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Sample records for pneumocystis

  1. Pneumocystis

    PubMed Central

    Gigliotti, Francis; Limper, Andrew H.; Wright, Terry

    2014-01-01

    Since its initial misidentification as a trypanosome some 100 years ago, Pneumocystis has remained recalcitrant to study. Although we have learned much, we still do not have definitive answers to such basic questions as, where is the reservoir of infection, how does Pneumocystis reproduce, what is the mechanism of infection, and are there true species of Pneumocystis? The goal of this review is to provide the reader the most up to date information available about the biology of Pneumocystis and the disease it produces. PMID:25367973

  2. Pneumocystis Pneumonia (For Parents)

    MedlinePlus

    ... Feeding Your 1- to 2-Year-Old Pneumocystis Pneumonia KidsHealth > For Parents > Pneumocystis Pneumonia A A A What's in this article? About PCP Diagnosing PCP Treating PCP Pneumocystis pneumonia (PCP) is an infection caused by Pneumocystis jiroveci , ...

  3. Pneumocystis pneumonia.

    PubMed

    Gilroy, Shelley A; Bennett, Nicholas J

    2011-12-01

    Pneumocystis (carinii) jiroveci pneumonia can occur in immunocompromised individuals, especially hematopoietic stem and solid organ transplant recipients and those receiving immunosuppressive agents, and is the most common opportunistic infection in persons with advanced human immunodeficiency virus (HIV) infection. The Pneumocystis genus was initially mistaken as a trypanosome and later as a protozoan. Genetic analysis identified the organism as a unicellular fungus. Pneumocystis jiroveci is the species responsible for human infections. A slow indolent time course with symptoms of pneumonia progressing over weeks to months is characteristic in HIV-infected patients. Fulminant respiratory failure associated with fever and dry cough is typical in non-HIV-infected patients. Definitive diagnosis relies on histopathological testing of sputum, induced or sampled by fiberoptic bronchoscopy with bronchoalveolar lavage. The first-line drug for treatment and prevention is trimethoprim-sulfamethoxazole.

  4. Pneumocystis pneumonia: an update.

    PubMed

    Sritangratanakul, Sureeporn; Nuchprayoon, Surang; Nuchprayoon, Issarang

    2004-09-01

    Pneumocystis pneumonia is a major cause of illness and death in immunocompromised hosts. The numbers of pneumocystis pneumonia cases in Thailand have increased each year from 1992 to 2000 and peaked in 2000 at 6,255 cases. The microbe that causes pneumocystis pneumonia in humans is called Pneumocystis jirovecii. Pneumocystis sp. was discovered nearly a century ago, but the knowledge of Pneumocystis sp. remained poorly understood, until the molecular biology techniques help scientists verify it fungus nature. In the past, Pneumocystis sp. was misclassified as protozoan due to its morphologic features. Later, it was reclassified as fungus due to DNA analysis. Cotrimaxazole, the combination of trimethoprim-sulfamethoxazole, is the drug of choice for treatment and prophylaxis of pneumocystis pneumonia. However, increasing evidence of mutations in the enzyme dihydropteroate synthase (DHPS), the target of sulfa drugs represent emergence of sulfa resistance.

  5. Pneumocystis jiroveci pneumonia

    MedlinePlus

    ... medlineplus.gov/ency/article/000671.htm Pneumocystis jiroveci pneumonia To use the sharing features on this page, please enable JavaScript. Pneumocystis jiroveci pneumonia is a fungal infection of the lungs. The ...

  6. Pneumocystis infections: the iceberg?

    PubMed

    Dei-Cas, E

    2000-01-01

    Pneumocystis carinii pneumonia (PCP) is a well-recognized lung disease of immunocompromised patients, but the real impact of Pneumocystis infection in humans remains to be discovered. Pneumocystis represents probably one of the more frequent infectious agents faced by humans. Seroconversion revealed P. carinii primary infection in > 90% of infants and small children, but the infection source and the clinical or pathological changes associated with this first contact with the parasite remain unknown. Pneumocystis organisms are atypical microfungi able to attach specifically to type-I alveolar epithelial cells, and to proliferate, provoking severe pneumonitis. A deep impairment of cell-mediated immunity associated with changes in pulmonary surfactant make it possible for Pneumocystis to grow within the host. Alveolar type-II cell hypertrophy, macrophagic infiltrate and intra-alveolar foamy eosinophilic material are the most typical changes. CD4+ T-lymphocytes and interferon play a major role in host defense against P. carinii. Alveolar macrophages phagocytose P. carinii via the macrophage-mannose receptor and produce reactive free-radicals and nitric oxide under Pneumocystis stimulation. Furthermore, PCP is associated with an early decrease of surfactant phospholipids, increased hydrophilic surfactant protein (SP) levels and decreased hydrophobic SPs. Normal surfactant improves PCP, and consistently, it inhibits the parasite growth. New detection tools have revealed that hospitalized patients can be latently infected with Pneumocystis and that immunocompetent hosts develop transient Pneumocystis infections. Pneumocystis organisms circulate in human populations, being able to infect hosts with diverse susceptibility levels. In fact, airborne Pneumocystis infection can display a large spectrum of clinical presentations and most likely, we recognize at present only the tip of the iceberg.

  7. Clinical and translational research in pneumocystis and pneumocystis pneumonia.

    PubMed

    Huang, L

    2011-02-01

    Pneumocystis pneumonia (PcP) remains a significant cause of morbidity and mortality in immunocompromised persons, especially those with human immunodeficiency virus (HIV) infection. Pneumocystis colonization is described increasingly in a wide range of immunocompromised and immunocompetent populations and associations between Pneumocystis colonization and significant pulmonary diseases such as chronic obstructive pulmonary disease (COPD) have emerged. This mini-review summarizes recent advances in our clinical understanding of Pneumocystis and PcP, describes ongoing areas of clinical and translational research, and offers recommendations for future clinical research from researchers participating in the "First centenary of the Pneumocystis discovery".

  8. Pneumocystis Jiroveci Pneumonia

    DTIC Science & Technology

    2008-10-01

    Pneumocystis jiroveci (formerly P. carinii) Pneumonia (PJP). A 60 year old HIV+ male with a CD4+ count of 144 cells/mm3 complaining of cough ...case the lucency is too wide and irregular for a Mach band. Clinically, patients with PJP demonstrate nonspecific complaints. Fever, cough

  9. Current understanding of Pneumocystis immunology

    PubMed Central

    Kelly, Michelle N; Shellito, Judd E

    2013-01-01

    Pneumocystis jirovecii is the opportunistic fungal organism that causes Pneumocystis pneumonia (PCP) in humans. Similar to other opportunistic pathogens, Pneumocystis causes disease in individuals who are immunocompromised, particularly those infected with HIV. PCP remains the most common opportunistic infection in patients with AIDS. Incidence has decreased greatly with the advent of HAART. However, an increase in the non-HIV immunocompromised population, noncompliance with current treatments, emergence of drug-resistant strains and rise in HIV+ cases in developing countries makes Pneumocystis a pathogen of continued interest and a public health threat. A great deal of research interest has addressed therapeutic interventions to boost waning immunity in the host to prevent or treat PCP. This article focuses on research conducted during the previous 5 years regarding the host immune response to Pneumocystis, including innate, cell-mediated and humoral immunity, and associated immunotherapies tested against PCP. PMID:20020829

  10. S-adenosylmethionine and Pneumocystis.

    PubMed

    Merali, Salim; Clarkson, Allen Boykin

    2004-08-15

    Pneumocystis is a parasitic fungus causing pneumonia in immunosuppressed mammals and S-adenosylmethionine a key intermediary metabolite for all cells. Other than a species of Rickettsia bacteria and an aberrant strain of the protozoan Amoeba proteus, Pneumocystis is the only cell known unable to synthesize AdoMet; it must extract this key compound from its host. This was discovered using a culture system and confirmed by observing depletion of AdoMet in the plasma of infected animals. Depletion also occurs in patients with Pneumocystis pneumonia (PcP), a phenomenon suggested as a basis for a method for diagnosis and evaluation of response to therapy. Preliminary data indicate that deliberate reduction of host lung AdoMet by nicotine treatment is therapeutic in the rat model of Pneumocystis pneumonia.

  11. Pneumocystis melanins confer enhanced organism viability.

    PubMed

    Icenhour, Crystal R; Kottom, Theodore J; Limper, Andrew H

    2006-06-01

    Pneumocystis continues to represent an important opportunistic fungal pathogen of those with compromised immunity. Thus, it is crucial to identify factors that affect its viability and pathogenicity. We previously reported the first identification of melanins in Pneumocystis. In the present study, we sought to further characterize these components and define the function for these melanins. Melanins extracted from Pneumocystis and melanized Pneumocystis cells were analyzed by electron spin resonance spectroscopy, revealing spectra consistent with melanins from other fungi. Immunofluorescence assays using anti-melanin monoclonal antibodies showed that melanins are widely present across Pneumocystis host species, including mouse-, ferret-, and human-derived Pneumocystis organisms, as well as Pneumocystis carinii derived from rat. Using immunoelectron microscopy, melanins were found to localize to the cell wall and cytoplasm of P. carinii cysts, as well as to intracystic bodies within mature cysts. Next, the role of melanins on the maintenance of Pneumocystis viability was determined by using quantitative reverse transcription-PCR measurement of the heat shock protein mRNA under adverse environmental conditions. Using a new method to promote the melanization of Pneumocystis, we observed that strongly melanized Pneumocystis retained viability to a greater degree when exposed to UV irradiation or desiccation compared to less-pigmented organisms. These studies support our previous identification of Pneumocystis melanins across the genus, further characterize these Pneumocystis components, and demonstrate that melanins protect Pneumocystis from environmental stressors.

  12. Pneumocystis pneumonia associated with human immunodeficiency virus.

    PubMed

    Miller, Robert F; Huang, Laurence; Walzer, Peter D

    2013-06-01

    Pneumocystis pneumonia (PCP) is caused by the yeastlike fungus Pneumocystis. Despite the widespread availability of specific anti-Pneumocystis prophylaxis and of combination antiretroviral therapy (ART), PCP remains a common AIDS-defining presentation. PCP is increasingly recognized among persons living in Africa. Pneumocystis cannot be cultured and bronchoalveolar lavage is the gold standard diagnostic test to diagnose PCP. Use of adjunctive biomarkers for diagnosis requires further evaluation. Trimethoprim-sulfamethoxazole remains the preferred first-line treatment regimen. In the era of ART, mortality from PCP is approximately 10% to 12%. The optimal time to start ART in a patient with PCP remains uncertain.

  13. Characterizing Pneumocystis in the Lungs of Bats: Understanding Pneumocystis Evolution and the Spread of Pneumocystis Organisms in Mammal Populations

    PubMed Central

    Akbar, Haroon; Pinçon, Claire; Aliouat-Denis, Cecile-Marie; Derouiche, Sandra; Taylor, Maria-Lucia; Pottier, Muriel; Carreto-Binaghi, Laura-Helena; González-González, Antonio E.; Courpon, Aurore; Barriel, Véronique; Guillot, Jacques; Chabé, Magali; Suarez-Alvarez, Roberto O.; Aliouat, El Moukhtar; Dei-Cas, Eduardo

    2012-01-01

    Bats belong to a wide variety of species and occupy diversified habitats, from cities to the countryside. Their different diets (i.e., nectarivore, frugivore, insectivore, hematophage) lead Chiroptera to colonize a range of ecological niches. These flying mammals exert an undisputable impact on both ecosystems and circulation of pathogens that they harbor. Pneumocystis species are recognized as major opportunistic fungal pathogens which cause life-threatening pneumonia in severely immunocompromised or weakened mammals. Pneumocystis consists of a heterogeneous group of highly adapted host-specific fungal parasites that colonize a wide range of mammalian hosts. In the present study, 216 lungs of 19 bat species, sampled from diverse biotopes in the New and Old Worlds, were examined. Each bat species may be harboring a specific Pneumocystis species. We report 32.9% of Pneumocystis carriage in wild bats (41.9% in Microchiroptera). Ecological and behavioral factors (elevation, crowding, migration) seemed to influence the Pneumocystis carriage. This study suggests that Pneumocystis-host association may yield much information on Pneumocystis transmission, phylogeny, and biology in mammals. Moreover, the link between genetic variability of Pneumocystis isolated from populations of the same bat species and their geographic area could be exploited in terms of phylogeography. PMID:23001662

  14. HIV-associated Pneumocystis pneumonia.

    PubMed

    Huang, Laurence; Cattamanchi, Adithya; Davis, J Lucian; den Boon, Saskia; Kovacs, Joseph; Meshnick, Steven; Miller, Robert F; Walzer, Peter D; Worodria, William; Masur, Henry

    2011-06-01

    During the past 30 years, major advances have been made in our understanding of HIV/AIDS and Pneumocystis pneumonia (PCP), but significant gaps remain. Pneumocystis is classified as a fungus and is host-species specific, but an understanding of its reservoir, mode of transmission, and pathogenesis is incomplete. PCP remains a frequent AIDS-defining diagnosis and is a frequent opportunistic pneumonia in the United States and in Europe, but comparable epidemiologic data from other areas of the world that are burdened with HIV/AIDS are limited. Pneumocystis cannot be cultured, and bronchoscopy with bronchoalveolar lavage is the gold standard procedure to diagnose PCP, but noninvasive diagnostic tests and biomarkers show promise that must be validated. Trimethoprim-sulfamethoxazole is the recommended first-line treatment and prophylaxis regimen, but putative trimethoprim-sulfamethoxazole drug resistance is an emerging concern. The International HIV-associated Opportunistic Pneumonias (IHOP) study was established to address these knowledge gaps. This review describes recent advances in the pathogenesis, epidemiology, diagnosis, and management of HIV-associated PCP and ongoing areas of clinical and translational research that are part of the IHOP study and the Longitudinal Studies of HIV-associated Lung Infections and Complications (Lung HIV).

  15. Pneumocystis carinii, an opportunist in immunocompromised patients.

    PubMed Central

    Bartlett, M S; Smith, J W

    1991-01-01

    Pneumocystis carinii has been recognized as a cause of pneumonia in immunocompromised patients for over 40 years. Until the 1980s, Pneumocystis pneumonia (pneumocystosis) was most often seen in patients undergoing chemotherapy for malignancy or transplantation. Infection could be prevented by trimethoprim-sulfamethoxazole prophylaxis; thus, it was an uncommon clinical problem. With the onset of the AIDS epidemic, Pneumocystis pneumonia has become a major problem in the United States because it develops in approximately 80% of patients with AIDS and because almost two-thirds of patients have adverse reactions to anti-Pneumocystis drugs. Thus, physicians and laboratories in any community may be called upon to diagnose and provide care for patients with Pneumocystis pneumonia. The classification of the organism is currently controversial, but it is either a protozoan or a fungus. P. carinii appears to be acquired during childhood by inhalation and does not cause clinical disease in healthy persons but remains latent. If the person becomes immunosuppressed, the latent infection may become activated and lead to clinical disease. Damage of type I pneumocytes by Pneumocystis organisms leads to the foamy alveolar exudate which is characteristic of the disease. Diagnosis is established by morphologic demonstration of Pneumocystis organisms in material from the lungs. Current efforts to find better anti-Pneumocystis drugs should provide more effective therapy and prophylaxis. Images PMID:2070342

  16. FDG PET Imaging in Pneumocystis Pneumonia.

    PubMed

    Kono, Masanori; Yamashita, Hiroyuki; Kubota, Kazuo; Kano, Toshikazu; Mimori, Akio

    2015-08-01

    A 69-year-old woman with rheumatoid arthritis and pleuritis presented with dyspnea. On admission, she was afebrile and had an oxygen saturation of 97% on ambient air. Chest radiography and CT revealed only subtle ground-glass opacities. However, FDG PET revealed pathological uptake in both lungs. A diagnosis of Pneumocystis pneumonia was made based on a positive β-D-glucan assay and polymerase chain reaction amplification of Pneumocystis jirovecii from the sputum. Posttreatment FDG PET revealed resolution of the previously noted uptake. This case illustrates that FDG PET can be used to diagnose Pneumocystis pneumonia when the CT findings are equivocal.

  17. Pneumocystis pneumonia: importance of gallium scan for early diagnosis and description of a new immunoperoxidase technique to demonstrate Pneumocystis carinii

    SciTech Connect

    Levin, M.; McLeod, R.; Young, Q.; Abrahams, C.; Chambliss, M.; Walzer, P.; Kabins, S.A.

    1983-07-01

    Pneumocystis pneumonia presented in a homosexual with fever, a normal chest radiograph, and pulmonary gallium uptake. Bronchial washings yielded Mycobaterium tuberculosis, but despite antituberculosis therapy he remained febrile, and gallium uptake in the lung increased. Subsequently, silver stain of transbronchial lung biopsy obtained 2 months earlier at the time that tuberculosis was diagnosed showed many Pneumocystis cysts in alveolar spaces. In contrast to Pneumocystis cysts in infected lung tissue from other humans, our patient's Pneumocystis cysts reacted more avidly with antiserum to rat Pneumocystis than with antiserum to human pneumocystis, raising the possibility that organisms that infect humans may have varied surface antigenic properties.

  18. Molecular diagnosis of Pneumocystis pneumonia in dogs.

    PubMed

    Danesi, Patrizia; Ravagnan, Silvia; Johnson, Lynelle R; Furlanello, Tommaso; Milani, Adelaide; Martin, Patricia; Boyd, Susan; Best, Matthew; Galgut, Bradley; Irwin, Peter; Canfield, Paul J; Krockenberger, Mark B; Halliday, Catriona; Meyer, Wieland; Malik, Richard

    2017-02-23

    Pneumocystis pneumonia (PCP) is a life-threatening fungal disease that can occur in dogs. The aim of this study was to provide a preliminary genetic characterisation of Pneumocystis carinii f.sp.'canis' (P. canis) in dogs and thereby develop a reliable molecular protocol to definitively diagnose canine PCP. We investigated P. canis in a variety of lung specimens from dogs with confirmed or strongly suspected PCP (Group 1, n = 16), dogs with non-PCP lower respiratory tract problems (Group 2, n = 65) and dogs not suspected of having PCP or other lower respiratory diseases (Group 3, n = 11). Presence of Pneumocystis DNA was determined by nested PCR of the large and small mitochondrial subunit rRNA loci and by a real-time quantitative polymerase chain reaction (qPCR) assay developed using a new set of primers. Molecular results were correlated with the presence of Pneumocystis morphotypes detected in cytological/histological preparations. Pneumocystis DNA was amplified from 13/16 PCP-suspected dogs (Group 1) and from 4/76 dogs of control Groups 2 and 3 (combined). The latter four dogs were thought to have been colonized by P. canis. Comparison of CT values in 'infected' versus 'colonized' dogs was consistent with this notion, with a distinct difference in molecular burden between groups (CT ≤ 26 versus CT range (26 Pneumocystis species, thereby confirming the accuracy of qPCR amplicon for Pneumocystis in dogs. Using qPCR, Pneumocystis DNA can be detected in specimens from the respiratory tract and a CT value can be interpreted to distinguish infection versus colonization.

  19. [Pneumocystis jirovecii: what does this mean?].

    PubMed

    Herrag, M; Elfassy Fihry, M T; Alaoui Yazidi, A

    2010-12-01

    Pneumocystis was discovered nearly a century ago. It causes fatal pneumonia in immunocompromised individuals, especially in AIDS patients. Knowledge of the different species remained rudimentary until the mid-eighties when DNA analysis revealed its extensive diversity. In fact, it is no longer considered as a zoonosis. Pneumocystis organisms derived from different hosts have very different DNA sequences, indicating multiple species. Due to the genetic and functional disparities, the organism that causes human PCP is now named Pneumocystis jirovecii/Frenkel, 1999. We continue to call Pneumocystis carinii the species found in rats. This will allow for a single international language and avoid confusion. Changing the organism's name does not preclude the use of the well-known acronym PCP because it can also be read "PneumoCystis Pneumonia." The DNA sequences and genotypage have shown that variations exist among samples of P. jiroveci. Molecular biology is helpful in the study of the mechanisms of transmission, which can only occur in the same host and the different resistances as well as providing a better understanding of the relationship between host and pathogen. P. jirovecii pneumonia in immunosuppressed patients was previously thought to result from the reactivation of a latent infection acquired in early childhood. However, today, it is believed to result from a new infection from an exogenous source.

  20. Pneumocystis carinii pneumonia: the status of Pneumocystis biochemistry.

    PubMed

    Kaneshiro, E S

    1998-01-01

    Pneumocystis carinii pneumonia remains a prevalent opportunistic disease among immunocompromised individuals. Although aggressive prophylaxis has decreased the number of acute P. carinii pneumonia cases, many patients cannot tolerate the available drugs, and experience recurrence of the infection, which can be fatal. It is now generally agreed that the organism should be placed with the fungi, but the identification of extant fungal species representing its closest kins, remains debated. Most recent data indicate that P. carinii represents a diverse group of organisms. Since the lack of methods for the continuous subcultivation of this organism hampered P. carinii research, molecular cloning and nucleotide sequencing approaches led the way for understanding the biochemical nature of this pathogen. However, within the last 5 years, the development of improved protocols for isolating and purifying viable organisms from infected mammalian host lungs has enabled direct biochemical and metabolism studies on the organism. The protein moiety of the major high mol. wt surface antigen, represented by numerous isoforms, is encoded by different genes. These proteins are post-transcriptionally modified by carbohydrates and lipids. The organism has the shikimic acid pathway that leads to the formation of compounds which mammals cannot synthesise (e.g., folic acid), hence drugs that inhibit these pathways are effective against the pathogen. Ornithine decarboxylase has now been detected; rapid and complete depletion of polyamines occurs in response to difluoromethylornithine (DFMO). Instead of ergosterol (the major sterol of higher fungi), P. carinii synthesises distinct delta7, C-24-alkylated sterols. An unusual C32 sterol, pneumocysterol, has been identified in human-derived P. carinii. Another signature lipid discovered is cis-9,10-epoxy stearic acid. CoQ10, identified as the major ubiquinone homologue, is synthesised de novo by P. carinii. Atovaquone and other

  1. The Lipids of Pneumocystis carinii

    PubMed Central

    Kaneshiro, Edna S.

    1998-01-01

    Information about a number of Pneumocystis carinii lipids obtained by the analyses of organisms isolated and purified from infected lungs of corticosteroid-immunosuppressed rats has been reported in recent years. Of the common opportunistic protists associated with AIDS (Cryptosporidium, Toxoplasma, and the microsporidia), more is currently known about the lipids of P. carinii than the others. Lipids that are synthesized by the organism but not by humans are attractive targets for drug development. Thus, the elucidation of Δ7C-24-alykylated sterol and cis-9,10-epoxystearic acid biosyntheses in P. carinii is currently being examined in detail, since these have been identified as P. carinii-specific lipids. The development of low-toxicity drugs that prevent sterol C-24 alkylation and the specific inhibition of the lipoxygenase that forms cis-9,10-epoxystearic acid might prove fruitful. Although humans can synthesize coenzyme Q10, the anti-P. carinii activity and low toxicity of ubiquinone analogs such as atovaquone suggest that the electron transport chain in the pathogen may differ importantly from that in the host. Although resistance to atovaquone has been observed, development of other naphthoquinone drugs would provide a broader armamentarium of drugs to treat patients with P. carinii pneumonia. Studies of bronchoalveolar lavage fluid and of infected lungs have demonstrated that the infection causes a number of chemical abnormalities. Bronchoalveolar lavage fluid obtained after the removal of lung cellular material and the organisms has been shown to contain larger amounts of surfactant proteins and smaller amounts of phospholipids than do comparable samples from P. carinii-free lungs. Increased phospholipase activity, inhibition of surfactant secretion by type II cells, and uptake and catabolism of lipids by the pathogen may explain this phenomenon related to P. carinii pneumonia. Although not yet thoroughly examined, initial studies on the uptake and

  2. [Pneumocystis pneumonia in HIV-negative adults].

    PubMed

    Rouyer, M; Stoclin, A; Blanc, F-X

    2015-12-01

    In HIV-negative adults, Pneumocystis jirovecii pneumonia can be observed when immunodeficiency is present, especially in case of drug-induced immune suppression (steroids, chemotherapy, transplantation). Clinical, radiological, and biological presentations are different in HIV-positive and HIV-negative individuals with different immunodeficiency profiles. In HIV-negative patients, dyspnea occurs more quickly (median duration of 5 days to get a diagnosis), diagnosis is more difficult because of less Pneumocystis in bronchoalveolar lavage, and mortality is higher than in HIV-positive individuals. Lung CT-scan typically shows diffuse ground glass opacities, but peri-bronchovascular condensations or ground glass opacities clearly limited by interlobular septa can also be observed. Lymphopenia is common but CD4+ T-cells count is rarely performed. HIV-negative patients with Pneumocystis pneumonia are co-infected with bacteria, viruses or fungi in about 30% cases. Bronchoalveolar lavage is often more neutrophilic than in HIV-positive individuals. PCR and β-D-glucan have good sensitivity but poor specificity to diagnose Pneumocystis pneumonia. Trimethoprim-sulfamethoxazole remains the first choice of treatment. Duration is 14 days in HIV-negative patients whereas it is typically of 21 days in HIV-positive individuals. Adjunctive corticosteroids are of beneficial effect in HIV-positive adult patients with substantial hypoxaemia but are not recommended in HIV-negative patients, as they could be deleterious in some individuals.

  3. Pneumocystis Carinii Pneumonia Following 5-Fluorouracil Administration

    PubMed Central

    Hardy, Robert; Cummings, Clinton; Faulkner, Marquetta; Obianyo, Ifeanyi

    1987-01-01

    A 54-year-old man who had been treated with monthly courses of 5-fluorouracil for one year developed Pneumocystis carinii pneumonia. No evidence of significant, permanent, immunologic impairment was evident one year after the patient became infected. An infection associated with 5-fluorouracil treatment is implicated. ImagesFigure 1Figure 2Figure 3Figure 4 PMID:3501015

  4. Distribution of Pneumocystis jirovecii in lungs from colonized COPD patients

    PubMed Central

    Sivam, Sheila; Sciurba, Frank C.; Lucht, Lorrie A.; Zhang, Yingze; Duncan, Steven R.; Norris, Karen A.; Morris, Alison

    2011-01-01

    Pneumocystis jirovecii has been detected in lung tissue from patients with chronic obstructive pulmonary disease (COPD) and is associated with disease severity. The regional distribution of the organism in lungs is unknown, but differences in distribution of Pneumocystis could affect estimates of colonization prevalence. We examined the distribution of Pneumocystis in the lungs of 19 non-HIV-infected patients with COPD who were undergoing lung transplantation. DNA was extracted from explanted lungs. We found Pneumocystis colonization in lung tissue of 42.1% of patients with advanced COPD; however, there was significant regional variation in colonization between lung segments of individual patients. Colonization was detected more commonly in the lower and middle lobes than the upper lobes. These findings suggest that single samples from an individual may underestimate the prevalence of Pneumocystis colonization and future studies may obtain a higher yield of Pneumocystis colonization detection when sampling the lower lobes. PMID:21851870

  5. [A Case of Pneumocystis Pneumonia after Cetuximab-based Bioradiotherapy].

    PubMed

    Shinohara, Asano; Kogo, Ryunosuke; Uryu, Hideoki; Yasumatsu, Ryuji; Nakashima, Torahiko; Komune, Shizuo

    2016-03-01

    Reports of drug-induced interstitial pneumonia caused by Cetuximab have been increasing. Pneumocystis pneumonia is important as a differential diagnosis of drug-induced interstitial pneumonia. We report herein on a 64-year-old man with pneumocystis pneumonia after cetuximab-based bioradiotherapy for laryngeal cancer. After radiotherapy, the patient developed multi-drug resistant pneumonia. Chest CT imaging revealed diffuse ground-glass opacities in the lung field. He was diagnosed as having pneumocystis pneumonia based on the bronchoalveolar lavage (BAL) findings, and then his symptoms improved after treatment with Trimethoprim/Sulfamethoxazole. It is important to assess the risk factor for pneumocystis pneumonia for early its detection and treatment.

  6. Oral Immunization of Mice with Live Pneumocystis murina Protects against Pneumocystis Pneumonia.

    PubMed

    Samuelson, Derrick R; de la Rua, Nicholas M; Charles, Tysheena P; Ruan, Sanbao; Taylor, Christopher M; Blanchard, Eugene E; Luo, Meng; Ramsay, Alistair J; Shellito, Judd E; Welsh, David A

    2016-03-15

    Pneumocystis pneumonia is a major cause of morbidity and mortality in immunocompromised patients, particularly those infected with HIV. In this study, we evaluated the potential of oral immunization with live Pneumocystis to elicit protection against respiratory infection with Pneumocystis murina. C57BL/6 mice vaccinated with live P. murina using a prime-boost vaccination strategy were protected from a subsequent lung challenge with P. murina at 2, 7, 14, and 28 d postinfection even after CD4(+) T cell depletion. Specifically, vaccinated immunocompetent mice had significantly faster clearance than unvaccinated immunocompetent mice and unvaccinated CD4-depleted mice remained persistently infected with P. murina. Vaccination also increased numbers of CD4(+) T cells, CD8(+) T cells, CD19(+) B cells, and CD11b(+) macrophages in the lungs following respiratory infection. In addition, levels of lung, serum, and fecal P. murina-specific IgG and IgA were increased in vaccinated animals. Furthermore, administration of serum from vaccinated mice significantly reduced Pneumocystis lung burden in infected animals compared with control serum. We also found that the diversity of the intestinal microbial community was altered by oral immunization with P. murina. To our knowledge, our data demonstrate for the first time that an oral vaccination strategy prevents Pneumocystis infection.

  7. Oral immunization of mice with live Pneumocystis murina protects against Pneumocystis pneumonia

    PubMed Central

    Samuelson, Derrick R.; de la Rua, Nicholas M.; Charles, Tysheena P.; Ruan, Sanbao; Taylor, Christopher M.; Blanchard, Eugene E.; Luo, Meng; Ramsay, Alistair J.; Shellito, Judd E.; Welsh, David A.

    2016-01-01

    Pneumocystis pneumonia is a major cause of morbidity and mortality in immunocompromised patients; particularly those infected with human immunodeficiency virus. In this study, we evaluated the potential of oral immunization with live Pneumocystis to elicit protection against respiratory infection with Pneumocystis murina. C57BL/6 mice vaccinated with live P. murina using a prime-boost vaccination strategy were protected from a subsequent lung challenge with P. murina at 2, 7, 14, and 28 days post infection even after CD4+ T cell depletion. Specifically, vaccinated immunocompetent mice had significantly faster clearance than unvaccinated immunocompetent mice and unvaccinated CD4-depleted mice remained persistently infected with P. murina. Vaccination also increased numbers of CD4+ T cells, CD8+ T cells, CD19+ B cells, and CD11b+ macrophages in the lungs following respiratory infection. In addition, levels of lung, serum, and fecal P. murina-specific IgG and IgA were increased in vaccinated animals. Further, administration of serum from vaccinated mice significantly reduced Pneumocystis lung burden in infected animals compared to control serum. We also found that the diversity of the intestinal microbial community was altered by oral immunization with P. murina. Our data demonstrate for the first time that an oral vaccination strategy prevents Pneumocystis infection. PMID:26864029

  8. Pneumocystis jirovecii Rtt109, a novel drug target for Pneumocystis pneumonia in immunosuppressed humans.

    PubMed

    Dahlin, Jayme L; Kottom, Theodore; Han, Junhong; Zhou, Hui; Walters, Michael A; Zhang, Zhiguo; Limper, Andrew H

    2014-07-01

    Pneumocystis pneumonia (PcP) is a significant cause of morbidity and mortality in immunocompromised patients. In humans, PcP is caused by the opportunistic fungal species Pneumocystis jirovecii. Progress in Pneumocystis research has been hampered by a lack of viable in vitro culture methods, which limits laboratory access to human-derived organisms for drug testing. Consequently, most basic drug discovery research for P. jirovecii is performed using related surrogate organisms such as Pneumocystis carinii, which is derived from immunosuppressed rodents. While these studies provide useful insights, important questions arise about interspecies variations and the relative utility of identified anti-Pneumocystis agents against human P. jirovecii. Our recent work has identified the histone acetyltransferase (HAT) Rtt109 in P. carinii (i.e., PcRtt109) as a potential therapeutic target for PcP, since Rtt109 HATs are widely conserved in fungi but are absent in humans. To further address the potential utility of this target in human disease, we now demonstrate the presence of a functional Rtt109 orthologue in the clinically relevant fungal pathogen P. jirovecii (i.e., PjRtt109). In a fashion similar to that of Pcrtt109, Pjrtt109 restores H3K56 acetylation and genotoxic resistance in rtt109-null yeast. Recombinant PjRtt109 is an active HAT in vitro, with activity comparable to that of PcRtt109 and yeast Rtt109. PjRtt109 HAT activity is also enhanced by the histone chaperone Asf1 in vitro. PjRtt109 and PcRtt109 showed similar low micromolar sensitivities to two reported small-molecule HAT inhibitors in vitro. Together, these results demonstrate that PjRtt109 is a functional Rtt109 HAT, and they support the development of anti-Pneumocystis agents directed at Rtt109-catalyzed histone acetylation as a novel therapeutic target for human PcP.

  9. Pneumocystis carinii infections in zoo animals.

    PubMed

    Poelma, F G

    1975-01-01

    Pneumocystis carinii was found to be present in the lungs of twenty-three zoo animals in the Netherlands. The following species were represented: red kangaroo, common tree shrew, Senegal-Galago, Demidoff's-Galago, brown howler monkey, woolly monkey, long-haired spider monkey, white-eared marmoset, chimpanzee, three-toed sloth, palm squirrel, red panda, fennec fox, tree hyrax and large-toothed hyrax.

  10. Pneumocystis jirovecii pneumonia in developing countries*

    PubMed Central

    De Armas Rodríguez, Y.; Wissmann, G.; Müller, A.L.; Pederiva, M.A.; Brum, M.C.; Brackmann, R.L.; Capó De Paz, V.; Calderón, E.J.

    2011-01-01

    Pneumocystis pneumonia (PcP) is a serious fungal infection among immunocompromised patients. In developed countries, the epidemiology and clinical spectrum of PcP have been clearly defined and well documented. However, in most developing countries, relatively little is known about the prevalence of pneumocystosis. Several articles covering African, Asian and American countries were reviewed in the present study. PcP was identified as a frequent opportunistic infection in AIDS patients from different geographic regions. A trend to an increasing rate of PcP was apparent in developing countries from 2002 to 2010. PMID:21894262

  11. Thymopoietic and Bone Marrow Response to Murine Pneumocystis Pneumonia▿

    PubMed Central

    Shi, Xin; Zhang, Ping; Sempowski, Gregory D.; Shellito, Judd E.

    2011-01-01

    CD4+ T cells play a key role in host defense against Pneumocystis infection. To define the role of naïve CD4+ T cell production through the thymopoietic response in host defense against Pneumocystis infection, Pneumocystis murina infection in the lung was induced in adult male C57BL/6 mice with and without prior thymectomy. Pneumocystis infection caused a significant increase in the number of CCR9+ multipotent progenitor (MPP) cells in the bone marrow and peripheral circulation, an increase in populations of earliest thymic progenitors (ETPs) and double negative (DN) thymocytes in the thymus, and recruitment of naïve and total CD4+ T cells into the alveolar space. The level of murine signal joint T cell receptor excision circles (msjTRECs) in spleen CD4+ cells was increased at 5 weeks post-Pneumocystis infection. In thymectomized mice, the numbers of naïve, central memory, and total CD4+ T cells in all tissues examined were markedly reduced following Pneumocystis infection. This deficiency of naïve and central memory CD4+ T cells was associated with delayed pulmonary clearance of Pneumocystis. Extracts of Pneumocystis resulted in an increase in the number of CCR9+ MPPs in the cultured bone marrow cells. Stimulation of cultured bone marrow cells with ligands to Toll-like receptor 2 ([TLR-2] zymosan) and TLR-9 (ODN M362) each caused a similar increase in CCR9+ MPP cells via activation of the Jun N-terminal protein kinase (JNK) pathway. These results demonstrate that enhanced production of naïve CD4+ T lymphocytes through the thymopoietic response and enhanced delivery of lymphopoietic precursors from the bone marrow play an important role in host defense against Pneumocystis infection. PMID:21343353

  12. Eosinophils Contribute to Early Clearance of Pneumocystis murina Infection.

    PubMed

    Eddens, Taylor; Elsegeiny, Waleed; Nelson, Michael P; Horne, William; Campfield, Brian T; Steele, Chad; Kolls, Jay K

    2015-07-01

    Pneumocystis pneumonia remains a common opportunistic infection in the diverse immunosuppressed population. One clear risk factor for susceptibility to Pneumocystis is a declining CD4(+) T cell count in the setting of HIV/AIDS or primary immunodeficiency. Non-HIV-infected individuals taking immunosuppressive drug regimens targeting T cell activation are also susceptible. Given the crucial role of CD4(+) T cells in host defense against Pneumocystis, we used RNA sequencing of whole lung early in infection in wild-type and CD4-depleted animals as an unbiased approach to examine mechanisms of fungal clearance. In wild-type mice, a strong eosinophil signature was observed at day 14 post Pneumocystis challenge, and eosinophils were increased in the bronchoalveolar lavage fluid of wild-type mice. Furthermore, eosinophilopoiesis-deficient Gata1(tm6Sho)/J mice were more susceptible to Pneumocystis infection when compared with BALB/c controls, and bone marrow-derived eosinophils had in vitro Pneumocystis killing activity. To drive eosinophilia in vivo, Rag1(-/-) mice were treated with a plasmid expressing IL-5 (pIL5) or an empty plasmid control via hydrodynamic injection. The pIL5-treated mice had increased serum IL-5 and eosinophilia in the lung, as well as reduced Pneumocystis burden, compared with mice treated with control plasmid. In addition, pIL5 treatment could induce eosinophilia and reduce Pneumocystis burden in CD4-depleted C57BL/6 and BALB/c mice, but not eosinophilopoiesis-deficient Gata1(tm6Sho)/J mice. Taken together, these results demonstrate that an early role of CD4(+) T cells is to recruit eosinophils to the lung and that eosinophils are a novel candidate for future therapeutic development in the treatment of Pneumocystis pneumonia in the immunosuppressed population.

  13. Pneumocystis sp. in bats evaluated by qPCR.

    PubMed

    Cavallini Sanches, E M; Ferreiro, L; Andrade, C P; Pacheco, S M; Almeida, L L; Spanamberg, A; Wissmann, G

    2013-03-01

    Molecular techniques have revealed a high prevalence of Pneumocystis colonization in wild mammals. Accurate quantification of Pneumocystis sp. is essential for the correct interpretation of many research experiments investigating this organism. The objectives of this study were to detect the presence of Pneumocystis sp. in bats by qPCR, and to distinguish colonization from infection. Probes and primers for real time PCR (qPCR) were designed based on the gene of major surface glycoprotein (MSG) of Pneumocystis sp., in order to analyze 195 lung tissue samples from bats captured (2007-2009). All samples were also analyzed by nested PCR, using oligonucleotide primers designed for the gene encoding the mitochondrial small subunit rRNA (mtSSU rRNA) to confirm the results. The qPCR assay was standardized using a standard curve made with the DNA extracted from bronchoalveolar lavage positive for Pneumocystis jirovecii. The average Ct was found to be between 13 and 14 (calibration curve) for the detection of infection with Pneumocystis sp. and above these values for colonization. It was considered as negative samples the ones that had Ct values equal to 50. Out of the total 195 samples, 47 (24.1%) bat lung DNA samples were positive for Pneumocystis sp. by qPCR. The most common bat species found were: Tadarida brasiliensis (23.4%), Histiotus velatus (17.0%), Desmodus rotundus (14.9%) and Molossus molossus (8.5%). The average cycle threshold of the positive samples (bats) was 25.8 and standard deviation was 1.7. The DNA samples with Ct values greater than 14 suggest that these animals might be colonized by Pneumocystis sp. Results obtained in this study demonstrated the usefulness of the qPCR procedure for identification of Pneumocystis sp. and for distinction between its colonizing or infectious status in bats.

  14. Current insights into the biology and pathogenesis of Pneumocystis pneumonia.

    PubMed

    Thomas, Charles F; Limper, Andrew H

    2007-04-01

    The fungal infection Pneumocystis pneumonia is the most prevalent opportunistic infection in patients with AIDS. Although the analysis of this opportunistic fungal pathogen has been hindered by the inability to isolate it in pure culture, the use of molecular techniques and genomic analysis have brought insights into its complex cell biology. Analysis of the intricate relationship between Pneumocystis and the host lung during infection has revealed that the attachment of Pneumocystis to the alveolar epithelium promotes the transition of the organism from the trophic to the cyst form. It also revealed that Pneumocystis infection elicits the production of inflammatory mediators, culminating in lung injury and impaired gas exchange. Here we discuss these and other recent findings relating to the biology and pathogenesis of this intractable fungus.

  15. Pneumocystis carinii, Toxoplasma gondii, Cytomegalovirus and the Compromised Host

    PubMed Central

    Ryning, Frank W.; Mills, John

    1979-01-01

    Pneumocystis carinii and Toxoplasma gondii are the two major parasitic protozoan pathogens in the immunocompromised host. Both organisms cause latent infection in humans and many animals. Cats are the definitive hosts for toxoplasmosis; the animal vector for pneumocystis (if any) has not been defined. Toxoplasma is an obligate intracellular parasite, whereas the available evidence suggests that Pneumocystis carinii exists primarily extracellularly. In compromised hosts, pneumocystis infection usually involves only lungs, whereas toxoplasma causes a generalized infection with encephalitis being the principal clinical manifestation. Both types of infection are treated with combinations of folate antagonists (trimethoprim or pyrimethamine with sulfonamide). Both parasites are associated with cytomegalovirus infection in immunosuppressed hosts, an association which may be due to symbiosis between parasites, or to an additive immunosuppressive effect of dual infection on the hosts. ImagesFigure 1.Figure 3.Figure 4.Figure 7.Figure 8.Figure 9. PMID:217182

  16. Characterization of a distinct host response profile to Pneumocystis murina asci during clearance of pneumocystis pneumonia.

    PubMed

    Linke, Michael J; Ashbaugh, Alan; Collins, Margaret S; Lynch, Keeley; Cushion, Melanie T

    2013-03-01

    Pneumocystis spp. are yeast-like fungi that cause pneumocystis pneumonia (PcP) in immunocompromised individuals and exacerbate chronic lung diseases in immunocompetent individuals. The Pneumocystis life cycle includes trophic forms and asci (cyst forms). The cell walls of Pneumocystis asci contain β-1,3-D-glucan, and treatment of PcP with β-1,3-D-glucan synthase inhibitors, such as anidulafungin, results in depletion of asci, but not trophic forms. The pulmonary host response during immune reconstitution (IR)-mediated clearance of PcP in anidulafungin-treated and untreated mice was characterized to identify ascus-specific responses. During IR, similar numbers of trophic forms were present in the anidulafungin-treated and untreated mice; however, asci were only present in the untreated mice. IR resulted in a significant reduction of trophic forms from the lungs in both groups and asci in the untreated group. The presence of asci in untreated mice correlated with increased β-glucan content in the lungs. The untreated mice mounted immune responses associated with a deleterious host inflammatory response, including increased CD8(+) T cell influx and expression of macrophage inflammatory response markers. A more robust cellular response was also observed in the untreated mice, with increased numbers of macrophages and neutrophils that were associated with greater lung damage. Markers of a Th17 response were also elevated in the untreated mice. These results suggest that the host mounts unique responses to asci and trophic forms. That these 2 life cycle stages provoked distinct host response profiles has significant implications for clearance and interpretation of the host immune responses to PcP.

  17. No recurrence of Pneumocystis jirovecii Pneumonia after solid organ transplantation regardless of secondary prophylaxis.

    PubMed

    Kim, Tark; Sung, Heungsup; Lee, Yu-Mi; Hong, Hyo-Lim; Kim, Sung-Han; Choi, Sang-Ho; Woo, Jun Hee; Kim, Yang Soo; Lee, Sang-Oh

    2012-11-01

    There are no data on the efficacy of secondary prophylaxis against Pneumocystis pneumonia after solid organ transplantation. Therefore, we investigated the rate of recurrence of Pneumocystis pneumonia after solid organ transplantation in a retrospective cohort study. Between 2005 and 2011, a total of 41 recipients recovered from Pneumocystis pneumonia. Of these, 22 (53.7%) received secondary prophylaxis. None of the 41 recipients experienced recurrence of Pneumocystis pneumonia during the follow-up, regardless of secondary prophylaxis.

  18. Pneumocystis: a novel pathogen in chronic obstructive pulmonary disease?

    PubMed

    Morris, Alison; Sciurba, Frank C; Norris, Karen A

    2008-02-01

    Chronic obstructive pulmonary disease (COPD) results in significant morbidity and mortality. Smoking has long been recognized as the primary risk factor for development of COPD, but factors determining the severity or pattern of disease in smokers are largely unknown. Recent interest has focused on the potential role of infectious agents and the associated host response in accelerating progression of airway obstruction or in perpetuating its progression following discontinuation of tobacco exposure. Pneumocystis jirovecii is a fungal pathogen that causes pneumonia in immunocompromised individuals. Recent evidence has linked this organism with COPD. Using sensitive molecular techniques, low levels of Pneumocystis have been detected in the respiratory tract of certain individuals and termed colonization. Several findings support the theory that colonization with Pneumocystis is involved in the "vicious circle" hypothesis of COPD in which colonization with organisms perpetuates an inflammatory and lung remodeling response. Pneumocystis colonization is more prevalent in smokers and in those with severe COPD. The presence of Pneumocystis in the lungs, even at low levels, produces inflammatory changes similar to those seen in COPD, with increases in numbers of neutrophils and CD8(+) lymphocytes. HIV-infected subjects who have had PCP develop permanent airway obstruction, and HIV-infected patients have a high prevalence of both emphysema and Pneumocystis colonization. In addition, a non-human primate model of colonization shows development of airway obstruction and radiographic emphysema. Additional studies are needed to confirm the role of Pneumocystis in the pathogenesis of COPD, given that this agent might be a treatable co-factor in disease progression.

