Sangeeta Joshi

HLA match likelihoods for Indian patients seeking unrelated donor transplantation grafts: a population-based study

BACKGROUND For patients who do not have a suitable human leukocyte antigen (HLA)-matched family donor, unrelated donor registries of adult volunteers and banked umbilical cord blood (UCB) units provide the potential for successful haemopoietic stem-cell transplantation. The size and genetic composition of such registries determines the proportion of patients who will be able to find a suitable match. We aimed to assess the proportion of positive matches for Indian patients. METHODS Using HLA data from ten existing donor and UCB registries and clinical transplant centres in India, we built population-based genetic models for 14 Indian regions to model Indian registry growth to predict the likelihood of identifying a suitable donor-either an adult donor or UCB-for Indian patients. We computed ranking tables of the top ten haplotypes in each regional group and compared these with four US samples from the National Marrow Donor Program (NMDP) registry. FINDINGS The mean proportion of individuals who would have a 10/10 adult donor match within India ranged from 14·4% with a registry size of 25 000 to 60·6% with a registry size of 1 000 000. Only when donor registries increased to 250 000 did the match rate within India exceed that found by searching the US-NMDP registry combined with an Indian registry of 25 000 donors. The proportion of matches increased logarithmically with increased registry size (R(2)=0·993). For a UCB registry size of 25 000, 96·4% of individuals would find a 4/6 match; however, only 18·3% would have a 6/6 match. INTERPRETATION Serial match modelling and follow-up comparisons can identify the relative and progressively greater value of an India-based donor registry and UCB banking network to serve the Indian population. Understanding regional HLA haplotype diversity could guide registry growth and maximise benefit to patients. Similar modelling could guide planning for the needs of other ethnically distinct populations. FUNDING University of Minnesota and the Indian Council for Medical Research.

Extraintestinal Infections Caused by Non-toxigenic Vibrio cholerae non-O1/non-O139

Vibrio cholerae is an aerobic, sucrose fermentative Gram-negative bacterium that generally prevails in the environment. Pathogenic V. cholerae is well-known as causative agent of acute diarrhea. Apart from enteric infections, V. cholerae may also cause other diseases. However, their role in causing extraintestinal infections is not fully known as it needs proper identification and evaluation. Four cases of extraintestinal infections due to V. cholerae non-O1/non-O139 have been investigated. The isolates were screened for phenotypic and genetic characteristics with reference to their major virulence genes. Serologically distinct isolates harbored rtx, msh, and hly but lacked enteric toxin encoding genes that are generally present in toxigenic V. cholerae. Timely detection of this organism can prevent fatalities in hospital settings. The underlying virulence potential of V. cholerae needs appropriate testing and intervention.

Proinflammatory chemokines are major mediators of exuberant immune response associated with Influenza A (H1N1) pdm09 virus infection

In India, the case fatality ratio of the pandemic A (H1N1) pdm09 influenza was relatively higher when compared to seasonal Influenza A infection. Hypercytokinemia or “cytokine storm” has been previously implicated in the pathogenesis of other influenza viruses. The present study was undertaken to compare the cytokine profiles of A (H1N1) pdm09 influenza and seasonal H3 infection in Indian population and to correlate the findings with disease severity. Plasma levels of 18 cytokines/chemokines were measured by flow‐cytometry using a bead based assay in patients infected with A (H1N1) pdm09 virus (n = 96) and Influenza A seasonal H3 virus (n = 30) categorised into mild, moderate, and severe groups along with healthy controls (n = 36). There was an overall trend indicating an exuberant cytokine/chemokine response in A (H1N1) pdm09 as compared to seasonal H3 influenza, which was more evident in severe cases, suggesting a role for these cytokines/chemokines in the pathogenesis of A(H1N1) pdm09. Increased levels of CXCL‐8/IL‐8, IL‐10, IL‐6, and IL‐17A were seen in both A(H1N1) pdm09 influenza and seasonal H3 cases when compared to healthy controls. However, dysregulated production of proinflammatory chemokines was seen more pronounced in A (H1N1) pdm09 influenza cases as compared to seasonal H3 cases. This study has brought forth the potential role of chemokines as prognostic indicators of disease severity and outcome. Further research on modulating the host immune response to limit severity of the disease could help in the treatment and management of influenza.

