Is malaria the cause for decline in the wild population of the Indian White-backed vulture (Gyps bengalensis)?

The populations of three species of Gyps vultures have shown a decline of more than 95% between 1988 and 1999 in the Indian subcontinent and are now classified as 'critically endangered'. The indiscriminate and widespread veterinary use of diclofenac has been implicated for the decline of the White-backed vulture (Gyps bengalensis) in Pakistan, India and Nepal. Similar trends in population decline as seen in the northern regions have also been recorded in Central and South India, but the cause for the decline was not investigated. Here we report a study carried out in a densely forested and sparsely populated region in Central India. An intracellular malarial parasite was identified from the tissues of both live and dead Whitebacked vultures. Further, amplification and sequence analysis of the consensus sequence of the mitochondrial small and large sub-unit rRNA genes indicated a 95-96% similarity with the mitochondrial sequence of Plasmodium falciparum (DQ642845) and other Plasmodium species. In addition, amplification and sequencing of a 502 bp fragment of the mitochondrial cyt b gene identified the haemoprotozoan with Plasmodium sp. AP70, an avian malarial parasite. During the course of this study we also rescued two terminally ill vultures with symptoms of malaria, and treatment with anti-malarials led to their recovery. None of the affected vultures had diclofenac residues, thus implying that malaria could be an additional cause for the decline for the White-backed vulture population

The impact of tick-borne pathogen infection in Indian bovines is determined by host type but not the genotype of Theileria annulata

Tick-borne pathogens (TBP) are a major source of production loss and a welfare concern in livestock across the globe. Consequently, there is a trade-off between keeping animals that are tolerant to TBP infection, but are less productive than more susceptible breeds. Theileria annulata is a major TBP of bovines, with different host types (i.e. exotic and native cattle breeds, and buffalo) displaying demonstrable differences in clinical susceptibility to infection. However, the extent to which these differences are driven by genetic/physiological differences between hosts, or by different parasite populations/genotypes preferentially establishing infection in different host breeds and species is unclear. In this study, three different bovine host types in India were blood sampled to test for the presence of various TBP, including Theileria annulata, to determine whether native cattle (Bos indicus breeds), crossbreed cattle (Bos taurus x Bos indicus breeds) or water buffalo (Bubalus bubalis) differ in the physiological consequences of infection. Population genetic analyses of T. annulata isolated from the three different host types was also performed, using a panel of mini- and micro-satellite markers, to test for sub-structuring of the parasite population among host types. We discovered that compared to other host types, “carrier” crossbreed cattle showed a higher level of haematological pathology when infected with T. annulata. Despite this finding, we found no evidence for differences in the genotypes of T. annulata infecting different host types, although buffalo appeared to harbour fewer mixed parasite genotype infections, indicating they are not the major reservoir of parasite diversity. The apparent tolerance/resistance of native breed cattle and buffalo to the impacts of T. annulata infection is thus most likely to be driven by host genotype, rather than differences in the parasite population. Our results suggest that an improved understanding of the genetic factors that underpin disease resistance could help to ameliorate future economic loss due to TBP or tropical theileriosis

Primary vaginal Ewing's sarcoma or primitive neuroectodermal tumor in a 17-year-old woman: a case report

<p>Abstract</p> <p>Introduction</p> <p>Primary Ewing's sarcoma or primitive neuroectodermal tumor of the genital tract of women is uncommon. Rarer still is its occurrence in the vagina, with only five cases described so far. Out of these, only one case was confirmed using molecular analysis.</p> <p>Case presentation</p> <p>We present an extremely rare case of Ewing's sarcoma or primitive neuroectodermal tumor in a 17-year-old Indian girl. She presented with a vaginal mass that was initially diagnosed as a malignant round cell tumor. Immunohistochemistry showed diffuse positivity for vimentin, membranous positivity for MIC2, and positivity for BCL2 and FLI-1. On the other hand, she was negative for cytokeratin, epithelial membrane antigen, desmin, Myo D-1, myogenin and smooth muscle actin. A diagnosis of primitive neuroectodermal tumor was thus offered. Furthermore, a molecular analysis of our patient using reverse transcription-polymerase chain reaction technique showed positivity for t(11; 22) (q24; q12) (EWSR1-FLI1), thus confirming the diagnosis of a Ewing's sarcoma/primitive neuroectodermal tumor. Our patient was offered chemotherapy on Institutional protocol EFT 2001.</p> <p>Conclusion</p> <p>This is a rare case of primary vaginal Ewing's sarcoma or primitive neuroectodermal tumor, which was confirmed with molecular analysis, in the youngest patient known so far. This study reinforces the value of integrating morphological features with membranous MIC2 positivity, along with application of molecular techniques in objective identification of an Ewing's sarcoma or primitive neuroectodermal tumor at uncommon sites.</p

Investigation of Immune Biomarkers Using Subcutaneous Model of M. tuberculosis Infection in BALB/c Mice: A Preliminary Report

Evaluation and screening of vaccines against tuberculosis depends on development of proper cost effective disease models along with identification of different immune markers that can be used as surrogate endpoints of protection in preclinical and clinical studies. The objective of the present study was therefore evaluation of subcutaneous model of M.tuberculosis infection along with investigation of different immune biomarkers of tuberculosis infection in BALB/c mice. Groups of mice were infected subcutaneously with two different doses : high (2×106 CFU) and low doses (2×102 CFU) of M.tuberculosis and immune markers including humoral and cellular markers were evaluated 30 days post M.tuberculosis infections. Based on results, we found that high dose of subcutaneous infection produced chronic disease with significant (p<0.001) production of immune markers of infection like IFNγ, heat shock antigens (65, 71) and antibody titres against panel of M.tuberculosis antigens (ESAT-6, CFP-10, Ag85B, 45kDa, GroES, Hsp-16) all of which correlated with high bacterial burden in lungs and spleen. To conclude high dose of subcutaneous infection produces chronic TB infection in mice and can be used as convenient alternative to aerosol models in resource limited settings. Moreover assessment of immune markers namely mycobacterial antigens and antibodies can provide us valuable insights on modulation of immune response post infection. However further investigations along with optimization of study protocols are needed to justify the outcome of present study and establish such markers as surrogate endpoints of vaccine protection in preclinical and clinical studies in futur

Phytosome-conjugated carvacrol: A novel approach for improving growth performance, intestinal morphology and economics of production in Broiler Chicken

Essential oils are plant-derived aromatic volatile oils, and they contain bioactive compounds that have been shown to improve poultry nutrition. However, considering problems associated with the solubility and bioavailability of polyphenolic compounds, the study was planned to find out the effect of the novel feed-grade delivery system, phytosomes for conjugation of plant-derived polyphenolic compound carvacrol on the growth performance of broiler chickens. The experiment was conducted, on 240 broiler chicks for a period of 6 weeks. The chicks were divided into 4 groups having 4 replicates of 15 birds each. The birds in the control group (T0) offered a standard diet as per BIS (2007) specification. Group T1 received a standard diet supplemented with Bacitracin Methylene Disalicylate (BMD) antibiotic at standard dose and group T2 received a standard diet supplemented with carvacrol essential oil @100 mg/kg feed. Group T3 received a standard diet supplemented with phytosome-conjugated carvacrol essential oil (carvacrol @16.6%) @100 mg/kg feed. The performance of all the treatment groups was assessed with respect to the different performance parameters. The supplementation of phytosome-conjugated carvacrol essential oil (carvacrol @16.6%) @ 100 mg/kg feed was found beneficial in terms of growth performance, feed efficiency, and intestinal morphometry. In terms of economics of broiler production, the results revealed that the addition of phytosome- conjugated carvacrol essential oil and carvacrol essential oil in diets was found beneficial in reducing the cost of broiler production, thereby enhancing the margin of profit in broiler production and fetching higher net profit than the control group

PCR diagnosis of tick-borne pathogens in Maharashtra state, India indicates fitness cost associated with carrier infections is greater for crossbreed than native cattle breeds

Tick-borne pathogens (TBP) are responsible for significant economic losses to cattle production, globally. This is particularly true in countries like India where TBP constrain rearing of high yielding Bos taurus, as they show susceptibility to acute tick borne disease (TBD), most notably tropical theileriosis caused by Theileria annulata. This has led to a programme of cross breeding Bos taurus (Holstein-Friesian or Jersey) with native Bos indicus (numerous) breeds to generate cattle that are more resistant to disease. However, the cost to fitness of subclinical carrier infection in crossbreeds relative to native breeds is unknown, but could represent a significant hidden economic cost. In this study, a total of 1052 bovine blood samples, together with associated data on host type, sex and body score, were collected from apparently healthy animals in four different agro-climatic zones of Maharashtra state. Samples were screened by PCR for detection of five major TBPs: T. annulata, T. orientalis, B. bigemina, B. bovis and Anaplasma spp.. The results demonstrated that single and co-infection with TBP are common, and although differences in pathogen spp. prevalence across the climatic zones were detected, simplistic regression models predicted that host type, sex and location are all likely to impact on prevalence of TBP. In order to remove issues with autocorrelation between variables, a subset of the dataset was modelled to assess any impact of TBP infection on body score of crossbreed versus native breed cattle (breed type). The model showed significant association between infection with TBP (particularly apicomplexan parasites) and poorer body condition for crossbreed animals. These findings indicate potential cost of TBP carrier infection on crossbreed productivity. Thus, there is a case for development of strategies for targeted breeding to combine productivity traits with disease resistance, or to prevent transmission of TBP in India for economic benefit

Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials

Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting