Limited asymptomatic carriage of Pneumocystis jiroveci in human immunodeficiency virus-infected patients

Forty-seven bronchoalveolar lavage fluid samples from 16 human immunodeficiency virus (HIV)-infected patients were used to test the latency model of Pneumocystis infection in the human host. Identification of DNA sequence polymorphisms at 4 independent loci were used to genotype Pneumocystis jiroveci from the 35 samples that contained detectable P. jiroveci DNA. Eighteen of those 35 samples came from patients who did not have Pneumocystis pneumonia (PCP) and had confirmed alternative diagnoses. Seven patients had asymptomatic carriage of P. jiroveci over periods of less than or equal to9.5 months after an episode of PCP, and in all 7 cases, a change in genotype from that in the original episode of PCP was observed. The absence of P. jiroveci DNA in one-fourth of the 47 samples and the observed changes in genotype during asymptomatic carriage do not support the latency model of infection. Asymptomatic carriage in HIV-infected patients may play a role in transmission of P. jiroveci and may even supply a reservoir for future infections

In vitro and in vivo Expression of Interstitial Collagenase/MMP-1 by Human Mast Cells

Degradation of the extracellular matrix occurs under physiological and pathological conditions, thought to be principally mediated by a family of neutral proteolytic enzymes termed the matrix metalloproteinases (MMPs). The present study was initiated to determine whether mast cells have the ability to produce these proteases in diseased and normal human tissue. Immunohistochemistry and in situ hybridization was performed to localize interstitial collagenase protein and mRNA transcripts in diseased human tissue. The human mast cell line HMC-1 was cultured under serum free conditions, stimulated with phorbol mystrate acetate (PMA) and supernatants analyzed by Western blotting and zymography to determine the profile of secreted MMPs. The dog mast cell line BR, known to secrete gelatinolytic enzymes, was used in parallel studies. Total RNA was extracted and analyzed by RT-PCR for the expression of tissue inhibitors of MMP (TIMPs). Collagenase-1 protein and mRNA were expressed by tryptase and chymase positive human mast cells in all tissue analyzed. This proteinase wa also detected in the cytoplasm and conditioned media of HMC-1 cells. PMA induced gelatinolytic activity in both mast cell lines examined. TIMP-1 immunoreactivity was detected and TIMP-1, and-2 (but not TIMP-3) mRNA transcripts were amplified from HMC-1 cells. This is the first demonstration of the expression of collagenase-1 by human mast cells in both inflamed and normal tissues, and by a human mast cell line. MMPs secreted by these cells could contribute to the extensive matrix lysis characteristic of diseases such as rheumatoid arthritis and inflammatory ocular disorders. Alternatively collagenase-1 production by mast cells may play a critical role in cell invasion and migration into sites of inflammation

Peripheral blood responses to specific antigens and CD28 in sarcoidosis

SummaryBackgroundPotential antigens inducing sarcoid inflammation include mycobacterial and auto-antigens. Paradoxically, peripheral anergy to common recall antigens also occurs, possibly due to impaired dendritic cell or regulatory T-cell responses, or impaired T-cell co-stimulation. The purpose of this study was to compare peripheral blood responses of patients with sarcoidosis to candidate antigens, and examine CD28 T-cell co-stimulation.MethodsPeripheral blood mononuclear cell (PBMC) responses were examined from patients with sarcoidosis (n=16) and healthy control subjects (n=22) following PBMC stimulation with: anti-CD3/CD28 coated beads; Mycobacterium tuberculosis ESAT-6 and KatG peptides; vimentin and lysyl tRNA peptides; and common recall antigens, including cytomegalovirus (CMV) cell lysate as well as CMV, Epstein-Barr virus, influenza virus (CEF) peptides.ResultsESAT-6/KatG peptide stimulation induced greater numbers of IFN-γ producing T-cells, and elevated IL-2, IL-6 and TNF-α production in sarcoidosis compared to purified protein derivative (PPD)-negative healthy control subjects. PBMCs from patients with sarcoidosis showed reduced IFN-γ producing T-cells following stimulation with CMV lysate, CEF peptides and CD3/CD28 beads; and reduced IL-4 and TNF-α production following CD3/CD28 activation.ConclusionsPatients with sarcoidosis exhibit greater PBMC responses to M. tuberculosis antigens compared to PPD-negative controls, but reduced T-cell responses to common recall antigens. One contributing mechanism may be impairment of T-cell CD28 co-stimulation

A New Name for Pneumocystis from Humans and New Perspectives on the Host-Pathogen Relationship

The disease known as Pneumocystis carinii pneumonia (PCP) is a major cause of illness and death in persons with impaired immune systems. While the genus Pneumocystis has been known to science for nearly a century, understanding of its members remained rudimentary until DNA analysis showed its extensive diversity. Pneumocystis organisms from different host species have very different DNA sequences, indicating multiple species. In recognition of its genetic and functional distinctness, the organism that causes human PCP is now named Pneumocystis jiroveci Frenkel 1999. Changing the organism’s name does not preclude the use of the acronym PCP because it can be read “Pneumocystis pneumonia.” DNA varies in samples of P. jiroveci, a feature that allows reexamination of the relationships between host and pathogen. Instead of lifelong latency, transient colonization may be the rule

Excessive Exposure to Secondhand Tobacco Smoke among Hospitality Workers in Kyrgyzstan

The aim of this study was to assess the levels of secondhand smoke (SHS) exposure of men and women in public places in Kyrgyzstan. This cross-sectional study involved 10 bars and restaurants in Bishkek the capital city of Kyrgyzstan. Smoking was allowed in all establishments. Median (interquartile range) air nicotine concentrations were 6.82 (2.89, 8.86) μg/m3. Employees were asked about their smoking history and exposure to SHS at work. Employees were exposed to SHS for mean (SD) 13.5 (3.6) hours a day and 5.8 (1.4) days a week. Women were exposed to more hours of SHS at work compared to men. Hospitality workers are exposed to excessive amounts of SHS from customers. Legislation to ban smoking in public places including bars and restaurants is urgently needed to protect workers and patrons from the harmful effects of SHS

Strain Typing Methods and Molecular Epidemiology of Pneumocystis Pneumonia

Several typing methods, with different strengths and weaknesses, are available for studies of Pneumocystis pneumonia

Neglected Diseases in the News: A Content Analysis of Recent International Media Coverage Focussing on Leishmaniasis and Trypanosomiasis

In recent years, there has been a flurry of activity to reverse the neglect that has characterised NTDs, mostly focussed on drug development. The drug gap may be explained by market failure, yet other forces also conspire to cause the neglect of NTDs. One problem is the low visibility of these diseases. By comparison, the high-profile “big three” infectious diseases of AIDS, tuberculosis, and malaria have received increased donor attention and funding with greater visibility. Efforts to remove the “neglect” from NTDs must involve raising their profile. This study, focussing on three of the most neglected diseases, aims to provide a context of the current media situation—the what, where, and why of NTD coverage—to support future advocacy work