Efficacious, effective, and embedded interventions: Implementation research in infectious disease control

Background: Research in infectious disease control is heavily skewed towards high end technology; development of new drugs, vaccines and clinical interventions. Oft ignored, is the evidence to inform the best strategies that ensure the embedding of interventions into health systems and amongst populations. In this paper we undertake an analysis of the challenge in the development of research for the sustainable implementation of disease control interventions. Results: We highlight the fundamental differences between the research paradigms associated with the development of technologies and interventions for disease control on the one hand and the research paradigms required for enhancing the sustainable uptake of those very same interventions within the communities on the other. We provide a definition for implementation research in an attempt to underscore its critical role and explore the multidisciplinary science needed to address the challenges in disease control. Conclusion: The greatest value for money in health research lies in the sustainable and effective implementation of already proven, efficacious solutions. The development of implementation research that can help provide some solutions on how this can be achieved is sorely needed

B7-H1 Blockade Increases Survival of Dysfunctional CD8+ T Cells and Confers Protection against Leishmania donovani Infections

Experimental visceral leishmaniasis (VL) represents an exquisite model to study CD8+ T cell responses in a context of chronic inflammation and antigen persistence, since it is characterized by chronic infection in the spleen and CD8+ T cells are required for the development of protective immunity. However, antigen-specific CD8+ T cell responses in VL have so far not been studied, due to the absence of any defined Leishmania-specific CD8+ T cell epitopes. In this study, transgenic Leishmania donovani parasites expressing ovalbumin were used to characterize the development, function, and fate of Leishmania-specific CD8+ T cell responses. Here we show that L. donovani parasites evade CD8+ T cell responses by limiting their expansion and inducing functional exhaustion and cell death. Dysfunctional CD8+ T cells could be partially rescued by in vivo B7-H1 blockade, which increased CD8+ T cell survival but failed to restore cytokine production. Nevertheless, B7-H1 blockade significantly reduced the splenic parasite burden. These findings could be exploited for the design of new strategies for immunotherapeutic interventions against VL

Evaluation of Leishmania donovani Protein Disulfide Isomerase as a Potential Immunogenic Protein/Vaccine Candidate against Visceral Leishmaniasis

In Leishmania species, Protein disulfide isomerase (PDI) - a redox chaperone, is reported to be involved in its virulence and survival. This protein has also been identified, through proteomics, as a Th1 stimulatory protein in the soluble lysate of a clinical isolate of Leishmania donovani (LdPDI). In the present study, the molecular characterization of LdPDI was carried out and the immunogenicity of recombinant LdPDI (rLdPDI) was assessed by lymphocyte proliferation assay (LTT), nitric oxide (NO) production, estimation of Th1 cytokines (IFN-γ and IL-12) as well as IL-10 in PBMCs of cured/endemic/infected Leishmania patients and cured L. donovani infected hamsters. A significantly higher proliferative response against rLdPDI as well as elevated levels of IFN-γ and IL-12 were observed. The level of IL-10 was found to be highly down regulated in response to rLdPDI. A significant increase in the level of NO production in stimulated hamster macrophages as well as IgG2 antibody and a low level of IgG1 in cured patient's serum was observed. Higher level of IgG2 antibody indicated its Th1 stimulatory potential. The efficacy of pcDNA-LdPDI construct was further evaluated for its prophylactic potential. Vaccination with this construct conferred remarkably good prophylactic efficacy (∼90%) and generated a robust cellular immune response with significant increases in the levels of iNOS transcript as well as TNF-α, IFN-γ and IL-12 cytokines. This was further supported by the high level of IgG2 antibody in vaccinated animals. The in vitro as well as in vivo results thus indicate that LdPDI may be exploited as a potential vaccine candidate against visceral Leishmaniasis (VL)

HEC Digital Library Resources: Its purpose of Usage and Impact on Teaching and Research Activities in the Universities of Khyber Pakhtunkhwa-Pakistan

The study aimed to evaluate the impact and purpose of using Higher Education Commission (HEC) digital library resources by the faculty members in the universities of Khyber Pakhtunkhwa, Pakistan. The population of study comprised of 280 social science faculty members working in the public sector universities of Khyber Pakhtunkhwa. Census Based survey method was used to solicit both genders’ views for this study. A quantitative survey procedure was employed for data collection, obtaining 89.2% response rate. Majority of faculty members who were lecturers participated in survey. The study indicates that both male and female respondents have knowledge about the HEC digital library resources. However, male faculty members used these resources more than female. The faculty members between the age group of 31- 40 years were major users of these resources. Among them MS/Phil faculty members use these resources extensively to fulfill their teaching and research needs. The results of the study showed that majority of the faculty members used HEC digital library resources for the purposes of teaching and research, writing articles, updating their knowledge, improving professional competencies, and guiding research students respectively. Results further showed that these resources have a significant impact on respondents’ teaching and research performance. The study suggests that in order to enhance the impact and effectiveness of HEC digital library resources in the public and private sector university of Khyber Pakhtunkhwa, it was suggested to make necessary planning to increase its usage among the faculty members which will increase their research and academic outputs

