Safety and immunogenicity of ChAd63-KH vaccine in post-kala-azar dermal leishmaniasis patients in Sudan.

Post-kala-azar dermal leishmaniasis (PKDL) is a chronic, stigmatizing skin condition occurring frequently after apparent clinical cure from visceral leishmaniasis. Given an urgent need for new treatments, we conducted a phase IIa safety and immunogenicity trial of ChAd63-KH vaccine in Sudanese patients with persistent PKDL. LEISH2a (ClinicalTrials.gov: NCT02894008) was an open-label three-phase clinical trial involving sixteen adult and eight adolescent patients with persistent PKDL (median duration, 30 months; range, 6-180 months). Patients received a single intramuscular vaccination of 1 × 1010 viral particles (v.p.; adults only) or 7.5 × 1010 v.p. (adults and adolescents), with primary (safety) and secondary (clinical response and immunogenicity) endpoints evaluated over 42-120 days follow-up. AmBisome was provided to patients with significant remaining disease at their last visit. ChAd63-KH vaccine showed minimal adverse reactions in PKDL patients and induced potent innate and cell-mediated immune responses measured by whole-blood transcriptomics and ELISpot. 7/23 patients (30.4%) monitored to study completion showed >90% clinical improvement, and 5/23 (21.7%) showed partial improvement. A logistic regression model applied to blood transcriptomic data identified immune modules predictive of patients with >90% clinical improvement. A randomized controlled trial to determine whether these clinical responses were vaccine-related and whether ChAd63-KH vaccine has clinical utility is underway.

Association of Serum Vitamin D (25OHD) Level with Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Acute exacerbations of COPD is characterized by a change in the patients baseline dyspnoea, cough and/or sputum that is beyond normal day to day differences and guides to a change in standard medications in a patient with COPD. Vitamin D influences the innate & adaptive immune system, and exerts pleiotropic antimicrobial and anti-inflammatory responses. Vitamin D deficiency is frequent among COPD patients but its contributory role in disease exacerbations is widely debated. This study was aimed to assess relationship between reduced serum vitamin D (25-OHD) level with COPD severity and acute exacerbation. This observational cross-sectional study was carried out in the department of Respiratory Medicine, NIDCH, Mohakhali, Dhaka, Bangladesh from October 2016 to September 2017. Consecutive 80 hospital admitted patients with acute exacerbation of chronic obstructive pulmonary disease diagnosed on the basis of clinical history & pulmonary function tests and 78 age & sex matched controls were investigated for serum vitamin D (25-OHD) level. Among the COPD patients, 37% had Vitamin D deficiency (<20ng/ml) and 28.75% had Vitamin D insufficiency (20-29ng/ml). Mean vitamin D (25-OHD) level of COPD patients (25.82±10.62ngm/ml) was found to be significantly lower than healthy controls (32.57±11.32ngm/ml). Vitamin D deficiency was found, by Pearson correlation test, to be significantly associated with severity of COPD. Multivariate analysis showed that age (in years), FEV1 (percent predicted), frequent exacerbators (≥2 in the last year), and smoking (>40 pack year) were significantly associated with Vitamin D deficiency. Acute exacerbation of chronic obstructive pulmonary disease patients was found to have vitamin D deficiency and vitamin D deficiency was significantly associated with severity of COPD. Vitamin D deficiency was also associated with frequent disease exacerbation.