An immunogenicity, safety and post-marketing surveillance of a novel adsorbed human diploid cell rabies vaccine (Rabivax) in Indian subjects

In 1999, Serum Institute of India indigenously developed an adsorbed human diploid cell rabies vaccine (Rabivax). During 2000-04, this new vaccine was subjected to a series of immunogenecity and safety studies. Initially, an experimental batch of Rabivax (adsorbed) was assessed on ten healthy adult volunteers and its response was comparable with that of Merieux inactivated rabies vaccine (MIRV, lyophilized) which was used as a control. Subsequently, Rabivax (adsorbed) was assessed on forty-five suspect rabid dog bite cases with MIRV as control. The vaccine was found to be equally safe and immunogenic as MIRV and showed better rabies virus neutralizing antibody (RVNA) response on day 90 than MIRV. A post-licensing study conducted on 150 cases of suspect rabid animal bites showed it to be safe and immunogenic. To assess its long-term sero-efficacy some of these subjects tested after one year of follow up showed that 84% of them had adequate RVNA titers. In addition, a routine post-marketing surveillance done on 1608 animal bite cases demonstrated that Rabivax (adsorbed) was safe and efficacious. The adverse events to Rabivax (adsorbed) included pain at injection site (3.4%), swelling with induration (2.8%), fever and headache (1.4%). No serious adverse event was reported from the studies. In conclusion, Rabivax (adsorbed) is an immunogenic, safe and efficacious vaccine for rabies prophylaxis in humans.     

An Incidental Finding at Transplant Assessment: Case Report

A 43-year-old woman with chronic hypersensitivity pneumonitis was referred for lung transplant assessment. An echocardiogram as part of her work-up revealed a large left atrial myxoma, presenting a conundrum on how best to manage her combined pathology. Because of the level of pulmonary disease, early intervention to remove the myxoma was not thought be viable without postoperative support. Use of extracorporeal membrane oxygenation to bridge patients for lung transplant is feasible, yet risks increased perioperative mortality. We present the first reported case of simultaneous cardiac myxoma removal and lung transplant.     

Proboscis lateralis with ipsilateral sinonasal and olfactory pathway aplasia

Proboscis lateralis is a rare craniofacial malformation characterized by absence of nasal cavity on one side with a trunk-like nasal appendage protruding from superomedial portion of the ipsilateral orbit. High-resolution computed tomography and magnetic resonance imaging are extremely useful in evaluating this congenital condition and the wide spectrum of associated anomalies occurring in the surrounding anatomical regions and brain. We present a case of proboscis lateralis in a 2-year-old girl with associated ipsilateral sinonasal aplasia, orbital cyst, absent olfactory bulb and olfactory tract. Absence of ipsilateral olfactory pathway in this rare disorder has been documented on high-resolution computed tomography and magnetic resonance imaging by us for the first time in English medical literature.     

Emerging Role of Micro-RNAs in the Regulation of Angiogenesis

During development, angiogenesis occurs as a controlled series of events leading to neovascularization that supports changing tissue requirements. Several pro- and antiangiogenic factors orchestrate a complex, dynamic process to allow initial sprouting and invasion, subsequent pruning and remodeling, and finally maturation and survival of blood vessels. In the last decade, a new class of small RNA molecules termed micro-RNAs (miRs) have emerged as key regulators of several cellular processes including angiogenesis. Micro-RNAs such as miR-132, miR-126, miR-296, miR-145, and miR-92a have been shown to play pro- and antiangiogenic roles in the vasculature of both endothelial cells and perivascular cells. However, in pathological situations such as cancer or inflammation, the same angiogenic signaling pathways and miRs are dysregulated and exploited, typically resulting in poorly organized vessels with leaky and tortuous properties. This article is a brief overview of specific miRs that have been reported to play a role in the vasculature. The authors explore emerging principles that suggest miRs insulate cellular processes from external perturbations and provide robustness to biological systems in the context of angiogenesis.     

Approach to cataract with persistent hyperplastic primary vitreous

Persistent hyperplastic primary vitreous (PHPV) is a congenital anomaly in which the hyaloid vasculature persists beyond fetal life. In cases in which cataract is associated with PHPV, intraoperative bleeding is a potential complication during cataract surgery. The pars plana approach along with endocoagulation has been used in such cases. We describe an alternative approach using a Fugo plasma blade via an anterior route. This approach provides better control over the posterior capsulotomy along with minimal traction over the retina and, most important, hemostasis during surgery.     

Immunogenicity and safety study of Indirab: A Vero cell based chromatographically purified human rabies vaccine

A chromatographically purified Vero cell rabies vaccine, Indirab manufactured by Bharat Biotech International Limited, Hyderabad, India was subjected to safety and immunogenicity studies by both intramuscular and intradermal routes of administration in parallel with a reference vaccine, Verorab. A Pre-exposure study was undertaken in 239 subjects by intramuscular (IM) route (Study I), Post-exposure study in 188 patients by intramuscular route (Study II) and Simulated post-exposure study in 134 subjects by intradermal (ID) route (Study III). All subjects in these studies were administered with either the test or the reference vaccine as per WHO approved intramuscular and intradermal regimens. The blood samples were collected on days 0, 14 and 35 in case of Study 1, and days 0, 14, 28 and 90 in case of studies II and III. In all studies both vaccine groups had adequate antibody titers (>0.5 IU/mL) on all days tested post-vaccination and there was no significant difference in the titers observed (p > 0.05). Some side effects like pain, induration, itching and fever were noted in both vaccine groups in all studies. Both vaccines were well tolerated. Hence it can be concluded that Indirab is as safe and immunogenic as Verorab when administered by both intramuscular and intradermal routes.     

Phase II study of MLN8237 (alisertib), an investigational Aurora A kinase inhibitor, in patients with platinum-resistant or -refractory epithelial ovarian, fallopian tube, or primary peritoneal carcinoma

ObjectivesAurora A kinase (AAK), a key mitotic regulator, is implicated in the pathogenesis of several tumors, including ovarian cancer. This single-arm phase II study assessed single-agent efficacy and safety of the investigational AAK inhibitor MLN8237 (alisertib), in patients with platinum-refractory or ‐resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma.MethodsAdult women with malignant, platinum-treated disease received MLN8237 50 mg orally twice daily for 7 days plus 14 days' rest (21-day cycles). The primary endpoint was combined objective tumor response rate per Response Evaluation Criteria in Solid Tumors (RECIST) and/or CA-125 criteria. Secondary endpoints included response duration, clinical benefit rate, progression-free survival (PFS), time-to-progression (TTP), and safety.ResultsThirty-one patients with epithelial ovarian (n = 25), primary peritoneal (n = 5), and fallopian tube carcinomas (n = 1) were enrolled. Responses of 6.9–11.1 month duration were observed in 3 (10%) patients with platinum-resistant ovarian cancer. Sixteen (52%) patients achieved stable disease with a mean duration of response of 2.86 months and which was durable for ≥ 3 months in 6 (19%). Median PFS and TTP were 1.9 months. Most common drug-related grade ≥ 3 adverse events were neutropenia (42%), leukopenia (23%), stomatitis, and thrombocytopenia (each 19%); 6% reported febrile neutropenia.ConclusionsThese data suggest that MLN8237 has modest single-agent antitumor activity and may produce responses and durable disease control in some patients with platinum-resistant ovarian cancer. MLN8237 is currently undergoing evaluation in a phase I/II trial with paclitaxel in recurrent ovarian cancer.