  19. Pneumocystis Pneumonia Presenting as an Enlarging Solitary Pulmonary Nodule.

    PubMed

    Patel, Krunal Bharat; Gleason, James Benjamin; Diacovo, Maria Julia; Martinez-Galvez, Nydia

    2016-01-01

    Pneumocystis pneumonia is a life threatening infection that usually presents with diffuse bilateral ground-glass infiltrates in immunocompromised patients. We report a case of a single nodular granulomatous Pneumocystis pneumonia in a male with diffuse large B-cell lymphoma after R-CHOP therapy. He presented with symptoms of productive cough, dyspnea, and right-sided pleuritic chest pain that failed to resolve despite treatment with multiple antibiotics. Chest X-ray revealed right lower lobe atelectasis and CT of chest showed development of 2 cm nodular opacity with ground-glass opacities. Patient underwent bronchoscopy and biopsy that revealed granulomatous inflammation in a background of organizing pneumonia pattern with negative cultures. Respiratory symptoms resolved but the solitary nodular opacity increased in size prompting a surgical wedge resection which revealed granulomatous Pneumocystis pneumonia infection. This case is the third documented report of Pneumocystis pneumonia infection within a solitary pulmonary nodule in an individual with hematologic neoplasm. Although Pneumocystis pneumonia most commonly occurs in patients with HIV/acquired immunodeficiency syndrome and with diffuse infiltrates, the diagnosis should not be overlooked when only a solitary nodule is present.

  20. Pneumocystis Pneumonia Presenting as an Enlarging Solitary Pulmonary Nodule

    PubMed Central

    Diacovo, Maria Julia; Martinez-Galvez, Nydia

    2016-01-01

    Pneumocystis pneumonia is a life threatening infection that usually presents with diffuse bilateral ground-glass infiltrates in immunocompromised patients. We report a case of a single nodular granulomatous Pneumocystis pneumonia in a male with diffuse large B-cell lymphoma after R-CHOP therapy. He presented with symptoms of productive cough, dyspnea, and right-sided pleuritic chest pain that failed to resolve despite treatment with multiple antibiotics. Chest X-ray revealed right lower lobe atelectasis and CT of chest showed development of 2 cm nodular opacity with ground-glass opacities. Patient underwent bronchoscopy and biopsy that revealed granulomatous inflammation in a background of organizing pneumonia pattern with negative cultures. Respiratory symptoms resolved but the solitary nodular opacity increased in size prompting a surgical wedge resection which revealed granulomatous Pneumocystis pneumonia infection. This case is the third documented report of Pneumocystis pneumonia infection within a solitary pulmonary nodule in an individual with hematologic neoplasm. Although Pneumocystis pneumonia most commonly occurs in patients with HIV/acquired immunodeficiency syndrome and with diffuse infiltrates, the diagnosis should not be overlooked when only a solitary nodule is present. PMID:27648318

  1. Pathobiology of Pneumocystis pneumonia: life cycle, cell wall and cell signal transduction.

    PubMed

    Skalski, Joseph H; Kottom, Theodore J; Limper, Andrew H

    2015-09-01

    Pneumocystis is a genus of ascomycetous fungi that are highly morbid pathogens in immunosuppressed humans and other mammals. Pneumocystis cannot easily be propagated in culture, which has greatly hindered understanding of its pathobiology. The Pneumocystis life cycle is intimately associated with its mammalian host lung environment, and life cycle progression is dependent on complex interactions with host alveolar epithelial cells and the extracellular matrix. The Pneumocystis cell wall is a varied and dynamic structure containing a dominant major surface glycoprotein, β-glucans and chitins that are important for evasion of host defenses and stimulation of the host immune system. Understanding of Pneumocystis cell signaling pathways is incomplete, but much has been deduced by comparison of the Pneumocystis genome with homologous genes and proteins in related fungi. In this mini-review, the pathobiology of Pneumocystis is reviewed, with particular focus on the life cycle, cell wall components and cell signal transduction.

  2. Infection with Pneumocystis carinii is prevalent in healthy Gambian children.

    PubMed

    Wakefield, A E; Stewart, T J; Moxon, E R; Marsh, K; Hopkin, J M

    1990-01-01

    Pneumocystis pneumonia is rarely identified in the many immunosuppressed individuals with acquired immune deficiency syndrome (AIDS) and malnutrition in Africa. To test whether infection with Pneumocystis carinii occurs in the continent we conducted a comparative serological study, measuring by enzyme-linked immunosorbent assay antibodies to the parasite in 150 healthy young individuals from both Britain and the Gambian savanna. The prevalence of significant titres of antibody to P. carinii steadily increased with age and included more than 70% of both populations by 8 years of age. Infection with P. carinii is, therefore, common in the Gambia. Thus opportunistic pneumocystis pneumonia may be an important but largely unrecognized disease in the continent, though its impact is probably diminished by the prevalence of fatal tuberculous infection, particularly in the AIDS population.

  3. Dihydropteroate synthase gene mutations in Pneumocystis and sulfa resistance.

    PubMed

    Huang, Laurence; Crothers, Kristina; Atzori, Chiara; Benfield, Thomas; Miller, Robert; Rabodonirina, Meja; Helweg-Larsen, Jannik

    2004-10-01

    Pneumocystis pneumonia (PCP) remains a major cause of illness and death in HIV-infected persons. Sulfa drugs, trimethoprim-sulfamethoxazole (TMP-SMX) and dapsone are mainstays of PCP treatment and prophylaxis. While prophylaxis has reduced the incidence of PCP, its use has raised concerns about development of resistant organisms. The inability to culture human Pneumocystis, Pneumocystis jirovecii, in a standardized culture system prevents routine susceptibility testing and detection of drug resistance. In other microorganisms, sulfa drug resistance has resulted from specific point mutations in the dihydropteroate synthase (DHPS) gene. Similar mutations have been observed in P. jirovecii. Studies have consistently demonstrated a significant association between the use of sulfa drugs for PCP prophylaxis and DHPS gene mutations. Whether these mutations confer resistance to TMP-SMX or dapsone plus trimethoprim for PCP treatment remains unclear. We review studies of DHPS mutations in P. jirovecii and summarize the evidence for resistance to sulfamethoxazole and dapsone.

  4. Functional Characterization of Pneumocystis carinii Inositol Transporter 1

    PubMed Central

    Collins, Margaret S.; Sesterhenn, Thomas; Porollo, Aleksey; Vadukoot, Anish Kizhakkekkara; Merino, Edward J.

    2016-01-01

    ABSTRACT Fungi in the genus Pneumocystis live in the lungs of mammals, where they can cause a fatal pneumonia (PCP [Pneumocystis pneumonia]) in hosts with compromised immune systems. The absence of a continuous in vitro culture system for any species of Pneumocystis has led to limited understanding of these fungi, especially for the discovery of new therapies. We recently reported that Pneumocystis carinii, Pneumocystis murina, and most significantly, Pneumocystis jirovecii lack both enzymes necessary for myo-inositol biosynthesis but contain genes with homologies to fungal myo-inositol transporters. Since myo-inositol is essential for eukaryotic viability, the primary transporter, ITR1, was functionally and structurally characterized in P. carinii. The predicted structure of P. carinii ITR1 (PcITR1) contained 12 transmembrane alpha-helices with intracellular C and N termini, consistent with other inositol transporters. The apparent Km was 0.94 ± 0.08 (mean ± standard deviation), suggesting that myo-inositol transport in P. carinii is likely through a low-affinity, highly selective transport system, as no other sugars or inositol stereoisomers were significant competitive inhibitors. Glucose transport was shown to use a different transport system. The myo-inositol transport was distinct from mammalian transporters, as it was not sodium dependent and was cytochalasin B resistant. Inositol transport in these fungi offers an attractive new drug target because of the reliance of the fungi on its transport, clear differences between the mammalian and fungal transporters, and the ability of the host to both synthesize and transport this critical nutrient, predicting low toxicity of potential inhibitors to the fungal transporter. PMID:27965450

  5. Continuous axenic cultivation of Pneumocystis carinii

    PubMed Central

    Merali, Salim; Frevert, Ute; Williams, Jonathan H.; Chin, Kevin; Bryan, Richard; Clarkson, Allen B.

    1999-01-01

    Continuous axenic culture of Pneumocystis carinii has been achieved. A culture vessel is used that allows for frequent medium exchange without disturbance of organisms that grow attached to a collagen-coated porous membrane. The growth medium is based on Minimal Essential Medium with Earle’s salt supplemented with S-adenosyl-l-methionine, putrescine, ferric pyrophosphate, N-acetyl glucosamine, putrescine, p-aminobenzoic acid, l-cysteine and l-glutamine, and horse serum. Incubation is in room air at 31°C. The pH of the medium begins at 8.8 and rises to ≈9 as the cells grow. Doubling times calculated from growth curves obtained from cultures inoculated at moderate densities ranged from 35 to 65 hours. With a low-density inoculum, the doubling time is reduced to 19 hours. The morphology of cultured organisms in stained smears and in transmission electron micrographs is that of P. carinii, and P. carinii-specific mAbs label the cultured material. Cultured organisms are infective for immunosuppressed rats and can be stored frozen and used to reinitiate culture. PMID:10051654

  6. Radioimmunoimaging of pneumocystis carinii infection in rats

    SciTech Connect

    Vallabhajosula, S.; Shane, L.B.; Goldsmith, S.J.; Lipszyc, H.; Walzer, P.

    1984-01-01

    Pneumocystis carinil pneumonia (PCP) is seen in patients with impaired immunity due to chemotherapeutic suppression or to a primary disorder, congenital or AIDS. Although radiogallium imaging has been helpful in the workup of PCP, it is non-specific. Since there is no early specific non-invasive method to diagnose PCP, the authors are developing an imaging technique using radiolabeled antibodies. Fulminant PCP was induced in rats by injecting cortisone, 20mg 2-3 times/wk for 8 wks. PC cells isolated from rat lung were injected into rabbits. The antiserum thus derived was separated and purified using Protein-A bound sepharose column with identification of IgG by polyacrylamide gel electrophoresis. Both rabbit antipneumocystis antibodies and purified IgG(Sigma) were iodinated with I-131 to a high specific activity (3-5..mu..Ci/ug) using a lactoperoxidase method. /sup 131/I-labeled specific and non-specific IgG were injected into rats with PC infection and imaged with an Anger camera. After sacrifice, I-131 activity/gram tissue (lung, liver, heart) was determined and expressed as organ ratios. An increased uptake of specific antibody in lungs of rats with PCP was demonstrated by organ counting and imaging. This increase was not seen in normal controls or rats injected with non-specific IgG. These data provide a basis for radioimmunoimaging of infectious diseases.

  7. PCR diagnosis of Pneumocystis pneumonia: a bivariate meta-analysis.

    PubMed

    Lu, Yuan; Ling, Guoya; Qiang, Chenyi; Ming, Qinshou; Wu, Cong; Wang, Ke; Ying, Zouxiao

    2011-12-01

    We undertook a bivariate meta-analysis to assess the overall accuracy of respiratory specimen PCR assays for diagnosing Pneumocystis pneumonia. The summary sensitivity and specificity were 0.99 (95% confidence interval, 0.96 to 1.00) and 0.90 (0.87 to 0.93). Subgroup analyses showed that quantitative PCR analysis and the major surface glycoprotein gene target had the highest specificity value (0.93). Respiratory specimen PCR results are sufficient to confirm or exclude the disease for at-risk patients suspected of having Pneumocystis pneumonia.

  8. Prevention of infection caused by Pneumocystis carinii in transplant recipients.

    PubMed

    Fishman, J A

    2001-10-15

    Pneumocystis carinii remains an important pathogen in patients who undergo solid-organ and hematopoietic transplantation. Infection results from reactivation of latent infection and via de novo acquisition of infection from environmental sources. The risk of infection depends on the intensity and duration of immunosuppression and underlying immune deficits. The risk is greatest after lung transplants, in individuals with invasive cytomegalovirus disease, during intensive immunosuppression for allograft rejection, and during periods of neutropenia. Prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMZ) prevents many opportunistic infections, including infection with P. carinii, Toxoplasma gondii, and community-acquired respiratory, gastrointestinal, and urinary tract pathogens. Intolerance of TMP-SMZ is common; desensitization is useful less often in transplant patients than in patients with AIDS. Alternative agents provide a narrower spectrum of protection than does TMP-SMZ and less adequate protection against Pneumocystis species. Clinically, the diagnosis of breakthrough Pneumocystis pneumonia often requires invasive procedures. Strategies for the prevention of Pneumocystis infection must be individualized on the basis of a stratification of risk for each patient.

  9. Surfactant changes during experimental pneumocystosis are related to Pneumocystis development.

    PubMed

    Aliouat, E M; Escamilla, R; Cariven, C; Vieu, C; Mullet, C; Dei-Cas, E; Prévost, M C

    1998-03-01

    Pneumocystosis-related surfactant changes have been reported in both humans and corticosteroid-treated experimental hosts. As corticosteroids induce an increase in pulmonary surfactant, some findings could be considered as controversial. The aim of this study was to investigate whether the surfactant composition changes during experimental pneumocystosis were related to the Pneumocystis development. In this work two corticosteroid-untreated animal models were used: rabbits, which develop spontaneous pneumocystosis at weaning; and severe combined immunodeficiency mice, which were intranasally inoculated with Pneumocystis carinii. Surfactant phospholipid and protein content was explored by bronchoalveolar lavage. The in vitro effect of surfactant on P. carinii growth was also explored. In the two models, the surfactant phospholipid/protein ratio was significantly increased, whereas parasite rates were low. This ratio decreases with the slope increase of the parasite growth curve. These early surfactant changes suggested that Pneumocystis proliferation requires alveolar lining fluid changes, and that normal surfactant is not suitable for parasite development. In this way, in vitro experiments presented here have revealed an inhibitory effect of synthetic or seminatural surfactants on the P. carinii growth. Further studies are needed to determine how Pneumocystis induces the reported early modifications of the surfactant, and why the parasite development is inhibited by pulmonary surfactant.

  10. CD4+ T-Cell-Independent Secondary Immune Responses to Pneumocystis Pneumonia

    PubMed Central

    de la Rua, Nicholas M.; Samuelson, Derrick R.; Charles, Tysheena P.; Welsh, David A.; Shellito, Judd E.

    2016-01-01

    Pneumocystis pneumonia is a major cause of morbidity and mortality among immunocompromised patients, especially in the context of HIV/AIDS. In the murine model of Pneumocystis pneumonia, CD4+ T-cells are required for clearance of a primary infection of Pneumocystis, but not the memory recall response. We hypothesized that the memory recall response in the absence of CD4+ T-cells is mediated by a robust memory humoral response, CD8+ T-cells, and IgG-mediated phagocytosis by alveolar macrophages. To investigate the role of CD8+ T-cells and alveolar macrophages in the immune memory response to Pneumocystis, mice previously challenged with Pneumocystis were depleted of CD8+ T-cells or alveolar macrophages prior to re-infection. Mice depleted of CD4+ T-cells prior to secondary challenge cleared Pneumocystis infection within 48 h identical to immunocompetent mice during a secondary memory recall response. However, loss of CD8+ T-cells or macrophages prior to the memory recall response significantly impaired Pneumocystis clearance. Specifically, mice depleted of CD8+ T-cells or alveolar macrophages had significantly higher fungal burden in the lungs. Furthermore, loss of alveolar macrophages significantly skewed the lung CD8+ T-cell response toward a terminally differentiated effector memory population and increased the percentage of IFN-γ+ CD8+ T-cells. Finally, Pneumocystis-infected animals produced significantly more bone marrow plasma cells and Pneumocystis-specific IgG significantly increased macrophage-mediated killing of Pneumocystis in vitro. These data suggest that secondary immune memory responses to Pneumocystis are mediated, in part, by CD8+ T-cells, alveolar macrophages, and the production of Pneumocystis-specific IgG. PMID:27242785

  11. CD4(+) T-Cell-Independent Secondary Immune Responses to Pneumocystis Pneumonia.

    PubMed

    de la Rua, Nicholas M; Samuelson, Derrick R; Charles, Tysheena P; Welsh, David A; Shellito, Judd E

    2016-01-01

    Pneumocystis pneumonia is a major cause of morbidity and mortality among immunocompromised patients, especially in the context of HIV/AIDS. In the murine model of Pneumocystis pneumonia, CD4(+) T-cells are required for clearance of a primary infection of Pneumocystis, but not the memory recall response. We hypothesized that the memory recall response in the absence of CD4(+) T-cells is mediated by a robust memory humoral response, CD8(+) T-cells, and IgG-mediated phagocytosis by alveolar macrophages. To investigate the role of CD8(+) T-cells and alveolar macrophages in the immune memory response to Pneumocystis, mice previously challenged with Pneumocystis were depleted of CD8(+) T-cells or alveolar macrophages prior to re-infection. Mice depleted of CD4(+) T-cells prior to secondary challenge cleared Pneumocystis infection within 48 h identical to immunocompetent mice during a secondary memory recall response. However, loss of CD8(+) T-cells or macrophages prior to the memory recall response significantly impaired Pneumocystis clearance. Specifically, mice depleted of CD8(+) T-cells or alveolar macrophages had significantly higher fungal burden in the lungs. Furthermore, loss of alveolar macrophages significantly skewed the lung CD8(+) T-cell response toward a terminally differentiated effector memory population and increased the percentage of IFN-γ(+) CD8(+) T-cells. Finally, Pneumocystis-infected animals produced significantly more bone marrow plasma cells and Pneumocystis-specific IgG significantly increased macrophage-mediated killing of Pneumocystis in vitro. These data suggest that secondary immune memory responses to Pneumocystis are mediated, in part, by CD8(+) T-cells, alveolar macrophages, and the production of Pneumocystis-specific IgG.

  12. Pneumocystis colonization in older adults and diagnostic yield of single versus paired noninvasive respiratory sampling.

    PubMed

    Vargas, Sergio L; Pizarro, Patricia; López-Vieyra, Mónica; Neira-Avilés, Patricia; Bustamante, Rebeca; Ponce, Carolina A

    2010-02-01

    The presence of Pneumocystis was assessed in oropharyngeal wash specimens from 110 adults (median age, 76 years; age range, 69-95 years), 66 of whom had a paired nasal swab specimen. Pneumocystis jirovecii DNA was detected in 12.8% of oropharyngeal wash specimens, and the frequency increased to 21.5% in paired specimens. Pneumocystis colonization is prevalent in older adults. Double noninvasive sampling increases the diagnostic yield.

  13. Pneumocystis carinii in Africa: an emerging pathogen?

    PubMed

    Russian, D A; Kovacs, J A

    1995-11-11

    There are quite a few pathogens which can cause pneumonia. Identifying the agent of infection simplifies therapy by allowing the appropriate treatment to be targeted with a minimum amount of toxic drugs. Empirical therapy is ideally reserved for settings in which the patient is not acutely ill, there is a high probability of a single, easily treated pathogen, and rapid diagnostic facilities are available if treatment fails. Empirical therapy, however, is often necessary in many AIDS-endemic regions where diagnostic tests are unavailable due to limited resources. In such circumstances, a treatment algorithm independent of extensive diagnostic testing and targeted against locally prevalent pathogens is called for. Malin and colleagues have reported finding Pneumocystis carinii pneumonia (PCP) among 33% of 64 patients in Zimbabwe observed with diffuse pneumonia unresponsive to penicillin. Untreated PCP is lethal. Further, despite three negative sputum smears for Mycobacterium tuberculosis, the organism was the most common pathogen ultimately identified, confirming previous reports and highlighting the importance of anti-TB therapy. The high incidence of PCP raises concerns that in certain parts of Africa treatment algorithms which do not consider PCP may need to be re-evaluated. Different patient selection criteria among studies with discordant results may partially explain the differences in the incidence of PCP in different parts of Africa. Otherwise, regional environmental differences, host genetic variation, and differences in the virulence of various strains of P. carinii may play a role. Data on the incidence of PCP in HIV-infected infants in Africa would provide insights into the role of P. carinii as a pathogen. The authors note that if the incidence of PCP is rising, even in selected areas, then prophylaxis in such areas with co-trimoxazole may be a cost-effective management approach which may also decrease the incidence of bacterial infections. Alternatively

  14. Exploring transplacental transmission of Pneumocystis oryctolagi in first-time pregnant and multiparous rabbit does.

    PubMed

    Sanchez, Catherine A; Chabé, Magali; Aliouat, El Moukhtar; Durand-Joly, Isabelle; Gantois, Nausicaa; Conseil, Valérie; López, Claudia; Duriez, Thérèse; Dei-Cas, Eduardo; Vargas, Sergio L

    2007-12-01

    Pneumocystis sp. is transmitted through the airborne route and presents a high host-species-specificity. Occasional reports of Pneumocystis pneumonia in still births and newborn infants suggest that other routes of transmission, e.g. transplacental might occur. The latter has been reported in rabbits but available data indicate that transplacental transmission of Pneumocystis seems not to occur in corticosteroid-treated rats and in SCID mice. The present study was undertaken to evaluate transplacental transmission of Pneumocystis oryctolagi. The spontaneously-acquired pneumocystosis rabbit model using hybrid California/New Zealand white female rabbits was selected because of similarities among rabbit and human placentas. Three different experiments were conducted in France and Chile. Pneumocystis organisms were detected by microscopy in the lungs of pregnant does and Pneumocystis DNA was found in the lungs of fetuses from the multiparous does from the second week to the end of gestation. Pneumocystis DNA was not detected in fetuses from primiparous does. Detection of Pneumocystis oryctolagi--DNA in fetuses of multiparous does and not in those of primiparous ones, suggests that transplacental transmission may be favored by multiple gestations. Whether Pneumocystis-DNA in fetal tissues from multiparous does resulted from transplacental passage of viable transmissible forms requires further investigation.

  15. β-Glucans Are Masked but Contribute to Pulmonary Inflammation During Pneumocystis Pneumonia.

    PubMed

    Kutty, Geetha; Davis, A Sally; Ferreyra, Gabriela A; Qiu, Ju; Huang, Da Wei; Sassi, Monica; Bishop, Lisa; Handley, Grace; Sherman, Brad; Lempicki, Richard; Kovacs, Joseph A

    2016-09-01

    β-glucans, which can activate innate immune responses, are a major component in the cell wall of the cyst form of Pneumocystis In the current study, we examined whether β-1,3-glucans are masked by surface proteins in Pneumocystis and what role β-glucans play in Pneumocystis-associated inflammation. For 3 species, including Pneumocystis jirovecii, which causes Pneumocystis pneumonia in humans, Pneumocystis carinii, and Pneumocystis murina, β-1,3-glucans were masked in most organisms, as demonstrated by increased exposure following trypsin treatment. Using quantitative polymerase chain reaction and microarray techniques, we demonstrated in a mouse model of Pneumocystis pneumonia that treatment with caspofungin, an inhibitor of β-1,3-glucan synthesis, for 21 days decreased expression of a broad panel of inflammatory markers, including interferon γ, tumor necrosis factor α, interleukin 1β, interleukin 6, and multiple chemokines/chemokine ligands. Thus, β-glucans in Pneumocystis cysts are largely masked, which likely decreases innate immune activation; this mechanism presumably was developed for interactions with immunocompetent hosts, in whom organism loads are substantially lower. In immunosuppressed hosts with a high organism burden, organism death and release of glucans appears to be an important contributor to deleterious host inflammatory responses.

  16. Pneumocystis jiroveci pneumonia and colonization in patients with advanced lung cancer

    PubMed Central

    TOGASHI, YOSUKE; MASAGO, KATSUHIRO; ITO, YUTAKA; SAKAMORI, YUICHI; OKUDA, CHIYUKI; FUKUHARA, AKIKO; NAGAI, HIROKI; KIM, YOUNG HAK; MISHIMA, MICHIAKI

    2013-01-01

    Pneumocystis jiroveci pneumonia (PCP) has long been recognized as a cause of mortality in immuno-compromised populations, including those with advanced lung cancer. Although Pneumocystis colonization has only recently been described due to the development of more sensitive molecular techniques, including polymerase chain reaction (PCR), it is unknown whether Pneumocystis colonization leads to the development of PCP. In the present study, we aimed to determine the prevalence of Pneumocystis colonization in advanced lung cancer patients. Furthermore, the association between PCP and Pneumocystis colonization was also investigated. Advanced lung cancer patients with no indication of PCP were evaluated to determine the prevalence of Pneumocystis colonization. We analyzed their oral wash (OW) samples and retrospectively evaluated advanced lung cancer patients with PCP by analyzing their sections of formalin-fixed, paraffin-embedded lung tissues obtained following a diagnosis of lung cancer. Pneumocystis colonization was determined by a PCR test for Pneumocystis jiroveci (P. jiroveci). No P. jiroveci was detected by PCR in the OW samples of 47 advanced lung cancer patients with no indication of PCP, or in the lung tissues of four advanced lung cancer patients with PCP. These results indicate that PCP is not associated with Pneumocystis colonization in advanced lung cancer patients, although this study is limited since this was a cross-sectional and retrospective study. PMID:23420670

  17. Update on the diagnosis and treatment of Pneumocystis pneumonia.

    PubMed

    Carmona, Eva M; Limper, Andrew H

    2011-02-01

    Pneumocystis is an opportunistic fungal pathogen that causes an often-lethal pneumonia in immunocompromised hosts. Although the organism was discovered in the early 1900s, the first cases of Pneumocystis pneumonia in humans were initially recognized in Central Europe after the Second World War in premature and malnourished infants. This unusual lung infection was known as plasma cellular interstitial pneumonitis of the newborn, and was characterized by severe respiratory distress and cyanosis with little or no fever and no pathognomic physical signs. At that time, only anecdotal cases were reported in adults and usually these patients had a baseline malignancy that led to a malnourished state. In the 1960-1970s additional cases were described in adults and children with hematological malignancies, but Pneumocystis pneumonia was still considered a rare disease. However, in the 1980s, with the onset of the HIV epidemic, Pneumocystis prevalence increased dramatically and became widely recognized as an opportunistic infection that caused potentially life-treating pneumonia in patients with impaired immunity. During this time period, prophylaxis against this organism was more generally instituted in high-risk patients. In the 1990s, with widespread use of prophylaxis and the initiation of highly active antiretroviral therapy (HAART) in the treatment of HIV-infected patients, the number of cases in this specific population decreased. However, Pneumocystis pneumonia still remains an important cause of severe pneumonia in patients with HIV infection and is still considered a principal AIDS-defining illness. Despite the decreased number of cases among HIV-infected patients over the past decade, Pneumocystis pneumonia continues to be a serious problem in immunodeficient patients with other immunosuppressive conditions. This is mostly due to increased use of immunosuppressive medications to treat patients with autoimmune diseases, following bone marrow and solid organ

  18. Comparison of different blood compartments for the detection of circulating DNA using a rat model of Pneumocystis pneumonia.

    PubMed

    Fréalle, E; Gantois, N; Aliouat-Denis, C M; Leroy, S; Zawadzki, C; Perkhofer, S; Aliouat, E M; Dei-Cas, E

    2015-09-01

    Pneumocystis is mostly found in the alveolar spaces, but circulation of viable organisms also occurs and suggests that the detection of DNA in blood could be used as a noninvasive procedure to improve the diagnosis of Pneumocystis pneumonia (PcP). In order to determine the optimal compartment for Pneumocystis DNA detection, we used a rat model of PcP and tested the presence of Pneumocystis with a quantitative mtLSU targeting real-time PCR in four blood compartments: whole blood, clot, serum and Platelet-Rich-Plasma (PRP). All samples from 4 Pneumocystis-free control rats were negative. Pneumocystis was detected in 79, 64, 57, and 57% of samples from 14 PcP rats, respectively, but DNA release was not related to pulmonary loads. These data confirm the potential usefulness of Pneumocystis DNA detection in the blood for PcP diagnosis and suggest that whole blood could be the most appropriate compartment for Pneumocystis detection.

  19. Pulmonary coinfection by Pneumocystis jiroveci and Cryptococcus neoformans.

    PubMed

    Javier, Bava; Susana, Lloveras; Santiago, Garro; Alcides, Troncoso

    2012-01-01

    We communicate the diagnosis by microscopy of a pulmonary coinfection produced by Cryptococcus neoformans and Pneumocystis jiroveci, from a respiratory secretion obtained by bronchoalveolar lavage of an AIDS patient. Our review of literature identified this coinfection as unusual presentation. Opportunistic infections associated with HIV infection are increasingly recognized. It may occur at an early stage of HIV-infection. Whereas concurrent opportunistic infections may occur, coexisting Pneumocystis jiroveci pneumonia (PCP) and disseminated cryptococcosis with cryptococcal pneumonia is uncommon. The lungs of individuals infected with HIV are often affected by opportunistic infections and tumours and over two-thirds of patients have at least one respiratory episode during the course of their disease. Pneumonia is the leading HIV-associated infection. We present the case of a man who presented dual Pneumocystis jiroveci and cryptococcal pneumonia in a patient with HIV. Definitive diagnosis of PCP and Cryptococcus requires demonstration of these organisms in pulmonary tissues or fluid. In patients with < 200/microliter CD4-lymphocytes, a bronchoalveolar lavage should be performed. This patient was successfully treated with amphotericin B and trimethoprim sulfamethoxazole. After 1 week the patient showed clinical and radiologic improvement and was discharged 3 weeks later.

  20. Low prevalence of Pneumocystis jirovecii lung colonization in Ugandan HIV-infected patients hospitalized with non-Pneumocystis pneumonia.

    PubMed

    Taylor, Steve M; Meshnick, Steven R; Worodria, William; Andama, Alfred; Davis, J Lucian; Cattamanchi, Adithya; den Boon, Saskia; Yoo, Samuel D; Goodman, Carol D; Huang, Laurence

    2012-02-01

    Pneumocystis jirovecii is an important opportunistic infection in human immunodeficiency virus (HIV)-infected patients. In the developed world, P. jirovecii epidemiology is marked by frequent colonization in immunosuppressed patients, but data on the prevalence of colonization are very limited in sub-Saharan Africa, where the majority of persons living with HIV reside. Our objective was to describe the epidemiology of P. jirovecii colonization among HIV-positive patients in a cross-sectional, hospital-based study of patients admitted with suspected pneumonia in Kampala, Uganda. P. jirovecii was detectable in bronchoalveolar lavage fluid from 7 (6%) of 124 consecutive patients with non-Pneumocystis pneumonia. Colonization was not associated with patient demographic or clinical information. This prevalence is substantially lower than in published studies in the developed world and suggests that there is a limited reservoir of organisms for clinical infections in this Ugandan population. These findings may partially explain the low incidence of Pneumocystis pneumonia in Uganda and other sub-Saharan African countries.

  1. Low prevalence of Pneumocystis jirovecii lung colonization in Ugandan HIV-infected patients hospitalized with non-Pneumocystis pneumonia

    PubMed Central

    Taylor, Steve M; Meshnick, Steven R; Worodria, William; Andama, Alfred; Davis, J. Lucian; Cattamanchi, Adithya; Boon, Saskia den; Yoo, Samuel D; Goodman, Carol D.; Huang, Laurence

    2011-01-01

    Pneumocystis jirovecii is an important opportunistic infection in HIV-infected patients. In the developed world, P. jirovecii epidemiology is marked by frequent colonization in immunosuppressed patients, but data on the prevalence of colonization is very limited in sub-Saharan Africa, where the majority of persons living with HIV reside. Our objective was to describe the epidemiology of P. jirovecii colonization among HIV-positive patients in a cross-sectional, hospital-based study of patients admitted with suspected pneumonia in Kampala, Uganda. P. jirovecii was detectable in bronchoalveolar lavage fluid from 7 of 124 (6%) consecutive patients with non-Pneumocystis pneumonia. Colonization was not associated with patient demographic or clinical information. This prevalence is substantially lower than in published studies in the developed world, and suggests that there is a limited reservoir of organisms for clinical infections in this Ugandan population. These findings may partially explain the low incidence of Pneumocystis pneumonia in Uganda and other sub-Saharan African countries. PMID:22153850

  2. Genotyping and phylogenetic analysis of Pneumocystis jirovecii isolates from India.

    PubMed

    Gupta, Rashmi; Mirdha, Bijay Ranjan; Guleria, Randeep; Agarwal, Sanjay Kumar; Samantaray, Jyotish Chandra; Kumar, Lalit; Kabra, Sushil Kumar; Luthra, Kalpana; Sreenivas, Vishnubhatla

    2010-08-01

    Pneumocystis jirovecii is the cause of Pneumocystis pneumonia (PCP) in immuno-compromised individuals. The aim of this study was to describe the genotypes/haplotypes of P. jirovecii in immuno-compromised individuals with positive polymerase chain reaction (PCR) result for PCP. The typing was based on sequence polymorphism at internal transcribed spacer (ITS) regions of rRNA operon. Phylogenetic relationship between Indian and global haplotypes was also studied. Between January 2005 to October 2008, 43 patients were found to be positive for Pneumocystis using PCR targeting mitochondrial large subunit rRNA (mt LSU rRNA) and ITS region. Genotyping of all the positive samples was performed at the ITS locus by direct sequencing. Nine ITS1 alleles (all previously known) and 11 ITS2 alleles (nine previously defined and two new) were observed. A total of 19 ITS haplotypes, including five novel haplotypes (DEL1r, Edel2, Hr, Adel3 and SYD1a), were observed. The most prevalent type was SYD1g (16.3%), followed by types Ea (11.6%), Ec (9.3%), Eg (6.9%), DEL1r (6.9%), Ne (6.9%) and Ai (6.9%). To detect mixed infection, 30% of the positive isolates were cloned and 4-5 clones were sequenced from each specimen. Cloning and sequencing identified two more haplotypes in addition to the 19 types. Mixed infection was identified in 3 of the 13 cloned samples (23.1%). Upon construction of a haplotype network of 21 haplotypes, type Eg was identified as the most probable ancestral type. The present study is the first study that describes the haplotypes of P. jirovecii based on the ITS gene from India. The study suggests a high diversity of P. jirovecii haplotypes in the population.

  3. The Ecology of Pneumocystis: Perspectives, Personal Recollections, and Future Research Opportunities

    PubMed Central

    Walzer, Peter D.

    2013-01-01

    I am honored to receive the second Lifetime Achievement Award by International Workshops on Opportunistic Protists (IWOP) and to give this lecture. My research involves Pneumocystis, an opportunistic pulmonary fungus that is a major cause of pneumonia (“PcP”) in the immunocompromised host. I decided to focus on Pneumocystis ecology here because it has not attracted much interest. Pneumocystis infection is acquired by inhalation, and the cyst stage appears to be the infective form. Several fungal lung infections, such as coccidiomycosis, are not communicable, but occur by inhaling < 5μ spores from environmental sources (buildings, parks), and can be affected by environmental factors. PcP risk factors include environmental constituents (temperature, humidity, SO2, CO) and outdoor activities (camping). Clusters of PcP have occurred, but no environmental source has been found. Pneumocystis is communicable and outbreaks of PcP, especially in renal transplant patients, are an ongoing problem. Recent evidence suggests that most viable Pneumocystis organisms detected in the air are confined to a patient’s room. Further efforts are needed to define the risk of Pneumocystis transmission in healthcare facilities; to develop more robust preventive measures; and to characterize the effects of climatological and air pollutant factors on Pneumocystis transmission in animal models similar to those used for respiratory viruses. PMID:24001365

  4. Absolute lymphocyte count as a predictor of Pneumocystis pneumonia in patients previously unknown to have HIV.

    PubMed

    Omene, Aghogho A; Ferguson, Robert P

    2012-01-01

    This is a retrospective review of patients admitted to an inner city community hospital with community-acquired pneumonia who were ultimately diagnosed with AIDS and Pneumocystis. Absolute lymphocyte count in our hospital is available immediately. In contrast, it can take 48 hours or longer to obtain more specific CD-4 counts and AIDS enzyme-linked immunosorbent assay (ELISA) serology. The association of lymphopenia with ultimate diagnosis of AIDS and Pneumocystis supports immediate empiric treatment for pneumocystis carinii pneumonia (PCP) in our highly HIV prevalent hospital.

  5. Sequencing and characterization of the complete mitochondrial genomes of three Pneumocystis species provide new insights into divergence between human and rodent Pneumocystis

    PubMed Central

    Ma, Liang; Huang, Da-Wei; Cuomo, Christina A.; Sykes, Sean; Fantoni, Giovanna; Das, Biswajit; Sherman, Brad T.; Yang, Jun; Huber, Charles; Xia, Yun; Davey, Emma; Kutty, Geetha; Bishop, Lisa; Sassi, Monica; Lempicki, Richard A.; Kovacs, Joseph A.

    2013-01-01

    Pneumocystis jirovecii is an important opportunistic pathogen associated with AIDS and other immunodeficient conditions. Currently, very little is known about its nuclear and mitochondrial genomes. In this study, we sequenced the complete mitochondrial genome (mtDNA) of this organism and its closely related species Pneumocystis carinii and Pneumocystis murina by a combination of sequencing technologies. Our study shows that P. carinii and P. murina mtDNA share a nearly identical number and order of genes in a linear configuration, whereas P. jirovecii has a circular mtDNA containing nearly the same set of genes but in a different order. Detailed studies of the mtDNA terminal structures of P. murina and P. carinii suggest a unique replication mechanism for linear mtDNA. Phylogenetic analysis supports a close association of Pneumocystis species with Taphrina, Saitoella, and Schizosaccharomyces, and divergence within Pneumocystis species, with P. murina and P. carinii being more closely related to each other than either is to P. jirovecii. Comparative analysis of four complete P. jirovecii mtDNA sequences in this study and previously reported mtDNA sequences for diagnosing and genotyping suggests that the current diagnostic and typing methods can be improved using the complete mtDNA data. The availability of the complete P. jirovecii mtDNA also opens the possibility of identifying new therapeutic targets.—Ma, L., Huang, D. W., Cuomo, C. A., Sykes, S., Fantoni, G., Das, B., Sherman, B. T., Yang, J., Huber, C., Xia, Y., Davey, E., Kutty, G., Bishop, L., Sassi, M., Lempicki, R. A., Kovacs, J. A. Sequencing and characterization of the complete mitochondrial genomes of three Pneumocystis species provide new insights into divergence between human and rodent Pneumocystis. PMID:23392351

  6. Low prevalence of Pneumocystis pneumonia in hospitalized patients with systemic lupus erythematosus: review of a clinical data warehouse.

    PubMed

    Kapoor, T M; Mahadeshwar, P; Nguyen, S; Li, J; Kapoor, S; Bathon, J; Giles, J; Askanase, A

    2017-01-01

    Objective In the era of powerful immunosuppression, opportunistic infections are an increasing concern in systemic lupus erythematosus. One of the best-studied opportunistic infections is Pneumocystis pneumonia; however, the prevalence of Pneumocystis pneumonia in systemic lupus erythematosus is not clearly defined. This study evaluates the prevalence of Pneumocystis pneumonia in hospitalized systemic lupus erythematosus patients, with a focus on validating the Pneumocystis pneumonia and systemic lupus erythematosus diagnoses with clinical information. Methods This retrospective cohort study evaluates the prevalence of Pneumocystis pneumonia in all systemic lupus erythematosus patients treated at Columbia University Medical Center-New York Presbyterian Hospital between January 2000 and September 2014, using electronic medical record data. Patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and patients with renal transplants (including both early and late post-transplant patients) represented immunocompromised control groups. Patients with systemic lupus erythematosus, Pneumocystis pneumonia, HIV/AIDS, or renal transplant were identified using diagnostic codes from the International Classification of Diseases, Ninth Revision (ICD-9). Results Out of 2013 hospitalized systemic lupus erythematosus patients, nine had presumed Pneumocystis pneumonia, yielding a low prevalence of Pneumocystis pneumonia in systemic lupus erythematosus of 0.45%. Three of the nine Pneumocystis pneumonia cases were patients with concomitant systemic lupus erythematosus and HIV/AIDS. Only one of these nine cases was histologically confirmed as Pneumocystis pneumonia, in a patient with concomitant systemic lupus erythematosus and HIV/AIDS and a CD4 count of 13 cells/mm(3). The prevalence of Pneumocystis pneumonia in renal transplant patients and HIV/AIDS patients was 0.61% and 5.98%, respectively. Conclusion Given the reported high rate of adverse effects

  7. Ubiquinone synthesis and its regulation in Pneumocystis carinii.

    PubMed

    Kaneshiro, Edna S; Basselin, Mireille; Merali, Salim; Kayser, Oliver

    2006-01-01

    The opportunistic pathogen Pneumocystis causes a type of pneumonia in individuals with defective immune systems such as AIDS patients. Atovaquone, an analog of ubiquinone (coenzyme Q [CoQ]), is effective in clearing mild to moderate cases of the infection. Rat-derived Pneumocystis carinii was the first organism in which CoQ synthesis was clearly demonstrated to occur in both mitochondrial and microsomal subcellular fractions. Atovaquone inhibits microsomal CoQ synthesis with no effect on mitochondrial CoQ synthesis. We here report on additional studies evaluating CoQ synthesis and its regulation in the organism. Buparvaquone also inhibited CoQ synthesis and it reduced the synthesis of all four CoQ homologs in the microsomal but not the mitochondrial fraction. Glyphosate, which inhibits a reaction in the de novo synthesis of the benzoquinone moiety of CoQ reduced cellular ATP levels. Bacterial and plant quinones, and several chemically synthesized phenolics, flavanoids, and naphthoquinones that inhibit electron transport in other organisms were shown to reduce CoQ synthesis in P. carinii. The inhibitory action of naphthoquinone compounds appeared to depend on their molecular size and structural flexibility rather than redox potential. Results of experiments examining the synthesis of the polyprenyl chain of CoQ were consistent with negative feedback control of CoQ synthesis. These studies on P. carinii suggest that cellular sites and the control of CoQ synthesis in different organisms and cell types might be more diverse than previously thought.

  8. Pneumocystis pneumonia in HIV patients: a diagnostic challenge till date.

    PubMed

    Kaur, Ravinder; Wadhwa, Anupriya; Bhalla, Preena; Dhakad, Megh Singh

    2015-08-01

    HIV has become a major health problem in India, patients commonly succumb to opportunistic infections (OIs), respiratory infections being an important cause of morbidity and their accurate diagnosis is still a challenge. Our aim was to study the occurrence of Pneumocystis pneumonia (PCP) in HIV/AIDS patients with respiratory complaints attending ART clinic and to compare various diagnostic methodologies. One hundred and twenty five HIV/AIDS patients presenting with respiratory symptoms like cough, fever, breathlessness etc, were enrolled, and induced sputum samples were collected. Samples were homogenized using glass beads and Dithiothretol. Smears were prepared and examined by Immunoflourescent staining (IFAT), Gomori methanamine silver staining (GMSS), Toludine blue O staining (TBO) and Giemsa staining for Pneumocystis jiroveci. Among the 125 patients who presented with respiratory complaints, 34 cases (27.2%) were diagnosed as having PCP. All 34 cases were detected by IFAT followed by GMSS, Giemsa and Toludine blue O staining in decreasing order. The mean CD4 count was 67.27cells/μl. PCP has become an important health problem in HIV/AIDS patients with low CD4 counts in India. IFAT remains the most sensitive method for the detection of this uncultivable organism. In resource poor settings where an immunoflourecent microscope is not available, diagnosis of PCP still remains problematic.

  9. Therapeutic efficacies of chitosan against Pneumocystis pneumonia of immunosuppressed rat.

    PubMed

    Liu, A-B; Pu, Y; Zheng, Y-Q; Cai, H; Ye, B

    2014-07-01

    This study was designed to investigate the therapeutic efficacy of chitosan on Pneumocystis pneumonia (PCP) in immunosuppressed rats. The PCP rat model was established using intramuscular injections of dexamethasone sodium phosphate. To estimate treatment effects of chitosan on rat PCP, weight gain, lung weight, lung weight/body weight (LW/BW) ratio and per cent survival were measured and the HSP70 mRNA expression of Pneumocystis carinii was detected using real-time PCR analysis. Rat lung tissues were stained with HE, and their pathological changes, inflammatory cells and alveolar macrophages were observed by light microscopy. Rat lymphocyte numbers and the concentrations of IL-10, IFN-γ and TNF-α were measured by flow cytometry and ELISA analysis. Additionally, the ultrastructure of P. carinii was examined by electron microscopy to evaluate the effects of chitosan on the protist. Our results demonstrated that chitosan has some apparent treatment effects on rat PCP by reducing HSP70 mRNA expression and lung inflammation, increasing the concentrations of IL-10 and IFN-γ as well as CD4(+) T-lymphocyte numbers, reducing the CD8(+) T-lymphocyte numbers and the concentration of TNF-α and inducing significant ultrastructural damage to P. carinii. Although its precise therapeutic mechanism has yet to be determined, these results lay a theoretical foundation for PCP chitosan therapy.

  10. Vitamin D as Supplemental Therapy for Pneumocystis Pneumonia.

    PubMed

    Lei, Guang-Sheng; Zhang, Chen; Zimmerman, Michelle K; Lee, Chao-Hung

    2015-12-14

    The combination of all-trans retinoic acid (ATRA) and primaquine (PMQ) has been shown to be effective for therapy of Pneumocystis pneumonia (PCP). Since a high concentration of ATRA has significant adverse effects, the possibility that vitamin D can be used to replace ATRA for PCP therapy was investigated. C57BL/6 mice were immunosuppressed by depleting CD4(+) cells and infected with Pneumocystis murina 1 week after initiation of immunosuppression. Three weeks after infection, the mice were treated orally for 3 weeks with vitamin D3 (VitD3) alone, PMQ alone, a combination of VitD3 and PMQ (VitD3-PMQ), or a combination of trimethoprim and sulfamethoxazole (TMP-SMX). Results showed that VitD3 (300 IU/kg/day) had a synergistic effect with PMQ (5 mg/kg/day) for therapy of PCP. Flow cytometric studies showed that this VitD3-PMQ combination recovered the CD11b(low) CD11c(high) alveolar macrophage population in mice with PCP as effectively as TMP-SMX. The VitD3-PMQ combination also reduced the massive infiltration of inflammatory cells into the lungs and the severity of lung damage. VitD3 was also shown to reduce the dose of TMP-SMX required for effective treatment of PCP. Taken together, results of this study suggest that a VitD3-PMQ combination can be used as an alternative therapy for PCP.