Evaluating Users’ Satisfaction on Academic Library Services and Facilities in Khyber Pakhtunkhwa-Pakistan

This study was set out to explore the level of satisfaction of the faculty members working in the south district (Karak) of Khyber Pakhtunkhwa-Pakistan from their college libraries’ services and facilities. In order to achieve the objectives of the study and the real picture of the level of satisfaction of faculty members, census based survey research method was adopted to collect data from the target population. Self-constructed and pilot tested questionnaire was used for data collection. Total 147 questionnaires were distributed out of which 120 filled questionnaires were received back with 81% response rate. The study found that majority of the users was satisfied from general infrastructural facilities but dissatisfied from almost all library services except circulation. The study recommends the provision of necessary library services and facilities for college faculty members to fulfill their educational, research and information needs

University Libraries in Khyber Pakhtunkhwa, Pakistan

This study was designed to investigate the history and administrative structure, financial management, collection, users and library staff of university libraries in Khyber Pakhtunkhwa, Pakistan. The study covered all those well-established public and private sector universities of the province which were chartered by the Government of Khyber Pakhtunkhwa, and recognized by HEC (Public= 18 and Private = 9, Total 27 universities). The newly established universities which were housed in rented buildings and had no proper library facilities were excluded from the study. Data was collected from the library professionals of universities through structured questionnaire. Results of the study show that University of Peshawar was established following the birth of Pakistan in 1950 and is generally known the “mother of all universities”. After independence in 1947 till 1995, the total number of universities in Khyber Pakhtunkhwa, both in public and private sectors were five which has now reached to 37. Centralized library system is the most dominating in all the private and majority of the public sector universities of Khyber Pakhtunkhwa. Budgets are randomly allocated for collection which varies from millions to thousands. The collection of university libraries includes both traditional and electronic resources. However, access to most of the electronic resources is provided through HEC Digital Library. University libraries in Khyber Pakhtunkhwa serve a wide range of users including graduates, post graduates, researchers, teaching community, administrative staff and to some extent the external users

University Libraries in Khyber Pakhtunkhwa, Pakistan

This study was designed to investigate the history and administrative structure, financial management, collection, users and library staff of university libraries in Khyber Pakhtunkhwa, Pakistan. The study covered all those well-established public and private sector universities of the province which were chartered by the Government of Khyber Pakhtunkhwa, and recognized by HEC (Public= 18 and Private = 9, Total 27 universities). The newly established universities which were housed in rented buildings and had no proper library facilities were excluded from the study. Data was collected from the library professionals of universities through structured questionnaire. Results of the study show that University of Peshawar was established following the birth of Pakistan in 1950 and is generally known the “mother of all universities”. After independence in 1947 till 1995, the total number of universities in Khyber Pakhtunkhwa, both in public and private sectors were five which has now reached to 37. Centralized library system is the most dominating in all the private and majority of the public sector universities of Khyber Pakhtunkhwa. Budgets are randomly allocated for collection which varies from millions to thousands. The collection of university libraries includes both traditional and electronic resources. However, access to most of the electronic resources is provided through HEC Digital Library. University libraries in Khyber Pakhtunkhwa serve a wide range of users including graduates, post graduates, researchers, teaching community, administrative staff and to some extent the external users

Primary defect in CD8+ lymphocytes in the antibody deficiency disease (common variable immunodeficiency): abnormalities in intracellular production of interferon-gamma (IFN-γ) in CD28+ (‘cytotoxic’) and CD28− (‘suppressor’) CD8+ subsets

We have measured by flow cytometry the ability of subsets of CD8+ CD3+ lymphocytes within mononuclear cell preparations to make intracellular cytokines (IL-2, tumour necrosis factor-alpha (TNF-α) and IFN-γ) on stimulation in vitro with phorbol myristate acetate (PMA) and ionomycin for 16 h. These CD8+ subsets were defined by the presence or absence of CD28 or HLA-DR. Subsets of normal CD8+ cells were compared with cells from the antibody deficiency disease common variable immunodeficiency (CVID). In CVID there was a significant increase in the production of IFN-γ in the CD8+ CD28+ subset (‘cytotoxic’). This reflects a shift in this disease towards an excessive Th1 response away from B cell help. Paradoxically, some CVID patients also showed a reduction in IFN-γ production in the CD8+ CD28− subset (‘suppressor’) which was associated with a failure of these cells to maintain a state of activation after a stimulus in vitro. The B cell problem in this disease is known to be related to a failure of T cell help shown by an inability to produce the antigen-specific CD4+ memory T cells needed for successful B cell maturation. The two pathological CD28 subsets of CD8+ cells we have found in CVID may both be detrimental to a normal CD4-dependent immune response. The CD28− suppressor subset expands and is unable to maintain activation and cytokine secretion, and the CD28+ cytotoxic subset is over-producing the Th1 cytokine IFN-γ