-sectional analytical study.

BACKGROUND: Not only is glutamine deficiency an independent predictor of mortality in intensive care unit (ICU) patients, but glutamine supplementation is also recommended for its proven outcome benefits. However, recent data suggest that early glutamine supplementation in certain patient groups increase mortality. The aim of this study was to investigate plasma glutamine levels of adult ICU patients in the South African setting and to determine relationships between glutamine levels, gender, diagnostic categories and selected inflammatory markers. The data from this study will be used as baseline measurement to support a large scale study that will be undertaken in the South African ICU population. METHODS: This cross-sectional, analytical study included 60 mixed adult ICU patients within 24 h post ICU admission. Plasma glutamine levels were determined on admission. The relationship between glutamine levels, Interleukin-6 (IL-6) and C-reactive protein (CRP); as well as gender- and diagnosis-related differences in glutamine levels were also investigated. A non-parametric ROC curve was computed to determine the CRP concentration cut-off point above which glutamine becomes deficient. RESULTS: The median plasma glutamine level (497 µmol/L) was in the normal range; however, 38.3 % (n = 23) of patients had deficient (<420 µmol/L) and 6.7 % (n = 4) had supra-normal glutamine levels (>930 µmol/L). No significant difference could be detected between glutamine levels and gender or diagnosis categories as a group. When only the medical and surgical categories were compared, the median plasma glutamine level of the medical patients were significantly lower than that of the surgical patients (p = 0.042). Glutamine showed inverse associations with CRP levels (r = -0.44, p < 0.05) and IL-6 concentrations (r = -0.23, p = 0.08). A CRP cut-off value of 95.5 mg/L was determined above which glutamine levels became deficient. CONCLUSIONS: About a third of patients (38 %) were glutamine deficient on admission to ICU, whereas some presented with supra-normal levels. While glutamine levels correlated inversely with inflammatory markers, and a CRP value of above 95.5 mg/L indicated potential glutamine deficiency, the clinical application of this finding needs further investigation.