  11. Defective nitric oxide production by alveolar macrophages during Pneumocystis pneumonia.

    PubMed

    Lasbury, Mark E; Liao, Chung-Ping; Hage, Chadi A; Durant, Pamela J; Tschang, Dennis; Wang, Shao-Hung; Zhang, Chen; Lee, Chao-Hung

    2011-04-01

    The effect of nitric oxide (NO) on Pneumocystis (Pc) organisms, the role of NO in the defense against infection with Pc, and the production of NO by alveolar macrophages (AMs) during Pneumocystis pneumonia (PCP) were investigated. The results indicate that NO was toxic to Pc organisms and inhibited their proliferation in culture. When the production of NO was inhibited by intraperitoneal injection of rats with the nitric oxide synthase inhibitor L-N(5)-(1-iminoethyl) ornithine, progression of Pc infection in immunocompetent rats was enhanced. Concentrations of NO in bronchoalveolar lavage fluids from immunosuppressed, Pc-infected rats and mice were greatly reduced, compared with those from uninfected animals, and AMs from these animals were defective in NO production. However, inducible nitric oxide synthase (iNOS) mRNA and protein concentrations were high in AMs from Pc-infected rats and mice. Immunoblot analysis showed that iNOS in AMs from Pc-infected rats existed primarily as a monomer, but the homo-dimerization of iNOS monomers was required for the production of NO. When iNOS dimerization cofactors, including calmodulin, were added to macrophage lysates, iNOS dimerization increased, whereas incubation of the same lysates with all cofactors except calmodulin did not rescue iNOS dimer formation. These data suggest that NO is important in the defense against Pc infection, but that the production of NO in AMs during PCP is defective because of the reduced dimerization of iNOS.

  12. Vitamin D as Supplemental Therapy for Pneumocystis Pneumonia

    PubMed Central

    Lei, Guang-Sheng; Zhang, Chen; Zimmerman, Michelle K.

    2015-01-01

    The combination of all-trans retinoic acid (ATRA) and primaquine (PMQ) has been shown to be effective for therapy of Pneumocystis pneumonia (PCP). Since a high concentration of ATRA has significant adverse effects, the possibility that vitamin D can be used to replace ATRA for PCP therapy was investigated. C57BL/6 mice were immunosuppressed by depleting CD4+ cells and infected with Pneumocystis murina 1 week after initiation of immunosuppression. Three weeks after infection, the mice were treated orally for 3 weeks with vitamin D3 (VitD3) alone, PMQ alone, a combination of VitD3 and PMQ (VitD3-PMQ), or a combination of trimethoprim and sulfamethoxazole (TMP-SMX). Results showed that VitD3 (300 IU/kg/day) had a synergistic effect with PMQ (5 mg/kg/day) for therapy of PCP. Flow cytometric studies showed that this VitD3-PMQ combination recovered the CD11blow CD11chigh alveolar macrophage population in mice with PCP as effectively as TMP-SMX. The VitD3-PMQ combination also reduced the massive infiltration of inflammatory cells into the lungs and the severity of lung damage. VitD3 was also shown to reduce the dose of TMP-SMX required for effective treatment of PCP. Taken together, results of this study suggest that a VitD3-PMQ combination can be used as an alternative therapy for PCP. PMID:26666941

  13. Genome analysis of three Pneumocystis species reveals adaptation mechanisms to life exclusively in mammalian hosts

    PubMed Central

    Ma, Liang; Chen, Zehua; Huang, Da Wei; Kutty, Geetha; Ishihara, Mayumi; Wang, Honghui; Abouelleil, Amr; Bishop, Lisa; Davey, Emma; Deng, Rebecca; Deng, Xilong; Fan, Lin; Fantoni, Giovanna; Fitzgerald, Michael; Gogineni, Emile; Goldberg, Jonathan M.; Handley, Grace; Hu, Xiaojun; Huber, Charles; Jiao, Xiaoli; Jones, Kristine; Levin, Joshua Z.; Liu, Yueqin; Macdonald, Pendexter; Melnikov, Alexandre; Raley, Castle; Sassi, Monica; Sherman, Brad T.; Song, Xiaohong; Sykes, Sean; Tran, Bao; Walsh, Laura; Xia, Yun; Yang, Jun; Young, Sarah; Zeng, Qiandong; Zheng, Xin; Stephens, Robert; Nusbaum, Chad; Birren, Bruce W.; Azadi, Parastoo; Lempicki, Richard A.; Cuomo, Christina A.; Kovacs, Joseph A.

    2016-01-01

    Pneumocystis jirovecii is a major cause of life-threatening pneumonia in immunosuppressed patients including transplant recipients and those with HIV/AIDS, yet surprisingly little is known about the biology of this fungal pathogen. Here we report near complete genome assemblies for three Pneumocystis species that infect humans, rats and mice. Pneumocystis genomes are highly compact relative to other fungi, with substantial reductions of ribosomal RNA genes, transporters, transcription factors and many metabolic pathways, but contain expansions of surface proteins, especially a unique and complex surface glycoprotein superfamily, as well as proteases and RNA processing proteins. Unexpectedly, the key fungal cell wall components chitin and outer chain N-mannans are absent, based on genome content and experimental validation. Our findings suggest that Pneumocystis has developed unique mechanisms of adaptation to life exclusively in mammalian hosts, including dependence on the lungs for gas and nutrients and highly efficient strategies to escape both host innate and acquired immune defenses. PMID:26899007

  14. A 32-Year-Old Female with AIDS, Pneumocystis jiroveci Pneumonia, and Methemoglobinemia

    PubMed Central

    Giangreco, Guillermo J.; Campbell, Dean; Cowan, Mark J.

    2013-01-01

    We report a case of methemoglobinemia with significant hemoglobin desaturation in a young female with AIDS who was being treated for Pneumocystis jiroveci pneumonia. A review of the etiology, pathophysiology, and treatment of methemoglobinemia is presented. PMID:24829836

  15. Neither classical nor alternative macrophage activation is required for Pneumocystis clearance during immune reconstitution inflammatory syndrome.

    PubMed

    Zhang, Zhuo-Qian; Wang, Jing; Hoy, Zachary; Keegan, Achsah; Bhagwat, Samir; Gigliotti, Francis; Wright, Terry W

    2015-12-01

    Pneumocystis is a respiratory fungal pathogen that causes pneumonia (Pneumocystis pneumonia [PcP]) in immunocompromised patients. Alveolar macrophages are critical effectors for CD4(+) T cell-dependent clearance of Pneumocystis, and previous studies found that alternative macrophage activation accelerates fungal clearance during PcP-related immune reconstitution inflammatory syndrome (IRIS). However, the requirement for either classically or alternatively activated macrophages for Pneumocystis clearance has not been determined. Therefore, RAG2(-/-) mice lacking either the interferon gamma (IFN-γ) receptor (IFN-γR) or interleukin 4 receptor alpha (IL-4Rα) were infected with Pneumocystis. These mice were then immune reconstituted with wild-type lymphocytes to preserve the normal T helper response while preventing downstream effects of Th1 or Th2 effector cytokines on macrophage polarization. As expected, RAG2(-/-) mice developed severe disease but effectively cleared Pneumocystis and resolved IRIS. Neither RAG/IFN-γR(-/-) nor RAG/IL-4Rα(-/-) mice displayed impaired Pneumocystis clearance. However, RAG/IFN-γR(-/-) mice developed a dysregulated immune response, with exacerbated IRIS and greater pulmonary function deficits than those in RAG2 and RAG/IL-4Rα(-/-) mice. RAG/IFN-γR(-/-) mice had elevated numbers of lung CD4(+) T cells, neutrophils, eosinophils, and NK cells but severely depressed numbers of lung CD8(+) T suppressor cells. Impaired lung CD8(+) T cell responses in RAG/IFN-γR(-/-) mice were associated with elevated lung IFN-γ levels, and neutralization of IFN-γ restored the CD8 response. These data demonstrate that restricting the ability of macrophages to polarize in response to Th1 or Th2 cytokines does not impair Pneumocystis clearance. However, a cell type-specific IFN-γ/IFN-γR-dependent mechanism regulates CD8(+) T suppressor cell recruitment, limits immunopathogenesis, preserves lung function, and enhances the resolution of PcP-related IRIS.

  16. Anti-CD20 antibody therapy and susceptibility to Pneumocystis pneumonia.

    PubMed

    Elsegeiny, Waleed; Eddens, Taylor; Chen, Kong; Kolls, Jay K

    2015-05-01

    Anti-CD20 antibody therapy has been a useful medication for managing non-Hodgkin's lymphoma as well as autoimmune diseases characterized by autoantibody generation. CD20 is expressed during most developmental stages of B lymphocytes; thus, CD20 depletion leads to B-lymphocyte deficiency. As the drug has become more widely used, there has been an increase in the number of case reports of patients developing Pneumocystis pneumonia. The role of anti-CD20 in Pneumocystis jirovecii infection is under debate due to the fact that most patients receiving it are on a regimen of multiple immunosuppressive medications. To address the specific role of CD20 depletion in host immunity against Pneumocystis, we examined a murine anti-CD20 depleting antibody. We demonstrated that anti-CD20 alone is permissive for Pneumocystis infection and that anti-CD20 impairs components of type II immunity, such as production of interleukin-4 (IL-4), IL-5, and IL-13 by whole-lung cells, in response to Pneumocystis murina. We also demonstrated that CD4(+) T cells from mice treated with anti-CD20 during Pneumocystis infection are incapable of mounting a protective immune response when transferred into Rag1(-/-) mice. Thus, CD20(+) cells are critical for generating protective CD4(+) T-cell immune responses against this organism.

  17. Combined quantification of pulmonary Pneumocystis jirovecii DNA and serum (1->3)-β-D-glucan for differential diagnosis of pneumocystis pneumonia and Pneumocystis colonization.

    PubMed

    Damiani, Céline; Le Gal, Solène; Da Costa, Cécilia; Virmaux, Michèle; Nevez, Gilles; Totet, Anne

    2013-10-01

    This study assessed a quantitative PCR (qPCR) assay for Pneumocystis jirovecii quantification in bronchoalveolar lavage (BAL) fluid samples combined with serum (1→3)-β-d-glucan (BG) level detection to distinguish Pneumocystis pneumonia (PCP) from pulmonary colonization with P. jirovecii. Forty-six patients for whom P. jirovecii was initially detected in BAL fluid samples were retrospectively enrolled. Based on clinical data and results of P. jirovecii detection, 17 and 29 patients were diagnosed with PCP and colonization, respectively. BAL fluid samples were reassayed using a qPCR assay targeting the mitochondrial large subunit rRNA gene. qPCR results and serum BG levels (from a Fungitell kit) were analyzed conjointly. P. jirovecii DNA copy numbers were significantly higher in the PCP group than in the colonization group (1.3 × 10(7) versus 3.4 × 10(3) copies/μl, P < 0.05). A lower cutoff value (1.6 × 10(3) copies/μl) achieving 100% sensitivity for PCP diagnosis and an upper cutoff value (2 × 10(4) copies/μl) achieving 100% specificity were determined. Applying these two values, 13/17 PCP patients and 19/29 colonized patients were correctly assigned to their patient groups. For the remaining 14 patients with P. jirovecii DNA copy numbers between the cutoff values, PCP and colonization could not be distinguished on the basis of qPCR results. Four of these patients who were initially assigned to the PCP group presented BG levels of ≥100 pg/ml. The other 10 patients, who were initially assigned to the colonization group, presented BG levels of <100 pg/ml. These results suggest that the combination of the qPCR assay, applying cutoff values of 1.6 × 10(3) and 2 × 10(4) copies/μl, and serum BG detection, applying a 100 pg/ml threshold, can differentiate PCP and colonization diagnoses.

  18. Late Onset Combined Immunodeficiency Presenting with Recurrent Pneumocystis jiroveci Pneumonia

    PubMed Central

    Baraboutis, Ioannis G.; Karnesis, Lazaros

    2014-01-01

    Late onset combined immunodeficiency (LOCID) is a recently described variant of common variable immunodeficiency (CVID), involving adult patients presenting with opportunistic infections and/or low CD4+ lymphocyte counts. A 36-year-old male with unremarkable past medical history presented with fever, respiratory failure, and lymphocytopenia. He was found to have Pneumocystis jiroveci pneumonia (PJP), subsequently complicated by recurrent hospital-acquired Pseudomonas aeruginosa pneumonia and immune reconstitution phenomena, attributed to restoration of immunoglobulin levels. Clinicians should be aware of LOCID, which could be confused with HIV infection/AIDS or idiopathic CD4 lymphocytopenia. In the English bibliography there is only one case report, where PJP was the initial presentation of CVID (that case would probably be classified as LOCID). Phenomena of immune reconstitution are described in various settings, including primary immunodeficiency, manifesting as temporary clinical and radiologic deterioration and leading to misperceptions of therapeutic failure and/or presence of alternative/additional diagnoses. PMID:24799913

  19. Inhibition of recombinant Pneumocystis carinii dihydropteroate synthetase by sulfa drugs.

    PubMed

    Hong, Y L; Hossler, P A; Calhoun, D H; Meshnick, S R

    1995-08-01

    Forty-four sulfa drugs were screened against crude preparations of recombinant Pneumocystis carinii dihydropteroate synthetase. The apparent Michaelis-Menten constants (Km) for p-aminobenzoic acid and 7,8-dihydro-6-hydroxymethylpterin pyrophosphate were 0.34 +/- 0.02 and 2.50 +/- 0.71 microM, respectively. Several sulfa drugs, including sulfathiazole, sulfachlorpyridazine, sulfamethoxypyridazine, and sulfathiourea, inhibited dihydropteroate synthetase approximately as well as sulfamethoxazole, as determined by the concentrations which cause 50% inhibition and/or by Ki. For all sulfones and sulfonamides tested, unsubstituted p-amino groups were necessary for activity, and sulfonamides containing an N1-heterocyclic substituent were found to be the most effective inhibitors. Folate biosynthesis in isolated intact P. carinii was approximately equally sensitive to inhibition by sulfamethoxazole, sulfachlorpyridazine, sulfamethoxypyridazine, sulfisoxazole, and sulfathiazole. Two of these drugs, sulfamethoxypyridazine and sulfisoxazole, are known to be less toxic than sulfamethoxazole and should be further evaluated for the treatment of P. carinii pneumonia.

  20. Sulfa use, dihydropteroate synthase mutations, and Pneumocystis jirovecii pneumonia.

    PubMed

    Stein, Cheryl R; Poole, Charles; Kazanjian, Powel; Meshnick, Steven R

    2004-10-01

    A systematic review was conducted to examine the associations in Pneumocystis jirovecii pneumonia (PCP) patients between dihydropteroate synthase (DHPS) mutations and sulfa or sulfone (sulfa) prophylaxis and between DHPS mutations and sulfa treatment outcome. Selection criteria included study populations composed entirely of PCP patients and mutation or treatment outcome results for all patients, regardless of exposure status. Based on 13 studies, the risk of developing DHPS mutations is higher for PCP patients receiving sulfa prophylaxis than for PCP patients not receiving sulfa prophylaxis (p < 0.001). Results are too heterogeneous (p < 0.001) to warrant a single summary effect estimate. Estimated effects are weaker after 1996 and stronger in studies that included multiple isolates per patient. Five studies examined treatment outcome. The effect of DHPS mutations on treatment outcome has not been well studied, and the few studies that have been conducted are inconsistent even as to the presence or absence of an association.

  1. Gallium accumulation in early pulmonary Pneumocystis carinii infection

    SciTech Connect

    Stevens, D.A.; Allegra, J.C.

    1986-09-01

    The accumulation of gallium 67 citrate in pulmonary Pneumocystis carinii is well known. The sensitivity of gallium uptake in detecting early inflammatory processes, even when conventional roentgenograms are normal, would seem to make it possible in immunocompromised patients to make a presumptive diagnosis of this serious infection early in its course without using invasive techniques to demonstrate the organism. However, the presence of gallium uptake in radiation pneumonitis, pulmonary drug toxicity, and other processes that also occur in this group limit its usefulness. In our two patients--a young woman with Hodgkin's disease and an elderly woman with small cell lung cancer--this technique proved helpful. Although the latter patient was successfully treated empirically, such empiric treatment should be reserved for patients unable or unwilling to undergo invasive tests. Pulmonary gallium uptake in patients with respiratory symptoms, even with a normal chest film, should prompt attempts to directly demonstrate the organism.

  2. Increasing Pneumocystis pneumonia, England, UK, 2000-2010.

    PubMed

    Maini, Rishma; Henderson, Katherine L; Sheridan, Elizabeth A; Lamagni, Theresa; Nichols, Gordon; Delpech, Valerie; Phin, Nick

    2013-03-01

    After an increase in the number of reported cases of Pneumocystis jirovecii pneumonia in England, we investigated data from 2000-2010 to verify the increase. We analyzed national databases for microbiological and clinical diagnoses of P. jirovecii pneumonia and associated deaths. We found that laboratory-confirmed cases in England had increased an average of 7% per year and that death certifications and hospital admissions also increased. Hospital admissions indicated increased P. jirovecii pneumonia diagnoses among patients not infected with HIV, particularly among those who had received a transplant or had a hematologic malignancy. A new risk was identified: preexisting lung disease. Infection rates among HIV-positive adults decreased. The results confirm that diagnoses of potentially preventable P. jirovecii pneumonia among persons outside the known risk group of persons with HIV infection have increased. This finding warrants further characterization of risk groups and a review of P. jirovecii pneumonia prevention strategies.

  3. Surface labeling of Pneumocystis carinii from in vitro culture

    SciTech Connect

    Radding, J.A.; Armstrong, M.Y.; Bogucki, M.S.; Richards, F.F. )

    1989-01-01

    Pneumocystis carinii is an opportunistic pathogen of man, carried as a commensal in healthy subjects. It frequently causes a fatal pneumonia in the immunosuppressed host. It is a major complication of HIV-1 infection in man (AIDS). Using surface radioiodination of rat-derived P. carinii trophozoites obtained from in vitro culture, a major surface glycoprotein (gp120) has been identified. The glycoprotein exhibits adherent behavior similar to that of the intact organism. Purification of gp120 by conventional methods was unsuccessful as the glycoprotein irreversibly bound to numerous column matrices. A combination of gel chromatography and hydroxyapatite chromatography in sodium dodecylsulfate was utilized to purify the glycoprotein. Some preliminary characterization of the glycoprotein is presented.

  4. Diagnosis of Pneumocystis pneumonia: evaluation of four serologic biomarkers.

    PubMed

    Esteves, F; Calé, S S; Badura, R; de Boer, M G; Maltez, F; Calderón, E J; van der Reijden, T J; Márquez-Martín, E; Antunes, F; Matos, O

    2015-04-01

    The diagnosis of Pneumocystis pneumonia (PCP) relies on microscopic visualization of Pneumocystis jirovecii organisms or DNA detection in pulmonary specimens. This study aimed to assess the usefulness of (1-3)-β-d-glucan (BG), Krebs von den Lungen-6 antigen (KL-6), lactate dehydrogenase (LDH) and S-adenosyl methionine (SAM) as serologic biomarkers in the diagnosis of PCP. Serum levels of BG, KL-6, LDH and SAM were investigated in 145 Portuguese patients, 50 patients from the Netherlands, 25 Spanish patients and 40 Portuguese blood donors. Data on clinical presentation, chest imaging and gasometry tests were available. PCP cases were confirmed by microscopy and PCR techniques. A cost-effectiveness analysis was performed. BG was found to be the most reliable serologic biomarker for PCP diagnosis, followed by KL-6, LDH and SAM. The BG/KL-6 combination test was the most accurate serologic approach for PCP diagnosis, with 94.3% sensitivity and 89.6% specificity. Although less sensitive/specific than the reference standard classic methods based on bronchoalveolar lavage followed by microscopic or molecular detection of P. jirovecii organisms, the BG/KL-6 test may provide a less onerous procedure for PCP diagnosis, as it uses a minimally invasive and inexpensive specimen (blood), which may be also a major benefit for the patient's care. The BG/KL-6 combination test should be interpreted within the clinical context, and it may be used as a preliminary screening test in patients with primary suspicion of PCP, or as an alternative diagnostic procedure in patients with respiratory failure or in children, avoiding the associated risk of complications by the use of bronchoscopy.

  5. Near-Universal Prevalence of Pneumocystis and Associated Increase in Mucus in the Lungs of Infants With Sudden Unexpected Death

    PubMed Central

    Vargas, Sergio L.; Ponce, Carolina A.; Gallo, Miriam; Pérez, Francisco; Astorga, J.-Felipe; Bustamante, Rebeca; Chabé, Magali; Durand-Joly, Isabelle; Iturra, Pablo; Miller, Robert F.; Aliouat, El Moukthar; Dei-Cas, Eduardo

    2013-01-01

    Background. Pneumocystis without obvious accompanying pathology is occasionally reported in autopsied infant lungs. Its prevalence and significance are unknown. Interestingly, this mild infection induces a strong activation of mucus secretion–related genes in young immunocompetent rodents that has not been explored in infants. Excess mucus is induced by multiple airway offenders through nonspecific pathways and would explain a cofactor role of Pneumocystis in respiratory disease. We undertook characterization of the prevalence of Pneumocystis and associated mucus in infant lungs. Methods. Samples from 128 infants (mean age, 101 days) who died suddenly and unexpectedly in Santiago during 1999–2004 were examined for Pneumocystis using nested polymerase chain reaction (nPCR) amplification of the P. jirovecii mtLSU ribosomal RNA gene and immunofluorescence microscopy (IF). Pneumocystis-negative infants 28 days and older and their age-closest positives were studied for MUC5AC expression and Pneumocystis burden by Western blot and quantitative PCR, respectively. Results. Pneumocystis DNA was detected by nPCR in 105 of the 128 infants (82.0%) and Pneumocystis organisms were visualized by IF in 99 (94.3%) of the DNA-positive infants. The infection was commonest at 3–4 months with 40 of 41 (97.6%) infants of that age testing positive. MUC5AC was significantly increased in Pneumocystis-positive tissue specimens (P = .013). Death was unexplained in 113 (88.3%) infants; Pneumocystis was detected in 95 (84.0%) of them vs 10 of 15 (66.7%) with explained death (P = .28). Conclusions. A highly focal Pneumocystis infection associated to increased mucus expression is almost universally present in the lungs of infants dying unexpectedly in the community regardless of autopsy diagnosis. PMID:23074306

  6. A case of pneumocystis pneumonia associated with everolimus therapy for renal cell carcinoma.

    PubMed

    Saito, Yoshinobu; Nagayama, Mikie; Miura, Yukiko; Ogushi, Satoko; Suzuki, Yasutomo; Noro, Rintaro; Minegishi, Yuji; Kimura, Go; Kondo, Yukihiro; Gemma, Akihiko

    2013-05-01

    A 76-year-old female with advanced renal cell carcinoma had been treated with everolimus for 3 months. She visited our hospital because of a cough and fever lasting a few days. Chest X-rays showed bilateral infiltrative shadows, and a chest computed tomography scan showed homogeneous ground-glass opacities with mosaic patterns, especially in the apical region. The laboratory results revealed a decreased white blood cell count with lymphocytopenia and high levels of lactate dehydrogenase, C-reactive protein and KL-6. Pneumonitis was suspected and, therefore, everolimus therapy was interrupted. At that time, the pneumonitis was thought to be drug-induced interstitial lung disease. However, it was not possible to rule out pneumocystis pneumonia, because the patient was immunocompromised and the computed tomography findings suggested the possibility of pneumocystis pneumonia. The pneumonitis progressed rapidly and the patient developed respiratory failure, so we performed bronchoalveolar lavage to make a definitive diagnosis, and simultaneously started treatment with prednisolone and trimethoprim-sulfamethoxazole to cover both interstitial lung disease and pneumocystis pneumonia. A polymerase chain reaction assay of the bronchoalveolar lavage fluid was positive for Pneumocystis carinii DNA, and the serum level of β-d-glucan was significantly elevated. Thus, the patient was diagnosed with pneumocystis pneumonia, which was cured by the treatment. Interstitial lung disease is a major adverse drug reaction associated with everolimus, and interstitial lung disease is the first condition suspected when a patient presents with pneumonitis during everolimus therapy. Pneumocystis pneumonia associated with everolimus therapy is rare, but our experience suggests that pneumocystis pneumonia should be considered as a differential diagnosis when pneumonitis is encountered in patients receiving everolimus therapy.

  7. Association between circulating DNA, serum (1->3)-β-D-glucan, and pulmonary fungal burden in Pneumocystis pneumonia.

    PubMed

    Costa, Jean-Marc; Botterel, Françoise; Cabaret, Odile; Foulet, Françoise; Cordonnier, Catherine; Bretagne, Stéphane

    2012-07-01

    Circulating Pneumocystis jirovecii DNA and (1→3)-β-d-glucan determined in 70 serum samples from immunocompromised patients were compared to fungal load in bronchoalveolar lavage fluids assessed using quantitative polymerase chain reaction. Both serum biomarkers are influenced by pulmonary fungal load, which should be taken into account when diagnosing Pneumocystis infection.

  8. Complexity of the MSG gene family of Pneumocystis carinii

    PubMed Central

    Keely, Scott P; Stringer, James R

    2009-01-01

    Background The relationship between the parasitic fungus Pneumocystis carinii and its host, the laboratory rat, presumably involves features that allow the fungus to circumvent attacks by the immune system. It is hypothesized that the major surface glycoprotein (MSG) gene family endows Pneumocystis with the capacity to vary its surface. This gene family is comprised of approximately 80 genes, which each are approximately 3 kb long. Expression of the MSG gene family is regulated by a cis-dependent mechanism that involves a unique telomeric site in the genome called the expression site. Only the MSG gene adjacent to the expression site is represented by messenger RNA. Several P. carinii MSG genes have been sequenced, which showed that genes in the family can encode distinct isoforms of MSG. The vast majority of family members have not been characterized at the sequence level. Results The first 300 basepairs of MSG genes were subjected to analysis herein. Analysis of 581 MSG sequence reads from P. carinii genomic DNA yielded 281 different sequences. However, many of the sequence reads differed from others at only one site, a degree of variation consistent with that expected to be caused by error. Accounting for error reduced the number of truly distinct sequences observed to 158, roughly twice the number expected if the gene family contains 80 members. The size of the gene family was verified by PCR. The excess of distinct sequences appeared to be due to allelic variation. Discounting alleles, there were 73 different MSG genes observed. The 73 genes differed by 19% on average. Variable regions were rich in nucleotide differences that changed the encoded protein. The genes shared three regions in which at least 16 consecutive basepairs were invariant. There were numerous cases where two different genes were identical within a region that was variable among family members as a whole, suggesting recombination among family members. Conclusion A set of sequences that

  9. [A Case of Pneumocystis Pneumonia during Chemotherapy for Recurrent Ovarian Cancer].

    PubMed

    Shiomi, Mayu; Okubo, Rieko; Miyagi, Kanoko; Murakami, Junko; Kuwaduru, Tomoichiro; Uragami, Kiri; Nakagawa, Mio; Yoshioka, Emi; Tsuruta, Tomohiko; Tashima, Rina; Hori, Kensuke; Ito, Kimihiko

    2015-07-01

    A 53-year-old patient with recurrent ovarian clear cell adenocarcinoma developed fever (39°C) and cough on day 28 of liposomal doxorubicin chemotherapy, the 4th cycle of the 4th regimen since initial treatment. Drug-induced interstitial pneumonia was suspected from a chest CT image showing diffuse ground-glass opacities; however, we deduced pneumocystis pneumonia from the elevated serum beta-D-glucan levels. After effective treatment with sulfamethoxazole and amphotericin B, the patient's symptoms and radiological findings improved. Pneumocystis pneumonia is an opportunistic infection that poses a risk not only for patients undergoing aggressive immunosuppressive therapy, those infected with HIV, and those with transplants, but also for patients undergoing chemotherapy. When pneumonia is diagnosed during chemotherapy, it is essential to consider the possibility of pneumocystis pneumonia.

  10. Prevention of infection due to Pneumocystis spp. in human immunodeficiency virus-negative immunocompromised patients.

    PubMed

    Rodriguez, Martin; Fishman, Jay A

    2004-10-01

    Pneumocystis infection in humans was originally described in 1942. The organism was initially thought to be a protozoan, but more recent data suggest that it is more closely related to the fungi. Patients with cellular immune deficiencies are at risk for the development of symptomatic Pneumocystis infection. Populations at risk also include patients with hematologic and nonhematologic malignancies, hematopoietic stem cell transplant recipients, solid-organ recipients, and patients receiving immunosuppressive therapies for connective tissue disorders and vasculitides. Trimethoprim-sulfamethoxazole is the agent of choice for prophylaxis against Pneumocystis unless a clear contraindication is identified. Other options include pentamidine, dapsone, dapsone-pyrimethamine, and atovaquone. The risk for PCP varies based on individual immune defects, regional differences, and immunosuppressive regimens. Prophylactic strategies must be linked to an ongoing assessment of the patient's risk for disease.

  11. Pneumocystis jiroveci (carinii) pneumonia after infliximab therapy: a review of 84 cases.

    PubMed

    Kaur, Nirmal; Mahl, Thomas C

    2007-06-01

    Anti-tumor necrosis factor-alpha therapy, infliximab, has become an established effective therapy for Crohn's disease and rheumatoid arthritis. However, infliximab has been associated with various opportunistic pathogens such as tuberculosis, histoplasmosis, listeriosis, aspergillosis, and Pneumocystis jiroveci (carinii) pneumonia. We reviewed the FDA Adverse Event Reporting System for cases of Pneumocystis associated with infliximab use from January 1998 through December 2003. The database revealed 84 cases of PCP following infliximab therapy. Concomitant immunosuppressive medications included methotrexate, prednisone, azathioprine, 6-mercaptopurine, and cyclosporine. Mean time between infliximab infusion and onset of symptoms of pneumonia, when reported, was 21 days (+/-18 days; n=40). Twenty-three of the 84 (27%) patients died. The use of infliximab is associated with PCP infection. Further, the mortality rate for Pneumocystis following the use of infliximab is significant. The potential for severe disease, mortality, and often subtle presentation of these infections warrant close follow-up and careful monitoring after therapy.

  12. Imidazoquines as antimalarial and anti-pneumocystis agents✶

    PubMed Central

    Vale, Nuno; Prudêncio, Miguel; Marques, Catarina A.; Collins, Margaret S.; Gut, Jiri; Nogueira, Fátima; Matos, Joana; Rosenthal, Philip J.; Cushion, Melanie T.; do Rosário, Virgílio E.; Mota, Maria M.; Moreira, Rui; Gomes, Paula

    2009-01-01

    Peptidomimetic imidazolidin-4-one derivatives of primaquine (imidazoquines) recently displayed in vitro activity against blood schizonts of a chloroquine-resistant strain of Plasmodium falciparum. Preliminary studies with a subset of such imidazoquines showed them to both block transmission of P. berghei malaria from mouse to mosquito and be highly stable towards hydrolysis at physiological conditions. This prompted us to have deeper insight into the activity of imidazoquines against both Plasmodia and Pneumocystis carinii, on which primaquine is also active. Full assessment of the in vivo transmission-blocking activity of imidazoquines, in vitro tissue-schizontocidal activity on P. berghei-infected hepatocytes, and in vitro anti-P. carinii activity is now reported. All compounds were active in these biological assays, with generally lower activity than the parent drug. However, imidazoquines’ stability against both oxidative deamination and proteolytic degradation suggest that they will probably have higher oral bioavailability and lower hematotoxicity than primaquine, which might translate into higher therapeutic indexes. PMID:19799426

  13. Analogs of Pentamidine as Potential Anti-Pneumocystis Chemotherapeutics

    PubMed Central

    Maciejewska, Dorota; Żabinski, Jerzy; Kaźmierczak, Pawel; Rezler, Mateusz; Krassowska-Świebocka, Barbara; Collins, Margaret S.; Cushion, Melanie T.

    2012-01-01

    A series of 20 pentamidine analogs were prepared using 2 general Schemes that evaluated heteroatoms, sulfobenzene and alkanediamide groups in the aliphatic linker and methoxy substituents attached to the benzene rings for efficacy against the fungal pathogen, Pneumocystis carinii in an ATP bioassay. All but one of the 20 bisamidines reduced the ATP content of the P. carinii over the 72 hr of the assay period. The highest activities were associated with the lack of methoxy groups and the presence of the O, N and S heteroatoms. Activity (IC50) for compounds 1, 5, 6, 10 ranged from 1.1 to 2.13 µM. The compound 11 with similar activity (1.33 µM), bears a sulfobenzene group at a nitrogen in the aliphatic linker. The alkanediamide-linked bisbenzamidines showed a moderate inhibition of ATP. Generally, the inclusion of a heteroatom in the aliphatic linker and absence of methoxy groups at the benzene rings were associated with higher activities in this assay. Of note, most of the compounds had little to no cytotoxicity in mammalian cell cultures. Although not quite as potent as other pentamidine derivatives, these compounds hold promise for decreased side effects within the mammalian host. PMID:22200403

  14. Experimental Pneumocystis carinii pneumonia in different strains of cortisonized mice.

    PubMed Central

    Walzer, P D; Powell, R D; Yoneda, K

    1979-01-01

    Pneumocystis carinii pneumonia was produced in eight different strains of mice by the administration of corticosteroids, low (8%)-protein diet, and tetracycline in the drinking water. Heavier degrees of P. carinii infection were most consistently found in C3H/HeN mice; intermediate levels occurred in BALB/c AnN, C57BL/6N, B10.A(2R), AKR/J, and Swiss Webster mice; lighter degrees were found in DBA/2N and DBA/IJ mice. Histopathologically, P. carinii organisms were morphologically indistinguishable from human and rat P. carinii, and elicited a predominantly mononuclear response that was similar among the various mouse strains. The optimal cortisone acetate regimen was 1 mg injected subcutaneously twice weekly. Higher doses shortened the life span of the mice, presumably by inducing overwhelming bacterial infection. This problem occurred not only in different strains of mice, but also in the same strain of mice obtained from different breeders. Thus, cortisonized mice should be useful in the study of experimental P. carinii infection. Success of this model depends on the corticosteroid dose, as well as the strain, source, general health, and preexisting microbial flora of the mice chosen for study. Images PMID:313907

  15. Binary fission of Pneumocystis carinii trophozoites grown in vitro.

    PubMed

    Richardson, J D; Queener, S F; Bartlett, M; Smith, J

    1989-01-01

    Trophozoites grown in vitro were shown to undergo binary fission by transmission electron microscopy (TEM). Standard fixation with subsequent embedding in Spurr was employed using 3% glutaraldehyde and 1% osmium tetroxide with 5% sucrose added to both fixatives and 0.1 M cacodylate buffer washes. Trophozoites were grown on WI-38 cells in vitro. Trophozoites were found in various stages of fission. The dividing trophozoite has daughter cells that are rounder than the pleomorphic, non-dividing trophozoites. Tubular forms external to the dividing trophozoites were decreased in number; tubular forms when present were concentrated around the forming septa. Nuclear material was sometimes, but not always, well defined in both daughter cells. There was no concentration of nuclear material at the poles. Vacuoles without membrane were present in the dividing forms. Separate nuclear regions were sometimes found in the dividing trophozoites. These observations suggest that binary fission does occur in culture; however, the significance of binary fission to the life cycle of Pneumocystis carinii (Pc) is not yet clear.

  16. Nursing care of the adult client with infection due to Pneumocystis carinii.

    PubMed

    Ungvarski, P J

    1991-01-01

    Since the beginning of the AIDS epidemic, Pneumocystis carinii pneumonia (PCP) has been the most prevalent opportunistic infection diagnosed in people with AIDS. After a decade of care and research, significant progress has been achieved not only in treating PCP but also in preventing it. Concomitantly, new problems have surfaced, for example, nosocomial spread of mycobacterium tuberculosis and occupational hazards, both related to treating people living with AIDS (PWAs) with PCP. The author provides a comprehensive overview of infection due to Pneumocystis carinii, as seen in adults with HIV infection, and the related nursing issues.

  17. Application of DNA amplification to pneumocystosis: presence of serum Pneumocystis carinii DNA during human and experimentally induced Pneumocystis carinii pneumonia

    PubMed Central

    1992-01-01

    Pneumocystis carinii pneumonia is a leading cause of morbidity and mortality in patients with the acquired immunodeficiency syndrome (AIDS). Much remains unknown about the basic biology of P. carinii and studies of this infection have been hampered by the lack of cultivation methods. We developed a sensitive and specific assay for P. carinii by utilizing DNA amplification of the P. carinii dihydrofolate reductase (DHFR) gene. By this method, P. carinii DNA was detected in the lungs of rats with experimentally induced P. carinii pneumonia 2 wk before the onset of histopathological changes. DNA amplification analysis of serum demonstrated that by 10 wk of corticosteroid treatment, 12 of 12 (100%) infected rats had circulating DHFR DNA. P. carinii DHFR DNA also was detected in the serum of patients with AIDS and active P. carinii pneumonia (12 of 14 sera collected prospectively). Patients with advanced AIDS but without a history of P. carinii pneumonia were negative by this assay (0 of 6 sera examined). Serum polymerase chain reaction may facilitate investigations into the natural history and epidemiology of P. carinii infection, provide insight into the pathogenesis of parasite dissemination, and offer a useful, noninvasive diagnostic test for the detection of human pneumocystosis. PMID:1402679

  18. Pneumocystis carinii causes a distinctive interstitial pneumonia in immunocompetent laboratory rats that had been attributed to "rat respiratory virus".

    PubMed

    Henderson, K S; Dole, V; Parker, N J; Momtsios, P; Banu, L; Brouillette, R; Simon, M A; Albers, T M; Pritchett-Corning, K R; Clifford, C B; Shek, W R

    2012-05-01

    A prevalent and distinctive infectious interstitial pneumonia (IIP) of immunocompetent laboratory rats was suspected to be caused by a putative virus, termed rat respiratory virus, but this was never substantiated. To study this disease, 2 isolators were independently populated with rats from colonies with endemic disease, which was perpetuated by the regular addition of naive rats. After Pneumocystis was demonstrated by histopathology and polymerase chain reaction (PCR) in the lungs of rats from both isolators and an earlier bedding transmission study, the relationship between Pneumocystis and IIP was explored further by analyzing specimens from 3 contact transmission experiments, diagnostic submissions, and barrier room breeding colonies, including 1 with and 49 without IIP. Quantitative (q) PCR and immunofluorescence assay only detected Pneumocystis infection and serum antibodies in rats from experiments or colonies in which IIP was diagnosed by histopathology. In immunocompetent hosts, the Pneumocystis concentration in lungs corresponded to the severity and prevalence of IIP; seroconversion occurred when IIP developed and was followed by the concurrent clearance of Pneumocystis from lungs and resolution of disease. Experimentally infected immunodeficient RNU rats, by contrast, did not seroconvert to Pneumocystis or recover from infection. qPCR found Pneumocystis at significantly higher concentrations and much more often in lungs than in bronchial and nasal washes and failed to detect Pneumocystis in oral swabs. The sequences of a mitochondrial ribosomal large-subunit gene region for Pneumocystis from 11 distinct IIP sources were all identical to that of P. carinii. These data provide substantial evidence that P. carinii causes IIP in immunocompetent rats.

  19. Pneumocystis polymerase chain reaction and blood (1→3)-β-D-glucan assays to predict survival with suspected Pneumocystis jirovecii pneumonia.

    PubMed

    Matsumura, Yasufumi; Ito, Yutaka; Yamamoto, Masaki; Matsushima, Aki; Nagao, Miki; Takakura, Shunji; Iinuma, Yoshitsugu; Ichiyama, Satoshi

    2014-02-01

    Pneumocystis polymerase chain reaction (PCR) and blood (1→3)-β-D-glucan assays are known to be useful for the diagnosis of Pneumocystis pneumonia (PCP). However, their impact on the outcome of clinically suspected PCP patients has not yet been elucidated. Between January 2008 and July 2011, we prospectively observed 190 immunocompromised patients who had ground-glass opacity on chest computed tomography scans and were suspected to have PCP. The blood β-D-glucan levels of these patients were measured, and PCR was used to detect Pneumocystis jirovecii in the respiratory samples. The 30-day mortality rates and related factors were assessed. The 30-day mortality rate of all included patients was 21.6%. Both β-D-glucan-positive (10.1%) and PCR-positive patients (15.0%) had significantly lower mortality rates than β-D-glucan-negative (28.1%) or PCR-negative patients (30.1%). All of the 13 definite PCP patients had positive PCR and β-D-glucan results, received anti-PCP treatments, and survived. Among the 72 patients who were negative for microscopic detection of P. jirovecii but received anti-PCP treatments, positive PCR results (odds ratio [OR], 0.14; 95% confidence interval [CI], 0.02-0.74), a high Sequential Organ Failure Assessment score (OR, 1.42; CI, 1.08-1.88), and positive β-D-glucan levels (OR 0.25, CI 0.06-1.02) were associated with mortality rates using stepwise logistic regression analyses. A positive Pneumocystis PCR or β-D-glucan test was a candidate predictor of survival in patients who were suspected of having PCP, even though negative for visual detection by microscopy.

  20. AIDS-related Pneumocystis jirovecii genotypes in French Guiana.

    PubMed

    Le Gal, Solène; Blanchet, Denis; Damiani, Céline; Guéguen, Paul; Virmaux, Michèle; Abboud, Philippe; Guillot, Geneviève; Kérangart, Stéphane; Merle, Cédric; Calderon, Enrique; Totet, Anne; Carme, Bernard; Nevez, Gilles

    2015-01-01

    The study described Pneumocystis jirovecii (P. jirovecii) multilocus typing in seven AIDS patients living in French Guiana (Cayenne Hospital) and seven immunosuppressed patients living in Brest, metropolitan France (Brest Hospital). Archival P. jirovecii specimens were examined at the dihydropteroate synthase (DHPS) locus using a PCR-RFLP technique, the internal transcribed spacer (ITS) 1 and ITS 2 and the mitochondrial large subunit rRNA (mtLSUrRNA) gene using PCR and sequencing. Analysis of typing results were combined with an analysis of the literature on P. jirovecii mtLSUrRNA types and ITS haplotypes. A wild DHPS type was identified in six Guianese patients and in seven patients from metropolitan France whereas a DHPS mutant was infected in the remaining Guianese patient. Typing of the two other loci pointed out a high diversity of ITS haplotypes and an average diversity of mtLSUrRNA types in French Guiana with a partial commonality of these haplotypes and types described in metropolitan France and around the world. Combining DHPS, ITS and mtLSU types, 12 different multilocus genotypes (MLGs) were identified, 4 MLGs in Guianese patients and 8 MLGs in Brest patients. MLG analysis allows to discriminate patients in 2 groups according to their geographical origin. Indeed, none of the MLGs identified in the Guianese patients were found in the Brest patients and none of the MLGs identified in the Brest patients were found in the Guianese patients. These results show that in French Guiana (i) PCP involving DHPS mutants occur, (ii) there is a diversity of ITS and mtLSUrRNA types and (iii) although partial type commonality in this territory and metropolitan France can be observed, MLG analysis suggests that P. jirovecii organisms from French Guiana may present specific characteristics.

  1. IMP dehydrogenase from Pneumocystis carinii as a potential drug target.

    PubMed Central

    O'Gara, M J; Lee, C H; Weinberg, G A; Nott, J M; Queener, S F

    1997-01-01

    Mycophenolic acid, a specific inhibitor of IMP dehydrogenase (IMPDH; EC 1.1.1.205), is a potent inhibitor of Pneumocystis carinii growth in culture, suggesting that IMPDH may be a sensitive target for chemotherapy in this organism. The IMPDH gene was cloned as a first step to characterizing the enzyme and developing selective inhibitors. A 1.3-kb fragment containing a portion of the P. carinii IMPDH gene was amplified by PCR with two degenerate oligonucleotides based on conserved sequences in IMPDH from humans and four different microorganisms. Northern hybridization analysis showed the P. carinii IMPDH mRNA to be approximately 1.6 kb. The entire cDNA encoding P. carinii IMPDH was isolated and cloned. The deduced amino acid sequence of P. carinii IMPDH shared homology with bacterial (31 to 38%), protozoal (48 to 59%), mammalian (60 to 62%), and fungal (62%) IMPDH enzymes. The IMPDH cDNA was expressed by using a T7 expression system in an IMPDH-deficient strain of Escherichia coli (strain S phi 1101). E. coli S phi 1101 cells containing the P. carinii IMPDH gene were able to grow on medium lacking guanine, implying that the protein expressed in vivo was functional. Extracts of these E. coli cells contained IMPDH activity that had an apparent Km for IMP of 21.7 +/- 0.3 microM and an apparent Km for NAD of 314 +/- 84 microM (mean +/- standard error of the mean; n = 3), and the activity was inhibited by mycophenolic acid (50% inhibitory concentration, 24 microM; n = 2). PMID:8980752

  2. Environmental Risk Factors for Pneumocystis Pneumonia Hospitalizations in HIV Patients

    PubMed Central

    Djawe, Kpandja; Levin, Linda; Swartzman, Alexandra; Fong, Serena; Roth, Brenna; Subramanian, Anuradha; Grieco, Katherine; Jarlsberg, Leah; Miller, Robert F.; Huang, Laurence; Walzer, Peter D.

    2013-01-01

    Background. Pneumocystis pneumonia (PcP) is the second leading cause of morbidity and mortality in human immunodeficiency virus (HIV)–infected patients in the United States. Although the host risk factors for the development of PcP are well established, the environmental (climatological, air pollution) risk factors are poorly understood. The major goal of this study was to determine the environmental risk factors for admissions of HIV-positive patients with PcP to a single medical center. Methods. Between 1997 and 2008, 457 HIV-positive patients with microscopically confirmed PcP were admitted to the San Francisco General Hospital. A case-crossover design was applied to identify environmental risk factors for PcP hospitalizations. Climatological and air pollution data were collected from the Environmental Protection Agency and Weather Warehouse databases. Conditional logistic regression was used to evaluate the association of each environmental factor and PcP hospital admission. Results. Hospital admissions were significantly more common in the summer than in the other seasons. Increases in temperature and sulfur dioxide levels were independently associated with hospital admissions for PcP, but the effects of sulfur dioxide were modified by increasing carbon monoxide levels. Conclusions. This study identifies both climatological and air pollution constituents as independent risk factors for hospitalization of HIV-positive patients with PcP in San Francisco. Thus, the environmental effects on PcP are more likely complex than previously thought. Further studies are needed to understand how these factors exert their effects and to determine if these factors are associated with PcP in other geographic locations. PMID:23042978

  3. Pneumocystis carinii mutations associated with sulfa and sulfone prophylaxis failures in immunocompromised patients.

    PubMed

    Armstrong, W; Meshnick, S; Kazanjian, P

    2000-01-01

    Recent studies have shown that mutations in two amino acid positions of the Pneumocystis carinii dihydropteroate synthase gene are significantly more common in immunocompromised patients with P. carinii pneumonia who fail sulfa or sulfone prophylaxis. This paper reviews the studies that suggest that these mutations may be responsible for some failures of prophylaxis in P. carinii.

  4. Sulfa resistance and dihydropteroate synthase mutants in recurrent Pneumocystis carinii pneumonia.

    PubMed

    Nahimana, Aimable; Rabodonirina, Meja; Helweg-Larsen, Jannik; Meneau, Isabelle; Francioli, Patrick; Bille, Jacques; Hauser, Philippe M

    2003-07-01

    Failure of sulfa or sulfone prophylaxis is associated with mutations in Pneumocystis carinii gene coding for dihydropteroate synthase (DHPS). The DHPS genotype was analyzed in AIDS patients who had two separate episodes of P. carinii pneumonia. The results suggest that DHPS mutations can be selected de novo within patients by the pressure of a sulfa or sulfone drug.

  5. Finding your way through Pneumocystis sequences in the NCBI gene database.

    PubMed

    Weissenbacher-Lang, Christiane; Nedorost, Nora; Weissenböck, Herbert

    2014-01-01

    Pneumocystis sequences can be downloaded from GenBank for purposes as primer/probe design or phylogenetic studies. Due to changes in nomenclature and assignment, available sequences are presented with a variety of inhomogeneous information, which renders practical utilization difficult. The aim of this study was the descriptive evaluation of different parameters of 532 Pneumocystis sequences of mitochondrial and ribosomal origin downloaded from GenBank with regard to completeness and information content. Pneumocystis sequences were characterized by up to four different names. Official changes in nomenclature have only been partly implemented and the usage of the "forma specialis", a special feature of Pneumocystis, has only been established fragmentary in the database. Hints for a mitochondrial or ribosomal genomic origin could be found, but can easily be overlooked, which renders the download of wrong reference material possible. The specification of the host was either not available or variable regarding the used language and the localization of this information in the title or several subtitles, which limits their applicability in phylogenetic studies. Declaration of products and geographic origin was incomplete. The print version of this manuscript is completed by an online database which contains detailed information to every accession number included in the meta-analysis.

  6. Outcomes and duration of Pneumocystis jiroveci pneumonia therapy in infants with severe combined immunodeficiency.

    PubMed

    Lundgren, Ingrid S; Englund, Janet A; Burroughs, Lauri M; Torgerson, Troy R; Skoda-Smith, Suzanne

    2012-01-01

    This retrospective review of patients with severe combined immunodeficiency and Pneumocystis jiroveci pneumonia (PCP) evaluated the relationship between duration of therapy to treat PCP and overall survival. We found that 80% of patients receiving only 21 days of antibiotics survived to 12 months beyond hematopoietic cell transplant, whereas only 25% of patients who required longer treatment for PCP survived to stem cell engraftment.

  7. Presentation of severe combined immunodeficiency with respiratory syncytial virus and pneumocystis co-infection.

    PubMed

    Domínguez-Pinilla, Nerea; Allende-Martínez, Luis; Corral Sánchez, María Dolores; Arocena, Jaime de Inocencio; González-Granado, Luis Ignacio

    2015-04-01

    Severe combined immunodeficiency can cause severe, life-threatening viral, bacterial and fungal infections at an early age. We report a case of a 4-month-old boy with co-infection by respiratory syncytial virus and Pneumocystis jiroveci infection that led to recognition of severe combined immunodeficiency.

  8. Comparative Genomics Suggests That the Human Pathogenic Fungus Pneumocystis jirovecii Acquired Obligate Biotrophy through Gene Loss

    PubMed Central

    Cissé, Ousmane H.; Pagni, Marco; Hauser, Philippe M.

    2014-01-01

    Pneumocystis jirovecii is a fungal parasite that colonizes specifically humans and turns into an opportunistic pathogen in immunodeficient individuals. The fungus is able to reproduce extracellularly in host lungs without eliciting massive cellular death. The molecular mechanisms that govern this process are poorly understood, in part because of the lack of an in vitro culture system for Pneumocystis spp. In this study, we explored the origin and evolution of the putative biotrophy of P. jirovecii through comparative genomics and reconstruction of ancestral gene repertoires. We used the maximum parsimony method and genomes of related fungi of the Taphrinomycotina subphylum. Our results suggest that the last common ancestor of Pneumocystis spp. lost 2,324 genes in relation to the acquisition of obligate biotrophy. These losses may result from neutral drift and affect the biosyntheses of amino acids and thiamine, the assimilation of inorganic nitrogen and sulfur, and the catabolism of purines. In addition, P. jirovecii shows a reduced panel of lytic proteases and has lost the RNA interference machinery, which might contribute to its genome plasticity. Together with other characteristics, that is, a sex life cycle within the host, the absence of massive destruction of host cells, difficult culturing, and the lack of virulence factors, these gene losses constitute a unique combination of characteristics which are hallmarks of both obligate biotrophs and animal parasites. These findings suggest that Pneumocystis spp. should be considered as the first described obligate biotrophs of animals, whose evolution has been marked by gene losses. PMID:25062922

  9. Pneumocystis jirovecii pneumonia in non-HIV-infected patients in the era of novel immunosuppressive therapies.

    PubMed

    Tasaka, Sadatomo; Tokuda, Hitoshi

    2012-12-01

    In human immunodeficiency virus (HIV)-infected patients, Pneumocystis jirovecii pneumonia (PCP) is a well-known opportunistic infection, and its management has been established. However, PCP is an emerging threat to immunocompromised patients without HIV infection, such as those receiving novel immunosuppressive therapeutics for malignancy, organ transplantation, or connective tissue diseases. Clinical manifestations of PCP are quite different between patients with and without HIV infections. In patients without HIV infection, PCP rapidly progresses, is difficult to diagnose correctly, and causes severe respiratory failure with a poor prognosis. High-resolution computed tomography findings are different between PCP patients with HIV infection and those without. These differences in clinical and radiologic features are the result of severe or dysregulated inflammatory responses that are evoked by a relatively small number of Pneumocystis organisms in patients without HIV infection. In recent years, the usefulness of PCR and serum β-D-glucan assay for rapid and noninvasive diagnosis of PCP has been revealed. Although corticosteroid adjunctive to anti-Pneumocystis agents has been shown to be beneficial in some populations, the optimal dose and duration remain to be determined. Recent investigations revealed that Pneumocystis colonization is prevalent, and that asymptomatic carriers are at risk for developing PCP and can serve as the reservoir for the spread of Pneumocystis by person-to-person transmission. These findings suggest the need for chemoprophylaxis in immunocompromised patients without HIV infection, although its indication and duration are still controversial. Because a variety of novel immunosuppressive therapeutics have been emerging in medical practice, further innovations in the diagnosis and treatment of PCP are needed.

  10. Pneumocystis jirovecii pneumonia in non-HIV-infected patients in the era of novel immunosuppressive therapies.

    PubMed

    Tasaka, Sadatomo; Tokuda, Hitoshi

    2014-11-01

    In human immunodeficiency virus (HIV)-infected patients, Pneumocystis jirovecii pneumonia (PCP) is a well-known opportunistic infection, and its management has been established. However, PCP is an emerging threat to immunocompromised patients without HIV infection, such as those receiving novel immunosuppressive therapeutics for malignancy, organ transplantation, or connective tissue diseases. Clinical manifestations of PCP are quite different between patients with and without HIV-infections. In patients without HIV infection, PCP rapidly progresses, is difficult to diagnose correctly, and causes severe respiratory failure with a poor prognosis. High-resolution computed tomography findings are different between PCP patients with HIV infection and those without. These differences in clinical and radiologic features are the result of severe or dysregulated inflammatory responses that are evoked by a relatively small number of Pneumocystis organisms in patients without HIV infection. In recent years, the usefulness of PCR and serum β-D-glucan assay for rapid and noninvasive diagnosis of PCP has been revealed. Although corticosteroid adjunctive to anti-Pneumocystis agents has been shown to be beneficial in some populations, the optimal dose and duration remain to be determined. Recent investigations revealed that Pneumocystis colonization is prevalent, and that asymptomatic carriers are at riskfor developing PCP and can serve as the reservoir for the spread of Pneumocystis by person-to-person transmission. These findings suggest the need for chemoprophylaxis in immunocompromised patients without HIV infection, although its indication and duration are still controversial. Because a variety of novel immunosuppressive therapeutics have been emerging in medical practice, further innovations in the diagnosis and treatment of PCP are needed.

  11. Ploidy of cell-sorted trophic and cystic forms of Pneumocystis carinii.

    PubMed

    Martinez, Anna; Aliouat, El Moukhtar; Standaert-Vitse, Annie; Werkmeister, Elisabeth; Pottier, Muriel; Pinçon, Claire; Dei-Cas, Eduardo; Aliouat-Denis, Cécile-Marie

    2011-01-01

    Once regarded as an AIDS-defining illness, Pneumocystis pneumonia (PcP) is nowadays prevailing in immunocompromised HIV-negative individuals such as patients receiving immunosuppressive therapies or affected by primary immunodeficiency. Moreover, Pneumocystis clinical spectrum is broadening to non-severely-immunocompromised subjects who could be colonized by the fungus while remaining asymptomatic for PcP, thus being able to transmit the infection by airborne route to susceptible hosts. Although the taxonomical position of the Pneumocystis genus has been clarified, several aspects of its life cycle remain elusive such as its mode of proliferation within the alveolus or its ploidy level. As no long-term culture model exists to grow Pneumocystis organisms in vitro, an option was to use a model of immunosuppressed rat infected with Pneumocystis carinii and sort life cycle stage fractions using a high-through-put cytometer. Subsequently, ploidy levels of the P. carinii trophic and cystic form fractions were measured by flow cytometry. In the cystic form, eight contents of DNA were measured thus strengthening the fact that each mature cyst contains eight haploid spores. Following release, each spore evolves into a trophic form. The majority of the trophic form fraction was haploid in our study. Some less abundant trophic forms displayed two contents of DNA indicating that they could undergo (i) mating/fusion leading to a diploid status or (ii) asexual mitotic division or (iii) both. Even less abundant trophic forms with four contents of DNA were suggestive of mitotic divisions occurring following mating in diploid trophic forms. Of interest, was the presence of trophic forms with three contents of DNA, an unusual finding that could be related to asymmetrical mitotic divisions occurring in other fungal species to create genetic diversity at lower energetic expenses than mating. Overall, ploidy data of P. carinii life cycle stages shed new light on the complexity of its

  12. Ploidy of Cell-Sorted Trophic and Cystic Forms of Pneumocystis carinii

    PubMed Central

    Martinez, Anna; Aliouat, El Moukhtar; Standaert-Vitse, Annie; Werkmeister, Elisabeth; Pottier, Muriel; Pinçon, Claire; Dei-Cas, Eduardo; Aliouat-Denis, Cécile-Marie

    2011-01-01

    Once regarded as an AIDS-defining illness, Pneumocystis pneumonia (PcP) is nowadays prevailing in immunocompromised HIV-negative individuals such as patients receiving immunosuppressive therapies or affected by primary immunodeficiency. Moreover, Pneumocystis clinical spectrum is broadening to non-severely-immunocompromised subjects who could be colonized by the fungus while remaining asymptomatic for PcP, thus being able to transmit the infection by airborne route to susceptible hosts. Although the taxonomical position of the Pneumocystis genus has been clarified, several aspects of its life cycle remain elusive such as its mode of proliferation within the alveolus or its ploidy level. As no long-term culture model exists to grow Pneumocystis organisms in vitro, an option was to use a model of immunosuppressed rat infected with Pneumocystis carinii and sort life cycle stage fractions using a high-through-put cytometer. Subsequently, ploidy levels of the P. carinii trophic and cystic form fractions were measured by flow cytometry. In the cystic form, eight contents of DNA were measured thus strengthening the fact that each mature cyst contains eight haploid spores. Following release, each spore evolves into a trophic form. The majority of the trophic form fraction was haploid in our study. Some less abundant trophic forms displayed two contents of DNA indicating that they could undergo (i) mating/fusion leading to a diploid status or (ii) asexual mitotic division or (iii) both. Even less abundant trophic forms with four contents of DNA were suggestive of mitotic divisions occurring following mating in diploid trophic forms. Of interest, was the presence of trophic forms with three contents of DNA, an unusual finding that could be related to asymmetrical mitotic divisions occurring in other fungal species to create genetic diversity at lower energetic expenses than mating. Overall, ploidy data of P. carinii life cycle stages shed new light on the complexity of its

  13. High prevalence of dihydropteroate synthase mutations in Pneumocystis jirovecii isolated from patients with Pneumocystis pneumonia in South Africa.

    PubMed

    Dini, Leigh; du Plessis, Mignon; Frean, John; Fernandez, Victor

    2010-06-01

    Pneumocystis jirovecii pneumonia (PCP) is an important cause of morbidity and mortality in immunocompromised patients. Sulfa-containing drugs are used for the treatment and prophylaxis of PCP. Mutations in the P. jirovecii fas gene, which encodes dihydropteroate synthase (DHPS), are associated with prior exposure to sulfa drugs, and their appearance suggests the emergence of variants with reduced sulfa susceptibility. The present study examined the prevalence of DHPS mutations in P. jirovecii strains isolated from South African patients with PCP. P. jirovecii infection was investigated by immunofluorescence microscopy and quantitative real-time PCR with respiratory specimens from 712 patients (93% of whom were >15 years of age) with suspected PCP consecutively received for the detection of P. jirovecii over 1 year. PCR amplification and sequencing of the DHPS fas gene was attempted with DNA from the P. jirovecii-positive samples. P. jirovecii infection was confirmed by immunofluorescence microscopy in 168/712 (24%) of the patients. Carriage of the fungus was revealed by real-time PCR in 17% of the patients with negative microscopy results. The P. jirovecii fas gene was successfully amplified from specimens from 151 patients and sequenced. Mutations resulting in the Thr55Ala and/or Pro57Ser amino acid substitution were detected in P. jirovecii strains from 85/151 (56%) patients. The high frequency of PCP episodes with P. jirovecii harboring DHPS mutations in South Africa indicates that populations of this fungus are evolving under the considerable selective pressure exerted by sulfa-containing antibiotics. These results, similar to previous observations of sulfa drug resistance in bacterial populations, underscore the importance of the rational use of sulfa medications either prophylactically against PCP or for the treatment of other infections.

  14. Histoplasma capsulatum and Pneumocystis spp. co-infection in wild bats from Argentina, French Guyana, and Mexico

    PubMed Central

    2014-01-01

    Background Histoplasma capsulatum and Pneumocystis organisms cause host infections primarily affecting the lung tissue. H. capsulatum is endemic in the United States of America and Latin American countries. In special environments, H. capsulatum is commonly associated with bat and bird droppings. Pneumocystis-host specificity has been primarily studied in laboratory animals, and its ability to be harboured by wild animals remains as an important issue for understanding the spread of this pathogen in nature. Bats infected with H. capsulatum or Pneumocystis spp. have been found, with this mammal serving as a probable reservoir and disperser; however, the co-infection of bats with both of these microorganisms has never been explored. To evaluate the impact of H. capsulatum and Pneumocystis spp. infections in this flying mammal, 21 bat lungs from Argentina (AR), 13 from French Guyana (FG), and 88 from Mexico (MX) were screened using nested-PCR of the fragments, employing the Hcp100 locus for H. capsulatum and the mtLSUrRNA and mtSSUrRNA loci for Pneumocystis organisms. Results Of the 122 bats studied, 98 revealed H. capsulatum infections in which 55 of these bats exhibited this infection alone. In addition, 51 bats revealed Pneumocystis spp. infection of which eight bats exhibited a Pneumocystis infection alone. A total of 43 bats (eight from AR, one from FG, and 34 from MX) were found co-infected with both fungi, representing a co-infection rate of 35.2% (95% CI = 26.8-43.6%). Conclusion The data highlights the H. capsulatum and Pneumocystis spp.co-infection in bat population’s suggesting interplay with this wild host. PMID:24495513

  15. Nonadherence to Primary Prophylaxis against Pneumocystis jirovecii Pneumonia

    PubMed Central

    Heffelfinger, James D.; Voetsch, Andrew C.; Nakamura, Glenn V.; Sullivan, Patrick S.; McNaghten, A. D.; Huang, Laurence

    2009-01-01

    Background Despite the effectiveness of prophylaxis, Pneumocystis jirovecii pneumonia (PCP) continues to be the most common serious opportunistic infection among HIV-infected persons. We describe factors associated with nonadherence to primary PCP prophylaxis. Methodology/Principal Findings We used 2000–2004 data from the Supplement to HIV/AIDS Surveillance (SHAS) project, a cross-sectional interview project of HIV-infected persons ≥18 years conducted in 18 states. We limited the analysis to persons who denied having prior PCP, reported having a current prescription to prevent PCP, and answered the question “In the past 30 days, how often were you able to take the PCP medication(s) exactly the way your doctor told you to take them?” We used multivariable logistic regression to describe factors associated with nonadherence. Of 1,666 subjects prescribed PCP prophylaxis, 305 (18.3%) were nonadherent. Persons were more likely to be nonadherent if they reported using marijuana (adjusted odds ratio [aOR] = 1.6, 95% confidence interval [CI] = 1.1–2.4), non-injection drugs other than marijuana (aOR = 1.5, 95% CI = 1.0–2.1), or injection drugs (aOR = 2.3, 95% CI = 1.3–4.1) in the past year; their mental health was “not good” for ≥1 day during the past month (aOR = 1.6, 95% CI = 1.2–2.2); their most recent CD4 count was <200 cells/μL (aOR = 1.6, 95% CI = 1.1–2.2); or taking ART usually (aOR = 9.6, 95% CI = 6.7–13.7) or sometimes/rarely/never (aOR = 18.4, 95% CI = 11.1–30.4), compared with always, as prescribed. Conclusion/Significance Providers should inquire about and promote strategies to improve adherence to PCP prophylaxis, particularly among persons who use illicit drugs, have mental health issues, and who are not compliant with ART to reduce the occurrence of PCP. PMID:19319199

  16. Characterization of PCEng2, a {beta}-1,3-endoglucanase homolog in Pneumocystis carinii with activity in cell wall regulation.

    PubMed

    Villegas, Leah R; Kottom, Theodore J; Limper, Andrew H

    2010-08-01

    Pneumocystis jirovecii pneumonia is an opportunistic fungal infection that causes severe respiratory impairment in immunocompromised patients. The viability of Pneumocystis organisms is dependent on the cyst cell wall, a structural feature that is regulated by essential cell wall-associated enzymes. The formation of the glucan-rich cystic wall has been previously characterized, but glucan degradation in the organism-specifically, degradation during trophic excystment-is not yet fully understood. Most studies of basic Pneumocystis biology have been conducted in Pneumocystis carinii or Pneumocystis murina, the varieties of this genus that infect rats and mice, respectively. Furthermore, all known treatments for P. jirovecii were initially discovered through studies of P. carinii. Accordingly, in this study, we have identified a P. carinii beta-1,3-endoglucanase gene (PCEng2) that is demonstrated to play a significant role in cell wall regulation. The cDNA sequence contained a 2.2-kb open reading frame with conserved amino acid domains homologous to similar fungal glycosyl hydrolases (GH family 81). The gene transcript showed up-regulation in cystic isolates, and the expressed protein was detected within both cyst and trophic forms. Complementation assays in Eng2-deleted Saccharomyces cerevisiae strains showed restoration of the cell wall separation defect during proliferation, demonstrating the importance of PCEng2 protein. during fungal growth. These findings suggest that regulation of cyst cell wall beta-glucans is a fundamental process during completion of the Pneumocystis life cycle.

  17. Selective ablation of lung epithelial IKK2 impairs pulmonary Th17 responses and delays the clearance of Pneumocystis.

    PubMed

    Perez-Nazario, Nelissa; Rangel-Moreno, Javier; O'Reilly, Michael A; Pasparakis, Manolis; Gigliotti, Francis; Wright, Terry W

    2013-11-01

    Pneumocystis is an atypical fungal pathogen that causes severe, often fatal pneumonia in immunocompromised patients. Healthy humans and animals also encounter this pathogen, but they generate a protective CD4(+) T cell-dependent immune response that clears the pathogen with little evidence of disease. Pneumocystis organisms attach tightly to respiratory epithelial cells, and in vitro studies have demonstrated that this interaction triggers NF-κB-dependent epithelial cell responses. However, the contribution of respiratory epithelial cells to the normal host response to Pneumocystis remains unknown. IκB kinase 2 (IKK2) is the upstream kinase that is critical for inducible NF-κB activation. To determine whether IKK2-dependent lung epithelial cell (LEC) responses contribute to the anti-Pneumocystis immune response in vivo, transgenic mice with LEC-specific deletion of IKK2 (IKK2(ΔLEC)) were generated. Compared to wild-type mice, IKK2(ΔLEC) mice exhibited a delayed onset of Th17 and B cell responses in the lung and delayed fungal clearance. Importantly, delayed Pneumocystis clearance in IKK2(ΔLEC) mice was associated with an exacerbated immune response, impaired pulmonary function, and altered lung histology. These data demonstrate that IKK2-dependent LEC responses are important regulators of pulmonary adaptive immune responses and are required for optimal host defense against Pneumocystis infection. LECs likely set the threshold for initiation of the pulmonary immune response and serve to prevent exacerbated lung inflammation by promoting the rapid control of respiratory fungal infection.

  18. What Do Pneumocystis Organisms Tell Us about the Phylogeography of Their Hosts? The Case of the Woodmouse Apodemus sylvaticus in Continental Europe and Western Mediterranean Islands

    PubMed Central

    Michaux, Johan; Barriel, Véronique; Pinçon, Claire; Aliouat-Denis, Cécile Marie; Pottier, Muriel; Noël, Christophe; Viscogliosi, Eric; Aliouat, El Moukhtar; Dei-Cas, Eduardo; Morand, Serge; Guillot, Jacques

    2015-01-01

    Pneumocystis fungi represent a highly diversified biological group with numerous species, which display a strong host-specificity suggesting a long co-speciation process. In the present study, the presence and genetic diversity of Pneumocystis organisms was investigated in 203 lung samples from woodmice (Apodemus sylvaticus) collected on western continental Europe and Mediterranean islands. The presence of Pneumocystis DNA was assessed by nested PCR at both large and small mitochondrial subunit (mtLSU and mtSSU) rRNA loci. Direct sequencing of nested PCR products demonstrated a very high variability among woodmouse-derived Pneumocystis organisms with a total number of 30 distinct combined mtLSU and mtSSU sequence types. However, the genetic divergence among these sequence types was very low (up to 3.87%) and the presence of several Pneumocystis species within Apodemus sylvaticus was considered unlikely. The analysis of the genetic structure of woodmouse-derived Pneumocystis revealed two distinct groups. The first one comprised Pneumocystis from woodmice collected in continental Spain, France and Balearic islands. The second one included Pneumocystis from woodmice collected in continental Italy, Corsica and Sicily. These two genetic groups were in accordance with the two lineages currently described within the host species Apodemus sylvaticus. Pneumocystis organisms are emerging as powerful tools for phylogeographic studies in mammals. PMID:25830289

  19. Pneumocystis pneumonia in a non-HIV patient on chronic corticosteroid therapy: a question of prophylaxis.

    PubMed

    Plakke, Michael J; Jalota, Leena; Lloyd, Benjamin J

    2013-03-01

    A man in his late 50s with a history of membranoproliferative glomerulonephritis presented with fever and mild dyspnoea. He was HIV-negative and had been on corticosteroids as immunosuppression for 6 months prior to tapering them off 1 week before presentation. He was not taking prophylaxis for Pneumocystis jirovecii pneumonia. After unsuccessful treatment for community-acquired pneumonia, his condition worsened and he required intubation and mechanical ventilation. Full respiratory workup including bronchoscopy revealed P jirovecii as a source for the patient's infection. He was treated successfully with a 21-day course of trimethoprim-sulfamethoxazole  and eventually weaned off the ventilator. He has had no complications to date. In our review of this case and the existing literature, we believe that proper utilisation of prophylaxis for pneumocystis pneumonia may have prevented our patient's transfer to intensive care unit. In our article, we discuss this issue and explore current evidence for prophylaxis.

  20. Outcomes and Duration of Pneumocystis jirovecii Pneumonia Therapy in Infants with Severe Combined Immunodeficiency

    PubMed Central

    Lundgren, Ingrid S.; Englund, Janet A.; Burroughs, Lauri M.; Torgerson, Troy R.; Skoda-Smith, Suzanne

    2011-01-01

    This retrospective review of patients with severe combined immunodeficiency and Pneumocystis jirovecii pneumonia (PCP) evaluated the relationship between duration of therapy to treat PCP and overall survival. We found that 80% of patients receiving only 21 days of antibiotics survived to 12 months beyond hematopoetic cell transplant, whereas only 25% of patients who required longer treatment for PCP survived to stem cell engraftment. PMID:21817949

  1. Exacerbation of Pneumocystis carinii pneumonia in immunodeficient (scid) mice by concurrent infection with a pneumovirus.

    PubMed

    Bray, M V; Barthold, S W; Sidman, C L; Roths, J; Smith, A L

    1993-04-01

    scid mice naturally infected with Pneumocystis carinii and inoculated with a normally apathogenic pneumovirus had significantly higher P. carinii cyst counts and developed significantly more severe P. carinii-related disease than did sham-inoculated, P. carinii-infected scid mice. P. carinii-free, virus-infected scid mice survived for 2 months despite high pulmonary virus titers. These results show that a respiratory virus infection can exacerbate P. carinii disease in an immunocompromised-rodent model.

  2. Deferoxamine and eflornithine (DL-alpha-difluoromethylornithine) in a rat model of Pneumocystis carinii pneumonia.

    PubMed Central

    Clarkson, A B; Sarić, M; Grady, R W

    1990-01-01

    The iron chelator deferoxamine and the polyamine biosynthesis inhibitor eflornithine (DL-alpha-difluoromethylornithine) were examined for anti-Pneumocystis carinii activity in the rat model of P. carinii pneumonia. The activity of deferoxamine at 250, 500, and 1,000 mg/kg given intraperitoneally provides evidence that iron chelation is a promising novel approach to P. carinii chemotherapy. Results with eflornithine at 2, 3, and 4% in drinking water confirm and extend previously reported activity in the rat model. PMID:2285303

  3. Pneumocystis Pneumonia in Human Immunodeficiency Virus-infected Adults and Adolescents: Current Concepts and Future Directions.

    PubMed

    Tasaka, Sadatomo

    2015-01-01

    Pneumocystis jirovecii pneumonia (PCP) is one of the most common opportunistic infections in human immunodeficiency virus-infected adults. Colonization of Pneumocystis is highly prevalent among the general population and could be associated with the transmission and development of PCP in immunocompromised individuals. Although the microscopic demonstration of the organisms in respiratory specimens is still the golden standard of its diagnosis, polymerase chain reaction has been shown to have a high sensitivity, detecting Pneumocystis DNA in induced sputum or oropharyngeal wash. Serum β-D-glucan is useful as an adjunctive tool for the diagnosis of PCP. High-resolution computed tomography, which typically shows diffuse ground-glass opacities, is informative for the evaluation of immunocompromised patients with suspected PCP and normal chest radiography. Trimethoprim-sulfamethoxazole (TMP-SMX) is the first-line agent for the treatment of mild to severe PCP, although it is often complicated with various side effects. Since TMP-SMX is widely used for the prophylaxis, the putative drug resistance is an emerging concern.

  4. Outbreaks and clustering of Pneumocystis pneumonia in kidney transplant recipients: a systematic review.

    PubMed

    de Boer, Mark G J; de Fijter, Johannes W; Kroon, Frank P

    2011-10-01

    From 1980 onwards, an increasing number of outbreaks of Pneumocystis pneumonia (PCP) among kidney transplant recipients have been reported. The cause of these outbreaks is unclear and different explanations have been provided. We performed a systematic review to provide a comprehensive overview of the epidemiologic characteristics as well as the involved clinical risk factors. A total of 15 peer-reviewed English language articles published from 1980 onward were included. Outbreak settings were all marked by absence of adequate chemoprophylaxis, frequent inter-patient contacts and lack of isolation measures taken during hospitalization of PCP cases. PCP-associated mortality rates significantly decreased from a weighted mean of 38% before 1990 to 19% and 13% in the following two decades. Clinical risk factors for PCP in outbreak settings were largely similar to non-outbreak settings. Genotyping by multilocus sequence typing (MLST) or comparison of the internal transcribed spacer (ITS) regions 1 and 2 showed that the outbreaks are most frequently caused by a predominant or a single Pneumocystis strain. Pooled epidemiological data and genotyping results strongly support the theory that interhuman transmission of Pneumocystis occurred. No seasonal trend was noted. The results emphasize the need for chemoprophylaxis in kidney transplant recipients despite a low baseline incidence of PCP in this population, and support the current CDC recommendation with regard to isolation of patients with PCP during hospitalization.

  5. Pneumocystis and Histoplasma infections in wild animals from the Amazon region of Brazil.

    PubMed

    Lainson, R; Shaw, J J

    1975-01-01

    Routine examination of tissues from wild forest rodents from Amapá, north Brazil, revealed Pneumocystis carinii in lung smears from a newly captured Oryzomys capito (Cricetidae). Acute, fatal infections with this parasite are also recorded in a number of captive "coatimundis", Nasua narica (Carnivora: Procyonidae) and a sloth, Bradypus tridactylus (Edentata). Pneumocystis was also encountered in lung smears from a newly captured and apparently healthy sloth, Choloepus didactylus. The presence of infection in newly captured animals leads us to believe that the fatal, fulminating pneumocystosis seen in the captive Nasua and Bradypus was due to exacerbation of pre-existant infections acquired in their natural forest environment. Pneumocystis carinii is a well known cause of fatal, interstitial plasma-cell pneumonia in human infants and sometimes the weakened adult: the keeping of exotic pets such as the coatimundi is, therefore, not without some hazard in this respect. Histoplasma, another well known pathogen for man, was isolated from 4 rodents, Proechimys guyanensis (Echimyidae), all from virgin forest along the newly opened Trans Amazon Highway, Pará State, and from a single sloth, Choloepus didactylus, from near Belém, Pará. All these animals showed no symptoms of infection: isolation of the parasite was made by the inoculation of laboratory hamsters with saline suspensions of triturated liver and spleen.

  6. Influence of Pneumocystis carinii on nitrite production by rat alveolar macrophages.

    PubMed

    Simonpoli, A M; Rajagopalan-Levasseur, P; Brun-Pascaud, M; Bertrand, G; Pocidalo, M A; Girard, P M

    1996-01-01

    Nitrite production by rat alveolar macrophages was studied to determine the role of L-arginine oxidation in the interaction between these cells and Pneumocystis carinii. Alveolar macrophages from rats obtained from two different breeders were used: rats from Janvier breeder had latent P. carinii infection, while those from Charles River breeder were bred in a germ-free environment. Pneumocystis carinii increased in vitro nitrite generation by unstimulated alveolar macrophages from Janvier rats only, and this was blocked by NG-monomethyl-L-arginine. Incubation of cells from Janvier and Charles River rats with lipopolysaccharide and/or interferon-gamma increased nitrite production to a similar extent. Pneumocystis carinii partially decreased nitrite release by activated alveolar macrophages, and this was still inhibited by NG-monomethyl-L-arginine. In the presence of P. carinii, superoxide dismutase used as a superoxide anion scavenger had no effect on nitrite production by activated cells. These results show that prior exposure to P. carinii leads to nitric oxide production by rat alveolar macrophages. Although the magnitude of this production seems to be moderate, it is of biological significance since cells of P. carinii-naive rats do not generate nitrite whereas those of latently infected rats do.

  7. Pneumocystis Pneumonia in Human Immunodeficiency Virus–infected Adults and Adolescents: Current Concepts and Future Directions

    PubMed Central

    Tasaka, Sadatomo

    2015-01-01

    Pneumocystis jirovecii pneumonia (PCP) is one of the most common opportunistic infections in human immunodeficiency virus–infected adults. Colonization of Pneumocystis is highly prevalent among the general population and could be associated with the transmission and development of PCP in immunocompromised individuals. Although the microscopic demonstration of the organisms in respiratory specimens is still the golden standard of its diagnosis, polymerase chain reaction has been shown to have a high sensitivity, detecting Pneumocystis DNA in induced sputum or oropharyngeal wash. Serum β-D-glucan is useful as an adjunctive tool for the diagnosis of PCP. High-resolution computed tomography, which typically shows diffuse ground-glass opacities, is informative for the evaluation of immunocompromised patients with suspected PCP and normal chest radiography. Trimethoprim–sulfamethoxazole (TMP-SMX) is the first-line agent for the treatment of mild to severe PCP, although it is often complicated with various side effects. Since TMP-SMX is widely used for the prophylaxis, the putative drug resistance is an emerging concern. PMID:26327786

  8. Pneumocystis pneumonia in patients treated with long-term steroid therapy for symptom palliation: a neglected infection in palliative care.

    PubMed

    Yamaguchi, Takashi; Nagai, Yuki; Morita, Tatsuya; Kiuchi, Daisuke; Matsumoto, Mina; Hisahara, Ko; Hisanaga, Takayuki

    2014-12-01

    We report 3 cases of pneumocystis pneumonia (PCP) in patients with advanced cancer who received palliative care. All patients received long-term steroid therapy for symptom management. A diagnosis of PCP was based on clinical symptoms and a positive Pneumocystis jiroveci polymerase chain reaction test from induced sputum specimens. Despite appropriate treatment, only 1 patient recovered from PCP. Long-term steroid, often prescribed in palliative care settings, is the most common risk factor for PCP in non-HIV patients. Pneumocystis pneumonia may cause distressing symptoms such as severe dyspnea, and the mortality rate is high. Therefore, it is important to consider PCP prophylaxis for high-risk patients and to diagnose PCP early and provide appropriate treatment to alleviate PCP-related symptoms and avert unnecessary shortening of a patient's life expectancy.

  9. Treatment with Interleukin-7 Restores Host Defense against Pneumocystis in CD4+ T-Lymphocyte-Depleted Mice

    PubMed Central

    Samuelson, D. R.; Assouline, B.; Morre, M.; Shellito, J. E.

    2015-01-01

    Pneumocystis pneumonia (PCP) is a major cause of morbidity and mortality in patients with HIV infection. CD4+ T lymphocytes are critical for host defense against this infection, but in the absence of CD4+ T lymphocytes, CD8+ T lymphocytes may provide limited host defense. The cytokine interleukin-7 (IL-7) functions to enhance lymphocyte proliferation, survival, and recruitment of immune cells to sites of infection. However, there is little known about the role of IL-7 in PCP or its potential use as an immunotherapeutic agent. We hypothesized that treatment with recombinant human IL-7 (rhIL-7) would augment host defense against Pneumocystis and accelerate pathogen clearance in CD4-depleted mice. Control and CD4-depleted mice were infected with Pneumocystis, and rhIL-7 was administered via intraperitoneal injection. Our studies indicate that endogenous murine IL-7 is part of the normal host response to Pneumocystis murina and that administration of rhIL-7 markedly enhanced clearance of Pneumocystis in CD4-depleted mice. Additionally, we observed increased recruitment of CD8+ T lymphocytes to the lungs and decreased apoptosis of pulmonary CD8+ T lymphocytes in rhIL-7-treated animals compared to those in untreated mice. The antiapoptotic effect of rhIL-7 was associated with increased levels of Bcl-2 protein in T lymphocytes. rhIL-7 immunotherapy in CD4-depleted mice also increased the number of gamma interferon (IFN-γ)-positive CD8+ central memory T lymphocytes in the lungs. We conclude that rhIL-7 has a potent therapeutic effect in the treatment of murine Pneumocystis pneumonia in CD4-depleted mice. This therapeutic effect is mediated through enhanced recruitment of CD8+ T cells and decreased apoptosis of lung T lymphocytes, with a preferential action on central memory CD8+ T lymphocytes. PMID:26483405

  10. Point prevalence of Pneumocystis pneumonia in patients with non-Hodgkin lymphoma according to the number of cycles of R-CHOP chemotherapy.

    PubMed

    Kim, Tark; Choi, Sang-Ho; Kim, Sung-Han; Jeong, Jin-Yong; Woo, Jun Hee; Kim, Yang Soo; Sung, Heungsup; Kim, Mi-Na; Yoon, Dok Hyun; Suh, Cheolwon; Lee, Sang-Oh

    2013-01-01

    R-CHOP chemotherapy composed of rituximab, cyclophosphamide, adriamycin, vincristine, and prednisolone which might increase the risk of Pneumocystis pneumonia in patients with non-Hodgkin lymphoma. We estimated the point prevalence of Pneumocystis pneumonia in non-Hodgkin lymphoma patients according to the number of R-CHOP cycles and investigated whether cytoreduction by chemotherapy is associated with Pneumocystis pneumonia development. We retrospectively established a cohort of patients who received R-CHOP for non-Hodgkin lymphoma in our institution. Using this cohort, we estimated the incidence rate and point prevalence of definite and probable Pneumocystis pneumonia. To assess factors associated with Pneumocystis pneumonia development several clinical variables, including absolute neutrophil and lymphocyte count at the time of non-Hodgkin lymphoma diagnosis and when the last R-CHOP cycle was administered, were compared between patients with and without Pneumocystis pneumonia. Of 713 patients in the cohort, 14 and 18 patients were diagnosed with definite and probable Pneumocystis pneumonia, respectively. The overall incidence of definite and definite plus probable PCP in NHL patients receiving R-CHOP were 2.0 % (14/713; 95 % CI, 1.1-3.3 %) and 4.5 % (32/713; 95 % CI, 3.2-6.4 %), respectively. This corresponded to 3.8 (95 % CI, 2.2-6.4) and 8.4 (95 % CI, 5.9-11.9) per 1000 persons. Many cases of Pneumocystis pneumonia (22/32, 68.7 %) developed after administration of the fourth R-CHOP cycle. However, there was no statistical difference in Pneumocystis pneumonia prevalence between patients receiving four or more cycles of R-CHOP and fewer than. Higher absolute neutrophil count (4,742/mm(3) vs. 2,627/mm(3); p < 0.01) was associated with Pneumocystis pneumonia development at the last R-CHOP cycle, while absolute lymphocyte count at the time of NHL diagnosis was not. Contrary to expectations, Pneumocystis pneumonia is not a frequent complication of R

  11. [Pneumocystis carinii pneumonia in a HTLV-I carrier with monoclonal proliferation of HTLV-I infected lymphocyte].

    PubMed

    Kawahigashi, N; Furukawa, Y; Tara, M; Niina, K

    1996-04-01

    A 63-year-old woman had Pneumocystis carinii pneumonia without any apparent underlying disease such as cancers or HIV infection. Although she reacted positively for HTLV-I antibody, hematological findings and clinical symptoms did not suggest that this patient had an ATL. Southern blot analysis revealed that HTLV-I infected lymphocytes had already proliferated monoclonally. The development of overt ATL should be carefully monitored in this type of patient as Pneumocystis carinii infection in HTLV-I carriers were reported to be a predictive sign of ATL and the monoclonal integration of a HTLV-I genome in the lymphocytes in this patient also suggests the presence of neoplastic clone.

  12. A molecular model of the folate binding site of Pneumocystis carinii dihydrofolate reductase

    NASA Astrophysics Data System (ADS)

    Southerland, William M.

    1994-04-01

    The inhibition of Pneumocystis carinii dihydrofolate reductase (DHFR) continues to be the major treatment strategy for P. carinii pneumonia (PCP). The design of new anti-pneumocystis agents would be significantly enhanced by the availability of a 3D model of the methotrexate (MTX) binding site of the P. carinii DHFR. However, an X-ray crystal structure of the P. carinii DHFR is not yet available. Alignment of the amino acid sequences of P. carinii and Lactobacillus casei DHFRs indicates that the two proteins show approximately 80% homology among MTX binding-site residues. This high level of homology suggests that the L. casei DHFR MTX binding-site structure could serve as a structural template in developing a model of the P. carinii DHFR MTX binding site. Therefore, the X-ray crystal structure of L. casei DHFR was used to develop a 3D model of the methotrexate binding site of P. carinii DHFR. The molecular modeling and dynamics software QUANTA/CHARMm was used. Amino acid residue mutations and deletions were performed using QUANTA and macromolecular minimizations were achieved with CHARMm. The MTX binding-site residues of L. casei DHFR were mutated to the corresponding residues of the P. carinii DHFR sequence. The resulting structure was extensively minimized. The resulting P. carinii MTX binding-site model showed significant differences in hydrogen-bonding patterns from the L. casei MTX binding site. Also, the P. carinii site is more hydrophobic than the corresponding L. casei site. Analysis of atom-to-atom close contacts between methotrexate and protein binding-site residues indicates that the P. carinii MTX binding-site complex is primarily stabilized by hydrophobic interactions, while the L. casei complex is mostly stabilized by electrostatic interactions. The model is consistent with the observed increased sensitivity of P. carinii DHFR to lipid-soluble inhibitors and provides a rational basis for the design of new anti-pneumocystis agents.

  13. Diversity of Pneumocystis jirovecii during Infection Revealed by Ultra-Deep Pyrosequencing

    PubMed Central

    Alanio, Alexandre; Gits-Muselli, Maud; Mercier-Delarue, Séverine; Dromer, Françoise; Bretagne, Stéphane

    2016-01-01

    Pneumocystis jirovecii is an uncultivable fungal pathogen responsible for Pneumocystis pneumonia (PCP) in immunocompromised patients, the physiopathology of which is only partially understood. The diversity of the Pneumocystis strains associated with acute infection has mainly been studied by Sanger sequencing techniques precluding any identification of rare genetic events (< 20% frequency). We used next-generation sequencing to detect minority variants causing infection, and analyzed the complexity of the genomes of infection-causing P. jirovecii. Ultra-deep pyrosequencing (UDPS) of PCR amplicons of two nuclear target region [internal transcribed spacer 2 (ITS2) and dihydrofolate reductase (DHFR)] and one mitochondrial DNA target region [the mitochondrial ribosomal RNA large subunit gene (mtLSU)] was performed on 31 samples from 25 patients. UDPS revealed that almost all patients (n = 23/25, 92%) were infected with mixtures of strains. An analysis of repeated samples from six patients showed that the proportion of each variant change significantly (by up to 30%) over time on treatment in three of these patients. A comparison of mitochondrial and nuclear UDPS data revealed heteroplasmy in P. jirovecii. The recognition site for the homing endonuclease I-SceI was recovered from the mtLSU gene, whereas its two conserved motifs of the enzyme were not. This suggests that heteroplasmy may result from recombination induced by unidentified homing endonucleases. This study sheds new light on the biology of P. jirovecii during infection. PCP results from infection not with a single microorganism, but with a complex mixture of different genotypes, the proportions of which change over time due to intricate selection and reinfection mechanisms that may differ between patients, treatments, and predisposing diseases. PMID:27252684

  14. Diversity of Pneumocystis jirovecii during Infection Revealed by Ultra-Deep Pyrosequencing.

    PubMed

    Alanio, Alexandre; Gits-Muselli, Maud; Mercier-Delarue, Séverine; Dromer, Françoise; Bretagne, Stéphane

    2016-01-01

    Pneumocystis jirovecii is an uncultivable fungal pathogen responsible for Pneumocystis pneumonia (PCP) in immunocompromised patients, the physiopathology of which is only partially understood. The diversity of the Pneumocystis strains associated with acute infection has mainly been studied by Sanger sequencing techniques precluding any identification of rare genetic events (< 20% frequency). We used next-generation sequencing to detect minority variants causing infection, and analyzed the complexity of the genomes of infection-causing P. jirovecii. Ultra-deep pyrosequencing (UDPS) of PCR amplicons of two nuclear target region [internal transcribed spacer 2 (ITS2) and dihydrofolate reductase (DHFR)] and one mitochondrial DNA target region [the mitochondrial ribosomal RNA large subunit gene (mtLSU)] was performed on 31 samples from 25 patients. UDPS revealed that almost all patients (n = 23/25, 92%) were infected with mixtures of strains. An analysis of repeated samples from six patients showed that the proportion of each variant change significantly (by up to 30%) over time on treatment in three of these patients. A comparison of mitochondrial and nuclear UDPS data revealed heteroplasmy in P. jirovecii. The recognition site for the homing endonuclease I-SceI was recovered from the mtLSU gene, whereas its two conserved motifs of the enzyme were not. This suggests that heteroplasmy may result from recombination induced by unidentified homing endonucleases. This study sheds new light on the biology of P. jirovecii during infection. PCP results from infection not with a single microorganism, but with a complex mixture of different genotypes, the proportions of which change over time due to intricate selection and reinfection mechanisms that may differ between patients, treatments, and predisposing diseases.

  15. Impact of HIV Infection Status on Interpretation of Quantitative PCR for Detection of Pneumocystis jirovecii

    PubMed Central

    Louis, M.; Guitard, J.; Jodar, M.; Ancelle, T.; Magne, D.; Lascols, O.

    2015-01-01

    Quantitative PCR (qPCR) is now a key diagnostic tool for Pneumocystis pneumonia. However, cutoffs to distinguish between infected and colonized patients according to their HIV status have not yet been determined. According to clinical, radiological, and biological data, we retrospectively classified bronchoalveolar lavage (BAL) samples subjected to qPCR over a 3-year period into four categories, i.e., definite PCP, probable PCP, Pneumocystis colonization, and no infection. Fungal burden was then analyzed according to the HIV status of the patients. Among 1,212 episodes of pneumonia screened in immunocompromised patients, 52 and 27 HIV-positive patients were diagnosed with a definite and probable PCP, whereas 4 and 22 HIV-negative patients had definite and probable PCP, respectively. Among patients with definite or a probable PCP, HIV-negative patients had a significantly lower burden than HIV-positive patients (P < 10−4). In both groups, the median fungal burden was significantly higher in patients with definite PCP than in colonized patients. A single cutoff at 1.5 × 104 copies/ml allowed to differentiate colonized and infected HIV-positive patients with 100% sensitivity and specificity. In HIV-negative patients, cutoff values of 2.87 × 104 and 3.39 × 103 copies/ml resulted in 100% specificity and sensitivity, respectively. Using cutoffs determined for the whole population would have led us to set aside the diagnosis of PCP in 9 HIV-negative patients with definite or probable PCP. qPCR appeared to be the most sensitive test to detect Pneumocystis in BAL samples. However, because of lower inocula in HIV-negative patients, different cutoffs must be used according to the HIV status to differentiate between colonized and infected patients. PMID:26468505

  16. Association between Pneumocystis spp. and co-infections with Bordetella bronchiseptica, Mycoplasma hyopneumoniae and Pasteurella multocida in Austrian pigs with pneumonia.

    PubMed

    Kureljušić, B; Weissenbacher-Lang, C; Nedorost, N; Stixenberger, D; Weissenböck, H

    2016-01-01

    In this retrospective study, 218 pig lung tissue samples were analyzed to examine a possible association between Pneumocystis spp. using in situ hybridization, Bordetella bronchiseptica (B.b.) using immunohistochemistry (IHC), Mycoplasma hyopneumoniae (M.h.) by quantitative PCR, and Pasteurella multocida (P.m.; IHC). Compared to the bacterial agents (B.b., 5%; M.h., 30%; P.m., 23%), Pneumocystis occurred with a higher prevalence (51%). Co-infections with two or three pathogens were present in 28% of the examined cases. Those of Pneumocystis and M.h. were most commonly seen, followed by Pneumocystis and P.m. and M.h. and P.m. Histologically, interstitial pneumonia was found in both the Pneumocystis positive lungs and lungs with a mild M.h. infection. The B.b. and P.m. positive lungs were mainly associated with suppurative bronchopneumonia and severe M.h. cases with fibrinous or fibrino-haemorrhagic pneumonia. In suckling piglets, the number of samples positive for Pneumocystis predominated, whereas samples from fattening pigs were mainly positive for bacteria or Pneumocystis and bacteria.

  17. Pneumocystis carinii pneumonia: a late presentation following treatment for stage IV neuroblastoma.

    PubMed

    Clarke, Edward; Glaser, Adam W; Picton, Susan V

    2003-09-01

    This report describes a child who develops Pneumocystis carinii pneumonia 7 months after high-dose chemotherapy for stage IV neuroblastoma. In addition to chemotherapy the child had also been treated with abdominal radiotherapy and 13-cis-retinoic acid. Standard practice has been to treat patients with prophylactic co-trimoxazole for 3 months after high-dose therapy, but this report highlights the intensity and complexity of current treatment for stage IV neuroblastoma and the need to be aware of prolonged lymphopenia after such treatment.

  18. Scintigraphic pattern of pneumothorax complicating Pneumocystis carinii pneumonia in patients with AIDS.

    PubMed

    Finestone, H; Goldfarb, C R; Ongseng, F; Wasserman, I; Garcia, H

    1990-08-01

    Spontaneous pneumothorax is a serious though infrequently reported pulmonary complication of AIDS. An unsuspected lung collapse was discovered via gallium scintigraphy for the study of Pneumocystis carinii pneumonia. Neither the pneumonia nor the pneumothorax were apparent on the most recent chest roentgenogram. In evaluating gallium images during the work-up of AIDS patients with associated pulmonary pathology, the possible complication of lung collapse should be considered. If pneumothorax is suspected on gallium imaging, a chest roentgenogram in expiration must be obtained for prompt delineation of this serious, yet correctable, condition.

  19. Early development of immune reconstitution inflammatory syndrome related to Pneumocystis pneumonia after antiretroviral therapy.

    PubMed

    Mok, Hoi Ping; Hart, Elizabeth; Venkatesan, Pradhib

    2014-04-01

    Immune reconstitution inflammatory syndrome is a recognized complication after the initiation of combination antiretroviral therapy (cART). We report a patient who developed life-threatening pulmonary immune reconstitution inflammatory syndrome (IRIS) three days after initiation of cART. We reviewed published cases of IRIS after Pneumocystis pneumonia (PCP), in particular the time from initiation of cART to IRIS event. The median duration from the initiation of cART to the onset of IRIS was 15 days in the 33 patients reviewed. This report alerts clinicians to the rapidity of the development of pulmonary IRIS following PCP after the initiation of cART.

  20. Recognition of Pneumocystis carinii by gram stain in impression smears of lung tissue.

    PubMed Central

    Felegie, T P; Pasculle, A W; Dekker, A

    1984-01-01

    In 12 of 20 (60%) biopsy-proven cases of Pneumocystis carinii pneumonia, the diagnosis was first suggested by examination of routine Gram stains of impression smears made from infected lung tissue and later confirmed by methenamine-silver staining. The cysts appeared as 5- to 7-microns unstained spheres, each containing six to eight intracystic gram-negative bodies (sporozoites). Although the Gram stain does not appear to be as sensitive as more traditional staining techniques for the detection of P. carinii, clinical microbiologists should be aware of the morphology of this organism in gram-stained specimens because this relatively simple procedure gives quick results. Images PMID:6084017

  1. Scintigraphic pattern of pneumothorax complicating Pneumocystis carinii pneumonia in patients with AIDS

    SciTech Connect

    Finestone, H.; Goldfarb, C.R.; Ongseng, F.; Wasserman, I.; Garcia, H. )

    1990-08-01

    Spontaneous pneumothorax is a serious though infrequently reported pulmonary complication of AIDS. An unsuspected lung collapse was discovered via gallium scintigraphy for the study of Pneumocystis carinii pneumonia. Neither the pneumonia nor the pneumothorax were apparent on the most recent chest roentgenogram. In evaluating gallium images during the work-up of AIDS patients with associated pulmonary pathology, the possible complication of lung collapse should be considered. If pneumothorax is suspected on gallium imaging, a chest roentgenogram in expiration must be obtained for prompt delineation of this serious, yet correctable, condition.

  2. Memory CD4+ T cells are required for optimal NK cell effector functions against the opportunistic fungal pathogen Pneumocystis murina.

    PubMed

    Kelly, Michelle N; Zheng, Mingquan; Ruan, Sanbao; Kolls, Jay; D'Souza, Alain; Shellito, Judd E

    2013-01-01

    Little is known about the role of NK cells or their interplay with other immune cells during opportunistic infections. Using our murine model of Pneumocystis pneumonia, we found that loss of NK cells during immunosuppression results in substantial Pneumocystis lung burden. During early infection of C57B/6 CD4(+) T cell-depleted mice, there were significantly fewer NK cells in the lung tissue compared with CD4(+) T cell-intact animals, and the NK cells present demonstrated decreased upregulation of the activation marker NKp46 and production of the effector cytokine, IFN-γ. Furthermore, coincubation studies revealed a significant increase in fungal killing when NK cells were combined with CD4(+) T cells compared with either cell alone, which was coincident with a significant increase in perforin production by NK cells. Finally, however, we found through adoptive transfer that memory CD4(+) T cells are required for significant NK cell upregulation of the activation marker NK group 2D and production of IFN-γ, granzyme B, and perforin during Pneumocystis infection. To the best of our knowledge, this study is the first to demonstrate a role for NK cells in immunity to Pneumocystis pneumonia, as well as to establish a functional relationship between CD4(+) T cells and NK cells in the host response to an opportunistic fungal pathogen.

  3. Pneumocystis pneumonia increases the clearance rate of inhaled /sup 99m/Tc DTPA from lung to blood

    SciTech Connect

    Jones, D.K.; Higenbottam, T.W.

    1985-10-01

    Despite no radiographic change, a patient with Pneumocystis pneumonia showed increased clearance of inhaled /sup 99m/Tc DTPA from lung to blood. Gas transfer for carbon monoxide was also reduced, but improved with treatment. This was paralleled by serial increase in the t1/2 LB.

  4. Cryptosporidium,Giardia, Cryptococcus, Pneumocystis genetic variability: cryptic biological species or clonal near-clades?

    PubMed

    Tibayrenc, Michel; Ayala, Francisco J

    2014-04-01

    An abundant literature dealing with the population genetics and taxonomy of Giardia duodenalis, Cryptosporidium spp., Pneumocystis spp., and Cryptococcus spp., pathogens of high medical and veterinary relevance, has been produced in recent years. We have analyzed these data in the light of new population genetic concepts dealing with predominant clonal evolution (PCE) recently proposed by us. In spite of the considerable phylogenetic diversity that exists among these pathogens, we have found striking similarities among them. The two main PCE features described by us, namely highly significant linkage disequilibrium and near-clading (stable phylogenetic clustering clouded by occasional recombination), are clearly observed in Cryptococcus and Giardia, and more limited indication of them is also present in Cryptosporidium and Pneumocystis. Moreover, in several cases, these features still obtain when the near-clades that subdivide the species are analyzed separately ("Russian doll pattern"). Lastly, several sets of data undermine the notion that certain microbes form clonal lineages simply owing to a lack of opportunity to outcross due to low transmission rates leading to lack of multiclonal infections ("starving sex hypothesis"). We propose that the divergent taxonomic and population genetic inferences advanced by various authors about these pathogens may not correspond to true evolutionary differences and could be, rather, the reflection of idiosyncratic practices among compartmentalized scientific communities. The PCE model provides an opportunity to revise the taxonomy and applied research dealing with these pathogens and others, such as viruses, bacteria, parasitic protozoa, and fungi.

  5. Unusual presentation of pneumocystis pneumonia in an immunocompetent patient diagnosed by open lung biopsy.

    PubMed

    Harris, Kassem; Maroun, Rabih; Chalhoub, Michel; Elsayegh, Dany

    2012-04-01

    Pneumocystis pneumonia (PCP) is the most common opportunistic infection in acquired immune deficiency syndrome (AIDS) patients. It is a fungal infection with Pneumocystis jiroveci which can be isolated from bronchoalveolar lavage of healthy subjects. The infection occurs mainly in HIV patients; with CD4 lymphocyte count drop to less than 200 cells/μL. PCP has been reported in non-HIV patients with other risk factors such as immunosuppressive medications, malignancies, and other inflammatory conditions. PCP has been rarely reported in immunocompetent subjects. However, in most of these patients, PCP occurred after a period of acute illness with bacterial pneumonia and antibiotic therapy. In this report, we describe a case of PCP in an immunocompetent patient with nonreactive HIV and no immunosuppressive risk factors. The patient had large pulmonary nodules discovered incidentally on chest film as preoperative evaluation for hip surgery. Bronchoalveolar lavage, transbronchial biopsies (TBB), and computed tomography (CT) guided needle biopsy were all negative for P. jiroveci. PCP diagnosis was made after open lung biopsy and wedge resection. To our knowledge, this is the first case of PCP in immunocompetent patient with negative BAL, TBB and CT guided biopsy. The diagnosis of PCP required open lung biopsy and the patient recovered without complications.

  6. Transcriptomic Analysis Reveals Significant B Lymphocyte Suppression in Corticosteroid-Treated Hosts with Pneumocystis Pneumonia.

    PubMed

    Hu, Yang; Wang, Dong; Zhai, Kan; Tong, Zhaohui

    2017-03-01

    Pneumocystis pneumonia (PCP) is an opportunistic, infectious disease that is prevalent in immunosuppressed hosts. Corticosteroid treatment is the most significant risk factor for patients with PCP who are human immunodeficiency virus negative, although little is known about how corticosteroids alter the host defense against Pneumocystis infection. In the present study, we used transcriptome analysis to examine the immune response in the lungs of corticosteroid-treated PCP mice. The results showed down-regulation in the genes related to both native immunity, such as antigen processing and presentation, inflammatory response, and phagocytosis, as well as B and T lymphocyte immunity. The repression of gene expression, corresponding to B cell immunity, including B cell signaling, homeostasis, and Ig production, was prominent. The finding was confirmed by quantitative PCR of mouse lungs and the peripheral blood of patients with PCP. Flow cytometry also revealed a significant depletion of B cells in corticosteroid-treated PCP mice. Our study has highlighted that corticosteroid treatment suppresses the B cell immunity in the PCP host, which is likely one of the main reasons that corticosteroid treatment may stimulate PCP development.

  7. Mutations in the Pneumocystis jirovecii DHPS gene confer cross-resistance to sulfa drugs.

    PubMed

    Iliades, Peter; Meshnick, Steven R; Macreadie, Ian G

    2005-02-01

    Pneumocystis jirovecii is a major opportunistic pathogen that causes Pneumocystis pneumonia (PCP) and results in a high degree of mortality in immunocompromised individuals. The drug of choice for PCP is typically sulfamethoxazole (SMX) or dapsone in conjunction with trimethoprim. Drug treatment failure and sulfa drug resistance have been implicated epidemiologically with point mutations in dihydropteroate synthase (DHPS) of P. jirovecii. P. jirovecii cannot be cultured in vitro; however, heterologous complementation of the P. jirovecii trifunctional folic acid synthesis (PjFAS) genes with an E. coli DHPS-disrupted strain was recently achieved. This enabled the evaluation of SMX resistance conferred by DHPS mutations. In this study, we sought to determine whether DHPS mutations conferred sulfa drug cross-resistance to 15 commonly available sulfa drugs. It was established that the presence of amino acid substitutions (T(517)A or P(519)S) in the DHPS domain of PjFAS led to cross-resistance against most sulfa drugs evaluated. The presence of both mutations led to increased sulfa drug resistance, suggesting cooperativity and the incremental evolution of sulfa drug resistance. Two sulfa drugs (sulfachloropyridazine [SCP] and sulfamethoxypyridazine [SMP]) that had a higher inhibitory potential than SMX were identified. In addition, SCP, SMP, and sulfadiazine (SDZ) were found to be capable of inhibiting the clinically observed drug-resistant mutants. We propose that SCP, SMP, and SDZ should be considered for clinical evaluation against PCP or for future development of novel sulfa drug compounds.

  8. Analysis of Pneumocystis jirovecii DHPS alleles implicated in sulfamethoxazole resistance using an Escherichia coli model system.

    PubMed

    Iliades, Peter; Meshnick, Steven R; Macreadie, Ian G

    2005-01-01

    Pneumocystis jirovecii is a major opportunistic pathogen that causes Pneumocystis pneumonia (PCP). Drug treatment failure has been associated epidemiologically with point mutations in the gene for dihydropteroate synthase which is part of a gene that encodes three covalently linked enzymes involved in folic acid synthesis (FAS). The evaluation of whether mutations found in P. jirovecii FAS lead to sulfa drug resistance is hampered by the lack of a culture system for P. jirovecii as well as the failure of P. jirovecii FAS to complement in a heterologous system. Therefore, we chose to model the P. jirovecii mutations in the Saccharomyces cerevisiae FAS protein (encoded by FOL1) via its expression in Escherichia coli. An optimized drug diffusion assay was used to evaluate the FAS mutants against 15 sulfa drugs. It was established that the single amino acid substitution, P599S, in the (DHPS) domain of FAS led to sulfa drug resistance, whereas the T597A substitution led to increased sensitivity. The presence of both mutations (T597A and P599S) was cooperative and led to increased sulfa drug resistance. Analysis of a novel double mutant, (T597V P599S) was found to have significantly higher sulfa drug resistance than the T597A P599S mutant. These data suggest that further amino acid substitutions may lead to the evolution of higher sulfa drug resistance. Two sulfa drugs (sulfachloropyridazine and sulfathiazole) were identified that had higher inhibitory potential than sulfamethoxazole, which is currently the preferred treatment for PCP.

  9. Molecular epidemiologic analysis of a Pneumocystis pneumonia outbreak among renal transplant patients.

    PubMed

    Urabe, N; Ishii, Y; Hyodo, Y; Aoki, K; Yoshizawa, S; Saga, T; Murayama, S Y; Sakai, K; Homma, S; Tateda, K

    2016-04-01

    Between 18 November and 3 December 2011, five renal transplant patients at the Department of Nephrology, Toho University Omori Medical Centre, Tokyo, were diagnosed with Pneumocystis pneumonia (PCP). We used molecular epidemiologic methods to determine whether the patients were infected with the same strain of Pneumocystis jirovecii. DNA extracted from the residual bronchoalveolar lavage fluid from the five outbreak cases and from another 20 cases of PCP between 2007 and 2014 were used for multilocus sequence typing to compare the genetic similarity of the P. jirovecii. DNA base sequencing by the Sanger method showed some regions where two bases overlapped and could not be defined. A next-generation sequencer was used to analyse the types and ratios of these overlapping bases. DNA base sequences of P. jirovecii in the bronchoalveolar lavage fluid from four of the five PCP patients in the 2011 outbreak and from another two renal transplant patients who developed PCP in 2013 were highly homologous. The Sanger method revealed 14 genomic regions where two differing DNA bases overlapped and could not be identified. Analyses of the overlapping bases by a next-generation sequencer revealed that the differing types of base were present in almost identical ratios. There is a strong possibility that the PCP outbreak at the Toho University Omori Medical Centre was caused by the same strain of P. jirovecii. Two different types of base present in some regions may be due to P. jirovecii's being a diploid species.

  10. Myeloid-derived suppressor cells impair alveolar macrophages through PD-1 receptor ligation during Pneumocystis pneumonia.

    PubMed

    Lei, Guang-Sheng; Zhang, Chen; Lee, Chao-Hung

    2015-02-01

    Myeloid-derived suppressor cells (MDSCs) were recently found to accumulate in the lungs during Pneumocystis pneumonia (PcP). Adoptive transfer of these cells caused lung damage in recipient mice, suggesting that MDSC accumulation is a mechanism of pathogenesis in PcP. In this study, the phagocytic activity of alveolar macrophages (AMs) was found to decrease by 40% when they were incubated with MDSCs from Pneumocystis-infected mice compared to those incubated with Gr-1(+) cells from the bone marrow of uninfected mice. The expression of the PU.1 gene in AMs incubated with MDSCs also was decreased. This PU.1 downregulation was due mainly to decreased histone 3 acetylation and increased DNA methylation caused by MDSCs. MDSCs were found to express high levels of PD-L1, and alveolar macrophages (AMs) were found to express high levels of PD-1 during PcP. Furthermore, PD-1 expression in AMs from uninfected mice was increased by 18-fold when they were incubated with MDSCs compared to those incubated with Gr-1(+) cells from the bone marrow of uninfected mice. The adverse effects of MDSCs on AMs were diminished when the MDSCs were pretreated with anti-PD-L1 antibody, suggesting that MDSCs disable AMs through PD-1/PD-L1 ligation during PcP.

  11. Pneumocystis jirovecii Pneumonia in Rheumatoid Arthritis Patients: Risks and Prophylaxis Recommendations

    PubMed Central

    Mori, Shunsuke; Sugimoto, Mineharu

    2015-01-01

    Pneumocystis jirovecii infection causes fulminant interstitial pneumonia (Pneumocystis pneumonia, PCP) in patients with rheumatoid arthritis (RA) who are receiving biological and/or nonbiological antirheumatic drugs. Recently, we encountered a PCP outbreak among RA outpatients at our institution. Hospital-acquired, person-to-person transmission appears to be the most likely mode of this cluster of P. jirovecii infection. Carriage of P. jirovecii seems a time-limited phenomenon in immunocompetent hosts, but in RA patients receiving antirheumatic therapy, clearance of this organism from the lungs is delayed. Carriers among RA patients can serve as sources and reservoirs of P. jirovecii infection for other susceptible patients in outpatient facilities. Development of PCP is a matter of time in such carriers. Considering the poor survival rates of PCP cases, prophylactic antibiotics should be considered for RA patients who are scheduled to receive antirheumatic therapy. Once a new case of PCP occurs, we should take prompt action not only to treat the PCP patient but also to prevent other patients from becoming new carriers of P. jirovecii. Short-term prophylaxis with trimethoprim-sulfamethoxazole is effective in controlling P. jirovecii infection and preventing future outbreaks of PCP among RA patients. PMID:26396551

  12. Small-intestine pneumocystis jiroveci pseudotumor as an acquired immunodeficiency syndrome-presenting illness: report of a case and review of the literature.

    PubMed

    Zhou, Yi; Shetty, Jayarama; Pins, Michael R

    2012-09-01

    A Pneumocystis jiroveci infection-associated mass clinically mimicking a malignancy (ie, pseudotumor) is rare and usually occurs in the lung in association with Pneumocystis pneumonia. Pneumocystis jiroveci pseudotumors of the small intestine are extremely rare and represent an unusual form of disseminated P jiroveci infection. We present a case of small-intestine P jiroveci pseudotumor as an acquired immunodeficiency syndrome-presenting illness in a patient with coinfection with cytomegalovirus, no pulmonary symptoms, and no known risk factors for human immunodeficiency virus infection. This case reinforces the potential importance of cytomegalovirus coinfection in the disseminated form of Pneumocystis infection and illustrates the importance of an expanded differential diagnosis when confronted with a clinically atypical mass lesion.

  13. Pentamidine for the treatment of Pneumocystis carinii pneumonia and other protozoal diseases.

    PubMed

    Pearson, R D; Hewlett, E L

    1985-11-01

    Pentamidine isethionate, discovered to have antiprotozoal activity in 1938, has recently been approved in the United States for the treatment of Pneumocystis carinii pneumonia. Despite frequent adverse reactions, which are at times life-threatening, pentamidine remains an important alternative to trimethoprim-sulfamethoxazole for the treatment of P. carinii pneumonia in patients with a history of allergy to sulfonamides or who have severe reactions or a lack of response to treatment with trimethoprim-sulfamethoxazole. Although not approved for other indications, pentamidine has been shown to be effective when used prophylactically against Trypanosoma brucei gambiense, the cause of West African sleeping sickness, as well as for treatment of the early hemolymphatic stage of that disease, and for treatment of some forms of leishmaniasis.

  14. Analysis of Pneumocystis carinii cysts with a fluorescence-activated cell sorter.

    PubMed Central

    Libertin, C R; Woloschak, G E; Wilson, W R; Smith, T F

    1984-01-01

    Human sera from Pneumocystis carinii-infected patients and specific rabbit antisera have antibodies against the cyst form of the organism. Lung tissue concentrations from cortisone-treated C3H/HeN mice and six open lung biopsy-positive patients were centrifuged and suspended, and immunofluorescent staining was done. We utilized the fluorescence-activated cell sorter to analyze and sort P. carinii cysts from lung homogenates into a morphologically distinct population. A quantitative basis was used for the definition of the cyst population by displaying the frequency of cells as a function of parameter (fluorescence intensity and light scatter) expression. In 14 of 15 histogram analyses, P. carinii-infected homogenates were differentiated from normal- and bacterial-control homogenates. The parameter range of light scatter (size) was 2 to 8 micron, and the fluorescence intensity was greater than a threshold based on the histogram profile. Images PMID:6392322

  15. Pneumocystis carinii and specific fungi have a common epitope, identified by a monoclonal antibody.

    PubMed Central

    Lundgren, B; Kovacs, J A; Nelson, N N; Stock, F; Martinez, A; Gill, V J

    1992-01-01

    Because Pneumocystis carinii may be related to fungi, we evaluated the reactivities of monoclonal antibodies raised against P. carinii with a variety of fungi. Fifty-two fungi and six protozoa were evaluated by immunofluorescence. One of three monoclonal antibodies (MAbs) tested (MAb 7D7) reacted with 15 fungi but no protozoa. Saccharomyces cerevisiae showed the strongest reactivity by immunofluorescence. The reactive antigen was characterized for four fungi by the immunoblot technique. In all cases the antigen that was reactive with MAb 7D7 was larger than the P. carinii antigens that reacted with 7D7. In further studies with P. carinii, Aspergillus species, and S. cerevisiae, we found that MAb 7D7 reacted with a carbohydrate component in all organisms. The presence of an epitope that is common to P. carinii and a number of fungi further supports the fungal nature of P. carinii. Images PMID:1371519

  16. Response of rat model of Pneumocystis carinii pneumonia to continuous infusion of deferoxamine.

    PubMed Central

    Merali, S; Chin, K; Grady, R W; Weissberger, L; Clarkson, A B

    1995-01-01

    The iron-chelating drug deferoxamine mesylate (DFO) is active against Pneumocystis carinii in vitro and in rat and mouse models of P. carinii pneumonia. Because DFO has a short half-life, daily divided or continuous dosage was expected to improve the dose response, as is the case with DFO treatment of malaria. Therefore, results of single daily intraperitoneal injections were compared with results of an evenly divided four-times-daily dosage and the efficacy of delivery with implanted infusion pumps. The highest bolus dosage (1,000 mg kg-1 of body weight day-1) was as effective as the standard combination of trimethoprim with sulfamethoxazole. Unexpectedly, very little improvement was observed with the divided or continuous dosage, and several mechanisms that could account for this are discussed. PMID:7492082

  17. Signal transduction in Pneumocystis carinii: characterization of the genes (pcg1) encoding the alpha subunit of the G protein (PCG1) of Pneumocystis carinii carinii and Pneumocystis carinii ratti.

    PubMed Central

    Smulian, A G; Ryan, M; Staben, C; Cushion, M

    1996-01-01

    Pneumocystis carinii is a eukaryotic organism that causes pneumonia in immunocompromised hosts. The cell biology and life cycle of the organism are poorly understood primarily because of the lack of a continuous in vitro cultivation system. These limitations have prevented investigation of the organism's infectious cycle and hindered the rational development of new antimicrobial therapies and implementation of measures to prevent exposure to the organism or transmission. The interaction of P. carinii with its host and its environment may be critical determinants of pathogenicity and life cycle. Signal transduction pathways are likely to be critical in regulating these processes. G proteins are highly conserved members of the pathways important in many cellular events, including cell proliferation and environmental sensing. To characterize signal transduction pathways in P. carinii, we cloned a G-protein alpha subunit (G-alpha) of P. carinii carinii and P. carinii ratti by PCR amplification and hybridization screening. The gene encoding the G-alpha was present in single copy on a 450-kb chromosome of P.c. ratti. The 1,062-bp G-alpha open reading frame is interrupted by nine introns. The predicted polypeptide showed 29 to 53% identity with known fungal G-alpha proteins with greatest homology to Neurospora crassa Gna-2. Northern (RNA) blot analysis and immunoprecipitation demonstrated expression of the G-alpha mRNA and protein P. carinii isolated from heavily infected animals. Some alteration in the level of transcription was noted in short-term maintenance in starvation or rich medium. Characterization of signal transduction in P. carinii will permit a better understanding of the reproductive capacity and other cellular processes in this family or organisms that cannot be cultured continuously. PMID:8641768

  18. [Pneumocystis pneumonia developed in two patients with rheumatoid arthritis during treatment of adalimumab].

    PubMed

    Ikeuchi, Hidekazu; Umemoto, Azusa; Tsukida, Mayuko; Sakurai, Noriyuki; Maeshima, Akito; Kuroiwa, Takashi; Hiromura, Keiju; Nojima, Yoshihisa

    2011-01-01

    While tumor necrosis factor (TNF) inhibitors have dramatically improved the clinical outcomes of rheumatoid arthritis (RA) in recent years, infectious complications are a serious concern. Adalimumab (ADA) is a newly-developed human monoclonal antibody against TNF-alpha. Here we report 2 cases of pneumocystis pneumonia (PCP) which developed in RA patients during ADA therapy. One patient is a 66-year-old woman who had a history of RA for 6 months. The patient was given ADA at 40 mg biweekly for her active arthritis which had been refractory to 6 mg/week of methotrexate (MTX), and 5 mg/day of prednisolone (PSL). One hundred and six days later, she was admitted to our hospital because of fever, cough, and dyspnea. Another patient is a 62-year-old man who had a history of RA for 3 years. Since his arthritis was so active even under the treatment with MTX (8 mg/week) and PSL (15 mg/day), the patient started to be given ADA at 40 mg biweekly. After 28 days, the patient was admitted to the hospital because of dyspnea. Chest roentgenogram and computed tomography revealed interstitial pneumonia in both patients. Beta-D-glucan levels were so high in their serum suggesting the diagnosis of PCP, which was confirmed by the detection of Pneumocystis jirovecii DNA in the sputa by polymerase chain reaction. The patients were immediately treated with sulfamethoxazole/trimethoprim and high-dose prednisolone, which successfully improved pneumonia, and they were discharged from the hospital on the 8(th) and 16(th) day, respectively. PCR and β-D-glucan were useful for the early diagnosis of PCP and lead to the timely induction of adequate treatment and the rescue of these patients.

  19. Quantitative PCR to diagnose Pneumocystis pneumonia in immunocompromised non-HIV patients.

    PubMed

    Mühlethaler, K; Bögli-Stuber, K; Wasmer, S; von Garnier, C; Dumont, P; Rauch, A; Mühlemann, K; Garzoni, C

    2012-04-01

    The utility of quantitative Pneumocystis jirovecii PCR in clinical routine for diagnosing Pneumocystis pneumonia (PCP) in immunocompromised non-HIV patients is unknown. We analysed bronchoalveolar lavage fluid with real-time quantitative P. jirovecii PCR in 71 cases with definitive PCP defined by positive immunofluorescence (IF) tests and in 171 randomly selected patients with acute lung disease. In those patients, possible PCP cases were identified by using a novel standardised PCP probability algorithm and chart review. PCR performance was compared with IF testing, clinical judgment and the PCP probability algorithm. Quantitative P. jirovecii PCR values >1,450 pathogens·mL(-1) had a positive predictive value of 98.0% (95% CI 89.6-100.0%) for diagnosing definitive PCP. PCR values of between 1 and 1,450 pathogens·mL(-1) were associated with both colonisation and infection; thus, a cut-off between the two conditions could not be identified and diagnosis of PCP in this setting relied on IF and clinical assessment. Clinical PCP could be ruled out in 99.3% of 153 patients with negative PCR results. Quantitative PCR is useful for diagnosing PCP and is complementary to IF. PCR values of >1,450 pathogens·mL(-1) allow reliable diagnosis, whereas negative PCR results virtually exclude PCP. Intermediate values require additional clinical assessment and IF testing. On the basis of our data and for economic and logistical limitations, we propose a clinical algorithm in which IF remains the preferred first test in most cases, followed by PCR in those patients with a negative IF and strong clinical suspicion for PCP.

  20. Evidence for a Pneumocystis carinii Flo8-like transcription factor: insights into organism adhesion.

    PubMed

    Kottom, Theodore J; Limper, Andrew H

    2016-02-01

    Pneumocystis carinii (Pc) adhesion to alveolar epithelial cells is well established and is thought to be a prerequisite for the initiation of Pneumocystis pneumonia. Pc binding events occur in part through the major Pc surface glycoprotein Msg, as well as an integrin-like molecule termed PcInt1. Recent data from the Pc sequencing project also demonstrate DNA sequences homologous to other genes important in Candida spp. binding to mammalian host cells, as well as organism binding to polystyrene surfaces and in biofilm formation. One of these genes, flo8, a transcription factor needed for downstream cAMP/PKA-pathway-mediated activation of the major adhesion/flocculin Flo11 in yeast, was cloned from a Pc cDNA library utilizing a partial sequence available in the Pc genome database. A CHEF blot of Pc genomic DNA yielded a single band providing evidence this gene is present in the organism. BLASTP analysis of the predicted protein demonstrated 41 % homology to the Saccharomyces cerevisiae Flo8. Northern blotting demonstrated greatest expression at pH 6.0-8.0, pH comparable to reported fungal biofilm milieu. Western blot and immunoprecipitation assays of PcFlo8 protein in isolated cyst and tropic life forms confirmed the presence of the cognate protein in these Pc life forms. Heterologous expression of Pcflo8 cDNA in flo8Δ-deficient yeast strains demonstrated that the Pcflo8 was able to restore yeast binding to polystyrene and invasive growth of yeast flo8Δ cells. Furthermore, Pcflo8 promoted yeast binding to HEK293 human epithelial cells, strengthening its functional classification as a Flo8 transcription factor. Taken together, these data suggest that PcFlo8 is expressed by Pc and may exert activity in organism adhesion and biofilm formation.

  1. High Prevalence of Pneumocystis jirovecii Dihydropteroate Synthase Gene Mutations in Patients with a First Episode of Pneumocystis Pneumonia in Santiago, Chile, and Clinical Response to Trimethoprim-Sulfamethoxazole Therapy.

    PubMed

    Ponce, Carolina A; Chabé, Magali; George, Claudio; Cárdenas, Alejandra; Durán, Luisa; Guerrero, Julia; Bustamante, Rebeca; Matos, Olga; Huang, Laurence; Miller, Robert F; Vargas, Sergio L

    2017-02-01

    Mutations in the dihydropteroate synthase (DHPS) gene of Pneumocystis jirovecii are associated with the failure of sulfa prophylaxis. They can develop by selection in patients receiving sulfa drugs or be acquired via person-to-person transmission. DHPS mutations raise concern about the decreasing efficacy of sulfa drugs, the main available therapeutic tool for Pneumocystis pneumonia (PCP). The prevalence of Pneumocystis DHPS mutations was examined in Pneumocystis isolates from 56 sulfa-prophylaxis-naive adults with a first episode of PCP from 2002 to 2010 in Santiago, Chile. Their clinical history was reviewed to analyze the effect of these mutations on response to trimethoprim-sulfamethoxazole (TMP-SMX) therapy and outcome. Mutant genotypes occurred in 22 (48%) of 46 HIV-infected patients and in 5 (50%) of 10 HIV-uninfected patients. Compared to patients with a wild-type genotype, those with mutant genotypes were more likely to experience sulfa treatment-limiting adverse reactions and to have a twice-longer duration of mechanical ventilation if mechanically ventilated. Specific genotypes did not associate with death, which occurred in none of the HIV-infected patients and in 50% of the non-HIV-infected patients. Chile has a high prevalence of DHPS mutations, which were presumably acquired through interhuman transmission because patients were not on sulfa prophylaxis. These results contrast with the low prevalence observed in other Latin American countries with similar usage of sulfa drugs, suggesting that additional sources of resistant genotypes may be possible. The twice-longer duration of mechanical ventilation in patients with mutant DHPS genotypes suggests a decreased efficacy of TMP-SMX and warrants collaborative studies to assess the relevance of DHPS mutations and further research to increase therapeutic options for PCP.

  2. Abnormal lung gallium-67 uptake preceding pulmonary physiologic impairment in an asymptomatic patient with Pneumocystis carinii pneumonia

    SciTech Connect

    Reiss, T.F.; Golden, J. )

    1990-05-01

    Pneumocystis carinii pneumonia was suggested by a diffuse, bilateral pulmonary uptake of gallium-67 in an asymptomatic, homosexual male with the antibody to the immunodeficiency virus (HIV) who was undergoing staging evaluation for lymphoma clinically localized to a left inguinal lymph node. Chest radiograph and pulmonary function evaluation, including lung volumes, diffusing capacity and arterial blood gases, were within normal limits. Bronchoalveolar lavage revealed Pneumocystis carinii organisms. In this asymptomatic, HIV-positive patient, active alveolar infection, evidenced by abnormal gallium-67 scanning, predated pulmonary physiologic abnormalities. This observation raises questions concerning the natural history of this disease process and the specificity of physiologic tests for excluding disease. It also has implications for the treatment of neoplasia in the HIV-positive patient population.

  3. Serum (1 → 3) β-D-glucan assay for discrimination between Pneumocystis jirovecii pneumonia and colonization.

    PubMed

    Tasaka, Sadatomo; Kobayashi, Seiki; Yagi, Kazuma; Asami, Takahiro; Namkoong, Ho; Yamasawa, Wakako; Ishii, Makoto; Hasegawa, Naoki; Betsuyaku, Tomoko

    2014-11-01

    Polymerase chain reaction (PCR) technique is being increasingly used for the microbiological diagnosis of Pneumocystis pneumonia (PCP). As PCR is highly sensitive, it can be positive even in a patient with Pneumocystis colonization. In this study, we evaluated whether the β-d-glucan assay could be used to differentiate between PCP and Pneumocystis jirovecii colonization in immunocompromised patients with pulmonary infiltrates. We retrospectively evaluated data from 166 consecutive patients who underwent bronchoalveolar lavage for the diagnosis of PCP. Serum levels of β-d-glucan in the negative, colonization, probable PCP, and definite PCP groups were 20.2 ± 6.3, 48.8 ± 15.9, 89.9 ± 20.2, 224.9 ± 25.9 pg/mL, respectively. The β-D-glucan levels in the definite PCP group were significantly higher than those in the other 3 groups (p < 0.001). Serum β-d-glucan levels in patients with either definite or probable PCP (173.1 ± 18.8 pg/mL) were significantly greater than those in patients with colonization who had positive PCR results but improved without anti-PCP treatment (p < 0.002). The cut-off level for discrimination was estimated to be 33.5 pg/mL, with which the positive predictive value was 0.925. These results indicate that β-D-glucan is a useful marker to differentiate between PCP and Pneumocystis colonization. A positive β-D-glucan assay result might be a good indication to begin anti-PCP treatment.

  4. The life cycle stages of Pneumocystis murina have opposing effects on the immune response to this opportunistic, fungal pathogen.

    PubMed

    Evans, Heather M; Bryant, Grady L; Garvy, Beth A

    2016-08-29

    The cyst cell wall β-glucans of Pneumocystis have been shown to stimulate immune responses in lung epithelial cells, dendritic cells, and alveolar macrophages. Little is known about how the trophic life forms, which do not have a fungal cell wall, interact with these innate immune cells. Here, we report differences in the responses of both neonatal and adult mice to the trophic and cystic life cycle stages of Pneumocystis murina The adult and neonatal immune responses to infection with Pneumocystis murina trophic forms were less robust than the response to infection with a physiologically normal mixture of cysts and trophic forms. Cysts promoted the recruitment of nonresident innate immune cells and T and B cells into the lungs. Cysts, but not trophic forms, stimulated increased IFN-γ cytokine concentrations in the alveolar spaces, and an increase in IFN-γ-producing CD4(+) T cells. In vitro, bone marrow-derived dendritic cells (BMDCs) stimulated with cysts produced the proinflammatory cytokines IL-1β and IL-6. In contrast, trophic forms suppressed β-glucan-, LTA-, and LPS-induced IL-1β, IL-6, and TNFα production by BMDCs and antigen presentation to CD4(+) T cells. The negative effects of trophic forms were not due to ligation of mannose receptor. Our results indicate that optimal innate and adaptive immune responses to Pneumocystis species are dependent on stimulation with the cyst life cycle stage. Conversely, trophic forms suppress β-glucan-induced proinflammatory responses in vitro, suggesting that the trophic forms dampen cyst-induced inflammation in vivo.

  5. Utility of reflex Gomori methenamine silver staining for Pneumocystis jirovecii on bronchoalveolar lavage cytologic specimens: a review.

    PubMed

    Nassar, Aziza; Zapata, Mauricio; Little, James V; Siddiqui, Momin T

    2006-11-01

    Pneumocystis jiroveci (Pj; formerly Pneumocystis carinii) is an opportunistic pathogen causing life-threatening pneumonia (Pneumocystis pneumonia) in immunosuppressed individuals. Its diagnosis is dependent on identification in bronchoalveolar lavage (BAL) specimens. Gomori's methenamine silver nitrate (GMS) stain has been advocated to highlight the organisms in BAL specimens. This study was performed to determine the utility of reflex GMS staining on all BAL specimens for identifying Pj.All BAL specimens from years 2000 to 2004 were processed as cytospins and stained with Papanicolaou (Pap) and GMS stains. A total of 2,984 BAL specimens were identified. A total of 116 (3.9% of total BAL) BAL specimens were diagnostic of Pj. The diagnostic specimens were grouped as follows: 103 (88.8% of total positive cases) Pj identified with both Pap and GMS staining; 11 (9.5% of total positive cases) Pj identified only with Pap staining; and 2 (1.7% of total positive cases) Pj identified only with GMS staining. In conclusion, the prevalence of Pj in BAL specimens is 3.9%, which can be attributed to improved management of immunocompromised patients. Performing reflex GMS staining on all BAL specimens does not improve the diagnostic identification of Pj since the majority (98.3%) of diagnoses can be rendered on Pap stained slides. A cost analysis for GMS staining on 2,879 GMS-negative BAL specimens was estimated at $143,950. Thus, from diagnostic and cost benefit perspectives, GMS staining can be recommended only on cases where Pap stain is negative, and the clinical presentation is consistent with Pneumocystis pneumonia.

  6. Coinfection pulmonaire par pneumocystis jirovecii et pseudomonas aeruginosa au cours du SIDA: à propos de deux cas

    PubMed Central

    Mamoudou, Savadogo; Bellaud, Guillaume; Ana, Canestri; Gilles, Pialoux

    2015-01-01

    Rapporter deux cas cliniques de coinfections pulmonaires par Pneumocystis jirovecii et par Pseudomonas aeruginosa chez des patients vivant avec le VIH. Les deux patients étaient âgés respectivement de 32 ans et 46 ans. Un patient a été pris en charge à l'hôpital Yalgado Ouédraogo de Ouagadougou au Burkina Faso et l'autre a été pris en charge à l'hôpital Ténon de Paris, en France. Les deux souffraient de pneumopathie confirmée à la radiographie et à la tomodensitométrie. L'un des patients était sévèrement immuno déprimé, contrairement à l'autre. L'examen bactériologique dans les crachats avait permis d'isoler Pseudomonas aeruginosa et Pneumocystis jirovecii chez les deux patients. Sous traitement, l’évolution a été favorable. Les coinfections morbides sont relativement fréquentes chez les patients vivant avec le VIH. Devant une symptomatologie respiratoire du sujet vivant avec le VIH, il faut savoir rechercher en plus du Bacille de Koch, Pneumocystis jirovecii et Pseudomonas aeruginosa par un lavage broncho alvéolaire. PMID:26516396

  7. Low prevalence of Pneumocystis pneumonia (PCP) but high prevalence of pneumocystis dihydropteroate synthase (dhps) gene mutations in HIV-infected persons in Uganda.

    PubMed

    Taylor, Steve M; Meshnick, Steven R; Worodria, William; Andama, Alfred; Cattamanchi, Adithya; Davis, J Lucian; Yoo, Samuel D; Byanyima, Patrick; Kaswabuli, Sylvia; Goodman, Carol D; Huang, Laurence

    2012-01-01

    Pneumocystis jirovecii pneumonia (PCP) is an important opportunistic infection in patients infected with HIV, but its burden is incompletely characterized in those areas of sub-Saharan Africa where HIV is prevalent. We explored the prevalence of both PCP in HIV-infected adults admitted with pneumonia to a tertiary-care hospital in Uganda and of putative P. jirovecii drug resistance by mutations in fungal dihydropteroate synthase (dhps) and dihydrofolate reductase (dhfr). In 129 consecutive patients with sputum smears negative for mycobacteria, 5 (3.9%) were diagnosed with PCP by microscopic examination of Giemsa-stained bronchoalveolar lavage fluid. Concordance was 100% between Giemsa stain and PCR (dhps and dhfr). PCP was more prevalent in patients newly-diagnosed with HIV (11.4%) than in patients with known HIV (1.1%; p = 0.007). Mortality at 2 months after discharge was 29% overall: 28% among PCP-negative patients, and 60% (3 of 5) among PCP-positive patients. In these 5 fungal isolates and an additional 8 from consecutive cases of PCP, all strains harbored mutant dhps haplotypes; all 13 isolates harbored the P57S mutation in dhps, and 3 (23%) also harbored the T55A mutation. No non-synonymous dhfr mutations were detected. PCP is an important cause of pneumonia in patients newly-diagnosed with HIV in Uganda, is associated with high mortality, and putative molecular evidence of drug resistance is prevalent. Given the reliability of field diagnosis in our cohort, future studies in sub-Saharan Africa can investigate the clinical impact of these genotypes.

  8. Pneumocystis Pneumonia

    MedlinePlus

    ... at Risk & Prevention Sources Diagnosis & Testing Treatment & Outcomes Health Professionals More Resources Sporotrichosis Other Pathogenic Fungi Exserohilum Cladosporium Who Gets Fungal Infections? People living with HIV/AIDS Organ Transplant Patients ...

  9. Therapeutic potential of caspofungin combined with trimethoprim-sulfamethoxazole for pneumocystis pneumonia: a pilot study in mice.

    PubMed

    Lobo, Maria Luísa; Esteves, Francisco; de Sousa, Bruno; Cardoso, Fernando; Cushion, Melanie T; Antunes, Francisco; Matos, Olga

    2013-01-01

    Pneumocystis pneumonia (PcP) is a major cause of mortality and morbidity in immunocompromised patients. There are limited alternative therapeutic choices to trimethoprim-sulfamethoxazole (TMP-SMX) which is the standard first line therapy/prophylaxis for PcP. The efficacy of low doses of caspofungin and caspofungin in association with TMP-SMX standard-prophylactic dose was evaluated in an experimental model of Pneumocystis. Susceptibility of Pneumocystis spp. to low doses of caspofungin and caspofungin/TMP-SMX was evaluated in Balb/c immunosuppressed mice, infected intranasally with P. murina. Caspofungin was administered once daily at 0.1 mg/kg, 0.05 mg/kg, and 0.001 mg/kg and TMP-SMX was administered by oral gavage (12.25 mg/62.5 mg/day), for 21 days. Efficacy was calculated based on the reduction in organism burden determined through quantitative fluorescent-based real-time PCR (qPCR). Serum β-1,3-D-glucan was measured as an additional marker of infection. The present data showed that caspofungin demonstrated anti-Pneumomocystis effect. However, the doses administrated were too low to achieve Pneumocystis eradication, which suggests that echinocandin treatment should not be administrated as mono-therapy. After 21 days of treatment, P. murina was not detected in the lungs of mice with either TMP-SMX or caspofungin/TMP-SMX. The results showed that, even at the lowest concentrations tested, the efficacy of caspofungin in association with TMP-SMX was higher than the efficacy of either drug used alone. The administration of caspofungin/TMP-SMX was at least 1.4 times more effective against P. murina infection than TMP-SMX used alone. The most promising result was achieved with the combination of caspofungin 0.05 mg/kg/day with TMP-SMX 12.5 mg-62.5 mg/day, which reduced the parasite burden to undetectable levels immediately at the 14(th) day of treatment, showing a highly marked anti-Pneumomocystis effect. These data suggest that the administration of low doses of

  10. Therapeutic Potential of Caspofungin Combined with Trimethoprim-Sulfamethoxazole for Pneumocystis Pneumonia: A Pilot Study in Mice

    PubMed Central

    Lobo, Maria Luísa; Esteves, Francisco; de Sousa, Bruno; Cardoso, Fernando; Cushion, Melanie T.; Antunes, Francisco; Matos, Olga

    2013-01-01

    Pneumocystis pneumonia (PcP) is a major cause of mortality and morbidity in immunocompromised patients. There are limited alternative therapeutic choices to trimethoprim-sulfamethoxazole (TMP-SMX) which is the standard first line therapy/prophylaxis for PcP. The efficacy of low doses of caspofungin and caspofungin in association with TMP-SMX standard-prophylactic dose was evaluated in an experimental model of Pneumocystis. Susceptibility of Pneumocystis spp. to low doses of caspofungin and caspofungin/TMP-SMX was evaluated in Balb/c immunosuppressed mice, infected intranasally with P. murina. Caspofungin was administered once daily at 0.1 mg/kg, 0.05 mg/kg, and 0.001 mg/kg and TMP-SMX was administered by oral gavage (12.25 mg/62.5 mg/day), for 21 days. Efficacy was calculated based on the reduction in organism burden determined through quantitative fluorescent-based real-time PCR (qPCR). Serum β-1,3-D-glucan was measured as an additional marker of infection. The present data showed that caspofungin demonstrated anti-Pneumomocystis effect. However, the doses administrated were too low to achieve Pneumocystis eradication, which suggests that echinocandin treatment should not be administrated as mono-therapy. After 21 days of treatment, P. murina was not detected in the lungs of mice with either TMP-SMX or caspofungin/TMP-SMX. The results showed that, even at the lowest concentrations tested, the efficacy of caspofungin in association with TMP-SMX was higher than the efficacy of either drug used alone. The administration of caspofungin/TMP-SMX was at least 1.4 times more effective against P. murina infection than TMP-SMX used alone. The most promising result was achieved with the combination of caspofungin 0.05 mg/kg/day with TMP-SMX 12.5 mg–62.5 mg/day, which reduced the parasite burden to undetectable levels immediately at the 14th day of treatment, showing a highly marked anti-Pneumomocystis effect. These data suggest that the administration of low doses of

  11. Effect of oral washes on the diagnosis of Pneumocystis carinii pneumonia with a low parasite burden and on detection of organisms in subclinical infections.

    PubMed

    Matos, O; Costa, M C; Lundgren, B; Caldeira, L; Aguiar, P; Antunes, F

    2001-08-01

    This study was designed to assess the efficacy of using oral washes (OWs) to diagnose Pneumocystis carinii pneumonia (PCP) in patients with a low parasite burden and to detect cases of subclinical infection. A total of 104 paired induced sputum (IS) samples and OWs from 104 HIV-seropositive patients and 32 OWs from immunocompetent healthy controls were studied. All of the control samples were negative. Fifty-two IS specimens were positive for Pneumocystis carinii, and 26 of these cases were also detected in the OWs using conventional stain or polymerase chain reaction. Twenty-four of the PCP cases had a high or a moderate parasite load and 28 had a low parasite load; among them, Pneumocystis carinii was detected in the OWs of 15 and 11 cases, respectively. Fifteen of the 104 IS samples studied belonged to patients who were asymptomatic carriers or who had a subclinical infection, and Pneumocystis carinii was detected in the OWs of 4 of these cases. The parasite was not detected in 37 IS samples and in 74 OWs. The results of this study indicate that in patients with a low pulmonary parasite burden, the number of organisms reaching the oral cavity is insufficient for reliable detection in OWs. Thus, OWs are less useful than IS samples for detecting Pneumocystis carinii in cases of pneumonia in which a low parasite burden and/or subclinical infection are present.

  12. Fungal colonization with Pneumocystis correlates to increasing chloride channel accessory 1 (hCLCA1) suggesting a pathway for up-regulation of airway mucus responses, in infant lungs

    PubMed Central

    Pérez, Francisco J.; Ponce, Carolina A.; Rojas, Diego A.; Iturra, Pablo A.; Bustamante, Rebeca I.; Gallo, Myriam; Hananias, Karime; Vargas, Sergio L.

    2014-01-01

    Fungal colonization with Pneumocystis is associated with increased airway mucus in infants during their primary Pneumocystis infection, and to severity of COPD in adults. The pathogenic mechanisms are under investigation. Interestingly, increased levels of hCLCA1 – a member of the calcium-sensitive chloride conductance family of proteins that drives mucus hypersecretion – have been associated with increased mucus production in patients diagnosed with COPD and in immunocompetent rodents with Pneumocystis infection. Pneumocystis is highly prevalent in infants; therefore, the contribution of Pneumocystis to hCLCA1 expression was examined in autopsied infant lungs. Respiratory viruses that may potentially increase mucus, were also examined. hCLCA1 expression was measured using actin-normalized Western-blot, and the burden of Pneumocystis organisms was quantified by qPCR in 55 autopsied lungs from apparently healthy infants who died in the community. Respiratory viruses were diagnosed using RT-PCR for RSV, metapneumovirus, influenza, and parainfluenza viruses; and by PCR for adenovirus. hCLCA1 levels in virus positive samples were comparable to those in virus-negative samples. An association between Pneumocystis and increased hCLCA1 expression was documented (P=0.028). Additionally, increasing Pneumocystis burden correlated with increasing hCLCA1 protein expression levels (P=0.017). Results strengthen the evidence of Pneumocystis-associated up-regulation of mucus-related airway responses in infant lungs. Further characterization of this immunocompetent host-Pneumocystis-interaction, including assessment of potential clinical significance, is warranted. PMID:25379375

  13. Common invasive fungal diseases: an overview of invasive candidiasis, aspergillosis, cryptococcosis, and Pneumocystis pneumonia.

    PubMed

    Schmiedel, Yvonne; Zimmerli, Stephan

    2016-01-01

    Every year, Candida, Aspergillus, Cryptococcus and Pneumocystis infect an estimated two million individuals worldwide. Most are immunocompromised or critically ill. Candida is the most common fungal pathogen of the critically ill and of recipients of transplanted abdominal organs. In high-risk haemato-oncological patients, in contrast, the introduction of antifungal prophylaxis with fluconazole and later with mould-active posaconazole has led to a remarkable reduction of invasive candidiasis and is likely to have a similar effect on invasive aspergillosis. Invasive aspergillosis remains the dominant invasive fungal disease (IFD) of haemato-oncological patients and solid-organ transplant recipients and is increasingly found in individuals with exacerbated chronic obstructive pulmonary disease on corticosteroids. In the developed world, owing to antiretroviral therapy Pneumocystis pneumonia and cryptococcosis have become rare in patients with human immunodeficiency virus (HIV) and are mainly found in solid-organ transplant recipients or immunocompromised patients. In the developing world, cryptococcosis remains a common and highly lethal disease of HIV positive individuals. With invasive candidiasis and invasive aspergillosis, timely diagnosis is the principal challenge. The clinical presentation is nonspecific and current diagnostic tests lack sensitivity and specificity. The combination of several tests improves sensitivity, but not specificity. Standardised polymerase chain-reaction-based assays may be promising tools for more rapid and specific diagnosis of candidiasis and invasive aspergillosis. Nevertheless, initiation of treatment is often based solely on clinical suspicion. Empirical therapy, however, may lead to over-treatment of patients without IFD or it may miss its target in the case of resistance. Despite the success of antifungal prophylaxis in reducing the incidence of IFDs in haemato-oncological patients, there are a considerable number of

  14. Spontaneous Pneumocystis carinii pneumonia in immunodeficient mutant scid mice. Natural history and pathobiology.

    PubMed Central

    Roths, J. B.; Marshall, J. D.; Allen, R. D.; Carlson, G. A.; Sidman, C. L.

    1990-01-01

    The opportunistic pathogen Pneumocystis carinii (Pc) poses a major clinical health problem in individuals with immune deficiency, including those patients with human immunodeficiency (HIV)-associated acquired immune deficiency disease (AIDS). Heretofore, in vivo investigations of the biology of Pc and pathogenesis of pneumocystosis have generally employed steroid-induced immune suppression with antibiotic prophylaxis and protein deprivation. This approach has many drawbacks, chief among them being the widespread, multiple interacting effects caused by the inducing agents. Athymic (nude) mice and rats have been used, but are less than ideal, as the immune defect primarily affects T lymphocytes. This article describes the natural history, pathobiology, and environmental effects on Pc pneumonitis in nonaxenically housed mice homozygous for the autosomal recessive mutation 'severe combined immunodeficiency' (scid), which almost totally lack both cell-mediated and antibody-mediated immune functions. The predictability, unequivocal expression, high morbidity, and well-defined genetic basis make scid/scid mutant mice the model of choice for in vivo studies of spontaneous pneumocystosis. Images Figure 3 Figure 6 PMID:2349968

  15. Activity of bilobalide, a sesquiterpene from Ginkgo biloba, on Pneumocystis carinii.

    PubMed Central

    Atzori, C; Bruno, A; Chichino, G; Bombardelli, E; Scaglia, M; Ghione, M

    1993-01-01

    The sesquiterpene bilobalide, extracted from Ginkgo biloba leaves, was tested in vitro and in vivo for the ability to inhibit Pneumocystis carinii growth. Bilobalide was inhibitory to trophozoites cultured on human embryonic lung fibroblasts (HEL 299) at approximately the same concentration as trimethoprim plus sulfamethoxazole (lowest effective concentration, 50 micrograms of bilobalide per ml versus 9/45 microgram of trimethoprim-sulfamethoxazole per ml), inducing microscopically detectable morphological changes in the cytoplasm of the parasite. In pharmacologically immunosuppressed Sprague-Dawley rats transtracheally infected with a suspension of about 5 x 10(6) P. carinii trophozoites per ml, the daily intraperitoneal administration of bilobalide (10 mg/kg of body weight for 8 days) lowered the number of organisms by approximately 2 logs (that is, about 99%). There was no apparent toxicity either in uninfected HEL 299 feeder cells or in infected and uninfected animals. These studies suggest that the sesquiterpene bilobalide might be useful for therapy of and prophylaxis against P. carinii infections in humans. Images PMID:8363381

  16. ECIL guidelines for treatment of Pneumocystis jirovecii pneumonia in non-HIV-infected haematology patients.

    PubMed

    Maschmeyer, Georg; Helweg-Larsen, Jannik; Pagano, Livio; Robin, Christine; Cordonnier, Catherine; Schellongowski, Peter

    2016-09-01

    The initiation of systemic antimicrobial treatment of Pneumocystis jirovecii pneumonia (PCP) is triggered by clinical signs and symptoms, typical radiological and occasionally laboratory findings in patients at risk of this infection. Diagnostic proof by bronchoalveolar lavage should not delay the start of treatment. Most patients with haematological malignancies present with a severe PCP; therefore, antimicrobial therapy should be started intravenously. High-dose trimethoprim/sulfamethoxazole is the treatment of choice. In patients with documented intolerance to this regimen, the preferred alternative is the combination of primaquine plus clindamycin. Treatment success should be first evaluated after 1 week, and in case of clinical non-response, pulmonary CT scan and bronchoalveolar lavage should be repeated to look for secondary or co-infections. Treatment duration typically is 3 weeks and secondary anti-PCP prophylaxis is indicated in all patients thereafter. In patients with critical respiratory failure, non-invasive ventilation is not significantly superior to intubation and mechanical ventilation. The administration of glucocorticoids must be decided on a case-by-case basis.

  17. Post-transplant Pneumocystis jirovecii pneumonia--a re-emerged public health problem?

    PubMed

    Chapman, Jeremy R; Marriott, Deborrah J; Chen, Sharon C-A; MacDonald, Peter S

    2013-08-01

    Pneumocystis jirovecii is a unicellular organism that in individuals with impaired immunity may cause pneumonia that can progress from minor illness to severe inflammatory pneumonia (PCP) with respiratory failure and death. Despite antimicrobial prophylaxis, which has reduced the incidence of PCP, clusters of late infections have been reported among kidney transplant recipients worldwide. A nosocomial PCP cluster was first recognized in 2010 at a Sydney hospital, but PCP clusters have since occurred in almost half of the renal transplant units on the eastern Australian seaboard, refocussing attention on optimal prophylaxis regimens and the likelihood of patient-to-patient transmission. A consensus meeting was conducted to derive the lessons from this experience for responding to PCP outbreaks. These included: (1) acting quickly--clusters of PCP in kidney transplant recipients with patient-to-patient transmission required transplant programs to act quickly to institute prophylactic and treatment measures; (2) instituting universal prophylaxis for all patients seen in the affected unit; (3) reducing patient-to-patient transmission via airborne droplets in the outpatient waiting areas; (4) examining the P. jirovecii genotypes. The meeting also considered recommendations for the duration of prophylaxis following de novo transplant and, for the individuals in whom long term prophylaxis is required, separating units with and without clusters of PCP.

  18. [Pneumocystis jiroveci pneumonia characteristics in adults with AIDS with or without antiretroviral therapy].

    PubMed

    Bahamondes M, Laura; Villar Z, M José; Orellana C, Carolina; González R, Jimena; Montenegro U, Cristian

    2006-09-01

    Highly active antiretroviral therapy (HAART) has changed the epidemiology of Pneumocystis jiroveci pneumonia (PCP) in AIDS patients. Global incidence of PCP has decreased and now it is prevalent in AIDS patients who do not receive HAART or are unsuccessfully treated with persistent immune depression. Moreover, the immunologic response to HAART has caused a PCP form which is included in the immune restoration inflammatory syndrome (IRIS). As of late 2004, 75.5% of patients cared for at Dr. Lucio Córdova Infectious Diseases Hospital were receiving HAART. This study compares PCP clinical characteristics in patients under the effect of HAART (n: 6) with those without antiretroviral therapy (n: 12). Among those with HAART, 83.3% (5/6) were without immunologic responses and 16.7% with virologic response. The median CD4 counts were low in both groups: 20 cells/mm(3) without HAART and 51 cells/mm(3) with HAART. There were no differences in most of PCP characteristics, and no IRIS cases were observed. HAART-receiving group had less severe disease and lower frequency of both, complications and steroidal therapy prescription (P 0.023).

  19. Pneumocystis jirovecii multilocus genotyping profiles in patients from Portugal and Spain.

    PubMed

    Esteves, F; Montes-Cano, M A; de la Horra, C; Costa, M C; Calderón, E J; Antunes, F; Matos, O

    2008-04-01

    Pneumonia caused by the opportunistic organism Pneumocystis jirovecii is a clinically important infection affecting AIDS and other immunocompromised patients. The present study aimed to compare and characterise the frequency pattern of DNA sequences from the P. jirovecii mitochondrial large-subunit rRNA (mtLSU rRNA) gene, the dihydropteroate synthase (DHPS) gene and the internal transcribed spacer (ITS) regions of the nuclear rRNA operon in specimens from Lisbon (Portugal) and Seville (Spain). Total DNA was extracted and used for specific molecular sequence analysis of the three loci. In both populations, mtLSU rRNA gene analysis revealed an overall prevalence of genotype 1. In the Portuguese population, genotype 2 was the second most common, followed by genotype 3. Inversely, in the Spanish population, genotype 3 was the second most common, followed by genotype 2. The DHPS wild-type sequence was the genotype observed most frequently in both populations, and the DHPS genotype frequency pattern was identical to distribution patterns revealed in other European studies. ITS types showed a significant diversity in both populations because of the high sequence variability in these genomic regions. The most prevalent ITS type in the Portuguese population was Eg, followed by Cg. In contrast to other European studies, Bi was the most common ITS type in the Spanish samples, followed by Eg. A statistically significant association between mtLSU rRNA genotype 1 and ITS type Eg was revealed.

  20. Pneumocystis carinii infection: evidence for high prevalence in normal and immunosuppressed children.

    PubMed

    Pifer, L L; Hughes, W T; Stagno, S; Woods, D

    1978-01-01

    Using Pneumocystis carinii organisms propagated through three passages in embryonic chick epithelial lung cultures, specific antigens and antisera were prepared for use in counterimmunoelectrophoresis and indirect immunofluorescent antibody techniques. These methods proved to be specific and sensitive for the detection of P. carinii antigen and antibody, respectively, in sera, and were applied to the study of cancer patients with P. carinii pneumonitis (PCP), cancer patients without pneumonitis, and normal children. Antigenemia was detected in 95% of patients with PCP, in 15% of cancer patients without pneumonitis, and in none of the normal children tested. In cross-sectional and longitudinal studies of normal infants and children, acquisition of serum antibody to P. carinii was demonstrated to occur progressively with increase in age. By 4 years of age two thirds of the normal children were found to have antibody to P. carinii in titers of 1:16 or greater. These studies indicate that subclinical P. carinii infection is highly prevalent in normal children, analogous to other opportunistic infections where active disease is manifest predominantly in the compromised host.

  1. Atovaquone versus trimethoprim-sulfamethoxazole as Pneumocystis jirovecii pneumonia prophylaxis following renal transplantation.

    PubMed

    Gabardi, Steven; Millen, Peter; Hurwitz, Shelley; Martin, Spencer; Roberts, Keri; Chandraker, Anil

    2012-01-01

    Pneumocystis pneumonia (PCP) is associated with significant morbidity and mortality in renal transplant recipients (RTR). Trimethoprim-sulfamethoxazole (TMP-SMZ) is considered the prophylactic agent-of-choice. Some patients require an alternative owing to TMP-SMZ intolerance. This is the first evaluation of full-dose atovaquone vs. TMP-SMZ for PCP prevention in RTR. One hundred and eighty-five RTR were evaluated in this single-center, retrospective analysis. Patients received either single-strength TMP-SMZ daily (group I; n = 160) or 1500 mg/d of atovaquone and of a fluoroquinolone for one month (group II; n = 25). The primary endpoint was the incidence of PCP at 12 months post-transplant. There were no cases of PCP in either group. There were comparable rates of infections from bacterial pathogens and cytomegalovirus, but rates of BK viremia were significantly higher in group I (22.5%) vs. group II (4%; p = 0.03). The incidence of leukopenia was similar in both groups. Higher mean potassium levels were seen in group I at three months post-transplant but were comparable at all other time points. The need for dose reduction and/or premature discontinuation of therapy secondary to adverse events was more prevalent in TMP-SMZ-treated patients. In our experience, atovaquone appears to be effective in preventing PCP post-renal transplant and also demonstrates good tolerability.

  2. Pneumocystis carinii mutations are associated with duration of sulfa or sulfone prophylaxis exposure in AIDS patients.

    PubMed

    Kazanjian, P; Armstrong, W; Hossler, P A; Burman, W; Richardson, J; Lee, C H; Crane, L; Katz, J; Meshnick, S R

    2000-08-01

    This study was conducted to determine whether Pneumocystis carinii dyhydropteroate synthase (DHPS) gene mutations in AIDS patients with P. carinii pneumonia (PCP) are affected by duration of sulfa or sulfone prophylaxis and influence response to sulfa or sulfone therapy. The P. carinii DHPS genes from 97 AIDS patients with PCP between 1991 and 1999 from 4 medical centers were amplified, using polymerase chain reaction (PCR), and sequenced. Mutations were observed in 76% of isolates from patients exposed to sulfa or sulfone prophylaxis compared with 23% of isolates from patients not exposed (P=.001). Duration of prophylaxis increased the risk of mutations (relative risk [RR] for each exposure month, 1.06; P=.02). Twenty-eight percent of patients with mutations failed sulfa or sulfone treatment; mutations increased the risk of sulfa or sulfone treatment failure (RR, 2.1; P=0.01). Thus, an increased duration of sulfa or sulfone prophylaxis increases the chance of developing a P. carinii mutation. The majority of patients with mutations respond to sulfa or sulfone therapy.

  3. Pneumocystis carinii antigenemia in adults with malignancy, infection, or pulmonary disease.

    PubMed Central

    Pifer, L L; Niell, H B; Morrison, B J; Counce, J D; Freeman, J M; Woods, D R; Neely, C L

    1984-01-01

    A counterimmunoelectrophoresis test for Pneumocystis carinii antigenemia was employed to assess the extent of subclinical infection or colonization with this agent in adults with infection, pulmonary disease, or malignancy and in healthy homosexual men. Antigenemia was detected in 6 of 208 (3%) of normal controls, 3 of 28 (11%) of patients with pulmonary infection, 3 of 33 (9%) of those with chronic lung disease, 1 of 36 (3%) of patients with lung cancer, 7 of 271 (3%) of afebrile subjects with malignancy, 6 of 19 (32%) of febrile patients with malignancy, 2 of 22 (9%) of those with nonpulmonary infection, and 0 of 21 (0%) of healthy young homosexual men. These data suggest that P. carinii is a common commensal or saprophyte that becomes clinically significant only when host defenses are impaired. Antigenemia may occur intermittently during various disease states in the absence of positive clinical signs and should alert the physician to subacute infection or colonization. Treatment appears advisable when clinical data and counterimmunoelectrophoresis results concur. PMID:6334694

  4. Spontaneous Pneumocystis carinii pneumonia in immunodeficient mutant scid mice. Natural history and pathobiology.

    PubMed

    Roths, J B; Marshall, J D; Allen, R D; Carlson, G A; Sidman, C L

    1990-05-01

    The opportunistic pathogen Pneumocystis carinii (Pc) poses a major clinical health problem in individuals with immune deficiency, including those patients with human immunodeficiency (HIV)-associated acquired immune deficiency disease (AIDS). Heretofore, in vivo investigations of the biology of Pc and pathogenesis of pneumocystosis have generally employed steroid-induced immune suppression with antibiotic prophylaxis and protein deprivation. This approach has many drawbacks, chief among them being the widespread, multiple interacting effects caused by the inducing agents. Athymic (nude) mice and rats have been used, but are less than ideal, as the immune defect primarily affects T lymphocytes. This article describes the natural history, pathobiology, and environmental effects on Pc pneumonitis in nonaxenically housed mice homozygous for the autosomal recessive mutation 'severe combined immunodeficiency' (scid), which almost totally lack both cell-mediated and antibody-mediated immune functions. The predictability, unequivocal expression, high morbidity, and well-defined genetic basis make scid/scid mutant mice the model of choice for in vivo studies of spontaneous pneumocystosis.

  5. Prevalence of Pneumocystis jirovecii pneumonia (2010-2013): the first Croatian report.

    PubMed

    Babic-Erceg, Andrea; Vilibic-Cavlek, Tatjana; Erceg, Marijan; Mlinaric-Missoni, Emilija; Begovac, Josip

    2014-06-01

    Pneumocystis jirovecii is an important cause of interstitial pneumonia particularly among immunocompromised hosts. We analysed the prevalence of P. jirovecii pneumonia (PCP) among HIV-infected and HIV-uninfected patients presented with interstitial pneumonia or acute respiratory syndrome hospitalized in six Croatian tertiary care hospitals. Over four-year period (2010-2013), a total of 328 lower respiratory tract samples: 253 (77.1%) bronchoalveolar lavage fluid, 43 (13.1%) tracheal aspirates and 32 (9.8%) bronchial aspirates from 290 patients were examined by real-time polymerase chain reaction (PCR). PCP was detected in 23 (7.9%) patients. The prevalence of PCP differed significantly among tested groups (χ2 = 95.03; d.f. = 3; p < 0.001). HIV-infected patients were more often positive (56.6%, 95%CI = 37.3-72.4) compared to other groups (patients with malignant disease 7.7%, 95%CI = 2.6-20.3; transplant patients 7.7%, 95%CI = 2.2-24.1; patients with other diagnosis 1.5%, 95%CI = 0.5-4.4). Majority of HIV-positive patients (80%) were newly diagnosed cases. Our results indicate that HIV-infected patients still represents the main risk group for P. jirovecii infection. PCP is responsible for pneumonia in 56.6% HIV-positive patients in Croatia, primarily those who do not know that they are HIV infected.

  6. Role of APOBEC3F Gene Variation in HIV-1 Disease Progression and Pneumocystis Pneumonia.

    PubMed

    An, Ping; Penugonda, Sudhir; Thorball, Christian W; Bartha, Istvan; Goedert, James J; Donfield, Sharyne; Buchbinder, Susan; Binns-Roemer, Elizabeth; Kirk, Gregory D; Zhang, Wenyan; Fellay, Jacques; Yu, Xiao-Fang; Winkler, Cheryl A

    2016-03-01

    Human APOBEC3 cytidine deaminases are intrinsic resistance factors to HIV-1. However, HIV-1 encodes a viral infectivity factor (Vif) that degrades APOBEC3 proteins. In vitro APOBEC3F (A3F) anti-HIV-1 activity is weaker than A3G but is partially resistant to Vif degradation unlike A3G. It is unknown whether A3F protein affects HIV-1 disease in vivo. To assess the effect of A3F gene on host susceptibility to HIV- acquisition and disease progression, we performed a genetic association study in six well-characterized HIV-1 natural cohorts. A common six-Single Nucleotide Polymorphism (SNP) haplotype of A3F tagged by a codon-changing variant (p. I231V, with allele (V) frequency of 48% in European Americans) was associated with significantly lower set-point viral load and slower rate of progression to AIDS (Relative Hazards (RH) = 0.71, 95% CI: 0.56, 0.91) and delayed development of pneumocystis pneumonia (PCP) (RH = 0.53, 95% CI: 0.37-0.76). A validation study in the International Collaboration for the Genomics of HIV (ICGH) showed a consistent association with lower set-point viral load. An in vitro assay revealed that the A3F I231V variant may influence Vif mediated A3F degradation. Our results provide genetic epidemiological evidence that A3F modulates HIV-1/AIDS disease progression.

  7. Rapid clearance of inhaled aerosols of Technetium-99M DTPA in patients with pneumocystis carinii pneumonia

    SciTech Connect

    Mason, G.R.; Duane, G.B.; Effros, R.M.; Mena, I.

    1985-05-01

    Because infection with Pheumocystis carinii pneumonia (PCP) causes alteration of the type I epithelial cells as the primary event, the authors studied patients with PCP to determine if PCP causes rapid clearance of Tc-99m DTPA. Twenty normal non-smoking subjects and 7 non-smoking patients with histologically proven PCP were studied. Serial studies were obtained in three patients. Following a two-minute inhalation of 1.6 ..mu..m aerosol particles of Tc-99m DTPA in saline, the activity over three peripheral regions of interest (ROI) of each lung was monitored for the next 7 minutes. The rate of decline of activity over each ROI was expressed as per cent decline/min. In 7 patients with PCP, the average clearance was 7.5 +- 3.6% min., normal, 1.3 +- 0.6% min.(SD). Three patients studied from 5 to 38 days following therapy had improvement in the rate of clearance. This has been demonstrated to be persistent even after clinical recovery of the patient. The ability to quantitate injury to the pulmonary epithelium may directly reflect the ability of Pneumocystis carinii to invade the lung. The authors conclude that Tc-99m DTPA clearance may be a useful test to help diagnosis and monitor the activity of PCP infections.

  8. Intermittent Courses of Corticosteroids Also Present a Risk for Pneumocystis Pneumonia in Non-HIV Patients

    PubMed Central

    Calero-Bernal, Maria L.; Martin-Garrido, Isabel; Donazar-Ezcurra, Mikel; Limper, Andrew H.

    2016-01-01

    Introduction. Pneumocystis pneumonia (PCP) is rising in the non-HIV population and associates with higher morbidity and mortality. The aggressive immunosuppressive regimens, as well as the lack of stablished guidelines for chemoprophylaxis, are likely contributors to this increased incidence. Herein, we have explored the underlying conditions, immunosuppressive therapies, and clinical outcomes of PCP in HIV-negative patients. Methods. Retrospective analysis of PCP in HIV-negative patients at Mayo Clinic from 2006–2010. The underlying condition, immunosuppressive therapies, coinfection, and clinical course were determined. PCP diagnosis required symptoms of pneumonia and identification of the organisms by visualization or by a real-time polymerase chain reaction. Results. A total of 128 cases of PCP were identified during the study period. Hematological malignancies were the predisposing condition for 50% of the patients. While 87% had received corticosteroids or other immunosuppressive therapies for >4 weeks prior to the diagnosis, only 7 were receiving PCP prophylaxis. Up to 43% of patients were not on daily steroids. Sixty-seven patients needed Intensive Care Unit (ICU) and 53 received mechanical ventilation. The mortality for those patients requiring ICU was 40%. Conclusions. PCP diagnosis in the HIV-negative population requires a high level of suspicion even if patients are not receiving daily corticosteroids. Mortality remains high despite adequate treatment. PMID:27721666

  9. Serological diagnosis of pneumocystosis: production of a synthetic recombinant antigen for immunodetection of Pneumocystis jirovecii.

    PubMed

    Tomás, A L; Cardoso, F; Esteves, F; Matos, O

    2016-11-08

    Diagnosis of Pneumocystis pneumonia (PcP) relies on the detection of P. jirovecii in respiratory specimens obtained by invasive techniques. Thus, the development of a serological test is urgently needed as it will allow the diagnosis of PcP using blood, an inexpensive and non-invasive specimen. This study aims to combine the production of a multi-epitope synthetic recombinant antigen (RSA) and an ELISA test for detection of anti-P. jirovecii antibodies, in order to develop a new approach for PcP diagnosis. The RSA was selected and designed based on the study of the immunogenicity of the carboxyl-terminal domain of the major surface glycoprotein. This antigen was purified and used as an antigenic tool in an ELISA technique for detection of Ig, IgG and IgM antibodies anti-P. jirovecii (patent-pending no. PT109078). Serum specimens from 88 patients previously categorized in distinct clinical subgroups and 17 blood donors, were analysed. The IgM anti-P. jirovecii levels were statistically increased in patients with PcP (p = 0.001) and the ELISA IgM anti-P. jirovecii test presented a sensitivity of 100% and a specificity of 80.8%, when associated with the clinical diagnosis criteria. This innovative approach, provides good insights about what can be done in the future serum testing for PcP diagnosis.

  10. Pneumocystis jirovecii pneumonia: still a concern in patients with haematological malignancies and stem cell transplant recipients.

    PubMed

    Cordonnier, Catherine; Cesaro, Simone; Maschmeyer, Georg; Einsele, Hermann; Donnelly, J Peter; Alanio, Alexandre; Hauser, Philippe M; Lagrou, Katrien; Melchers, Willem J G; Helweg-Larsen, Jannik; Matos, Olga; Bretagne, Stéphane; Maertens, Johan

    2016-09-01

    Pneumocystis jirovecii can cause life-threatening pneumonia following treatment for haematological malignancies or after HSCT. The mortality rate of P. jirovecii pneumonia (PCP) in these patients is 30%-60%, especially after HSCT. The clinical presentation of PCP in haematology differs from that associated with HIV infection, with the disease being acute and more often severe, having a lower fungal burden and being more frequently linked to treatment with corticosteroids. Most cases occur in patients not receiving adequate prophylaxis. The development of new therapies, including targeted treatments and monoclonal antibodies in various haematological diseases, justifies constant vigilance in order to identify new at-risk populations and give prophylaxis accordingly. The fifth and sixth European Conferences on Infections in Leukaemia (ECIL-5 and ECIL-6) aimed to review risk factors for PCP in haematology patients and to establish evidence-based recommendations for PCP diagnosis, prophylaxis and treatment. This article focuses on the magnitude of the problem, the main differences in clinical presentation between haematology patients and other immunocompromised populations, especially HIV-infected patients, and the main risk factors.

  11. Role of APOBEC3F Gene Variation in HIV-1 Disease Progression and Pneumocystis Pneumonia

    PubMed Central

    An, Ping; Penugonda, Sudhir; Thorball, Christian W.; Bartha, Istvan; Goedert, James J.; Donfield, Sharyne; Buchbinder, Susan; Binns-Roemer, Elizabeth; Kirk, Gregory D.; Zhang, Wenyan; Fellay, Jacques; Yu, Xiao-Fang; Winkler, Cheryl A.

    2016-01-01

    Human APOBEC3 cytidine deaminases are intrinsic resistance factors to HIV-1. However, HIV-1 encodes a viral infectivity factor (Vif) that degrades APOBEC3 proteins. In vitro APOBEC3F (A3F) anti-HIV-1 activity is weaker than A3G but is partially resistant to Vif degradation unlike A3G. It is unknown whether A3F protein affects HIV-1 disease in vivo. To assess the effect of A3F gene on host susceptibility to HIV- acquisition and disease progression, we performed a genetic association study in six well-characterized HIV-1 natural cohorts. A common six-Single Nucleotide Polymorphism (SNP) haplotype of A3F tagged by a codon-changing variant (p. I231V, with allele (V) frequency of 48% in European Americans) was associated with significantly lower set-point viral load and slower rate of progression to AIDS (Relative Hazards (RH) = 0.71, 95% CI: 0.56, 0.91) and delayed development of pneumocystis pneumonia (PCP) (RH = 0.53, 95% CI: 0.37–0.76). A validation study in the International Collaboration for the Genomics of HIV (ICGH) showed a consistent association with lower set-point viral load. An in vitro assay revealed that the A3F I231V variant may influence Vif mediated A3F degradation. Our results provide genetic epidemiological evidence that A3F modulates HIV-1/AIDS disease progression. PMID:26942578

  12. Detection of Pneumocystis jirovecii in oral wash from immunosuppressed patients as a diagnostic tool

    PubMed Central

    Hviid, Cecilie Juul; Lund, Marianne; Sørensen, Allan; Ellermann- Eriksen, Svend; Jespersen, Bente; Dam, Mette Yde; Dahlerup, Jens Frederik; Benfield, Thomas; Jespersen, Sanne; Østergaard, Lars Jørgen; Laursen, Alex Lund

    2017-01-01

    Background Diagnosis of Pneumocystis jirovecii (PJ) pneumonia ordinarily requires invasive procedures that could be avoided by PCR methodologies, if these could be designed with adequate cut-off values for confounding background carriage. Methods We designed a novel quantitative real-time PCR assay to detect the mitochondrial large subunit rRNA gene of PJ in oral washes. To benchmark levels of PJ carriage versus infection, we tested asymptomatic immunosuppressed patients including Danish (n = 88) and West African HIV-infected (n = 142) patients, renal transplant recipients (n = 51), rheumatologic patients (n = 102), patients with inflammatory bowel diseases (n = 98), and healthy blood donors (controls, n = 50). The fungal burden in patients with PJ pneumonia (PCP, n = 7) was also investigated. Results Danish HIV-infected patients (with viremia/low CD4) and recent transplant recipients were at most risk of being carriers (prevalence of 23% and 16.7% respectively), whereas PJ was rarely detected among rheumatologic patients, patients with inflammatory bowel diseases, and untreated West African HIV patients. PJ was not detected among healthy controls. The fungal burden in patients with PCP fell rapidly on treatment. Conclusions The quantitative PCR method described could conceivably discriminate between carriage and disease, given suitable threshold values for the former, and predict treatment efficacy by measures of the fungal burden in daily oral washes. PMID:28358900

  13. CPAP, effective respiratory support in patients with AIDS-related Pneumocystis carinii pneumonia.

    PubMed

    Prevedoros, H P; Lee, R P; Marriot, D

    1991-11-01

    Human Immunodeficiency Virus (HIV) related Pneumocystis carinii pneumonia (PCP) associated with severe respiratory failure is an increasingly common problem in major centres and is associated with a high mortality in previous and recent studies. Early in the epidemic, alternatives to invasive intensive care treatment were utilized in our institution and found to be successful. When respiratory failure developed, mask CPAP was used instead of intubation and ventilation. A retrospective review of 175 cases of HIV infected patients with confirmed first presentation PCP was undertaken. Treatment with our protocol resulted in an overall hospital mortality of 9%. Those patients who did not require supplemental oxygen or respiratory support had no in-hospital mortality. The group who required supplemental oxygen had a mortality of 10%. If respiratory failure supervened (severe respiratory distress, PaO2 less than 50 mmHg, SaO2 less than 90% on mask oxygen), CPAP was introduced. The mortality in this group was 22%. Only two patients were admitted to the intensive care unit for respiratory support after failure of CPAP. Both patients were intubated and received intermittent positive pressure ventilation (IPPV). Both patients died.

  14. Pneumocystis jirovecii Can Be Productively Cultured in Differentiated CuFi-8 Airway Cells

    PubMed Central

    Schildgen, Verena; Mai, Stephanie; Khalfaoui, Soumaya; Lüsebrink, Jessica; Pieper, Monika; Tillmann, Ramona L.; Brockmann, Michael

    2014-01-01

    ABSTRACT Although Pneumocystis jirovecii is a well-known and serious pathogen, all previous attempts to isolate, cultivate, and propagate this fungus have failed. This serious challenge in microbiology was addressed in the present study. We examined whether P. jirovecii could be cultured in a permanent three-dimensional air-liquid interface culture system formed by CuFi-8 cells, a differentiated pseudostratified airway epithelial cell line. Cultured pseudostratified cells were inoculated with bronchoalveolar fluid that had been confirmed to be positive for P. jirovecii using PCR. Five days later, the cells and basal medium were harvested and tested for P. jirovecii using quantitative PCR (qPCR), commercially available immunofluorescence detection assays, and Grocott staining of formalin-fixed, paraffin-embedded thin sections of infected-cell cultures. We successfully productively cultivated and propagated P. jirovecii from these P. jirovecii-positive bronchoalveolar lavage fluid (BALF) samples. Furthermore, we provide evidence that P. jirovecii induced cytopathic effects on lung epithelial cells and was even invasive in cell culture. To the best of our knowledge, the cell culture system developed herein represents the first methodology to enable molecular analyses of this pathogen’s life cycle and further in vitro studies of P. jirovecii, such as assessments of drug sensitivity and resistance as well as investigations of the pathogen’s stability against environmental factors and disinfectants. PMID:24825015

  15. The incidence, mortality and timing of Pneumocystis jiroveci pneumonia after hematopoietic cell transplantation: a CIBMTR® analysis

    PubMed Central

    Williams, Kirsten M.; Ahn, Kwang Woo; Chen, Min; Aljurf, Mahmoud D.; Agwu, Allison L.; Chen, Allen R.; Walsh, Thomas J.; Szabolcs, Paul; Boeckh, Michael J.; Auletta, Jeffrey J.; Lindemans, Caroline A.; Zanis-Neto, Jose; Malvezzi, Mariester; Lister, John; de Toledo Codina, Jose Sanchez; Sackey, Kwesi; Holter Chakrabarty, Jennifer L.; Ljungman, Per; Wingard, John R.; Seftel, Matthew D.; Seo, Sachiko; Hale, Gregory A.; Wirk, Baldeep; Smith, Marilyn S.; Savani, Bipin N.; Lazarus, Hillard M.; Marks, David I.; Ustun, Celalettin; Abdel-Azim, Hisham; Dvorak, Christopher C.; Szer, Jeffrey; Storek, Jan; Yong, Agnes; Riches, Marcie R.

    2015-01-01

    Pneumocystis jiroveci pneumonia (PJP) is associated with high morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Little is known about PJP infections after HSCT because of the rarity of disease given routine prophylaxis. We report the results of a CIBMTR study evaluating the incidence, timing, prophylaxis agents, risk factors, and mortality of PJP after autologous (auto) and allogeneic (allo) HSCT. Between 1995 and 2005, 0.63% allo recipients and 0.28% auto recipients of first HSCT developed PJP. Cases occurred as early as 30 days to beyond a year after allo HSCT. A nested case cohort analysis with supplemental data (n=68 allo cases, n=111 allo controls) revealed that risk factors for PJP infection included lymphopenia and mismatch after HSCT. After allo or auto HSCT, overall survival was significantly poorer among cases vs. controls (p=0.0004). After controlling for significant variables, proportional hazards model revealed that PJP cases were 6.87 times more likely to die vs. matched controls (p<0.0001). We conclude PJP infection is rare after HSCT but is associated with high mortality. Factors associated with GVHD and with poor immune reconstitution are among the risk factors for PJP and suggest that protracted prophylaxis for PJP in high-risk HSCT recipients may improve outcomes. PMID:26726945

  16. Serological diagnosis of pneumocystosis: production of a synthetic recombinant antigen for immunodetection of Pneumocystis jirovecii

    PubMed Central

    Tomás, A. L.; Cardoso, F.; Esteves, F.; Matos, O.

    2016-01-01

    Diagnosis of Pneumocystis pneumonia (PcP) relies on the detection of P. jirovecii in respiratory specimens obtained by invasive techniques. Thus, the development of a serological test is urgently needed as it will allow the diagnosis of PcP using blood, an inexpensive and non-invasive specimen. This study aims to combine the production of a multi-epitope synthetic recombinant antigen (RSA) and an ELISA test for detection of anti-P. jirovecii antibodies, in order to develop a new approach for PcP diagnosis. The RSA was selected and designed based on the study of the immunogenicity of the carboxyl-terminal domain of the major surface glycoprotein. This antigen was purified and used as an antigenic tool in an ELISA technique for detection of Ig, IgG and IgM antibodies anti-P. jirovecii (patent-pending no. PT109078). Serum specimens from 88 patients previously categorized in distinct clinical subgroups and 17 blood donors, were analysed. The IgM anti-P. jirovecii levels were statistically increased in patients with PcP (p = 0.001) and the ELISA IgM anti-P. jirovecii test presented a sensitivity of 100% and a specificity of 80.8%, when associated with the clinical diagnosis criteria. This innovative approach, provides good insights about what can be done in the future serum testing for PcP diagnosis. PMID:27824115

  17. Management of Pneumocystis jirovecii Pneumonia in Kidney Transplantation to Prevent Further Outbreak

    PubMed Central

    Goto, Norihiko; Futamura, Kenta; Okada, Manabu; Yamamoto, Takayuki; Tsujita, Makoto; Hiramitsu, Takahisa; Narumi, Shunji; Watarai, Yoshihiko

    2015-01-01

    The outbreak of Pneumocystis jirovecii pneumonia (PJP) among kidney transplant recipients is emerging worldwide. It is important to control nosocomial PJP infection. A delay in diagnosis and treatment increases the number of reservoir patients and the number of cases of respiratory failure and death. Owing to the large number of kidney transplant recipients compared to other types of organ transplantation, there are greater opportunities for them to share the same time and space. Although the use of trimethoprim-sulfamethoxazole (TMP-SMX) as first choice in PJP prophylaxis is valuable for PJP that develops from infections by trophic forms, it cannot prevent or clear colonization, in which cysts are dominant. Colonization of P. jirovecii is cleared by macrophages. While recent immunosuppressive therapies have decreased the rate of rejection, over-suppressed macrophages caused by the higher levels of immunosuppression may decrease the eradication rate of colonization. Once a PJP cluster enters these populations, which are gathered in one place and uniformly undergoing immunosuppressive therapy for kidney transplantation, an outbreak can occur easily. Quick actions for PJP patients, other recipients, and medical staff of transplant centers are required. In future, lifelong prophylaxis may be required even in kidney transplant recipients. PMID:26609250

  18. Vascular Dysfunction in Pneumocystis-Associated Pulmonary Hypertension Is Related to Endothelin Response and Adrenomedullin Concentration.

    PubMed

    Siemsen, Dan W; Dobrinen, Erin; Han, Soo; Chiocchi, Kari; Meissner, Nicole; Swain, Steve D

    2016-02-01

    Pulmonary hypertension subsequent to an infectious disease can be due to vascular structural remodeling or to functional alterations within various vascular cell types. In our previous mouse model of Pneumocystis-associated pulmonary hypertension, we found that vascular remodeling was not responsible for observed increases in right ventricular pressures. Here, we report that the vascular dysfunction we observed could be explained by an enhanced response to endothelin-1 (20% greater reduction in lumen diameter, P ≤ 0.05), corresponding to an up-regulation of similar magnitude (P ≤ 0.05) of the endothelin A receptor in the lung tissue. This effect was potentially augmented by a decrease in production of the pulmonary vasodilator adrenomedullin of almost 70% (P ≤ 0.05). These changes did not occur in interferon-γ knockout mice similarly treated, which do not develop pulmonary hypertension under these circumstances. Surprisingly, we did not observe any relevant changes in the vascular endothelial nitric oxide synthase vasodilatory response, which is a common potential site of inflammatory alterations to pulmonary vascular function. Our results indicate the diverse mechanisms by which inflammatory responses to prior infections can cause functionally relevant changes in vascular responses in the lung, promoting the development of pulmonary hypertension.

  19. Genotypic variation of Pneumocystis jirovecii isolates in India based on sequence diversity at mitochondrial large subunit rRNA.

    PubMed

    Gupta, Rashmi; Mirdha, Bijay Ranjan; Guleria, Randeep; Agarwal, Sanjay Kumar; Samantaray, Jyotish Chandra; Kumar, Lalit; Kabra, Sushil Kumar; Luthra, Kalpana; Sreenivas, Vishnubhatla; Iyer, Venkateswaran K

    2011-03-01

    Pneumocystis pneumonia (PCP), a common and serious opportunistic infection in immunocompromised patients, is caused by Pneumocystis jirovecii (formerly known as Pneumocystis carinii f. sp. hominis). The aim of the present study was to describe the prevalence and distribution of genotypes of P. jirovecii based on sequence polymorphisms at mitochondrial large subunit ribosomal RNA (mt LSU rRNA) region in both HIV and non-HIV immunocompromised individuals with a positive PCR result for PCP in a tertiary health care centre in northern India. From January 2005 to October 2008, 50 patients [22 HIV-seropositive individuals, 10 post-renal transplant (PRT) recipients, 3 cancer patients, and 15 patients with various other kinds of immunosuppression] were found to be positive for P. jirovecii using PCR at the mt LSU rRNA gene. Genotyping of the positive samples was performed at the mt LSU rRNA locus. Genotype 2 was the most common accounting for 42% of total types. This was followed by the genotypes 3 (24%), 1 (20%), and 4 (8%). Mixed infection was observed in 3 cases (6%). The rates of genotype distribution were similar in HIV-seropositive individuals, cancer patients, and in patients with other kinds of immunosuppression. In the PRT recipients, genotype 1 was the most prevalent type (80%). This is the first study describing the prevalence of genotypes in HIV-infected and HIV-uninfected, immunocompromised patients based on the mt LSU rRNA gene from the Indian subcontinent. The most prevalent genotype observed was type 2 in contrast to many studies from other parts of the world where genotype 1 was the most prevalent type, suggesting geographical variation.

  20. Loop-mediated isothermal amplification method for diagnosing Pneumocystis pneumonia in HIV-uninfected immunocompromised patients with pulmonary infiltrates.

    PubMed

    Nakashima, Kei; Aoshima, Masahiro; Ohkuni, Yoshihiro; Hoshino, Eri; Hashimoto, Kohei; Otsuka, Yoshihito

    2014-12-01

    Loop-mediated isothermal amplification (LAMP) is becoming an established nucleic acid amplification method offering rapid, accurate, and cost-effective diagnosis of infectious diseases. We retrospectively evaluated 78 consecutive HIV-uninfected patients who underwent LAMP method for diagnosing Pneumocystis pneumonia (PCP). Diagnosis of PCP was made by the detection of Pneumocystis jirovecii (P. jirovecii) with positive LAMP or conventional staining (CS) (Grocott methenamine silver staining or Diff-Quick™) on the basis of compatible clinical symptoms and radiologic findings. Additionally, we reviewed HIV-uninfected immunocompromised patients who underwent subcontract PCR as a historical control. LAMP was positive in 10 (90.9%) of 11 positive-CS patients. Among 13 negative-CS patients with positive LAMP, 11 (84.6%) had PCP, and the remaining 2 were categorized as having P. jirovecii colonization. LDH levels in negative-CS PCP were higher than in positive-CS PCP (p = 0.026). (1 → 3)-β-D-glucan levels in negative-CS PCP were lower than in positive-CS PCP (p = 0.011). The interval from symptom onset to diagnosis as PCP in LAMP group (3.45 ± 1.77 days; n = 22) was shorter than in subcontract PCR group (6.90 ± 2.28 days; n = 10; p < 0.001). As for patients without PCP, duration of unnecessary PCP treatment in LAMP group (2; 2-3 days; n = 10) was shorter than in subcontract PCR group (7; 7-12.25 days; n = 6; p = 0.003). LAMP showed higher sensitivity (95.4%) and positive predictive value (91.3%) than subcontract PCR did. Pneumocystis LAMP method is a sensitive and cost-effective diagnostic method and is easy to administer in general hospitals. In-house LAMP method would realize early diagnosis of PCP, resulting in improving PCP prognosis and reducing unnecessary PCP-specific treatment.

  1. Utility of adding Pneumocystis jirovecii DNA detection in nasopharyngeal aspirates in immunocompromised adult patients with febrile pneumonia.

    PubMed

    Guigue, Nicolas; Alanio, Alexandre; Menotti, Jean; Castro, Nathalie De; Hamane, Samia; Peyrony, Olivier; LeGoff, Jérôme; Bretagne, Stéphane

    2015-04-01

    Detection of viral and bacterial DNA in nasopharyngeal aspirates (NPAs) is now a routine practice in emergency cases of febrile pneumonia. We investigated whether Pneumocystis jirovecii DNA could also be detected in these cases by conducting retrospective screening of 324 consecutive NPAs from 324 adult patients (198 or 61% were immunocompromised) admitted with suspected pulmonary infections during the 2012 influenza epidemic season, using a real-time quantitative polymerase chain reaction (PCR) assay (PjqPCR), which targets the P. jirovecii mitochondrial large subunit ribosomal RNA gene. These NPAs had already been tested for 22 respiratory pathogens (18 viruses and 4 bacteria), but we found that 16 NPAs (4.9%) were PjqPCR-positive, making P. jirovecii the fourth most prevalent of the 23 microorganisms in the screen. Eleven of the 16 PjqPCR-positive patients were immunocompromised, and five had underlying pulmonary conditions. Nine NPAs were also positive for another respiratory pathogen. Six had PjqPCR-positive induced sputa less than 3 days after the NPA procedure, and five were diagnosed with pneumocystis pneumonia (four with chronic lymphoproliferative disorders and one AIDS patient). In all six available pairs quantification of P. jirovecii DNA showed fewer copies in NPA than in induced sputum and three PjqPCR-negative NPAs corresponded to PjqPCR-positive bronchoalveolar lavage fluids, underscoring the fact that a negative PjqPCR screen does not exclude a diagnosis of pneumocystosis. Including P. jirovecii DNA detection to the panel of microorganisms included in screening tests used for febrile pneumonia may encourage additional investigations or support use of anti-pneumocystis pneumonia prophylaxis in immunocompromised patients.

  2. Immune reconstitution during Pneumocystis lung infection: disruption of surfactant component expression and function by S-nitrosylation.

    PubMed

    Atochina-Vasserman, Elena N; Gow, Andrew J; Abramova, Helen; Guo, Chang-Jiang; Tomer, Yaniv; Preston, Angela M; Beck, James M; Beers, Michael F

    2009-02-15

    Pneumocystis pneumonia (PCP), the most common opportunistic pulmonary infection associated with HIV infection, is marked by impaired gas exchange and significant hypoxemia. Immune reconstitution disease (IRD) represents a syndrome of paradoxical respiratory failure in patients with active or recently treated PCP subjected to immune reconstitution. To model IRD, C57BL/6 mice were selectively depleted of CD4(+) T cells using mAb GK1.5. Following inoculation with Pneumocystis murina cysts, infection was allowed to progress for 2 wk, GK1.5 was withdrawn, and mice were followed for another 2 or 4 wk. Flow cytometry of spleen cells demonstrated recovery of CD4(+) cells to >65% of nondepleted controls. Lung tissue and bronchoalveolar lavage fluid harvested from IRD mice were analyzed in tandem with samples from CD4-depleted mice that manifested progressive PCP for 6 wks. Despite significantly decreased pathogen burdens, IRD mice had persistent parenchymal lung inflammation, increased bronchoalveolar lavage fluid cellularity, markedly impaired surfactant biophysical function, and decreased amounts of surfactant phospholipid and surfactant protein (SP)-B. Paradoxically, IRD mice also had substantial increases in the lung collectin SP-D, including significant amounts of an S-nitrosylated form. By native PAGE, formation of S-nitrosylated SP-D in vivo resulted in disruption of SP-D multimers. Bronchoalveolar lavage fluid from IRD mice selectively enhanced macrophage chemotaxis in vitro, an effect that was blocked by ascorbate treatment. We conclude that while PCP impairs pulmonary function and produces abnormalities in surfactant components and biophysics, these responses are exacerbated by IRD. This worsening of pulmonary inflammation, in response to persistent Pneumocystis Ags, is mediated by recruitment of effector cells modulated by S-nitrosylated SP-D.

  3. Absence of mutations associated with sulfa resistance in Pneumocystis carinii dihydropteroate synthase gene from non-human primates.

    PubMed

    Demanche, C; Guillot, J; Berthelemy, M; Petitt, T; Roux, P; Wakefield, A E

    2002-06-01

    The dihydropteroate synthase (DHPS) gene from Pneumocystis carinii isolated from non-human primates was amplified using a polymerase chain reaction (PCR) and sequenced to analyse point mutations associated with sulfa resistance. P. carinii DHPS gene amplification was obtained from eight lung samples from five New World primate species and one Old World primate species. None of the animals had been exposed to sulfa drugs and only the wild-type P. carinii DHPS sequence at codons 55 and 57 was observed. These data support the hypothesis that high rates of DHPS mutants in P. carinii f. sp. hominis have arisen with increased use of sulfa drugs for P. carinii pneumonia prophylaxis.

  4. Diffuse pulmonary gallium accumulation with a normal chest radiogram in a homosexual man with pneumocystis carinii pneumonia. A case report

    SciTech Connect

    Moses, S.C.; Baker, S.R.; Seldin, M.F.

    1983-12-01

    A homosexual man with A.I.D.S. (acquired immunologic deficiency syndrome) and pneumocystis infestation was found to have diffuse Ga-67 uptake in the lungs with a coincident negative chest x-ray. While Ga-67 accumulates diffusely in the lungs in a variety of conditions, the present case is the first described in a patient with A.I.D.S. in which Ga-67 was positive before roentgenographic abnormalities were demonstrated. Thus, the use of Ga-67 scan, when A.I.D.S. is suspected, could help establish a diagnosis more promptly.

  5. Three-dimensional reconstruction of rabbit-derived Pneumocystis carinii from serial-thin sections. I: Trophozoite.

    PubMed

    Palluault, F; Pietrzyk, B; Dei-Cas, E; Slomianny, C; Soulez, B; Camus, D

    1991-01-01

    The highly complex ultrastructural morphology of the endomembrane system in Pneumocystis carinii led us to perform three-dimensional reconstruction from serial-thin sections using the CATIA (Conception Assistée Tridimensionnelle Inter Active) Dassault system program. The three-dimensional reconstruction of a small trophozoite made it possible to better understand the morphological relationship among organelles and to suggest cytophysiological hypotheses. By reconstructing other parasite stages, we gathered information about the evolution of organelles during the life cycle and about their physiology.

  6. Identification, characterization, and expression of the BiP endoplasmic reticulum resident chaperonins in Pneumocystis carinii.

    PubMed Central

    Stedman, T T; Buck, G A

    1996-01-01

    We have isolated, characterized, and examined the expression of the genes encoding BiP endoplasmic reticulum (ER) resident chaperonins responsible for transport, maturation, and proper folding of membrane and secreted proteins from two divergent strains of Pneumocystis carinii. The BiP genes, Pcbip and Prbip, from the P. c. carinii (prototype) strain and the P. c. rattus (variant) strain, respectively, are single-copy genes that reside on chromosomes of approximately 330 and approximately 350 kbp. Both genes encode approximately 72.5-kDa proteins that are most homologous to BiP genes from other organisms and exhibit the amino-terminal signal peptides and carboxyl-terminal ER retention sequences that are hallmarks of BiP proteins. We established short-term P. carinii cultures to examine expression and induction of Pcbip in response to heat shock, glucose starvation, inhibition of protein transport or N-linked glycosylation, and other conditions known to affect proper transport, glycosylation, and maturation of membrane and secreted proteins. These studies indicated that Pcbip mRNA is constitutively expressed but induced under conditions known to induce BiP expression in other organisms. In contrast to mammalian BiP genes but like other fungal BiP genes, P. carinii BiP mRNA levels are induced by heat shock. Finally, the Prbip and Pcbip coding sequences surprisingly exhibit only approximately 83% DNA and approximately 90% amino acid sequence identity and show only limited conservation in noncoding flanking and intron sequences. Analyses of the P. carinii BiP gene sequences support inclusion of P. carinii among the fungi but suggest a large divergence and possible speciation among P. carinii strains infecting a given host. PMID:8890193

  7. Induction of fibrinogen expression in the lung epithelium during Pneumocystis carinii pneumonia.

    PubMed

    Simpson-Haidaris, P J; Courtney, M A; Wright, T W; Goss, R; Harmsen, A; Gigliotti, F

    1998-09-01

    Pneumocystis carinii is an important pulmonary pathogen responsible for morbidity and mortality in patients with AIDS. The acute-phase response (APR), the primary mechanism used by the body to restore homeostasis following infection, is characterized by increased levels of circulating fibrinogen (FBG). Although the liver is the primary site of increased FBG synthesis during the APR, we unexpectedly discovered that FBG is synthesized and secreted by lung alveolar epithelial cells in vitro during an inflammatory stimulus. Therefore, we sought to determine whether lung epithelial cells produce FBG in vivo using animal models of P. carinii pneumonia (PCP). Inflammation was noted by an influx of macrophages to P. carinii-infected alveoli. Northern hybridization revealed that gamma-FBG mRNA increased two- to fivefold in P. carinii-infected lung tissue, while RNA in situ hybridization demonstrated increased levels of gamma-FBG mRNA in the lung epithelium. Immunoelectron microscopy detected lung epithelial cell-specific production of FBG, suggesting induction of a localized inflammatory response resembling the APR. A systemic APR was confirmed by a two- to fivefold upregulation of the levels of hepatic gamma-FBG mRNA in animals with PCP, resulting in a corresponding increase in levels of FBG in plasma. Furthermore, immunoelectron microscopy revealed the presence of FBG at the junction of cell membranes of trophic forms of P. carinii organisms aggregated along the alveolar epithelium. These results implicate FBG in the pathogenesis of PCP in a manner similar to that of the adhesive glycoproteins fibronectin and vitronectin, which are known to participate in intra-alveolar aggregation of organisms and adherence of P. carinii to the lung epithelium.

  8. Genotyping and coalescent phylogenetic analysis of Pneumocystis jiroveci from South Africa.

    PubMed

    Robberts, Frans J L; Liebowitz, Lynne D; Chalkley, Lynda J

    2004-04-01

    Sequence analysis of Pneumocystis jiroveci internal transcribed spacer (ITS) regions has become an important epidemiological tool. The objectives of the present study were to investigate sequence variations in the ITS1-5.8S ribosomal DNA (rDNA)-ITS2 regions; determine the P. jiroveci genotypes present in Cape Town, South Africa; and resolve the lineage evolution of the types by use of the coalescent theory. ITS regions were amplified from samples collected from 19 patients. PCR products were cloned, and four to five clones were sequenced from each specimen. Statistical parsimony was applied for coalescence-based network genotype analysis. The most prevalent type was Eg (14 of 19 patients, 33 of 83 clones), followed by Gg (4 of 19 patients, 7 of 83 clones), Eu (3 of 19 patients, 5 of 83 clones), and Gh (2 of 19 patients, 2 of 83 clones). Four new combinations (Eo, Je, Ge, and No), 11 new ITS1 sequences, and 13 new ITS2 sequences were identified. A new ITS2 type was detected in three patients and was designated type u. Coinfection appeared to be common, with 15 of 19 patients harboring more than one type and with up to six types per specimen. The resultant parsimony network identified Eg as the most probable ancestral haplotype and supported the occurrence of recombinational events within the population studied. Although the 5.8S rDNA region revealed only 13 clones containing one to two nucleotide polymorphisms, it may assist in defining types. Coalescent theory proposed that Eg is an ancestral type from which microevolutionary subtypes radiate.

  9. C27 to C32 sterols found in Pneumocystis, an opportunistic pathogen of immunocompromised mammals.

    PubMed

    Kaneshiro, E S; Wyder, M A

    2000-03-01

    Pneumocystis carinii is the paradigm of opportunistic infections in immunocompromised mammals. Prior to the acquired immunodeficiency syndrome (AIDS) pandemic and the use of immunosuppressive therapy in organ transplant and cancer patients, P. carinii was regarded as a curiosity, rarely observed clinically. Interest in this organism exploded when it was identified as the agent of P. carinii pneumonia (PcP), the direct cause of death among many AIDS patients. Aggressive prophylaxis has decreased the number of acute PcP cases, but it remains among the most prevalent opportunistic infections found within this patient population. The taxonomic assignment of P. carinii has long been argued; molecular genetics data now demonstrate that it is a fungus. Several antimycotic drugs are targeted against ergosterol or its biosynthesis, but these are not as effective against PcP as they are against other fungal infections. This can now be explained in part by the identification of the sterols of P. carinii. The organism lacks ergosterol but contains distinct C28 and C29 delta7 24-alkylsterols. Also, 24-methylenelanost-8-en-3beta-ol (C31) and pneumocysterol, (24Z)-ethylidenelanost-8-en-3beta-ol (C32) were recently identified in organisms infecting humans. Together, the delta7 24-alkylsterols and pneumocysterol are regarded as signature lipids of the pathogen that can be useful for the diagnosis of PcP, since no other lung pathogen is known to contain them. Cholesterol (C27), the dominant sterol component in P. carinii, is probably totally scavenged from the host. De novo synthesis of sterols has been demonstrated by the presence of lovastatin-sensitive 3-hydroxy-3-methylglutaryl-CoA reductase activity, the incorporation of radiolabeled mevalonate and squalene into P. carinii sterols, and the reduction in cellular ATP in cells treated with inhibitors of enzymes in sterol biosynthesis.

  10. Adjunctive steroid in HIV-negative patients with severe Pneumocystis pneumonia

    PubMed Central

    2013-01-01

    Background High-dose steroid therapy has been proven effective in AIDS-related Pneumocystis pneumonia (PCP) but not in non-AIDS-related cases. We evaluated the effects on survival of steroids in HIV-negative patients with PCP. Methods Retrospective study patients admitted to the ICU with hypoxemic PCP. We compared patients receiving HDS (≥1 mg/Kg/day prednisone equivalent), low-dose steroids (LDS group, <1 mg/Kg/day prednisone equivalent), and no steroids (NS group). Variables independently associated with ICU mortality were identified. Results 139 HIV-negative patients with PCP were included. Median age was 48 [40–60] years. The main underlying conditions were hematological malignancies (n=55, 39.6%), cancer (n=11, 7.9%), and solid organ transplantation (n=73, 52.2%). ICU mortality was 26% (36 deaths). The HDS group had 72 (51.8%) patients, the LDS group 35 (25%) patients, and the NS group 32 (23%) patients. Independent predictors of ICU mortality were SAPS II at ICU admission (odds ratio [OR], 1.04/point; [95%CI], 1.01-1.08, P=0.01), non-hematological disease (OR, 4.06; [95%CI], 1.19-13.09, P=0.03), vasopressor use (OR, 20.31; 95%CI, 6.45-63.9, P<0.001), and HDS (OR, 9.33; 95%CI, 1.97-44.3, P=0.02). HDS was not associated with the rate of ICU-acquired infections. Conclusions HDS were associated with increased mortality in HIV-negative patients with PCP via a mechanism independent from an increased risk of infection. PMID:23981859

  11. National Lupus Hospitalization Trends Reveal Rising Rates of Herpes Zoster and Declines in Pneumocystis Pneumonia

    PubMed Central

    Murray, Sara G.; Schmajuk, Gabriela; Trupin, Laura; Gensler, Lianne; Katz, Patricia P.; Yelin, Edward H.; Gansky, Stuart A.; Yazdany, Jinoos

    2016-01-01

    Objective Infection is a leading cause of morbidity and mortality in systemic lupus erythematosus (SLE). Therapeutic practices have evolved over the past 15 years, but effects on infectious complications of SLE are unknown. We evaluated trends in hospitalizations for severe and opportunistic infections in a population-based SLE study. Methods Data derive from the 2000 to 2011 United States National Inpatient Sample, including individuals who met a validated administrative definition of SLE. Primary outcomes were diagnoses of bacteremia, pneumonia, opportunistic fungal infection, herpes zoster, cytomegalovirus, or pneumocystis pneumonia (PCP). We used Poisson regression to determine whether infection rates were changing in SLE hospitalizations and used predictive marginals to generate annual adjusted rates of specific infections. Results We identified 361,337 SLE hospitalizations from 2000 to 2011 meeting study inclusion criteria. Compared to non-SLE hospitalizations, SLE patients were younger (51 vs. 62 years), predominantly female (89% vs. 54%), and more likely to be racial/ethnic minorities. SLE diagnosis was significantly associated with all measured severe and opportunistic infections. From 2000 to 2011, adjusted SLE hospitalization rates for herpes zoster increased more than non-SLE rates: 54 to 79 per 10,000 SLE hospitalizations compared with 24 to 29 per 10,000 non-SLE hospitalizations. Conversely, SLE hospitalizations for PCP disproportionately decreased: 5.1 to 2.5 per 10,000 SLE hospitalizations compared with 0.9 to 1.3 per 10,000 non-SLE hospitalizations. Conclusions Among patients with SLE, herpes zoster hospitalizations are rising while PCP hospitalizations are declining. These trends likely reflect evolving SLE treatment strategies. Further research is needed to identify patients at greatest risk for infectious complications. PMID:26731012

  12. Prevalence and genotype distribution of Pneumocystis jirovecii in Cuban infants and toddlers with whooping cough.

    PubMed

    Monroy-Vaca, Ernesto X; de Armas, Yaxsier; Illnait-Zaragozí, María T; Toraño, Gilda; Diaz, Raúl; Vega, Dania; Alvarez-Lam, Ileana; Calderón, Enrique J; Stensvold, Christen R

    2014-01-01

    This study describes the prevalence and genotype distribution of Pneumocystis jirovecii obtained from nasopharyngeal (NP) swabs from immunocompetent Cuban infants and toddlers with whooping cough (WC). A total of 163 NP swabs from 163 young Cuban children with WC who were admitted to the respiratory care units at two pediatric centers were studied. The prevalence of the organism was determined by a quantitative PCR (qPCR) assay targeting the P. jirovecii mitochondrial large subunit (mtLSU) rRNA gene. Genotypes were identified by direct sequencing of mtLSU ribosomal DNA (rDNA) and restriction fragment length polymorphism (RFLP) analysis of the dihydropteroate synthase (DHPS) gene amplicons. qPCR detected P. jirovecii DNA in 48/163 (29.4%) samples. mtLSU rDNA sequence analysis revealed the presence of three different genotypes in the population. Genotype 2 was most common (48%), followed in prevalence by genotypes 1 (23%) and 3 (19%); mixed-genotype infections were seen in 10% of the cases. RFLP analysis of DHPS PCR products revealed four genotypes, 18% of which were associated with resistance to sulfa drugs. Only contact with coughers (prevalence ratio [PR], 3.51 [95% confidence interval {CI}, 1.79 to 6.87]; P = 0.000) and exposure to tobacco smoke (PR, 1.82 [95% CI, 1.14 to 2.92]; P = 0.009) were statistically associated with being colonized by P. jirovecii. The prevalence of P. jirovecii in infants and toddlers with WC and the genotyping results provide evidence that this population represents a potential reservoir and transmission source of P. jirovecii.

  13. Pneumocystis colonization, airway inflammation, and pulmonary function decline in acquired immunodeficiency syndrome.

    PubMed

    Norris, Karen A; Morris, Alison; Patil, Sangita; Fernandes, Eustace

    2006-01-01

    As a result of improved diagnosis, treatment, and supportive care for HIV-infected patients, AIDS in developed countries has now become a chronic infection with prolonged survival time, but longterm complications are increasing contributors to morbidity and mortality. HIV-infected patients are at increased risk for the development of pulmonary complications, including chronic obstructive pulmonary disease (COPD); however, the mechanisms associated with this increased susceptibility have not been defined. Infectious agents may contribute to the development of COPD by upregulating inflammatory mediators in the lung that act in concert with cigarette smoke to promote lung pathology. Studies in human subjects and non-human primate models of AIDS suggest that the inflammatory response to asymptomatic carriage or colonization by the opportunistic pathogen, Pneumocystis sp. (Pc), is similar to that of COPD, which is characterized by influx of CD8+ T cells, neutrophils, and macrophages into the lungs. We have shown a high frequency of Pc colonization among asymptomatic HIV-infected subjects and in non-HIV infected subjects with COPD. To investigate the role of Pc in the progression of obstructive lung disease in HIV infections, we developed a non-human primate model of Pc colonizatoin and infection in simian immunodeficiency virus (SIV)-infected macaques. These animals develop a prolonged colonization state characterized by a persistent influx of CD8+ T cells and neutrophils, and local increases in IL-8, IFN-gamma, and TNF-alpha. SIV-infected Pc-colonized monkeys show progressive decline in pulmonary function compared to SIV-infected monkeys. We hypothesize that in the context of AIDS-immune dysfunction, Pc colonization induces inflammatory responses leading to changes in pulmonary function and architecture similar to that seen in emphysema. Information gained from these studies will lead to the development of interventions to prevent lung injury associated with Pc

  14. Mapping by sequencing the Pneumocystis genome using the ordering DNA sequences V3 tool.

    PubMed Central

    Xu, Zheng; Lance, Britton; Vargas, Claudia; Arpinar, Budak; Bhandarkar, Suchendra; Kraemer, Eileen; Kochut, Krys J; Miller, John A; Wagner, Jeff R; Weise, Michael J; Wunderlich, John K; Stringer, James; Smulian, George; Cushion, Melanie T; Arnold, Jonathan

    2003-01-01

    A bioinformatics tool called ODS3 has been created for mapping by sequencing. The tool allows the creation of integrated genomic maps from genetic, physical mapping, and sequencing data and permits an integrated genome map to be stored, retrieved, viewed, and queried in a stand-alone capacity, in a client/server relationship with the Fungal Genome Database (FGDB), and as a web-browsing tool for the FGDB. In that ODS3 is programmed in Java, the tool promotes platform independence and supports export of integrated genome-mapping data in the extensible markup language (XML) for data interchange with other genome information systems. The tool ODS3 is used to create an initial integrated genome map of the AIDS-related fungal pathogen, Pneumocystis carinii. Contig dynamics would indicate that this physical map is approximately 50% complete with approximately 200 contigs. A total of 10 putative multigene families were found. Two of these putative families were previously characterized in P. carinii, namely the major surface glycoproteins (MSGs) and HSP70 proteins; three of these putative families (not previously characterized in P. carinii) were found to be similar to families encoding the HSP60 in Schizosaccharomyces pombe, the heat-shock psi protein in S. pombe, and the RNA synthetase family (i.e., MES1) in Saccharomyces cerevisiae. Physical mapping data are consistent with the 16S, 5.8S, and 26S rDNA genes being single copy in P. carinii. No other fungus outside this genus is known to have the rDNA genes in single copy. PMID:12702676

  15. Aerosolized pentamidine: Effect on diagnosis and presentation of Pneumocystis carinii pneumonia

    SciTech Connect

    Jules-Elysee, K.M.; Stover, D.E.; Zaman, M.B.; Bernard, E.M.; White, D.A. )

    1990-05-15

    The objective of this study was to determine the effect of previous aerosolized pentamidine therapy on diagnosis and presentation of Pneumocystis carinii pneumonia. This was a retrospective study of fifty-two consecutive patients with P. carinii pneumonia and underlying infection with the human immunodeficiency virus (HIV) who had bronchoscopy. Twenty-one patients who were on aerosolized pentamidine therapy served as the study group. Thirty-one patients who had not received the drug served as the control group. The yield of bronchoalveolar lavage for P. carinii pneumonia was 62% for the study group and 100% for the control group (P less than 0.05). This lower yield was significant for the subset of patients having their first episode of P. carinii pneumonia. The yield of transbronchial biopsy was similar for both groups of patients (81% compared with 84%). The yield of bronchoscopy was not influenced by use of zidovudine. Review of lavage specimen slides suggested that there may be fewer organisms present in patients receiving aerosolized pentamidine. An atypical roentgenographic presentation of upper lobe predominant infiltrates was seen in 38% of the study patients and 7% of the control patients. In addition, pneumothoraces and cystic changes were also frequently seen in the study patients. Gallium scans, when done, were also atypical in the study group. Markers of the severity of disease, however, were similar in both groups. The yield of bronchoalveolar lavage for P. carinii pneumonia in HIV-infected patients is lower in patients receiving aerosolized pentamidine. Unusual roentgenographic presentations and atypical gallium scans are also found in this setting.

  16. Molecular epidemiology of Pneumocystis jiroveci in human immunodeficiency virus-positive and -negative immunocompromised patients in The Netherlands.

    PubMed

    Vanspauwen, Marijke J; Knops, Vera E J; Bruggeman, Cathrien A; van Mook, Walther N K A; Linssen, Catharina F M

    2014-10-01

    Pneumocystis jiroveci infections can cause pneumocystis pneumonia (PCP) or lead to colonization without signs of PCP. Over the years, different genotypes of P. jiroveci have been discovered. Genomic typing of P. jiroveci in different subpopulations can contribute to unravelling the pathogenesis, transmission and spread of the different genotypes. In this study, we wanted to determine the distribution of P. jiroveci genotypes in immunocompetent and immunocompromised patients in The Netherlands and determine the clinical relevance of these detected mutations. A real-time PCR targeting the major surface glycoprotein gene (MSG) was used as a screening test for the presence of P. jiroveci DNA. Samples positive for MSG were genotyped based on the internal transcribed spacer (ITS) and dihydropteroate synthase (DHPS) genes. Of the 595 included bronchoalveolar lavage fluid samples, 116 revealed the presence of P. jiroveci DNA. A total of 52 of the 116 samples were ITS genotyped and 58 DHPS genotyped. The ITS genotyping revealed 17 ITS types, including two types that have not been described previously. There was no correlation between ITS genotype and underlying disease. All ITS- and DHPS-genotyped samples were found in immunocompromised patients. Of the 58 DHPS-genotyped samples, 50 were found to be WT. The other eight samples revealed a mixed genotype consisting of WT and type 1. The majority of the latter recovered on trimethoprim-sulfamethoxazole suggesting no clinical relevance for this mutation.

  17. Prognosis of pneumocystis pneumonia complicated in patients with rheumatoid arthritis (RA) and non-RA rheumatic diseases.

    PubMed

    Yoshida, Yuji; Takahashi, Yuko; Minemura, Nobuyoshi; Ueda, Yo; Yamashita, Hiroyuki; Kaneko, Hiroshi; Mimori, Akio

    2012-08-01

    Clinical presentation of pneumocystis pneumonia (PCP) during immunosuppressive therapy for rheumatic diseases was compared between patients with rheumatoid arthritis (RA; n = 7) and those without RA (non-RA; n = 12) based on a chart review. Both RA and non-RA patients with PCP were treated with methotrexate (n = 7) combined with steroids (n = 6) and/or biologics (n = 4). RA-PCP patients were found to have a higher mortality rate than non-RA-PCP patients (3/7 vs. 0/12, respectively; p = 0.036) due to a later exacerbation of interstitial pneumonia and a higher presentation rate of diffuse pulmonary lesions (4/7 vs. 1/12, respectively; p = 0.036) despite lower mean levels of serum beta-D: -glucan (314 ± 214 vs. 1139 ± 1114 pg/ml, respectively; p = 0.02) that suggested a lower burden of Pneumocystis jirovecii. In conclusion, PCP in RA patients with existing pulmonary lesions may trigger subsequent progression to lethal interstitial pneumonia.

  18. High prevalence of Pneumocystis jirovecii pneumonia among Mozambican children <5 years of age admitted to hospital with clinical severe pneumonia.

    PubMed

    Lanaspa, M; O'Callaghan-Gordo, C; Machevo, S; Madrid, L; Nhampossa, T; Acácio, S; de la Horra, C; Friaza, V; Campano, E; Alonso, P L; Calderón, E J; Roca, A; Bassat, Q

    2015-11-01

    We aimed to describe Pneumocystis jirovecii pneumonia (PCP) prevalence and features in children from sub-Saharan Africa and to investigate PCP-associated risk factors. During 2006-2007 we used molecular methods to test children younger than 5 years old admitted with severe pneumonia to a hospital in southern Mozambique for Pneumocystis infection. We recruited 834 children. PCP prevalence was 6.8% and HIV prevalence was 25.7%. The in-hospital and delayed mortality were significantly higher among children with PCP (20.8% vs. 10.2%, p 0.021, and 11.5% vs. 3.6%, p 0.044, respectively). Clinical features were mostly overlapping between the two groups. Independent risk factors for PCP were age less than a year (odds ratio (OR) 6.34, 95% confidence interval (CI) 1.86-21.65), HIV infection (OR 2.99, 95% CI 1.16-7.70), grunting (OR 2.64, 95% CI 1.04-6.73) and digital clubbing (OR 10.75, 95% CI 1.21-95.56). PCP is a common and life-threatening cause of severe pneumonia in Mozambican children. Mother-to-child HIV transmission prevention should be strengthened. Better diagnostic tools are needed.

  19. Loop-mediated isothermal amplification with the Procedure for Ultra Rapid Extraction kit for the diagnosis of pneumocystis pneumonia.

    PubMed

    Kawano, Shuichi; Maeda, Takuya; Suzuki, Takefumi; Abe, Tatsuhiro; Mikita, Kei; Hamakawa, Yusuke; Ono, Takeshi; Sonehara, Wataru; Miyahira, Yasushi; Kawana, Akihiko

    2015-03-01

    Loop-mediated isothermal amplification (LAMP) is an innovative molecular technique requiring only a heating device and isothermal conditions to amplify a specific target gene. The results of current microscopic diagnostic tools for pneumocystis pneumonia are not sufficiently consistent for detecting infection with a low-density of Pneumocystis jirovecii. Although polymerase chain reaction (PCR) is highly sensitive, it is not suitable for resource-limited facilities. LAMP is a potential diagnostic replacement for PCR in such settings but a critical disadvantage of DNA extraction was still remained. Therefore, we employed the Procedure for Ultra Rapid Extraction (PURE) kit, which uses a porous material, to isolate the DNA from clinical samples in a simple way in combination with previously reported LAMP procedure for diagnosing PCP. The detection limit of the PURE-LAMP method applied to artificial bronchoalveolar lavage fluid samples was 100 copies/tube, even with the use of massive blood-contaminated solutions. In addition, we concluded the diagnostic procedure within 1 h without the need for additional equipment. PURE-LAMP coupled with suitable primers for specific pathogens has good potential for diagnosing various infectious diseases.

  20. Pneumocystis carinii pneumonia: a comparison between patients with the acquired immunodeficiency syndrome and patients with other immunodeficiencies.

    PubMed

    Kovacs, J A; Hiemenz, J W; Macher, A M; Stover, D; Murray, H W; Shelhamer, J; Lane, H C; Urmacher, C; Honig, C; Longo, D L

    1984-05-01

    Clinical features of 49 episodes of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome were compared with those of 39 episodes in patients with other immunosuppressive diseases. At presentation patients with the syndrome were found to have a longer median duration of symptoms (28 days versus 5 days, p = 0.0001), lower mean respiratory rate (23.4 versus 30, p = 0.005), and higher median room air arterial oxygen tension (69 mm Hg versus 52 mm Hg, p = 0.0002). The survival rate from 1979 to 1983 was similar for the two groups (57% and 50% respectively). Patients with the syndrome had a higher incidence of adverse reactions to trimethoprim-sulfamethoxazole (22 of 34 versus 2 of 17, p = 0.0007). Survivors with the syndrome at initial presentation had a significantly lower respiratory rate, and higher room air arterial oxygen tension, lymphocyte count, and serum albumin level compared to nonsurvivors. Pneumocystis carinii pneumonia presents as a more insidious disease process in patients with the syndrome, and drug therapy in these patients is complicated by frequent adverse reactions.

  1. Modulation of inflammasome-mediated pulmonary immune activation by type I IFNs protects bone marrow homeostasis during systemic responses to Pneumocystis lung infection.

    PubMed

    Searles, Steve; Gauss, Katherine; Wilkison, Michelle; Hoyt, Teri R; Dobrinen, Erin; Meissner, Nicole

    2013-10-01

    Although acquired bone marrow failure (BMF) is considered a T cell-mediated autoimmune disease, possible innate immune defects as a cause for systemic immune deviations in response to otherwise innocuous infections have not been extensively explored. In this regard, we recently demonstrated an important role of type I IFNs in protecting hematopoiesis during systemic stress responses to the opportunistic fungal pathogen Pneumocystis in lymphocyte-deficient mice. Mice deficient in both lymphocytes and type I IFN receptor (IFrag(-/-) mice) develop rapidly progressing BMF due to accelerated bone marrow (BM) cell apoptosis associated with innate immune deviations in the BM in response to Pneumocystis lung infection. However, the communication pathway between lung and BM eliciting the induction of BMF in response to this strictly pulmonary infection has been unclear. In this study, we report that absence of an intact type I IFN system during Pneumocystis lung infection not only causes BMF in lymphocyte-deficient mice but also transient BM stress in lymphocyte-competent mice. This is associated with an exuberant systemic IFN-γ response. IFN-γ neutralization prevented Pneumocystis lung infection-induced BM depression in type I IFN receptor-deficient mice and prolonged neutrophil survival time in BM from IFrag(-/-) mice. IL-1β and upstream regulators of IFN-γ, IL-12, and IL-18 were also upregulated in lung and serum of IFrag(-/-) mice. In conjunction, there was exuberant inflammasome-mediated caspase-1 activation in pulmonary innate immune cells required for processing of IL-18 and IL-1β. Thus, absence of type I IFN signaling during Pneumocystis lung infection may result in deregulation of inflammasome-mediated pulmonary immune activation, causing systemic immune deviations triggering BMF in this model.

  2. The Interaction of Pneumocystis with the C-Type Lectin Receptor Mincle Exerts a Significant Role in Host Defense against Infection.

    PubMed

    Kottom, Theodore J; Hebrink, Deanne M; Jenson, Paige E; Nandakumar, Vijayalakshmi; Wüthrich, Marcel; Wang, Huafeng; Klein, Bruce; Yamasaki, Sho; Lepenies, Bernd; Limper, Andrew H

    2017-03-15

    Pneumocystis pneumonia (PCP) remains a major cause of morbidity and mortality within immunocompromised patients. In this study, we examined the potential role of macrophage-inducible C-type lectin (Mincle) for host defense against Pneumocystis Binding assays implementing soluble Mincle carbohydrate recognition domain fusion proteins demonstrated binding to intact Pneumocystis carinii as well as to organism homogenates, and they purified major surface glycoprotein/glycoprotein A derived from the organism. Additional experiments showed that rats with PCP expressed increased Mincle mRNA levels. Mouse macrophages overexpressing Mincle displayed increased binding to P. carinii life forms and enhanced protein tyrosine phosphorylation. The binding of P. carinii to Mincle resulted in activation of FcRγ-mediated cell signaling. RNA silencing of Mincle in mouse macrophages resulted in decreased activation of Syk kinase after P. carinii challenge, critical in downstream inflammatory signaling. Mincle-deficient CD4-depleted (Mincle(-/-)) mice showed a significant defect in organism clearance from the lungs with higher organism burdens and altered lung cytokine responses during Pneumocystis murina pneumonia. Interestingly, Mincle(-/-) mice did not demonstrate worsened survival during PCP compared with wild-type mice, despite the markedly increased organism burdens. This may be related to increased expression of anti-inflammatory factors such as IL-1Ra during infection in the Mincle(-/-) mice. Of note, the P. murina-infected Mincle(-/-) mice demonstrated increased expression of known C-type lectin receptors Dectin-1, Dectin-2, and MCL compared with infected wild-type mice. Taken together, these data support a significant role for Mincle in Pneumocystis modulating host defense during infection.

  3. Pneumocystis pneumonia in HIV-positive patients in Spain: epidemiology and environmental risk factors

    PubMed Central

    Alvaro-Meca, Alejandro; Palomares-Sancho, Ines; Diaz, Asuncion; Resino, Rosa; De Miguel, Angel Gil; Resino, Salvador

    2015-01-01

    Introduction Specific environmental factors may play a role in the development of Pneumocystis pneumonia (PCP) in HIV-positive patients. The aim of this study was to estimate the PCP incidence and mortality in hospitalized HIV-positive patients in Spain during the combination antiretroviral therapy (cART) era (1997 to 2011), as well as to analyze the climatological factors and air pollution levels in relation to hospital admissions and deaths. Methods We carried out a retrospective study. Data were collected from the National Hospital Discharge Database and the State Meteorological Agency of Spain. A case-crossover analysis was applied to identify environmental risk factors related to hospitalizations and deaths. For each patient, climatic factors and pollution levels were assigned based on readings from the nearest meteorological station to his or her postal code. Results There were 13,139 new PCP diagnoses and 1754 deaths in hospitalized HIV-positive patients from 1997 to 2011. The PCP incidence (events per 1000 person-years) dropped from 11.6 in 1997 to 2000, to 5.4 in 2004 to 2011 (p<0.001). The mortality (events per 10,000 person-years) also decreased from 14.3 in 1997 to 2000, to 7.5 in 2004 to 2011 (p<0.001). Most hospital admissions and deaths occurred in the winter season and the fewest occurred in the summer, overlapping respectively with the lowest and highest temperatures of the year in Spain. Moreover, lower temperatures prior to PCP admission, as well as higher concentrations of NO2 and particulate matter up to 10 m in size (PM10) at the time of admission were associated with higher likelihoods of hospital admission due to PCP when two weeks, one month, 1.5 months or two months were used as controls (p<0.01). Furthermore, higher concentrations of ozone at one month (p=0.007), 1.5 months (p<0.001) and two months (p=0.006) prior to admission were associated with higher likelihoods of hospital admission with PCP. For PCP-related deaths, lower

  4. Quantitative structure-activity relationship studies of a series of sulfa drugs as inhibitors of Pneumocystis carinii dihydropteroate synthetase.

    PubMed

    Johnson, T; Khan, I A; Avery, M A; Grant, J; Meshnick, S R

    1998-06-01

    Sulfone and sulfanilamide sulfa drugs have been shown to inhibit dihydropteroate synthetase (DHPS) isolated from Pneumocystis carinii. In order to develop a pharmacophoric model for this inhibition, quantitative structure-activity relationships (QSAR) for sulfa drugs active against DHPS have been studied. Accurate 50% inhibitory concentrations were collected for 44 analogs, and other parameters, such as partition coefficients and molar refractivity, were calculated. Conventional multiple regression analysis of these data did not provide acceptable QSAR. However, three-dimensional QSAR provided by comparative molecular field analysis did give excellent results. Upon removal of poorly correlated analogs, a data set of 36 analogs, all having a common NHSO2 group, provided a cross-validated r2 value of 0.699 and conventional r2 value of 0.964. The resulting pharmacophore model should be useful for understanding and predicting the binding of DHPS by new sulfa drugs.

  5. Rapid detection of mutations in the human-derived Pneumocystis carinii dihydropteroate synthase gene associated with sulfa resistance.

    PubMed

    Ma, L; Kovacs, J A

    2001-03-01

    Recent studies have shown that point mutations in the dihydropteroate synthase (DHPS) gene of human-derived Pneumocystis carinii are related to exposure to sulfa drugs and possibly represent the emergence of sulfa resistance. We developed a simple single-strand conformation polymorphism (SSCP) method to permit rapid detection of these mutations. With plasmid constructs, SSCP was able to detect as little as 10% of a minority population. The SSCP assay was compared to direct sequencing for typing the DHPS gene by examining 37 clinical isolates with known DHPS sequences and 41 clinical isolates with unknown DHPS sequences. The typing results were consistent between these two methods for all isolates except 11 in which mutations were detected by SSCP but not by direct sequencing. Sequencing of individual clones after subcloning confirmed the presence of mutations in a minority population as determined by SSCP. SSCP is a very simple and sensitive method for rapid identification of P. camii DHPS mutations.

  6. Molecular Evidence of Interhuman Transmission of Pneumocystis Pneumonia among Renal Transplant Recipients Hospitalized with HIV-Infected Patients

    PubMed Central

    Rabodonirina, Meja; Vanhems, Philippe; Couray-Targe, Sandrine; Gillibert, René-Pierre; Ganne, Christell; Nizard, Nathalie; Colin, Cyrille; Fabry, Jacques; Touraine, Jean-Louis; van Melle, Guy; Nahimana, Aimable; Francioli, Patrick

    2004-01-01

    Ten Pneumocystis jirovecii pneumonia (PCP) cases were diagnosed in renal transplant recipients (RTRs) during a 3-year period. Nosocomial transmission from HIV-positive patients with PCP was suspected because these patients shared the same hospital building, were not isolated, and were receiving suboptimal anti-PCP prophylaxis or none. P. jirovecii organisms were typed with the multitarget polymerase chain reaction–single-strand conformation polymorphism method. Among the 45 patients with PCP hospitalized during the 3-year period, 8 RTRs and 6 HIV-infected patients may have encountered at least 1 patient with active PCP within the 3 months before the diagnosis of their own PCP episode. In six instances (five RTRs, one HIV-infected patient), the patients harbored the same P. jirovecii molecular type as that found in the encountered PCP patients. The data suggest that part of the PCP cases observed in this building, particularly those observed in RTRs, were related to nosocomial interhuman transmission. PMID:15504262

  7. Three-dimensional reconstruction of rabbit-derived Pneumocystis carinii from serial-thin sections. II: Intermediate precyst.

    PubMed

    Palluault, F; Pietrzyk, B; Dei-Cas, E; Slomianny, C; Soulez, B; Camus, D

    1991-01-01

    Three-dimensional reconstruction of a binucleate intermediate precyst of Pneumocystis carinii was performed from serial-thin sections using the CATIA (Conception Assistée Tridimensionnelle Inter Active) Dassault system program. The presence of a mitochondrion, complex well-developed endoplasmic structures, and numerous Golgi vesicles was established. A better understanding of the ultrastructure of rabbit-derived P. carinii stages made it possible to formulate hypotheses on the evolution and physiology of the endomembrane system. Thus, the presence of the well-developed endoplasmic saccular structure and more than 230 Golgi vesicles in its vicinity might be implicated in the differentiation of the parasite surface structures and might also be related to nuclear division and individualization of intracystic bodies.

  8. IL-33 and M2a alveolar macrophages promote lung defense against the atypical fungal pathogen Pneumocystis murina.

    PubMed

    Nelson, Michael P; Christmann, Benjamin S; Werner, Jessica L; Metz, Allison E; Trevor, Jennifer L; Lowell, Clifford A; Steele, Chad

    2011-02-15

    We have recently reported that mice deficient in the myeloid Src-family tyrosine kinases Hck, Fgr, and Lyn (Src triple knockout [TKO]) had augmented innate lung clearance of Pneumocystis murina that correlated with a higher ability of alveolar macrophages (AMs) from these mice to kill P. murina. In this article, we show that despite possessing enhanced killing, AMs from naive Src TKO mice did not demonstrate enhanced inflammatory responses to P. murina. We subsequently discovered that both AMs and lungs from P. murina-infected Src TKO mice expressed significantly greater levels of the M2a markers RELM-α and Arg1, and the M2a-associated chemokines CCL17 and CCL22 than did wild-type mice. IL-4 and IL-13, the primary cytokines that promote M2a polarization, were not differentially produced in the lungs between wild-type and Src TKO mice. P. murina infection in Src TKO mice resulted in enhanced lung production of the novel IL-1 family cytokine IL-33. Immunohistochemical analysis of IL-33 in lung tissue revealed localization predominantly in the nucleus of alveolar epithelial cells. We further demonstrate that experimental polarization of naive AMs to M2a resulted in more efficient killing of P. murina compared with untreated AMs, which was further enhanced by the addition of IL-33. Administration of IL-33 to C57BL/6 mice increased lung RELM-α and CCL17 levels, and enhanced clearance of P. murina, despite having no effect on the cellular composition of the lungs. Collectively, these results indicate that M2a AMs are potent effector cells against P. murina. Furthermore, enhancing M2a polarization may be an adjunctive therapy for the treatment of Pneumocystis.

  9. Anti-CD3 antibody decreases inflammation and improves outcome in a murine model of Pneumocystis pneumonia

    PubMed Central

    Bhagwat, Samir P.; Wright, Terry W.; Gigliotti, Francis

    2009-01-01

    The T cell-mediated immune response elicited by Pneumocystis plays a key role in pulmonary damage and dysfunction during Pneumocystis pneumonia (PcP). Mice depleted of CD4+ and CD8+ T cells prior to infection are markedly protected from PcP-related respiratory deficit and death despite progressive lung infection. However, the therapeutic effectiveness of antibody-mediated disruption of T cell function in mice already displaying clinical symptoms of disease has not been determined. Therefore, a murine model of PcP-related immune reconstitution inflammatory syndrome was used to assess whether antibody to the pan-T cell molecule CD3 is effective for reducing the severity of PcP when administered after the onset of disease. Mice that received anti-CD3 antibody exhibited a rapid and dramatic halt in the PcP-associated pulmonary function decline within one week post-treatment, and a striking enhancement of survival rate compared to mice receiving control antibody. Physiological improvement in anti-CD3 treated mice was associated with a significant reduction in the number of CD4+ and CD8+ T cells recovered in lung lavage fluid. This effectiveness of anti-CD3 was noted whether or not the mice also received antibiotic therapy with trimethoprim-sulfamethoxazole. These data suggest that monoclonal antibody-mediated disruption of T cell function may represent a specific and effective adjunctive therapy to rapidly reverse the ongoing pathological immune response occurring during active PcP. Thus, the anti-human CD3 monoclonal antibody OKT3, which is already in clinical use, has the potential to be developed as an adjunctive therapy for PcP. PMID:19949093

  10. Retrospective Analysis of Bacterial and Viral Co-Infections in Pneumocystis spp. Positive Lung Samples of Austrian Pigs with Pneumonia

    PubMed Central

    Weissenbacher-Lang, Christiane; Kureljušić, Branislav; Nedorost, Nora; Matula, Bettina; Schießl, Wolfgang; Stixenberger, Daniela; Weissenböck, Herbert

    2016-01-01

    Aim of this study was the retrospective investigation of viral (porcine circovirus type 2 (PCV2), porcine reproductive and respiratory syndrome virus (PRRSV), torque teno sus virus type 1 and 2 (TTSuV1, TTSuV2)) and bacterial (Bordetella bronchiseptica (B. b.), Mycoplasma hyopneumoniae (M. h.), and Pasteurella multocida (P. m.)) co-infections in 110 Pneumocystis spp. positive lung samples of Austrian pigs with pneumonia. Fifty-one % were positive for PCV2, 7% for PRRSV, 22% for TTSuV1, 48% for TTSuV2, 6% for B. b., 29% for M. h., and 21% for P. m. In 38.2% only viral, in 3.6% only bacterial and in 40.0% both, viral and bacterial pathogens were detected. In 29.1% of the cases a co-infection with 1 pathogen, in 28.2% with 2, in 17.3% with 3, and in 7.3% with 4 different infectious agents were observed. The exposure to Pneumocystis significantly decreased the risk of a co-infection with PRRSV in weaning piglets; all other odds ratios were not significant. Four categories of results were compared: I = P. spp. + only viral co-infectants, II = P. spp. + both viral and bacterial co-infectants, III = P. spp. + only bacterial co-infectants, and IV = P. spp. single infection. The evaluation of all samples and the age class of the weaning piglets resulted in a predomination of the categories I and II. In contrast, the suckling piglets showed more samples of category I and IV. In the group of fattening pigs, category II predominated. Suckling piglets can be infected with P. spp. early in life. With increasing age this single infections can be complicated by co-infections with other respiratory diseases. PMID:27428002

  11. Copy Number Variation of Mitochondrial DNA Genes in Pneumocystis jirovecii According to the Fungal Load in BAL Specimens

    PubMed Central

    Valero, Clara; Buitrago, María José; Gits-Muselli, Maud; Benazra, Marion; Sturny-Leclère, Aude; Hamane, Samia; Guigue, Nicolas; Bretagne, Stéphane; Alanio, Alexandre

    2016-01-01

    Pneumocystis jirovecii is an unculturable fungus and the causative agent of Pneumocystis pneumonia, a life-threatening opportunistic infection. Although molecular diagnosis is often based on the detection of mtLSU rRNA mitochondrial gene, the number of copies of mitochondrial genes had not been investigated. We developed and optimized six real-time PCR assays in order to determine the copy number of four mitochondrial genes (mtSSU rRNA, mtLSU rRNA, NAD1, and CYTB) in comparison to nuclear genome (DHPS and HSP70) and tested 84 bronchoalveolar fluids of patients at different stages of the infection. Unexpectedly, we found that copy number of mitochondrial genes varied from gene to gene with mtSSU rRNA gene being more represented (37 copies) than NAD1 (23 copies), mtLSU rRNA (15 copies) and CYTB (6 copies) genes compared to nuclear genome. Hierarchical clustering analysis (HCA) allowed us to define five major clusters, significantly associated with fungal load (p = 0.029), in which copy number of mitochondrial genes was significantly different among them. More importantly, copy number of mtLSU rRNA, NAD1, and CYTB but not mtSSU rRNA differed according to P. jirovecii physiological state with a decreased number of copies when the fungal load is low. This suggests the existence of a mixture of various subspecies of mtDNA that can harbor different amplification rates. Overall, we revealed here an unexpected variability of P. jirovecii mtDNA copy number that fluctuates according to P. jirovecii’s physiological state, except for mtSSU that is the most stable and the most present mitochondrial gene. PMID:27672381

  12. [Pneumocystis Pneumonia in 107 HIV Infected Patients Admitted to the Department of Infectious Diseases at Santa Maria Hospital, Lisbon (2002 - 2013)].

    PubMed

    Grilo, Vilma; Pereira, Aida

    2016-10-01

    Introdução: A pneumonia por Pneumocystis jirovecii é das doenças infecciosas oportunistas mais comuns em infectados por vírus da imunodeficiência humana, sendo, actualmente, em Portugal a infecção definidora de sida mais reportada. Os objectivos deste estudo foram, analisar as características de uma população co-infectada por vírus da imunodeficiência humana e pneumonia por Pneumocystis jirovecii, comparando-a com as referências disponíveis, e avaliar comparativamente subpopulações de doentes, consoante o conhecimento prévio da infecção por vírus da imunodeficiência humana, o método de diagnóstico de pneumonia por Pneumocystis jirovecii e o resultado na alta. Material e Métodos: Realizámos um estudo restrospectivo pela análise dos registos clínicos de 107 doentes internados no Serviço de Doenças Infecciosas do Hospital de Santa Maria, entre 1 de janeiro de 2002 e 31 de dezembro de 2013, com o diagnóstico de pneumonia por Pneumocystis jirovecii e vírus da imunodeficiência humana. As características epidemiológicas e clínicas foram avaliadas, incluindo o estado imunitário, a carga vírica e a terapêutica instituída e foi realizado um estudo estatístico das variáveis.Resultados: Nesta população, os resultados demonstraram predomínio do sexo masculino (81,3%), idade entre 20 - 39 anos (59,2%), transmissão de vírus da imunodeficiência humana por via heterossexual (48,6%), e que 24,3% eram imigrantes. Apesar do conhecimento da infecção por vírus da imunodeficiência humana (62,6%), 76,2% destes doentes não apresentava seguimento médico sustentado. A contagem de linfócitos TCD4+ ≤ 200 células/mm3 (96,3%), carga vírica elevada e candidose orofaríngea (72%) foram os principais factores de risco para o desenvolvimento de pneumonia por Pneumocystis jirovecii, e os marcadores de gravidade, como a hipoxemia (78,5%) e a elevação da LDH (82,2%) não traduziram pior prognóstico. Apenas foi possível isolar

  13. Absence of Pneumocystis jirovecii Colonization in Human Immunodeficiency Virus-Infected Individuals With and Without Airway Obstruction and With Undetectable Viral Load

    PubMed Central

    Ronit, Andreas; Klitbo, Ditte Marie; Kildemoes, Anna Overgaard; Benfield, Thomas; Gerstoft, Jan; Vestbo, Jørgen; Jensen, Jørgen Skov; Kurtzhals, Jørgen; Nielsen, Susanne Dam

    2016-01-01

    Pneumocystis jirovecii colonization has been associated with non-acquired immune deficiency syndrome (AIDS) pulmonary comorbidity. We used spirometry to measure pulmonary function and analyzed oral wash specimens by quantitative polymerase chain reaction (PCR), targeting the large mitochondrial ribosomal subunit. For sensitivity control, a blinded subsample was subjected to touch-down PCRs, targeting both large and small ribosomal subunits and the major surface glycoprotein. Pneumocystis jirovecii deoxyribonucleic acid (DNA) was detected in 1 of 156 (95% confidence interval, .1%–3.5%) virologically suppressed human immunodeficiency virus (HIV)-infected individuals confirmed by all PCR methods. Thus, prevalence of P jirovecii colonization was low and unlikely to be a major cause of pulmonary comorbidity in this group of well treated HIV-infected individuals. PMID:27006967

  14. Legionella pneumophila and Pneumocystis jirovecii coinfection in an infant treated with adrenocorticotropic hormone for infantile spasm: case report and literature review.

    PubMed

    Musallam, Nadira; Bamberger, Ellen; Srugo, Isaac; Dabbah, Husein; Glikman, Daniel; Zonis, Zeev; Kessel, Aharon; Genizi, Jacob

    2014-02-01

    We describe an 8-month-old infant with infantile spasms treated with adrenocorticotropic hormone (ACTH) who presented with fatal Legionella pneumophila and Pneumocystis jirovecii infection. Emphasis is placed on the ensuing immunosuppression and infectious sequelae of ACTH therapy. Given that ACTH therapy may increase the risk of fatal infection, patients undergoing such treatment should be closely monitored, with particular attention paid to the functioning of the immune system.

  15. B cells modulate systemic responses to Pneumocystis murina lung infection and protect on-demand hematopoiesis via T cell-independent innate mechanisms when type I interferon signaling is absent.

    PubMed

    Hoyt, Teri R; Dobrinen, Erin; Kochetkova, Irina; Meissner, Nicole

    2015-02-01

    HIV infection results in a complex immunodeficiency due to loss of CD4(+) T cells, impaired type I interferon (IFN) responses, and B cell dysfunctions causing susceptibility to opportunistic infections such as Pneumocystis murina pneumonia and unexplained comorbidities, including bone marrow dysfunctions. Type I IFNs and B cells critically contribute to immunity to Pneumocystis lung infection. We recently also identified B cells as supporters of on-demand hematopoiesis following Pneumocystis infection that would otherwise be hampered due to systemic immune effects initiated in the context of a defective type I IFN system. While studying the role of type I IFNs in immunity to Pneumocystis infection, we discovered that mice lacking both lymphocytes and type I IFN receptor (IFrag(-/-)) developed progressive bone marrow failure following infection, while lymphocyte-competent type I IFN receptor-deficient mice (IFNAR(-/-)) showed transient bone marrow depression and extramedullary hematopoiesis. Lymphocyte reconstitution of lymphocyte-deficient IFrag(-/-) mice pointed to B cells as a key player in bone marrow protection. Here we define how B cells protect on-demand hematopoiesis following Pneumocystis lung infection in our model. We demonstrate that adoptive transfer of B cells into IFrag(-/-) mice protects early hematopoietic progenitor activity during systemic responses to Pneumocystis infection, thus promoting replenishment of depleted bone marrow cells. This activity is independent of CD4(+) T cell help and B cell receptor specificity and does not require B cell migration to bone marrow. Furthermore, we show that B cells protect on-demand hematopoiesis in part by induction of interleukin-10 (IL-10)- and IL-27-mediated mechanisms. Thus, our data demonstrate an important immune modulatory role of B cells during Pneumocystis lung infection that complement the modulatory role of type I IFNs to prevent systemic complications.

  16. Comparison of 2 real-time PCR assays for diagnosis of Pneumocystis jirovecii pneumonia in human immunodeficiency virus (HIV) and non-HIV immunocompromised patients.

    PubMed

    Montesinos, Isabel; Brancart, Françoise; Schepers, Kinda; Jacobs, Frederique; Denis, Olivier; Delforge, Marie-Luce

    2015-06-01

    A total of 120 bronchoalveolar lavage specimens from HIV and non-HIV immunocompromised patients, positive for Pneumocystis jirovecii by an "in house" real-time polymerase chain reaction (PCR), were evaluated by the Bio-Evolution Pneumocystis real-time PCR, a commercial quantitative assay. Patients were classified in 2 categories based on clinical and radiological findings: definite and unlikely Pneumocystis pneumonia (PCP). For the "in house" PCR, cycle threshold 34 was established as cut-off value to discriminate definite PCP from unlikely PCP with 65% and 85% of sensitivity and specificity, respectively. For the Bio-Evolution quantitative PCR, a cut-off value of 2.8×10(5)copies/mL was defined with 72% and 82% of sensitivity and specificity, respectively. Overlapped zones of results for definite and unlikely PCP were observed. Quantitative PCR is probably a useful tool for PCP diagnosis. However, for optimal management of PCP in non-HIV immunocompromised patients, operational thresholds should be assessed according to underlying diseases and other clinical and radiological parameters.

  17. Pneumonia associated with infection with pneumocystis, respiratory syncytial virus, chlamydia, mycoplasma, and cytomegalovirus in children in Papua New Guinea.

    PubMed Central

    Shann, F; Walters, S; Pifer, L L; Graham, D M; Jack, I; Uren, E; Birch, D; Stallman, N D

    1986-01-01

    Paired serum samples were collected from 94 children with pneumonia admitted to Goroka Hospital, Papua New Guinea. All but three of the children were aged 1-24 months. Only nine children were malnourished, with weight for age less than 70% of the Harvard median (three had weight for age less than 60% of the Harvard median). Pneumocystis carinii antigen was detected in the serum of 23 children. Twenty two children had serological evidence of recent infection with respiratory syncytial virus. Five children were probably infected with Chlamydia trachomatis at the time of the study, and there was less convincing serological evidence of current infection in a further 11 children. Five children showed a fourfold rise in antibody to Mycoplasma pneumoniae. Although only one child showed a fourfold rise in antibody to cytomegalovirus, 86 children had this antibody. No child showed a fourfold rise in antibody to Ureaplasma urealyticum or Legionella pneumophila. P carinii, respiratory syncytial virus, C trachomatis, M pneumoniae, and cytomegalovirus may be important causes of pneumonia in children in developing countries. PMID:3002538

  18. Pneumocystis jiroveci in Portuguese immunocompromised patients: association of specific ITS genotypes with treatment failure, bad clinical outcome and childhood.

    PubMed

    Matos, Olga; Lee, Chao-Hung; Jin, Shaoling; Li, Baozheng; Costa, Marina C; Gonçalves, Luzia; Antunes, Francisco

    2003-11-01

    We analyzed the genetic variation among isolates of Pneumocystis jiroveci from Portuguese immunocompromised patients with PCP at the internal transcribed spacer (ITS) regions of the nuclear rRNA operon and at the dihydropteroate synthase (DHPS) gene. Pulmonary secretions from 42 patients with PCP corresponding to 43 episodes were studied. Demographic, immunological, and clinical data were obtained from all patients. By combining the two regions ITS1 and ITS2, we found 17 different ITS types of P. jiroveci, two of them were new types (Pb and Pe). The four most prevalent ITS types were Eg (23.3%), Eb and Ne (11.6% each), and Bi (9.3%). A single type was detected in 95.3% of the samples and 4.7% had mixed infections with three different ITS types. DHPS mutants were present in 17 (46%), and the wildtype was present in 20 (54%) of 37 isolates. No association was found between ITS and DHPS types and between DHPS types and therapy or response to anti-PCP treatment. Type Ne presented an association with negative response to anti-PCP treatment (P<0.001) and with death before 120 days after PCP diagnosis (P=0.025). Type Eb was significantly more common in children than in adults (P=0.001). Our data suggest an association of specific ITS genotypes with treatment failure, bad clinical outcome and childhood.

  19. Detection of specific antibody by enzyme-linked immunosorbent assay and antigenemia by counterimmunoelectrophoresis in humans infected with Pneumocystis carinii.

    PubMed

    Maddison, S E; Hayes, G V; Slemenda, S B; Norman, L G; Ivey, M H

    1982-06-01

    A urea-soluble extract of cyst-rich material from rat lung heavily infected with Pneumocystis carinii was evaluated in an enzyme-linked immunosorption assay for antibody in 461 human sera. The highest level of reactivity occurred in sera submitted for serodiagnosis from proved or highly suspect cases. However, the range of reactivities in these groups, many of whom were on immunosuppressive therapy, was very wide. A more restricted lower range of reactivity was observed in both hospital-family contacts and healthy Serum Bank donors. Because of the overlap in levels of reactivity between the pneumocystosis and control groups, no concise cutoff value to separate infected from noninfected individuals could be made. Specificity of the reactions was shown by absorption of patients' and control sera with uninfected and P. carinii-infected human and rat lung tissue. The data support the concept that P. carinii is highly prevalent as a latent agent in the general population and is provoked to cause clinically manifest disease in the compromised host. Detection of circulating antigen appeared to be specific and possibly a useful adjunct to diagnosis, as 10 of the 14 proved or highly suspect patients with antigenemia did not have measurable antibody to P. carinii.

  20. Lethal exacerbation of Pneumocystis carinii pneumonia in severe combined immunodeficiency mice after infection by pneumonia virus of mice.

    PubMed

    Roths, J B; Smith, A L; Sidman, C L

    1993-04-01

    Mice homozygous for the mutant allele scid (severe combined immunodeficiency) have been described as excellent models for Pneumocystis carinii (Pc) pneumonia (PCP), a major health problem in patients with acquired immune deficiency syndrome (AIDS) and other immunodeficiency states. Other microorganisms have been shown to infect AIDS patients simultaneously with Pc, but whether one opportunist is able to directly influence the pathogenicity of another has not been determined previously. We have deliberately coinfected scid mice (with extent Pc infection) with a variety of primarily pneumotropic viruses and bacteria and have identified pneumonia virus of mice as causing a dramatic increase in the density of Pc organisms and the morbidity due to PCP in immunodeficient scid mice. This finding has clinical significance in the management of PCP, in that the identification and treatment of coinfecting pneumotropic pathogens may be as important as treatment targeted at Pc. A search for other synergistic (or antagonistic) microorganisms and determination of their mechanism(s) of action in altering the progression of PCP is indicated.

  1. Single and combined humoral and cell-mediated immunotherapy of Pneumocystis carinii pneumonia in immunodeficient scid mice.

    PubMed

    Roths, J B; Sidman, C L

    1993-05-01

    Homozygous mutant scid/scid (severe combined immunodeficiency) mice (referred to as scid mice) lack both specific humoral and cell-mediated immune functions and are exemplary in vivo models for analysis of host-parasite relationships. In our colony, scid mice routinely and predictably develop spontaneous Pneumocystis carinii pneumonia (PCP) with high morbidity. Previous studies have identified both T cells (specifically, CD4+ cells) and antibody as independent mechanisms of effective anti-P. carinii resistance; however, CD4+ T cells also cause an often fatal hyperinflammatory reaction. The current study has explored the optimal application of these immune components for conferring protection against P. carinii. Anti-P. carinii hyperimmune serum was highly effective at reducing the number of P. carinii organisms in early, intermediate, and advanced stages of PCP and was capable of increasing the mean life expectancy of P. carinii-infected scid mice by more than threefold if provided on a continuing basis. When a short course of hyperimmune-serum therapy was provided prior to transfer of P. carinii-sensitized normal lymphocytes, scid mice were rendered permanently free of P. carinii without the pathological sequelae of the hyperinflammatory reaction. These findings are discussed in the contexts of mechanism and clinical relevance.

  2. Risk factors of Pneumocystis pneumonia in solid organ recipients in the era of the common use of posttransplantation prophylaxis.

    PubMed

    Iriart, X; Challan Belval, T; Fillaux, J; Esposito, L; Lavergne, R-A; Cardeau-Desangles, I; Roques, O; Del Bello, A; Cointault, O; Lavayssière, L; Chauvin, P; Menard, S; Magnaval, J-F; Cassaing, S; Rostaing, L; Kamar, N; Berry, A

    2015-01-01

    Pneumocystis pneumonia (PCP) in solid organ transplant (SOT) recipients becomes rare in the immediate posttransplantation period thanks to generalized prophylaxis. We aimed to identify the predictive factors for PCP in the era of universal prophylaxis and to propose a strategy for preventing PCP beyond the first year after transplantation. In a retrospective case-control study, 33 SOT cases with PCP diagnosed between 2004 and 2010 were matched with two controls each to identify risk factors for PCP by uni- and multivariate analysis. All the patients benefited from 6 months of posttransplantation trimethoprim-sulfamethoxazole prophylaxis. Most PCP in SOT patients occurred during the second year posttransplantation (33%). By univariate analysis, age, nonuse of tacrolimus, total and CD4 lymphocyte counts, gamma-globulin concentration and cytomegalovirus (CMV) infection appeared to be PCP risk factors. In the final multivariate analysis, age (adjusted odds ratio [OR] 3.7, 95% confidence interval [CI]: 1.3-10.4), CMV infection (OR: 5.2, 95% CI: 1.8-14.7) and total lymphocyte count (OR: 3.9, 95% CI: 1.4-10.7) were found to be independently associated with PCP. The second year posttransplantation appeared to be the new period of highest risk of PCP. Age, CMV viremia and lymphocytes were the most pertinent predictive criteria to evaluate the risk of PCP in clinical practice.

  3. Pneumocystis jirovecii pneumonia in mycophenolate mofetil-treated patients with connective tissue disease: analysis of 17 cases.

    PubMed

    Zhang, Yongfeng; Zheng, Yi

    2014-12-01

    The association of Pneumocystis jirovecii pneumonia (PJP) with connective tissue disease (CTD) and mycophenolate mofetil's (MMF) potent activity against PJP have been separately reported. Until now, there have been no papers describing the occurrence of PJP following MMF treatment in CTD patients. The objective of this study was to describe the clinical features, risk factors, outcomes of PJP in patients with CTD and investigates the effects of MMF on the occurrence of PJP in China. In this retrospective cohort study, we performed a chart review, analyzing clinical features, treatment, and outcomes of PJP in patients with CTD in a single hospital. A total of 17 cases met the inclusion criteria of having PJP and a CTD diagnosis: systemic lupus erythematosus; polymyositis; dermatomyositis; rheumatoid arthritis; Wegener's granulomatosis; and microscopic polyangiitis. Sixteen patients were treated with glucocorticoids (GCs) plus immunosuppressive drugs. Only one patient had GCs without immunosuppressive drugs. Ten subjects (62.5 %) received MMF (1-1.5 g/day), and all ten had lymphopenia. The mortality rates of MMF and non-MMF patients were 50 and 14 %, respectively. This study is the first report of PJP following MMF plus GC treatment in patients with CTD. CTD itself may be a risk factor for PJP. When CTD patients receiving MMF therapy have low lymphocyte counts and/or CD4 lymphocyte counts <250/µL, we should be care of occurrence of PJP.

  4. ECIL guidelines for the diagnosis of Pneumocystis jirovecii pneumonia in patients with haematological malignancies and stem cell transplant recipients.

    PubMed

    Alanio, Alexandre; Hauser, Philippe M; Lagrou, Katrien; Melchers, Willem J G; Helweg-Larsen, Jannik; Matos, Olga; Cesaro, Simone; Maschmeyer, Georg; Einsele, Hermann; Donnelly, J Peter; Cordonnier, Catherine; Maertens, Johan; Bretagne, Stéphane

    2016-09-01

    The Fifth European Conference on Infections in Leukaemia (ECIL-5) convened a meeting to establish evidence-based recommendations for using tests to diagnose Pneumocystis jirovecii pneumonia (PCP) in adult patients with haematological malignancies. Immunofluorescence assays are recommended as the most sensitive microscopic method (recommendation A-II: ). Real-time PCR is recommended for the routine diagnosis of PCP ( A-II: ). Bronchoalveolar lavage (BAL) fluid is recommended as the best specimen as it yields good negative predictive value ( A-II: ). Non-invasive specimens can be suitable alternatives ( B-II: ), acknowledging that PCP cannot be ruled out in case of a negative PCR result ( A-II: ). Detecting β-d-glucan in serum can contribute to the diagnosis but not the follow-up of PCP ( A-II: ). A negative serum β-d-glucan result can exclude PCP in a patient at risk ( A-II: ), whereas a positive test result may indicate other fungal infections. Genotyping using multilocus sequence markers can be used to investigate suspected outbreaks ( A-II: ). The routine detection of dihydropteroate synthase mutations in cases of treatment failure is not recommended ( B-II: ) since these mutations do not affect response to high-dose co-trimoxazole. The clinical utility of these diagnostic tests for the early management of PCP should be further assessed in prospective, randomized interventional studies.

  5. ECIL guidelines for preventing Pneumocystis jirovecii pneumonia in patients with haematological malignancies and stem cell transplant recipients.

    PubMed

    Maertens, Johan; Cesaro, Simone; Maschmeyer, Georg; Einsele, Hermann; Donnelly, J Peter; Alanio, Alexandre; Hauser, Philippe M; Lagrou, Katrien; Melchers, Willem J G; Helweg-Larsen, Jannik; Matos, Olga; Bretagne, Stéphane; Cordonnier, Catherine

    2016-09-01

    The 5th European Conference on Infections in Leukaemia (ECIL-5) meeting aimed to establish evidence-based recommendations for the prophylaxis of Pneumocystis jirovecii pneumonia (PCP) in non-HIV-infected patients with an underlying haematological condition, including allogeneic HSCT recipients. Recommendations were based on the grading system of the IDSA. Trimethoprim/sulfamethoxazole given 2-3 times weekly is the drug of choice for the primary prophylaxis of PCP in adults ( A-II: ) and children ( A-I: ) and should be given during the entire period at risk. Recent data indicate that children may benefit equally from a once-weekly regimen ( B-II: ). All other drugs, including pentamidine, atovaquone and dapsone, are considered second-line alternatives when trimethoprim/sulfamethoxazole is poorly tolerated or contraindicated. The main indications of PCP prophylaxis are ALL, allogeneic HSCT, treatment with alemtuzumab, fludarabine/cyclophosphamide/rituximab combinations, >4 weeks of treatment with corticosteroids and well-defined primary immune deficiencies in children. Additional indications are proposed depending on the treatment regimen.

  6. Single and combined humoral and cell-mediated immunotherapy of Pneumocystis carinii pneumonia in immunodeficient scid mice.

    PubMed Central

    Roths, J B; Sidman, C L

    1993-01-01

    Homozygous mutant scid/scid (severe combined immunodeficiency) mice (referred to as scid mice) lack both specific humoral and cell-mediated immune functions and are exemplary in vivo models for analysis of host-parasite relationships. In our colony, scid mice routinely and predictably develop spontaneous Pneumocystis carinii pneumonia (PCP) with high morbidity. Previous studies have identified both T cells (specifically, CD4+ cells) and antibody as independent mechanisms of effective anti-P. carinii resistance; however, CD4+ T cells also cause an often fatal hyperinflammatory reaction. The current study has explored the optimal application of these immune components for conferring protection against P. carinii. Anti-P. carinii hyperimmune serum was highly effective at reducing the number of P. carinii organisms in early, intermediate, and advanced stages of PCP and was capable of increasing the mean life expectancy of P. carinii-infected scid mice by more than threefold if provided on a continuing basis. When a short course of hyperimmune-serum therapy was provided prior to transfer of P. carinii-sensitized normal lymphocytes, scid mice were rendered permanently free of P. carinii without the pathological sequelae of the hyperinflammatory reaction. These findings are discussed in the contexts of mechanism and clinical relevance. PMID:8478052

  7. Multiple myeloma presenting with bilateral ankle pain (microangiopathy) and complicated by streptococcal meningitis and Pneumocystis carinii pneumonia.

    PubMed

    Dunphy, Louise; Singh, Neeraj; Keating, Elizabeth

    2017-02-07

    Multiple myeloma is characterised by the neoplastic proliferation of a single clone of plasma cells producing a monoclonal immunoglobulin. This clone of plasma cells proliferates in the bone marrow, resulting in extensive skeletal destruction with osteolytic lesions, osteopenia and pathological fractures. Additional disease-related complications include hypercalcaemia, renal insufficiency, anaemia and infection. We present the case of a 64-year-old woman presenting with rapid onset, painful distal symmetrical lower limb weakness and an acute kidney injury. Owing to her IgG κ paraprotein (kappa light chain 4620, kappa:lambda ratio 826), she was diagnosed with probable plasma cell myeloma. This diagnosis was confirmed following a trephine biopsy. She required renal replacement therapy, inotropic support and a percutaneous tracheostomy. She became acutely confused with a Glasgow Coma Scale score of 10/15 and a CT head showed no acute pathology. Further investigation with a lumbar puncture confirmed the diagnosis of streptococcal meningitis. She was treated with intravenous acyclovir, ceftriaxone and fluconazole. Her non-bronchoalveolar lavage revealed a diagnosis of Pneumocystis carinii pneumonia and she required treatment with co-trimoxazole. This case report discusses the clinical presentation, diagnostic algorithm and treatment of myeloma. This manuscript offers an important clinical reminder to consider myeloma in the differential diagnosis in patients presenting with bone pain and acute kidney injury.

  8. Evaluation of a new commercial real-time PCR assay for diagnosis of Pneumocystis jirovecii pneumonia and identification of dihydropteroate synthase (DHPS) mutations.

    PubMed

    Montesinos, Isabel; Delforge, Marie-Luce; Ajjaham, Farida; Brancart, Françoise; Hites, Maya; Jacobs, Frederique; Denis, Olivier

    2017-01-01

    The PneumoGenius® real-time PCR assay is a new commercial multiplex real-time PCR method, which detects the Pneumocystis mitochondrial ribosomal large subunit (mtLSU) and two dihydropteroate synthase (DHPS) point mutations. To evaluate the clinical performance of this new real-time PCR assay we tested 120 extracted DNA samples from bronchoalveolar lavage specimens. These set of extracted DNA samples had already tested positive for Pneumocystis and patients had been classified in probable and unlikely PCP in a previous study. To evaluate de accuracy of the DHPS mutant's identification, an "in house" PCR and sequencing was performed. The sensitivity and specificity of PneumoGenius® PCR in discriminating between probable and unlikely Pneumocystis pneumonia (PCP) were 70% and 82% respectively. PneumoGenius® PCR was able to genotype more samples than "in house" DHPS PCR and sequencing. The same DHPS mutations were observed by both methods in four patients: two patients with a single mutation in position 171 (Pro57Ser) and two patients with a double mutation in position 165 (Thr55Ala) and in position 171 (Pro57Ser). A low rate of P. jirovecii (4.5%) harboring DHPS mutations was found, comparable to rates observed in other European countries. The PneumoGenius® real-time PCR is a suitable real-time PCR for PCP diagnosis and detection of DHPS mutants. The added value of DHPS mutation identification can assist in understanding the role of these mutations in prophylaxis failure or treatment outcome.

  9. Characterization of Pneumocystis carinii PHR1, a pH-regulated gene important for cell wall Integrity.

    PubMed

    Kottom, T J; Thomas, C F; Limper, A H

    2001-12-01

    Pneumocystis carinii remains an important opportunistic fungal pathogen causing life-threatening pneumonia in patients with AIDS and malignancy. Currently, little is known about how the organism adapts to environmental stresses and maintains its cellular integrity. We recently discovered an open reading frame approximately 600 bp downstream of the region coding GSC-1, a gene mediating beta-glucan cell wall synthesis in P. carinii. The predicted amino acid sequence of this new gene, termed P. carinii PHR1, exhibited 38% homology to Saccharomyces cerevisiae GAS1, a glycosylphosphatidylinositol-anchored protein essential to maintaining cell wall integrity, and 37% homology to Candida albicans PHR1/PHR2, pH-responsive genes encoding proteins recently implicated in cross-linking beta-1,3- and beta-1,6-glucans. In view of its homology to these related fungal genes, the pH-dependent expression of P. carinii PHR1 was examined. As in C. albicans, P. carinii PHR1 expression was repressed under acidic conditions but induced at neutral and more alkaline pH. PHR1-related proteins have been implicated in glucan cell wall stability under various environmental conditions. Although difficulties with P. carinii culture and transformation have traditionally limited assessment of gene function in the organism itself, we have successfully used heterologous expression of P. carinii genes in related fungi to address functional correlates of P. carinii-encoded proteins. Therefore, the potential role of P. carinii PHR1 in cell wall integrity was examined by assessing its ability to rescue an S. cerevisiae gas1 mutant with absent endogenous Phr1p-like activity. Interestingly, P. carinii PHR1 DNA successfully restored proliferation of S. cerevisiae gas1 mutants under lethal conditions of cell wall stress. These results indicate that P. carinii PHR1 encodes a protein responsive to environmental pH and capable of mediating fungal cell wall integrity.

  10. Effects of steroidal allenic phosphonic acid derivatives on the parasitic protists Leishmania donovani, Leishmania mexicana mexicana, and Pneumocystis carinii carinii.

    PubMed Central

    Beach, D H; Chen, F; Cushion, M T; Macomber, R S; Krudy, G A; Wyder, M A; Kaneshiro, E S

    1997-01-01

    Several pathogenic fungi and protozoa are known to have sterols distinct from those of their mammalian hosts. Of particular interest as targets for drug development are the biosyntheses of the sterols of important parasites such as the kinetoplastid flagellates and the AIDS-associated opportunistic protist Pneumocystis carinii. These pathogens synthesize sterols with an alkyl group at C-24, and some have a double bond at C-22 of the side chain. Humans and other mammalian hosts are incapable of C-24 alkylation and C-22 desaturation. In the present study, three steroidal compounds with side chains substituted by phosphonyl-linked groups were synthesized and tested for their effects on Leishmania donovani and L. mexicana mexicana culture growth. The compounds inhibited organism proliferation at concentrations in micrograms per milliliter. The most potent inhibitors of this group of compounds were characterized by two ethyl groups at the phosphate function. Leishmania organisms treated with 17-[2-(diethylphosphonato) ethylidienyl]3-methoxy-19-norpregna-1,3,5-triene exhibited reduced growth after transfer into inhibitor-free medium. Because there are currently no axenic methods available for the continuous subcultivation of P. carinii, the effects of these drugs on this organism were evaluated by two alternative screening methods. The same two diethyl phosphonosteroid compounds that inhibited Leishmania proliferation were also the most active against P. carinii as determined by the potent effect they had on reducing cellular ATP content. Cystic as well as trophic forms responded to the drug treatments, as evaluated by a dual fluorescent staining live-dead assay. Other modifications of steroidal phosphonates may lead to the development of related drugs with increased activity and specificity for the pathogens. PMID:8980773

  11. Development of a Rapid Real-Time PCR Assay for Quantitation of Pneumocystis carinii f. sp. carinii

    PubMed Central

    Larsen, Hans Henrik; Kovacs, Joseph A.; Stock, Frida; Vestereng, Vibeke H.; Lundgren, Bettina; Fischer, Steven H.; Gill, Vee J.

    2002-01-01

    A method for reliable quantification of Pneumocystis carinii in research models of P. carinii pneumonia (PCP) that is more convenient and reproducible than microscopic enumeration of organisms would greatly facilitate investigations of this organism. We developed a rapid quantitative touchdown (QTD) PCR assay for detecting P. carinii f. sp. carinii, the subspecies of P. carinii commonly used in research models of PCP. The assay was based on the single-copy dihydrofolate reductase gene and was able to detect <5 copies of a plasmid standard per tube. It was reproducibly quantitative (r = 0.99) over 6 log values for standards containing ≥5 copies/tube. Application of the assay to a series of 10-fold dilutions of P. carinii organisms isolated from rat lung demonstrated that it was reproducibly quantitative over 5 log values (r = 0.99). The assay was applied to a recently reported in vitro axenic cultivation system for P. carinii and confirmed our microscopy findings that no organism multiplication had occurred during culture. For all cultures analyzed, QTD PCR assays showed a decrease in P. carinii DNA that exceeded the expected decrease due to dilution of the inoculum upon transfer. In conclusion, a rapid, sensitive, and reproducible quantitative PCR assay for P. carinii f. sp. carinii has been developed and is applicable to in vivo as well as in vitro systems. The assay should prove useful for conducting studies in which quantification of organism burden or growth assessment is critical, such as in vitro antimicrobic susceptibility testing or in vivo immunopathological experiments. PMID:12149363

  12. Multicentre study highlighting clinical relevance of new high-throughput methodologies in molecular epidemiology of Pneumocystis jirovecii pneumonia.

    PubMed

    Esteves, F; de Sousa, B; Calderón, E J; Huang, L; Badura, R; Maltez, F; Bassat, Q; de Armas, Y; Antunes, F; Matos, O

    2016-06-01

    Pneumocystis jirovecii causes severe interstitial pneumonia (PcP) in immunosuppressed patients. This multicentre study assessed the distribution frequencies of epidemiologically relevant genetic markers of P. jirovecii in different geographic populations from Portugal, the USA, Spain, Cuba and Mozambique, and the relationship between the molecular data and the geographical and clinical information, based on a multifactorial approach. The high-throughput typing strategy for P. jirovecii characterization consisted of DNA pooling using quantitative real-time PCR followed by multiplex-PCR/single base extension. The frequencies of relevant P. jirovecii single nucleotide polymorphisms (mt85, SOD110, SOD215, DHFR312, DHPS165 and DHPS171) encoded at four loci were estimated in ten DNA pooled samples representing a total of 182 individual samples. Putative multilocus genotypes of P. jirovecii were shown to be clustered due to geographic differences but were also dependent on clinical characteristics of the populations studied. The haplotype DHFR312T/SOD110C/SOD215T was associated with severe AIDS-related PcP and high P. jirovecii burdens. The frequencies of this genetic variant of P. jirovecii were significantly higher in patients with AIDS-related PcP from Portugal and the USA than in the colonized patients from Portugal, and Spain, and children infected with P. jirovecii from Cuba or Mozambique, highlighting the importance of this haplotype, apparently associated with the severity of the disease and specific clinical groups. Patients from the USA and Mozambique showed higher rates of DHPS mutants, which may suggest the circulation of P. jirovecii organisms potentially related with trimethoprim-sulfamethoxazole resistance in those geographical regions. This report assessed the worldwide distribution of P. jirovecii haplotypes and their epidemiological impact in distinct geographic and clinical populations.

  13. Diagnosis of Pneumocystis jirovecii Pneumonia in Immunocompromised Patients by Real-Time PCR: a 4-Year Prospective Study

    PubMed Central

    Belaz, Sorya; Revest, Matthieu; Tattevin, Pierre; Jouneau, Stéphane; Decaux, Olivier; Chevrier, Sylviane; Le Tulzo, Yves; Gangneux, Jean-Pierre

    2014-01-01

    Pneumocystis jirovecii pneumonia (PCP) is a life-threatening infection in immunocompromised patients. Quantitative real-time PCR (qPCR) is more sensitive than microscopic examination for the detection of P. jirovecii but also detects colonized patients. Hence, its positive predictive value (PPV) needs evaluation. In this 4-year prospective observational study, all immunocompromised patients with acute respiratory symptoms who were investigated for PCP were included, totaling 659 patients (814 bronchoalveolar lavage fluid samples). Patients with negative microscopy but positive qPCR were classified through medical chart review as having retained PCP, possible PCP, or colonization, and their clinical outcomes were compared to those of patients with microscopically proven PCP. Overall, 119 patients were included for analysis, of whom 35, 41, and 43 were classified as having retained PCP, possible PCP, and colonization, respectively. The 35 patients with retained PCP had clinical findings similar to those with microscopically proven PCP but lower fungal loads (P < 0.001) and were mainly non-HIV-infected patients (P < 0.05). Although the mean amplification threshold was higher in colonized patients, it was not possible to determine a discriminant qPCR cutoff. The PPV of qPCR in patients with negative microscopy were 29.4% and 63.8% when considering retained PCP and retained plus possible PCP, respectively. Patients with possible PCP had a higher mortality rate than patients with retained PCP or colonization (63% versus 3% and 16%, respectively); patients who died had not received co-trimoxazole. In conclusion, qPCR is a useful tool to diagnose PCP in non-HIV patients, and treatment might be better targeted through a multicomponent algorithm including both clinical/radiological parameters and qPCR results. PMID:25009050

  14. Clinical Course, Radiological Manifestations, and Outcome of Pneumocystis jirovecii Pneumonia in HIV Patients and Renal Transplant Recipients

    PubMed Central

    Rauch, Andri; Furrer, Hansjakob; Cusini, Alexia; Meyer, Andreas M. J.; Weiler, Stefan; Huynh-Do, Uyen; Heverhagen, Johannes; Arampatzis, Spyridon; Christe, Andreas

    2016-01-01

    Background Pneumocystis jirovecii pneumonia (PCP) is a frequent opportunistic infection in immunocompromised patients. In literature, presentation and outcome of PCP differs between patients with human immunodeficiency virus (HIV) infection and renal transplant recipients (RTRs). Methods We conducted a cross-sectional study of patients with PCP based on the HIV and renal transplant registries at our institution. Radiological and clinical data from all confirmed PCP cases between 2005 and 2012 were compared. Results Forty patients were included: 16 with HIV and 24 RTRs. Radiologically, HIV patients had significantly more areas of diffuse lung affection (81% HIV vs. 25% RTR; p = 0.02), more ground glass nodules 5–10 mm (69% vs. 4%; p = <0.001) and enlarged hilar lymph nodes were found only in HIV patients (44%). Cough and dyspnea were the most common clinical signs (>80%) in both groups. Duration from illness onset to hospital presentation was longer in the HIV patients (median of 18 vs. 10 days (p = 0.02)), implying a less fulminant clinical course. Sixty percent of PCP cases in RTRs occurred >12 months after transplantation. Lengths of hospitalization, admission rates to the intensive care unit, and requirements for mechanical ventilation were similar. Outcome in both groups was favourable. Conclusions While important differences in radiological presentation of PCP between HIV patients and RTRs were found, clinical presentation was similar. PCP only rarely presented with fulminant respiratory symptoms requiring ICU admission, with similar results and outcomes for HIV patients and RTRs. Early diagnosis and treatment is mandatory for clinical success. PMID:27824870

  15. Comparison of a commercial real-time PCR assay, RealCycler® PJIR kit, progenie molecular, to an in-house real-time PCR assay for the diagnosis of Pneumocystis jirovecii infections.

    PubMed

    Guillaud-Saumur, Thibaud; Nevez, Gilles; Bazire, Amélie; Virmaux, Michèle; Papon, Nicolas; Le Gal, Solène

    2017-04-01

    We compared the RealCycler® PJIR kit (Progenie Molecular), available in Europe, to an in-house real-time PCR assay for the diagnosis of Pneumocystis jirovecii infections. Excellent agreement was found (concordance rate, 97.4%; Cohen's kappa, 0.918>0.8) showing that this commercial assay represents an alternative method for the diagnosis of P. jirovecii infections.

  16. Epidemiological Outbreaks of Pneumocystis jirovecii Pneumonia Are Not Limited to Kidney Transplant Recipients: Genotyping Confirms Common Source of Transmission in a Liver Transplantation Unit

    PubMed Central

    Dominique, Manon; Morio, Florent; Thepault, Rose-Anne; Franck-Martel, Claire; Tellier, Anne-Charlotte; Ferrandière, Martine; Hennequin, Christophe; Bernard, Louis; Salamé, Ephrem; Bailly, Éric; Chandenier, Jacques

    2016-01-01

    Over a 5-month period, four liver transplant patients at a single hospital were diagnosed with Pneumocystis jirovecii pneumonia (PCP). This unusually high incidence was investigated using molecular genotyping. Bronchoalveolar lavage fluids (BALF) obtained from the four liver recipients diagnosed with PCP were processed for multilocus sequence typing (MLST) at three loci (SOD, mt26s, and CYB). Twenty-four other BALF samples, which were positive for P. jirovecii and collected from 24 epidemiologically unrelated patients with clinical signs of PCP, were studied in parallel by use of the same method. Pneumocystis jirovecii isolates from the four liver recipients all had the same genotype, which was different from those of the isolates from all the epidemiologically unrelated individuals studied. These findings supported the hypothesis of a common source of contamination or even cross-transmission of a single P. jirovecii clone between the four liver recipients. Hospitalization mapping showed several possible encounters between these four patients, including outpatient consultations on one particular date when they all possibly met. This study demonstrates the value of molecular genotyping of P. jirovecii isolated from clinical samples for epidemiological investigation of PCP outbreaks. It is also the first description of a common source of exposure to a single P. jirovecii clone between liver transplant recipients and highlights the importance of prophylaxis in such a population. PMID:26935726

  17. Dihydropteroate synthase mutations in Pneumocystis pneumonia: impact of applying different definitions of prophylaxis, mortality endpoints and mutant in a single cohort.

    PubMed

    Yoon, Christina; Subramanian, Anuradha; Chi, Amy; Crothers, Kristina; Meshnick, Steven R; Taylor, Steve M; Beard, Charles B; Jarlsberg, Leah G; Lawrence, Gena G; Avery, Melissa; Swartzman, Alexandra; Fong, Serena; Roth, Brenna; Huang, Laurence

    2013-08-01

    Pneumocystis jirovecii dihydropteroate synthase (DHPS) gene mutations are well-reported. Although sulfa prophylaxis generally is associated with DHPS mutant infection, whether mutant infection is associated with poorer clinical outcomes is less clear. The differing definitions of sulfa prophylaxis and the different mortality endpoints used in these studies may be one explanation for the conflicting study results. Applying different definitions of prophylaxis, mortality endpoints and DHPS mutant to 301 HIV-infected patients with Pneumocystis pneumonia, we demonstrate that prophylaxis, irrespective of definition, increased the risk of infection with pure mutant (any prophylaxis: AOR 4.00, 95% CI: 1.83-8.76, P < 0.001) but not mixed genotypes (any prophylaxis: AOR 0.78, 95% CI: 0.26-2.36, P = 0.65). However, infection with mutant DHPS, irrespective of definition, was not associated with increased mortality (all-cause or PCP death) at the three time-intervals examined (all P > 0.05). Future studies should standardize key variables associated with DHPS mutant infection as well as examine DHPS mutant subtypes (pure mutant vs. mixed infections) - perhaps even individual DHPS mutant genotypes - so that data can be pooled to better address this issue.

  18. Effect of transcription factor GATA-2 on phagocytic activity of alveolar macrophages from Pneumocystis carinii-infected hosts.

    PubMed

    Lasbury, Mark E; Tang, Xing; Durant, Pamela J; Lee, Chao-Hung

    2003-09-01

    Alveolar macrophages from Pneumocystis carinii-infected hosts are defective in phagocytosis (W. Chen, J. W. Mills, and A. G. Harmsen, Int. J. Exp. Pathol. 73:709-720, 1992; H. