Pre-sensitization with tuberculosis and non-tuberculosis mycobacteria and its impact on TB incidence in different age groups: Chengalpattu BCG trial revisited.

Individuals pre-sensitized with Mycobacterium tuberculosis (MTB), non-tuberculosis mycobacteria, and its impact on TB incidence are relatively unexplored in a high TB burden setting. We conducted secondary data analysis of a double-blind, randomized Chengalpattu BCG trial, India. Induration to Purified Protein Derivative (PPD)-S and PPD-B were proxies for exposures to MTB and M. intracellulare respectively. Optimum cut-off for PPD-S and B were determined using Receiver-Operating Characteristic curves and induration ≥12 mm for PPD-S and ≥10 mm for PPD-B were considered strong reaction. Incidence rates of culture positive pulmonary TB per 100,000 person-years (PY) were calculated. Of 270,043 individuals with skin test results, children <14 years (n = 109,383, 64% showed strong-reaction to PPD-B and 17% to PPD-S) and adults between 25 and 34 years (n = 40,292, 98% were strong reactors to PPD-B and 73% to PPD-S). Overall incidence rate was lower in individuals with PPD-S < PPD-B (136, 95% CI: 130-141/100,000 PY) compared to individuals with PPD-S > PPD-B (447, 95% CI: 427-468/100,000 PY). Incidence rates of culture positive pulmonary TB was affected by early age of exposure to cross-reactive mycobacterial antigens represented by PPD-B and exposure to MTB represented by PPD-S during adolescence and early adulthood.

Repurposed antiviral drugs for COVID-19; interim WHO SOLIDARITY trial results

BACKGROUNDWHO expert groups recommended mortality trials in hospitalized COVID-19 of four re-purposed antiviral drugs. METHODSStudy drugs were Remdesivir, Hydroxychloroquine, Lopinavir (fixed-dose combination with Ritonavir) and Interferon-{beta}1a (mainly subcutaneous; initially with Lopinavir, later not). COVID-19 inpatients were randomized equally between whichever study drugs were locally available and open control (up to 5 options: 4 active and local standard-of-care). The intent-to-treat primary analyses are of in-hospital mortality in the 4 pairwise comparisons of each study drug vs its controls (concurrently allocated the same management without that drug, despite availability). Kaplan-Meier 28-day risks are unstratified; log-rank death rate ratios (RRs) are stratified for age and ventilation at entry. RESULTSIn 405 hospitals in 30 countries 11,266 adults were randomized, with 2750 allocated Remdesivir, 954 Hydroxychloroquine, 1411 Lopinavir, 651 Interferon plus Lopinavir, 1412 only Interferon, and 4088 no study drug. Compliance was 94-96% midway through treatment, with 2-6% crossover. 1253 deaths were reported (at median day 8, IQR 4-14). Kaplan-Meier 28-day mortality was 12% (39% if already ventilated at randomization, 10% otherwise). Death rate ratios (with 95% CIs and numbers dead/randomized, each drug vs its control) were: Remdesivir RR=0.95 (0.81-1.11, p=0.50; 301/2743 active vs 303/2708 control), Hydroxychloroquine RR=1.19 (0.89-1.59, p=0.23; 104/947 vs 84/906), Lopinavir RR=1.00 (0.79-1.25, p=0.97; 148/1399 vs 146/1372) and Interferon RR=1.16 (0.96-1.39, p=0.11; 243/2050 vs 216/2050). No study drug definitely reduced mortality (in unventilated patients or any other subgroup of entry characteristics), initiation of ventilation or hospitalisation duration. CONCLUSIONSThese Remdesivir, Hydroxychloroquine, Lopinavir and Interferon regimens appeared to have little or no effect on hospitalized COVID-19, as indicated by overall mortality, initiation of ventilation and duration of hospital stay. The mortality findings contain most of the randomized evidence on Remdesivir and Interferon, and are consistent with meta-analyses of mortality in all major trials. (Funding: WHO. Registration: ISRCTN83971151, NCT04315948)