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.

Adjusting Haemoglobin Values for Altitude Maximizes Combined Sensitivity and Specificity to Detect Iron Deficiency among Women of Reproductive Age in Johannesburg, South Africa.

In South Africa, haemoglobin (Hb) is measured to screen for iron deficiency (ID). However, low levels of Hb are only a late stage indicator of ID. Furthermore, Hb values are generally not adjusted for altitude even though recommended by WHO. We determined the Hb threshold with the highest combined sensitivity and specificity for detecting ID among South African women living at 1700 m above sea level. In a cross-sectional study of 492 18-25-year-old women, we measured Hb and iron status biomarkers. Using receiver operating characteristic curves, we determined the Hb threshold with maximum Youden Index for detecting ID. This threshold of <12.35 g/dL resulted in a 37.2% anaemia prevalence (20.9% IDA), and sensitivity and specificity of 55.7% and 73.9%, respectively. The WHO altitude-adjusted threshold of <12.5 g/dL resulted in a 39% anaemia prevalence (21.3% IDA), and sensitivity and specificity of 56.8% and 70.8%, respectively. In contrast, using the unadjusted Hb cut-off of <12 g/dL resulted in a 18.5% anaemia prevalence (12.6% IDA), and sensitivity and specificity of 35.1% and 88.6%, respectively. In this sample of South African women of reproductive age an Hb threshold <12.35 g/dL had the highest combined sensitivity and specificity for detecting ID. The diagnostic performance of this Receiver operating characteristic curve-determined threshold was comparable to the altitude-adjusted threshold proposed by WHO. Thus, clinical and public health practice in South Africa should adopt adjustment of Hb for altitude to avoid underestimation of ID and missing women in need for intervention.

Plasma phospholipid fatty acid patterns are associated with adiposity and the metabolic syndrome in black South Africans: a cross-sectional study.

BACKGROUND: Diets rich in n-6 polyunsaturated fatty acids (PUFAs) and saturated fatty acids (SFA) have been associated with increased risk of obesity and the metabolic syndrome (MetS), but the evidence is inconsistent, whereas diets high in n-3 long-chain (LC) -PUFAs are associated with lower risk. There is limited information about the association of plasma phospholipid fatty acids (FAs) with obesity and the MetS among black South Africans. OBJECTIVE: To investigate the association of dietary FAs and plasma phospholipid FA patterns, respectively, with measures of adiposity (body mass index, waist circumference, waist-to-height ratio) and the MetS in black South Africans. METHODS: Factor analysis was used to identify FA patterns from 11 dietary FAs and 26 individual plasma phospholipid FAs. Cross-sectional association of the identified patterns with measures of adiposity and the MetS was investigated. A random sample of 711 black South African adults aged 30 to 70 years (273 men, 438 women) from the North West Province was selected from the South African leg of the Prospective Urban and Rural Epidemiology (PURE) study. Sequential regression models adjusted for confounders were applied to investigate the association between dietary FAs and plasma phospholipid FA patterns with measures of adiposity and the MetS. RESULTS: Two patterns were derived from dietary FAs and six patterns from plasma phospholipid FAs that explained the cumulative variance of 89 and 73%, respectively. The association of FA patterns with adiposity and the MetS was weaker for dietary FA patterns than for plasma phospholipid FA patterns. The plasma phospholipid FA pattern with high loadings of saturated FAs (high-Satfat) and another with high loadings of n-3 very-long-chain PUFAs (n-3 VLC-PUFAs) were positively associated with measures of adiposity and the MetS, while patterns with positive loadings of LC monounsaturated fatty acids (n-9 LC-MUFA) and a positive loading of n-3 essential FAs (n-3 EFA) showed inverse associations with the MetS and some measures of adiposity. CONCLUSION: The n-9 LC-MUFA and n-3 EFA patterns seemed to provide possible protective associations with adiposity and the MetS, whereas the high-Satfat and n-3 VLC-PUFA patterns were associated with adiposity and the MetS in our study participants. The results are reflective of the metabolic difference between overweight and obese compared to lean individuals.