Salmonella typhimurium meningitis in infancy.

We report a case of meningitis due to Salmonella typhimurium in a four-month-old female infant. The child was brought to the pediatric emergency department with complaints of fever, cold, and generalized convulsion. On examination, the child was febrile and was having seizures. The anterior fontanelle was not bulging. Lumbar puncture was done and Salmonella typhimurium was isolated from cerebrospinal fluid. Initially the infant improved clinically with appropriate management, but had a fatal outcome due to nosocomial pneumonia.

Trends in antibiotic susceptibility of enteric fever isolates from South India, 2002–2013

Background Enteric fever is endemic in India. Trends in antibiotic resistance in Salmonella enterica subspecies enterica serovars Typhi and Paratyphi A isolates over the past 12 years were studied. Methods A retrospective analysis of consecutive blood culture isolates of Salmonella Typhi and Salmonella Paratyphi A was performed from 2002 to 2013. Antibiotic susceptibility testing was carried out for ampicillin, chloramphenicol, cotrimoxazole, nalidixic acid (NA), ciprofloxacin and ceftriaxone by disc diffusion. The minimum inhibitory concentration of ciprofloxacin and azithromycin was determined using E-test strips. Mantel-Haenszel extended chi-square test was used for analysis of trends across years. Results Three thousand two hundred ninety-six Salmonella spp. were isolated; of which, 1905 were identified as Salmonella Typhi (58%) and 1393 as Salmonella Paratyphi A (42%). Multidrug resistance (chloramphenicol, ampicillin and cotrimoxazole) was relatively stable throughout the study period. NA resistance increased from 18% in 2007 to 100% in 2013 among Salmonella Paratyphi A isolates and from 67% to 82% among Salmonella Typhi isolates. Complete susceptibility to ceftriaxone and azithromycin was observed in this study. Conclusions Knowledge of the local patterns of resistance would help in appropriate therapy for enteric fever. With increasing rates of fluoroquinolone resistance in our hospital setting, it is probably prudent to revert back to the first-line agents for treatment and save azithromycin and third-generation cephalosporins for difficult and non-responsive cases.

Antibiotic susceptibility pattern of Burkholderia cepacia complex and Stenotrophomonas maltophilia: A 5-year analysis

Indian Journal of Medical Microbiology ¦ Volume 35 ¦ Issue 2 ¦ April-June 2017 318 Dear Editor, Non-fermenting Gram-negative bacilli have emerged as significant pathogens over the years, causing serious infections, especially in immunocompromised patients. These organisms are ubiquitous in nature, particularly in soil, water and also in the hospital environment.[1] Among these non-fermenters, Burkholderia cepacia complex (BCC) and Stenotrophomonas maltophilia have a different susceptibility pattern compared to that of Pseudomonas aeruginosa. There are not many studies from South India analysing the susceptibility pattern of these organisms.

Dosing strategy based on prevailing aminoglycoside minimum inhibitory concentration in India: Evidence and issues

Aminoglycosides are important agents used for treating drug-resistant infections. The current dosing regimen of aminoglycosides does not achieve sufficient serum level concentration for the infected bacterial pathogen interpreted as susceptible based on laboratory testing. Minimum inhibitory concentration was determined for nearly 2000 isolates of Enterobacteriaceae and Pseudomonas aeruginosa by broth microdilution method. Results were interpreted based on CLSI and EUCAST interpretative criteria and the inconsistencies in the susceptibility profile were noted. This study provides insights into the inconsistencies existing in the laboratory interpretation and the corresponding clinical success rates. This urges the need for revising clinical breakpoints for amikacin, to resolve under dosing leading to clinical failure.

Cytoplasmic-anti-neutrophil cytoplasmic antibodies targeting myeloperoxidase in Wegener's granulomatosis: A rare phenomenon

Wegeners granulomatosis (WG) patients can rarely have antineutrophil cytoplasmic antibodies (ANCAs) directed against myeloperoxidase (MPO), producing a cytoplasmic pattern on indirect immunofluorescence (IIF). This has important implications in the diagnosis and pathophysiology of the disease. We present to you a report of three cases of WG, demonstrating a cytoplasmic-ANCA pattern on indirect IIF, but directed against MPO. It is necessary to diagnose a patient taking into account both the autoimmune test results and the clinical features.