Immunoxel (Dzherelo) is a water-alcohol extract of medicinal plants used in Ukraine as an adjunct immunotherapy to TB and HIV therapy. Four types of solid sublingual formulations of Immunoxel were made: sugar dragées, sugar-coated pills, gelatin pastilles and dried-honey lozenges. They were administered once-daily along with TB drugs. After 1 month, 84.1% of TB patients became sputum-negative with rates in individual groups of 89.5, 70, 76.9 and 100%, respectively. The conversion rate was independent of bodyweight, age, gender, differences in chemotherapy regimens or whether subjects had newly diagnosed TB, re-treated TB, multidrug-resistant TB or TB with HIV coinfection. Patients experienced earlier clinical improvement, faster defervescence, weight gain, a higher hemoglobin content and reduced inflammation as evidenced by lower leukocyte counts and erythrocyte sedimentation rate. By contrast, in the placebo group, only 19% of patients had converted. These findings imply that mucosal delivery of solid Immunoxel is equivalent to the original liquid formula given per os twice-daily for 2-4 months.
One-month Phase II trial was conducted in 43 sputum smear-positive patients with pulmonary tuberculosis randomized into treatment (n = 22) and placebo (n = 21) arms to investigate the safety and efficacy of an orally-administered therapeutic TB vaccine (V7) containing 10 μg of heat-killed Mycobacterium vaccae provided by Longcom company. Immunotherapy and control groups comprised 8 newly diagnosed (1stDx TB; 18.6%), 6 re-treated (RTB; 14%), and 29 multidrug-resistant (MDR-TB; 67.4%) cases distributed at 5:4:13 and 3:2:16 ratios, respectively. Both arms received conventional TB drugs administered under directly observed therapy. The average weight gain in V7 arm was modest, but statistically significant (0.6 kg; p = 0.004), while placebo patients lost 0.1 kg (p = 0.77). Except defervescence and increased lymphocyte percentage, other secondary endpoints such as erythrocyte sedimentation rate (ESR), leukocyte counts and hemoglobin content were not significantly affected. In control patients only one secondary endpoint, ESR, has improved. After one month mycobacterial clearance in sputum smears was observed in 31.8% (p = 0.03) and 9.5% (p = 0.83) of patients on V7 and placebo. However, the difference between outcomes in two arms was below significance threshold (p = 0.07). Thus, larger population of patients with prolonged follow-up is required to support these preliminary findings.
ObjectiveImmunotherapy of tuberculosis (TB) to shorten treatment duration represents an unmet medical need. Orally delivered, tableted TB vaccine (V7) containing heat-killed Mycobacterium vaccae (NCTC 11659) has been demonstrated in prior clinical studies to be safe and fast-acting immune adjunct.MethodsThe outcome of Phase III trial of V7 containing 10 µg of hydrolyzed M. vaccae was evaluated in 152 patients randomized at 2:1 ratio: V7 (N = 100), placebo (N = 52). Both arms received conventional 1st or 2nd line TB drugs co-administered with daily pill of V7 or placebo.ResultsAfter one month mycobacterial clearance was observed in 68% (P < 0.0001) and 23.1% (P = 0.04) of patients on V7 and placebo. Stratified conversion rates in V7 recipients with drug-sensitive and multidrug-resistant TB were 86.7% and 55.6% vs 27.2% and 15% in placebo. Patients on V7 gained on average 2.4 kg (P < 0.0001) vs 0.3 kg (P = 0.18) in placebo. Improvements in hemoglobin levels, erythrocyte sedimentation rate and leukocyte counts were significantly better than in controls. Liver function tests revealed that V7 can prevent chemotherapy-induced hepatic damage.ConclusionOral M. vaccae is safe, can overcome TB-associated weight loss and inflammation, reduce hepatotoxicity of TB drugs, improve sputum conversion three-fold OR 3.15; 95%CI (2.3,4.6), and cut treatment length by at least six-fold. Longer follow-up studies might be needed to further substantiate our findings (Clinicaltrials.gov: NCT01977768).
V5 is safe and effective as an immune adjunct to chemotherapy for TB and can potentially reduce the treatment duration down to 1 month.
reatment failed TB patients have very limited chances of survival. Open label trial of daily oral pill of V-5 Immunitor (V5) was conducted in 48 treatment-failed TB patients on palliative support consisting of isoniazid (H) and rifampicin (R). The subjects had the following forms of TB; cavitary: disseminated: MDR-TB: DR-TB: TB/HIV at 35:13:7:4:1 ratio. After 1 month 62.5% of V5-treated patients experienced negative sputum smear conversion (P < 0.0001), comprising 11 out of 12 (91.7%) converted among those who had drug-resistant TB and TB/HIV. TB-associated inflammation was downregulated as evidenced by normalization of leukocytosis 7.4 vs. 6.7 x 109 L (P = 0.01) and decreased erythrocyte sedimentation rate 20.5 vs. 14.9 mm/h (P < 0.0001). The mean body temperature normalized from 37.25° ± 0.6° to 36.98° ± 0.4° (P = 0.0002). The average body weight gain and body mass index (BMI) increased by 0.8 ± 0.7 kg and from 18.9 to 19.6 kg/m<sup>2</sup> respectively (P < 0.0001). Two patients (4.2%) died from illicit drug- and alcohol-abuse related causes. No adverse effects or reactivation of disease due to immune intervention were seen at any time. V5 is safe and in combination with a simple two-drug regimen was highly effective as an immune adjunct to produce favorable outcome among treatment-failed and/ or drug-resistant TB patients
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