A National Study of Outcomes among HIV-Infected Kidney Transplant Recipients

Kidney transplantation is a viable treatment for select patients with HIV and ESRD, but data are lacking regarding long-term outcomes and comparisons with appropriately matched HIV-negative patients. We analyzed data from the Scientific Registry of Transplant Recipients (SRTR; 2002–2011): 510 adult kidney transplant recipients with HIV (median follow-up, 3.8 years) matched 1:10 to HIV-negative controls. Compared with HIV-negative controls, HIV-infected recipients had significantly lower 5-year (75.3% versus 69.2%) and 10-year (54.4% versus 49.8%) post-transplant graft survival (GS) (hazard ratio [HR], 1.37; 95% confidence interval [95% CI], 1.15 to 1.64; P<0.001) that persisted when censoring for death (HR, 1.43; 95% CI, 1.12 to 1.84; P=0.005). However, compared with HIV-negative/hepatitis C virus (HCV)–negative controls, HIV monoinfected recipients had similar 5-year and 10-year GS, whereas HIV/HCV coinfected recipients had worse GS (5-year: 64.0% versus 52.0%, P=0.02; 10-year: 36.2% versus 27.0%, P=0.004 [HR, 1.38; 95% CI, 1.08 to 1.77; P=0.01]). Patient survival (PS) among HIV-infected recipients was 83.5% at 5 years and 51.6% at 10 years and was significantly lower than PS among HIV-negative controls (HR, 1.34; 95% CI, 1.08 to 1.68; P<0.01). However, PS was similar for HIV monoinfected recipients and HIV-negative/HCV-negative controls at both times. HIV/HCV coinfected recipients had worse PS compared with HIV-negative/HCV-infected controls (5-year: 67.0% versus 78.6%, P=0.007; 10-year: 29.3% versus 56.23%, P=0.002 [HR, 1.57; 95% CI, 1.11 to 2.22; P=0.01]). In conclusion, HIV-negative and HIV monoinfected kidney transplant recipients had similar GS and PS, whereas HIV/HCV coinfected recipients had worse outcomes. Although encouraging, these results suggest caution in transplanting coinfected patients.     

Dengue in the deserts: Search and Destroy Operations

Dengue, a viral disease transmitted by the Aedes mosquito has the potential to cause outbreaks in urban settings. Planned and coordinated actions including entomological surveillance need to be undertaken at the community level, through synergized efforts by all partners and stakeholders.The experience of conducting such a Task Force based action plan for prevention and control of dengue, in a desert township is highlighted in this study.     

rIL-22 as an adjuvant enhances the immunogenicity of rGroEL in mice and its protective efficacy against S. Typhi and S. Typhimurium

Salmonella infection, ranging from mild, self-limiting diarrhea to severe gastrointestinal, septicemic disease and enteric fever, is a global health problem both in humans and animals. Rapid development of microbial drug resistance has led to a need for efficacious and affordable vaccines against Salmonella. Microbial heat shock proteins (HSPs), including HSP60 and HSP70, are the dominant antigens that promote the host immune response. Co-administration of these antigens with cytokines, such as IL-22, which plays an important role in antimicrobial defense, can enhance the immune response and protection against pathogens. Therefore, the aim of the present study was to determine the immunogenicity of rGroEL (Hsp60) of S. Typhi, alone or administered in combination with murine rIL-22, and its protective efficacy against lethal infection with Salmonella, in mice. There was appreciable stimulation of the humoral and cell-mediated immune responses in mice immunized with rGroEL alone. However, co-administration of rGroEL with rIL-22 further boosted the antibody titers (IgG, IgG1 and IgG2a), T-cell proliferative responses and the secretion of both Th1 and Th2 cytokines. Additionally, rGroEL alone accorded 65%–70% protection against lethal challenge with S. Typhi and S. Typhimurium, which increased to 90% when co-administered with rIL-22.     

Co-administration of rIpaB domain of Shigella with rGroEL of S. Typhi enhances the immune responses and protective efficacy against Shigella infection

Shigella species cause severe bacillary dysentery in humans and are associated with high morbidity and mortality. The Invasion plasmid antigen (IpaB) protein, which is conserved across all Shigella spp., induces macrophage cell death and is required to invade host cells. The present study evaluates the immunogenicity and protective efficacy of the recombinant (r) domain region of IpaB (rIpaB) of S. flexneri. rIpaB was administered either alone or was co-administered with the rGroEL (heat shock protein 60) protein from S. Typhi as an adjuvant in a mouse model of intranasal immunization. The IpaB domain region (37 kDa) of S. flexneri was amplified from an invasion plasmid, cloned, expressed in BL21 Escherichia coli cells and purified. Immunization with the rIpaB domain alone stimulated both humoral and cell-mediated immune responses. Furthermore, robust antibody (IgG, IgA) and T-cell responses were induced when the rIpaB domain was co-administered with rGroEL. Antibody isotyping revealed higher IgG1 and IgG2a antibody titers and increased interferon-gamma (IFN-γ) secretion in the co-administered group. Immunization of mice with the rIpaB domain alone protected 60%–70% of the mice from lethal infection by S. flexneri, S. boydii and S. sonnei, whereas co-administration with rGroEL increased the protective efficacy to 80%–85%. Organ burden and histopathological studies also revealed a significant reduction in lung infection in the co-immunized mice compared with mice immunized with the rIpaB domain alone. This study emphasizes that the co-administration of the rIpaB domain and rGroEL protein improves immune responses in mice and increases protective efficacy against Shigella infection. This is also the first report to evaluate the potential of the GroEL (Hsp 60) protein of S. Typhi as an adjuvant molecule, thereby overcoming the need for commercial adjuvants.     

Surface Structure Characterization of Aspergillus fumigatus Conidia Mutated in the Melanin Synthesis Pathway and Their Human Cellular Immune Response

In Aspergillus fumigatus, the conidial surface contains dihydroxynaphthalene (DHN)-melanin. Six-clustered gene products have been identified that mediate sequential catalysis of DHN-melanin biosynthesis. Melanin thus produced is known to be a virulence factor, protecting the fungus from the host defense mechanisms. In the present study, individual deletion of the genes involved in the initial three steps of melanin biosynthesis resulted in an altered conidial surface with masked surface rodlet layer, leaky cell wall allowing the deposition of proteins on the cell surface and exposing the otherwise-masked cell wall polysaccharides at the surface. Melanin as such was immunologically inert; however, deletion mutant conidia with modified surfaces could activate human dendritic cells and the subsequent cytokine production in contrast to the wild-type conidia. Cell surface defects were rectified in the conidia mutated in downstream melanin biosynthetic pathway, and maximum immune inertness was observed upon synthesis of vermelone onward. These observations suggest that although melanin as such is an immunologically inert material, it confers virulence by facilitating proper formation of the A. fumigatus conidial surface.     

Common Hematological Disorders in Children

It is common for primary care physicians to be faced with children with hematological disorders in everyday practice. The article seeks to provide realistic information for the first-contact physician in handling common hematological diseases in children. Practical step-wise approach to understanding and investigating anemia and bleeding disorders is illustrated. Requirement of iron in normal children and management of iron deficiency anemia (IDA) and thalassemia is explained. The gold standard for IDA continues to be ferrous sulphate which has good bioavailability and is inexpensive. There is emerging concept of delayed clamping of umbilical cord at birth, particularly in regions with widespread IDA, to augment iron stores in infancy. Typical case scenarios of children with immune thrombocytopenia (ITP) and hemophilia are provided to facilitate the understanding of management in day to day practice. The vital role of the medical practitioner in shared care of patients with acute lymphoblastic leukemia and febrile neutropenia is emphasized. A risk based treatment algorithm for febrile neutropenia is provided.     

Imaging-based algorithmic approach to gallbladder wall thickening

Gallbladder(GB) wall thickening is a frequent finding caused by a spectrum of conditions. It is observed in many extracholecystic as well as intrinsic GB conditions. GB wall thickening can either be diffuse or focal. Diffuse wall thickening is a secondary occurrence in both extrinsic and intrinsic pathologies of GB, whereas, focal wall thickening is mostly associated with intrinsic GB pathologies. In the absence of specific clinical features, accurate etiological diagnosis can be challenging. The survival rate in GB carcinoma(GBC) can be improved if it is diagnosed at an early stage, especially when the tumor is confined to the wall. The pattern of wall thickening in GBC is often confused with benign diseases, especially chronic cholecystitis, xanthogranulomatous cholecystitis, and adenomyomatosis. Early recognition and differentiation of these conditions can improve the prognosis. In this minireview, the authors describe the patterns of abnormalities on various imaging modalities(conventional as well as advanced) for the diagnosis of GB wall thickening. This paper also illustrates an algorithmic approach for the etiological diagnosis of GB wall thickening and suggests a formatted reporting for GB wall abnormalities.