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Molecular and clinical study on prevalence of feline herpesvirus type 1 and calicivirus in correlation with feline leukemia and immunodeficiency viruses.

January 23, 2015 By Manish Butte

Molecular and clinical study on prevalence of feline herpesvirus type 1 and calicivirus in correlation with feline leukemia and immunodeficiency viruses.

Vet Res Forum. 2014;5(4):255-61

Authors: Najafi H, Madadgar O, Jamshidi S, Ghalyanchi Langeroudi A, Darzi Lemraski M

Abstract
Upper respiratory tract diseases (URTD) are common clinical problem in cats worldwide. Feline calicivirus (FCV) and feline herpesvirus type 1 (FHV-1) are the main primary pathogens. Feline immunodeficiency virus (FIV) and Feline leukemia virus (FeLV) are also among the most common infectious diseases of cats which suppress the immunity. Oropharyngeal and conjunctival swabs and blood samples were taken from 16 cats with clinical signs of URTD and 26 clinically healthy cats. PCR and RT-PCR were used to detect FHV/FIV or FCV/FeLV infections, respectively. Feline calicivirus was detected in all cats with URTD and 87.00% and 93.00% of them were positive for FIV and FeLV, respectively. Feline herpesvirus rate of infection was 43.00% in sick cats. In clinically normal cats, prevalence rates of FCV and FHV were about 50.00%, but FIV and FeLV rates (42.00% and 65.00% respectively) were higher compared to other studies. Stomatitis was observed in 50.00% of cats with URTD. The main causative agent of corneal ulcers is FHV-1, but in 50.00% of cats with corneal ulcers, FCV was detected alone. It seems new variants of Caliciviruses are the main causative agents to attack uncommon tissues like cornea, although retroviral infections may be in the background of these various signs. The high retroviral prevalence may be due to existence of large population of stray cats. This is the first molecular study of FeLV and FCV in Iran and seems that FCV and FHV prevalence rates in FIV or FeLV infected cats is more than other non-infected ones.

PMID: 25610576 [PubMed]

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Clinical Characteristics of Adults with Chronic Rhinosinusitis and Specific Antibody Deficiency.

January 23, 2015 By Manish Butte

Clinical Characteristics of Adults with Chronic Rhinosinusitis and Specific Antibody Deficiency.

J Allergy Clin Immunol Pract. 2014 Nov 25;

Authors: Kashani S, Carr TF, Grammer LC, Schleimer RP, Hulse KE, Kato A, Kern RC, Conley DB, Chandra RK, Tan BK, Peters AT

Abstract
BACKGROUND: Specific antibody deficiency (SAD) involves a deficient response to a polysaccharide vaccine in the setting of normal immunoglobulin G (IgG) levels and chronic infections. Patients with chronic rhinosinusitis (CRS) are often evaluated for SAD. There are limited data that describe patients with CRS and SAD.
OBJECTIVE: The objective of this study was to better characterize the role of SAD in CRS.
METHODS: We reviewed electronic records of adults with CRS who were evaluated for immunodeficiency with quantitative Ig levels and pre- and postantibody titers to a pneumococcal polysaccharide vaccine (PPV).
RESULTS: Fourteen pneumococcal serotypes were determined in 239 subjects from 2002 to 2009. Of these subjects, 64 had adequate protective titers of 1.3 μg/mL or higher in 7 or more serotypes of the 14 serotypes checked; 56 (23%) had less than 7 protective titers post-PPV and were diagnosed with SAD; and 119 had an adequate response to the vaccine with 7 or more serotypes being higher than 1.3 μg/mL (>50% response) and were characterized as “responders.” Subjects with SAD received more antibiotic courses relative to responders in the 2 years after immunization (3.19 ± 2.64 vs 2.19 ± 2.24, P < .05). Of 56 subjects with SAD, 10 (17.9%) received Ig replacement therapy. Subjects who received Ig had fewer numbers of protective pneumococcal titers post-PPV and had more pneumonia (40.0%) versus subjects with SAD who did not receive Ig (10.9%).
CONCLUSIONS: Of the 239 patients with CRS with normal IgG levels evaluated for immunodeficiency, 56 (23.4%) had SAD. A majority of patients with SAD may not need Ig replacement; however, a subset of patients with SAD benefit from Ig replacement.

PMID: 25609325 [PubMed – as supplied by publisher]

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Clinical and mutational features of Vietnamese children with X-linked agammaglobulinemia.

January 23, 2015 By Manish Butte

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Clinical and mutational features of Vietnamese children with X-linked agammaglobulinemia.

BMC Pediatr. 2014;14:129

Authors: Vu QV, Wada T, Le HT, Le HT, Van Nguyen AT, Osamu O, Yachie A, Nguyen SN

Abstract
BACKGROUND: X-linked agammaglobulinemia (XLA) is a primary immune deficiency characterized by recurrent bacterial infections and profoundly depressed serum immunoglobulin levels and circulating mature B cells. It is caused by mutations of the Bruton tyrosine kinase (BTK) gene and is the most common form of inherited antibody deficiency. To our knowledge, this is the first report of XLA from Vietnam.
METHODS: We investigated the BTK gene mutations and clinical features of four unrelated Vietnamese children.
RESULTS: The mean ages at onset and at diagnosis were 2.5 and 8 years, respectively. All patients had a medical history of otitis media, pneumonia, and septicemia at the time of diagnosis. Other infections reported included sinusitis, bronchiectasis, arthritis, skin infections, meningitis, and recurrent diarrhea. We identified one previously reported mutation (c.441G >A) and three novel mutations: two frameshifts (c.1770delG and c.1742 delG), and one nonsense (c.1249A >T).
CONCLUSIONS: The delayed diagnosis may be attributable to insufficient awareness of this rare disease on the background of frequent infections even in the immunocompetent pediatric population in Vietnam. Our results further support the importance of molecular genetic testing in diagnosis of XLA.

PMID: 24885015 [PubMed – indexed for MEDLINE]

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Autoimmune manifestations in SCID due to IL7R mutations: Omenn syndrome and cytopenias.

January 23, 2015 By Manish Butte

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Autoimmune manifestations in SCID due to IL7R mutations: Omenn syndrome and cytopenias.

Hum Immunol. 2014 Jul;75(7):662-6

Authors: Zago CA, Jacob CM, de Albuquerque Diniz EM, Lovisolo SM, Zerbini MC, Dorna M, Watanabe L, Fernandes JF, Rocha V, Oliveira JB, Carneiro-Sampaio M

Abstract
B+NK+SCID (severe combined immunodeficiency) due to IL7Rα deficiency represents approximately 10% of American SCID cases. To better understand the spectrum of autoimmune disorders associated with IL7Rα deficiency, we describe two unrelated IL7Rα-deficient female SCID infants whose clinical picture was dominated by autoimmune manifestations: one with intrauterine Omenn syndrome (OS) and another with persistent thrombocytopenic purpura since 4months of age. The OS baby harbored a homozygous p.C118Y mutation in IL7R. She presented dense eosinophilic infiltrates in several organs, including pancarditis, which may have contributed to her death (on the 2nd day of life). B cells were observed in lymph nodes, spleen, bone marrow and thymus. The second patient harbored compound heterozygous p.C118Y and p.I121NfsX8 mutations. She underwent a successful unrelated cord blood transplant. In conclusion, early OS can be observed in patients with IL7R mutations, and autoimmune cytopenias could also complicate the clinical course of SCID babies with this type of defect.

PMID: 24759676 [PubMed – indexed for MEDLINE]

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C1 inhibitor deficiency: 2014 United Kingdom Consensus Document.

January 22, 2015 By Manish Butte

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C1 inhibitor deficiency: 2014 United Kingdom Consensus Document.

Clin Exp Immunol. 2015 Jan 20;

Authors: Longhurst HJ, Tarzi MD, Ashworth F, Bethune C, Cale C, Dempster J, Gompels M, Jolles S, Seneviratne S, Symons C, Price A, Edgar D

Abstract
C1 inhibitor deficiency is a rare disorder manifesting with recurrent attacks of disabling and potentially life-threatening angioedema. Here we present an updated 2014 United Kingdom consensus document for the management of C1 inhibitor-deficient patients, representing a joint venture between the United Kingdom Primary Immunodeficiency Network and Hereditary Angioedema UK. To develop the consensus, we assembled a multi-disciplinary steering group of clinicians, nurses and a patient representative. This steering group first met in 2012, developing a total of 48 recommendations across 11 themes. The statements were distributed to relevant clinicians and a representative group of patients to be scored for agreement on a Likert scale. All 48 statements achieved a high degree of consensus, indicating strong alignment of opinion. The recommendations have evolved significantly since the 2005 document, with particularly notable developments including an improved evidence base to guide dosing and indications for acute treatment, greater emphasis on home therapy for acute attacks and a strong focus on service organisation. This article is protected by copyright. All rights reserved.

PMID: 25605519 [PubMed – as supplied by publisher]

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A narrow repertoire of transcriptional modules responsive to pyogenic bacteria is impaired in patients carrying loss-of-function mutations in MYD88 or IRAK4.

January 22, 2015 By Manish Butte

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A narrow repertoire of transcriptional modules responsive to pyogenic bacteria is impaired in patients carrying loss-of-function mutations in MYD88 or IRAK4.

Nat Immunol. 2014 Dec;15(12):1134-42

Authors: Alsina L, Israelsson E, Altman MC, Dang KK, Ghandil P, Israel L, von Bernuth H, Baldwin N, Qin H, Jin Z, Banchereau R, Anguiano E, Ionan A, Abel L, Puel A, Picard C, Pascual V, Casanova JL, Chaussabel D

Abstract
Loss of function of the kinase IRAK4 or the adaptor MyD88 in humans interrupts a pathway critical for pathogen sensing and ignition of inflammation. However, patients with loss-of-function mutations in the genes encoding these factors are, unexpectedly, susceptible to only a limited range of pathogens. We employed a systems approach to investigate transcriptome responses following in vitro exposure of patients’ blood to agonists of Toll-like receptors (TLRs) and receptors for interleukin 1 (IL-1Rs) and to whole pathogens. Responses to purified agonists were globally abolished, but variable residual responses were present following exposure to whole pathogens. Further delineation of the latter responses identified a narrow repertoire of transcriptional programs affected by loss of MyD88 function or IRAK4 function. Our work introduces the use of a systems approach for the global assessment of innate immune responses and the characterization of human primary immunodeficiencies.

PMID: 25344726 [PubMed – indexed for MEDLINE]

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Decreased immunoglobulin G levels after living-donor liver transplantation is a risk factor for bacterial infection and sepsis.

January 22, 2015 By Manish Butte

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Decreased immunoglobulin G levels after living-donor liver transplantation is a risk factor for bacterial infection and sepsis.

Transpl Infect Dis. 2014 Apr;16(2):225-31

Authors: Yoshizumi T, Shirabe K, Ikegami T, Yamashita N, Mano Y, Yoshiya S, Matono R, Harimoto N, Uchiyama H, Toshima T, Maehara Y

Abstract
BACKGROUND: Several studies have suggested an association between post-transplant immunoglobulin (Ig) levels and the development of infection in solid organ transplantation. We therefore conducted exploratory analyses of potential factors associated with bacterial infection/sepsis after living-donor liver transplantation (LDLT).
METHODS: Blood samples from 177 recipients who received primary LDLT between September 1999 and November 2011 were available for study. Hypogammaglobulinemia was defined as having at least 1 IgG level <650 mg/dL within 7 days after LDLT. Risk factors for developing post-transplant bacterial infection and sepsis within 3 months after LDLT were analyzed.
RESULTS: Fifty (28.2%) recipients experienced bacterial infection within 3 months of LDLT. Eighty-four (47.5%) recipients had hypogammaglobulinemia, although no recipients had hypogammaglobulinemia before LDLT. Hypogammaglobulinemia, undergoing hepaticojejunostomy, and portal pressure at closure >15 mmHg were independent risk factors for developing bacterial infection within 3 months of LDLT (P < 0.0001 P = 0.0008, and P = 0.011, respectively). The odds ratio (OR) and confidence interval (CI) for hypogammaglobulinemia were 4.79 and 2.27-10.7, respectively. Twenty-four (13.6%) recipients developed bacterial sepsis within 3 months. Hypogammaglobulinemia, operative time >14 h, model for end-stage liver disease score >15, and no mycophenolate mofetil use were independent risk factors for developing bacterial sepsis (P = 0.009, P = 0.001, P = 0.003, and P = 0.005, respectively). The OR and CI for hypogammaglobulinemia were 3.83 and 1.38-12.0, respectively.
CONCLUSIONS: Hypogammaglobulinemia within 7 days of LDLT was a significant risk factor for post-transplant bacterial infection and sepsis.

PMID: 24593220 [PubMed – indexed for MEDLINE]

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Chronic infections of the small intestine.

January 21, 2015 By Manish Butte

Chronic infections of the small intestine.

Curr Opin Gastroenterol. 2015 Jan 16;

Authors: Bourke B, Hussey S

Abstract
PURPOSE OF REVIEW: Chronic infections of the small intestine cause significant morbidity and mortality globally. This review focuses on the recent advances in the field of our understanding of selected intestinal infections.
RECENT FINDINGS: Primary and secondary immunodeficiency increase the susceptibility to many chronic intestinal infections. Endoscopy and intestinal biopsies are central to establishing a diagnosis of these conditions. Tuberculosis (TB) remains a major global health challenge. Emerging therapeutic agents to counteract multidrug-resistant strains have shown clinical efficacy, but concerns regarding mortality remain. PCR-based diagnostic TB tests have the potential to reduce diagnostic delays, but remain to be validated for intestinal infections. Adjunctive diagnostic imaging modalities can differentiate infections from Crohn’s disease with increasing accuracy. Whipple’s disease remains rare, but there have been substantial advances in our understanding of the causative organism Tropheryma whipplei. Extended treatment with broad-spectrum antibiotics is effective in most cases. The narrow therapeutic window and limited armamentarium for treating invasive filamentous fungal infections contribute to their significant morbidity and high rates of mortality.
SUMMARY: The speed and accuracy of diagnosing chronic intestinal infections have improved with recent imaging and laboratory methodologies. Significant research opportunities remain for clinicians and scientists to improve the diagnostic accuracy and clinical outcomes of chronic intestinal infections.

PMID: 25603404 [PubMed – as supplied by publisher]

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Analysis of specific IgG titers against tick-borne encephalitis in patients with primary antibody deficiency under immunoglobulin substitution therapy: impact of plasma donor origin.

January 21, 2015 By Manish Butte

Analysis of specific IgG titers against tick-borne encephalitis in patients with primary antibody deficiency under immunoglobulin substitution therapy: impact of plasma donor origin.

Front Immunol. 2014;5:675

Authors: Goldacker S, Witte T, Huzly D, Schlesier M, Peter HH, Warnatz K

Abstract
Immunoglobulin (Ig) replacement therapy is effective in reducing infections in patients with primary antibody deficiency (PAD). Diversity of specific antibodies is achieved by pooling plasma from over 1000 donors usually of a given geographic region. However, there is no agreement with regard to an optimal vaccination schedule for plasma donors. Especially for tick-borne encephalitis (TBE), regional vaccination rates differ widely among populations due to the epidemiology of the disease. We analyzed specific antibody titers against TBE in comparison to total IgG levels in 162 serum samples collected from 110 PAD patients substituted with polyvalent intravenous IgG or subcutaneous IgG. Some patients received different IgG products over time leading to a total number of 122 different patient-IgG product combinations. Positive TBE-specific IgG levels were detected in 35 cases when measured by standard ELISA and could be confirmed by demonstration of neutralizing antibodies in 31 cases. The detection of specific antibody levels correlated with the geographic origin of the IgG preparations. No titers were detectable in patients substituted with IgG products from North-American donors, whereas variable degrees of anti-TBE titers were observed in patients receiving products from different European countries. We suggest considering the patients’ personal risk for TBE when selecting an appropriate Ig preparation. These data support regional plasma donation in order to address the diverse local infection profile.

PMID: 25601868 [PubMed]

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Subcutaneous abscess due to the basidiomycete Phellinus mori in a patient with chronic granulomatous disease.

January 21, 2015 By Manish Butte

Subcutaneous abscess due to the basidiomycete Phellinus mori in a patient with chronic granulomatous disease.

Infection. 2015 Jan 20;

Authors: Shigemura T, Nakazawa Y, Amano Y, Sudo A, Watanabe M, Kobayashi M, Kobayashi N, Koike K, Agematsu K, Nishimura K

Abstract
Chronic granulomatous disease (CGD), a primary immunodeficiency caused by impaired phagocyte killing of intracellular pathogens, is characterized by recurrent, life-threatening, bacterial and fungal infections. As a result of improvements in microbiologic culture and identification techniques, a number of unique filamentous fungi have been reported as significant pathogens in patients with CGD. We report a case of subcutaneous basidiomycete Phellinus mori infection in a patient with CGD. To the best of our knowledge, this is the first reported case of human infection by this fungus. The causative fungus was identified on the basis of its morphological characteristics and nucleotide sequence on the internal transcribed spacer region of the ribosomal RNA gene. This is the fifth case report of filamentous basidiomycetes infecting a patient with CGD; all of these cases have been caused by Phellinus species. We highlight the importance of recognizing filamentous basidiomycetes Phellinus species as possible agents of non-Aspergillus fungal infections in patients with CGD.

PMID: 25600930 [PubMed – as supplied by publisher]

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