- Vaccine development for human mastadenovirus. [Review]
- JTJ Thorac Dis 2018; 10(Suppl 19):S2280-S2294
- Human mastadenovirus (HAdVs) can cause a broad spectrum of diseases in both children and adults, including acute respiratory infection, gastroenteritis, epidemic keratoconjunctivitis. Populations sus...
Human mastadenovirus (HAdVs) can cause a broad spectrum of diseases in both children and adults, including acute respiratory infection, gastroenteritis, epidemic keratoconjunctivitis. Populations susceptible to adenovirus infection include children, immunocompromised patients and military recruits. To date, seven species (A-G) including more than 79 genotypes have been characterized, of which HAdV-B3, B4, B7 and the recently reemerged types 14 and 55 often lead to severe pneumonia. The live oral enteric-coated adenovirus type 4 and 7 vaccine, which was approved for use in US military personnel of 17 through 50 years of age, had been shown to be safe and highly effective in numerous clinical trials and by ongoing surveillance of febrile respiratory illness. However, there is currently no vaccine approved for general use in children and adults in any part of the world. This review article will summarize the epidemiological data available for adenovirus and the effectiveness of the adenovirus vaccine in the US military. It will also provide a brief overview of innovative vaccine strategies, animal models for vaccine evaluation, and issues regarding vaccine production.
- Treatment of disseminated histoplasmosis in advanced HIV using itraconazole with increased bioavailability. [Journal Article]
- IJInt J STD AIDS 2018 Aug 16; :956462418788129
- Disseminated histoplasmosis (DH), an endemic mycosis caused by the dimorphic fungus Histoplasma capsulatum, is a life-threatening infection in immunocompromised hosts. A patient with newly-diagnosed ...
Disseminated histoplasmosis (DH), an endemic mycosis caused by the dimorphic fungus Histoplasma capsulatum, is a life-threatening infection in immunocompromised hosts. A patient with newly-diagnosed human immunodeficiency virus (HIV) infection presented with a violaceous, raised, indurated, pruritic rash over the face, arms and trunk on a background of significant weight loss, fevers with sweats, diarrhoea and worsening shortness of breath. His CD4+ T cell count was 14 cells/µl (12%). Histoplasmosis was diagnosed from histology, fungal stain and culture of skin biopsy. In addition to DH, he was found to have Pneumocystis jiroveci pneumonia and multi-resistant Salmonella choleraesuis bacteraemia. He improved with treatment with antibiotics and was commenced on conventional itraconazole, orally. Antiretroviral therapy was commenced soon after. He was unable to achieve therapeutic levels with the conventional formulation due to gastrointestinal side effects and had ongoing fevers. A newer formulation of oral itraconazole with improved bioavailability was commenced. He achieved therapeutic drug levels and had no further intolerance. His fevers settled and the rash improved. He has now completed one year of treatment and is well. To our knowledge this is the first case of moderate DH in an advanced HIV patient treated successfully with oral itraconazole with improved bioavailability.
- WU polyomavirus detected in children with severe respiratory failure. [Journal Article]
- JCJ Clin Virol 2018 Aug 09; 107:25-28
- CONCLUSIONS: WUPyV was detected in children with severe respiratory failure independently or concurrently with other pathogens. WUPyV can be a pathogen for children with a history of preterm birth or an underlying disease.
- Fatal Neutropenic Enterocolitis Caused by Stenotrophomonas maltophilia: A Rare and Underrecognized Entity. [Journal Article]
- IMIntern Med 2018 Aug 10
- Although Stenotrophomonas maltophilia causes substantial morbidity and mortality in immunocompromised patients, it has not been described as a causal pathogen of neutropenic enterocolitis (NEC). We d...
Although Stenotrophomonas maltophilia causes substantial morbidity and mortality in immunocompromised patients, it has not been described as a causal pathogen of neutropenic enterocolitis (NEC). We describe the first case of histologically-confirmed NEC caused by S. maltophilia accompanied by bacteremia and pneumonia after salvage chemotherapy for acute myeloid leukemia relapse following a second hematopoietic stem cell transplantation. S. maltophilia should be included as a pathogenic organism of NEC in severely immunocompromised patients to prevent a delayed diagnosis, which carries a high risk of inappropriate antimicrobial selection and fatal outcome.
- Could this be whooping cough? [Journal Article]
- EMEmerg Med J 2018 Aug 10
- Whooping cough is a notifiable bacterial respiratory infection caused by Bordetella pertussis It may produce serious disease, especially in immunocompromised individuals and very young children. The ...
Whooping cough is a notifiable bacterial respiratory infection caused by Bordetella pertussis It may produce serious disease, especially in immunocompromised individuals and very young children. The number of reported cases increases in the winter months and the incidence peaks every 4-5 years. However, this periodicity is variable and is inconsistent between different geographical regions. Bordetella pertussis infection (BPI) may be underdiagnosed because of its seasonality and the fact that clinical features may be indistinguishable from other respiratory disorders in the paediatric ED setting. Treatment with antibiotics reduces the period of infectivity but may not shorten the illness. This review discusses the epidemiology of the disease, its clinical features, diagnosis, treatment and the disposition of patients with BPI.
- Invasive aspergillosis in patients admitted to the intensive care unit with severe influenza: a retrospective cohort study. [Journal Article]
- LRLancet Respir Med 2018 Jul 31
- CONCLUSIONS: Influenza was identified as an independent risk factor for invasive pulmonary aspergillosis and is associated with high mortality. Future studies should assess whether a faster diagnosis or antifungal prophylaxis could improve the outcome of influenza-associated aspergillosis.
- Adult invasive pneumococcal disease in the Republic of Korea: risk medical conditions and mortality stratified to age groups. [Journal Article]
- IJInt J Infect Dis 2018 Jul 25
- CONCLUSIONS: This study suggests vaccine type IPD continues to have a substantial burden among older adults in the ROK, necessitating effective vaccination strategy for those at higher risks.
- CBLB Constrains Inactivated Vaccine-Induced CD8+ T Cell Responses and Immunity against Lethal Fungal Pneumonia. [Journal Article]
- JIJ Immunol 2018 Jul 27
- Fungal infections in CD4+ T cell immunocompromised patients have risen sharply in recent years. Although vaccines offer a rational avenue to prevent infections, there are no licensed fungal vaccines ...
Fungal infections in CD4+ T cell immunocompromised patients have risen sharply in recent years. Although vaccines offer a rational avenue to prevent infections, there are no licensed fungal vaccines available. Inactivated vaccines are safer but less efficacious and require adjuvants that may undesirably bias toward poor protective immune responses. We hypothesized that reducing the TCR signaling threshold could potentiate antifungal CD8+ T cell responses and immunity to inactivated vaccine in the absence of CD4+ T cells. In this study, we show that CBLB, a negative regulator of TCR signaling, suppresses CD8+ T cells in response to inactivated fungal vaccination in a mouse model of CD4+ T cell lymphopenia. Conversely, Cblb deficiency enhanced both the type 1 (e.g., IFN-γ) and type 17 (IL-17A) CD8+ T cell responses to inactivated fungal vaccines and augmented vaccine immunity to lethal fungal pneumonia. Furthermore, we show that immunization with live or inactivated vaccine yeast did not cause detectable pathologic condition in Cblb-/- mice. Augmented CD8+ T cell responses in the absence of CBLB also did not lead to terminal differentiation or adversely affect the expression of transcription factors T-bet, Eomes, and RORγt. Additionally, our adoptive transfer experiments showed that CBLB impedes the effector CD8+ T cell responses in a cell-intrinsic manner. Finally, we showed that ablation of Cblb overcomes the requirement of HIF-1α for expansion of CD8+ T cells upon vaccination. Thus, adjuvants that target CBLB may augment inactivated vaccines and immunity against systemic fungal infections in vulnerable patients.
- Cryptococcus neoformans empyema in a patient receiving ibrutinib for diffuse large B-cell lymphoma and a review of the literature. [Journal Article]
- BCBMJ Case Rep 2018 Jul 18; 2018
- We report a case of Cryptococcus neoformans pulmonary infection complicated by empyema in a 79-year-old man with diffuse large B-cell lymphoma treated with R-CHOP and ibrutinib. A literature review i...
We report a case of Cryptococcus neoformans pulmonary infection complicated by empyema in a 79-year-old man with diffuse large B-cell lymphoma treated with R-CHOP and ibrutinib. A literature review identified 25 cases of cryptococcal pleural disease published since 1980. Most cases were caused by the C. neoformans species in immunocompromised hosts with an exudative pleural effusion and lymphocyte-predominant infiltrate. The cryptococcal antigen test was often positive when pleural fluid and serum were tested. The outcome was favourable in most cases with antifungal therapy and either thoracocentesis or surgical resection. We also identified 40 cases of opportunistic infections, most commonly aspergillosis, cryptococcosis and Pneumocystis jirovecii pneumonia, in patients treated with ibrutinib. In vitro studies indicate Bruton tyrosine kinase inhibition impairs phagocyte function and offer a mechanism for the apparent association between ibrutinib and invasive fungal infections.
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- Severe herpes simplex virus pneumonia in an elderly, immunocompetent patient. [Journal Article]
- BCBMJ Case Rep 2018 Jul 18; 2018
- Although not common, herpes simplex virus (HSV) pneumonia can occur in immunocompromised patients. However, HSV pneumonia in immunocompetent hosts is very rare. The authors encountered a very rare ca...
Although not common, herpes simplex virus (HSV) pneumonia can occur in immunocompromised patients. However, HSV pneumonia in immunocompetent hosts is very rare. The authors encountered a very rare case of severe HSV pneumonia in an immunocompetent host. The patient was an 85-year-old Japanese woman who presented with severe intractable pneumonia refractory to empirical antimicrobial therapy. Furthermore, the causative microorganisms remained unknown. Therefore, cytological examination of bronchoalveolar lavage fluid and protected brush biopsy of the lower respiratory tract were performed, which indicated herpes virus-infected cells with nuclear inclusions; PCR assay was positive for HSV DNA. Accordingly, the patient was diagnosed with HSV pneumonia. Her respiratory condition improved immediately after initiation of acyclovir monotherapy. In selected cases of intractable pneumonia refractory to standard antimicrobial therapy, the possibility of HSV pneumonia should be pursued.