Evaluation of the non-toxic mutant of the diphtheria toxin K51E/E148K as carrier protein for meningococcal vaccines.

Diphtheria toxin mutant CRM197 is a common carrier protein for glycoconjugate vaccines, which has been proven an effective protein vector for, among others, meningococcal carbohydrates. The wide-range use of this protein in massive vaccine production requires constant increase of production yields and adaptability to an ever-growing market. Here we compare CRM197 with the alternative diphtheria non-toxic variant DT-K51E/E148K, an inactive mutant that can be produced in the periplasm of Escherichia coli. Biophysical characterization of DT-K51E/E148K suggested high similarity with CRM197, with main differences in their alpha-helical content, and a suitable purity for conjugation and vaccine preparation. Meningococcal serogroup A (MenA) glycoconjugates were synthesized using CRM197 and DT-K51E/E148K as carrier proteins, obtaining the same conjugation yields and comparable biophysical profiles. Mice were then immunized with these CRM197 and DT-K51E/E148K conjugates, and essentially identical immunogenic and protective effects were observed. Overall, our data indicate that DT-K51E/E148K is a readily produced protein that now allows the added flexibility of E. coli production in vaccine development and that can be effectively used as protein carrier for a meningococcal conjugate vaccine.

Knowledge, attitude and practices about leprosy among medical officers of Hyderabad urban district of Andhra Pradesh.

In India, MDT was implemented through vertical programme staff of the National Leprosy Eradication Programme till the year 2001, when it was integrated into general health services (GHS). Human resource development of GHS is a vital, preparatory action for successful integration of leprosy into GHS. District Technical Support Teams (DTST) have been formed with responsibility for building the capacity of medical and paramedical staff of urban health posts (UHPs). In this context, it is necessary to know the current levels of Knowledge, Attitude and Practices (KAP) about leprosy prevailing among health staff at a given point in time, so that required knowledge and skills can be imparted, if need be. The present study is an attempt in this direction for assessing the KAP status of health staff working in Hyderabad city. 402 staff members (352 females and 50 males) working in urban health posts, the Employees State Insurance Corporation and the Central Government Health Services dispensaries in Hyderabad urban district in Andhra Pradesh were included in the study carried out in 2004 in order to assess KAP, and some operational parameters. A questionnaire was used to elicit responses of 110 medical officers in urban Hyderabad and the data were analysed and discussed. Medical officers have shown consistent higher knowledge on leprosy, followed by nursing staff as compared to other paramedical workers Only 40% of the medical officers had the opportunity of seeing at least 1 case of leprosy in their practice. Medical Officers who received training in leprosy and possessed reference material on leprosy have shown higher knowledge and practice. More than half of the study subjects did not have specific training in leprosy. Two major operational problems expressed by the medical officers were managing big crowds in OPD and time lost in meetings. 96 (87.3%) of 110 medical officers felt integration of leprosy services into general health services can be effectively implemented. 78 (71%) expressed that a leprosy patient with severe reaction needed priority attention at the out-patient department indicating good understanding of reactions in leprosy and a positive attitude towards such patients. There is a need to organize training at regular intervals to cover new persons as well as reinforcing and updating the knowledge of those already trained.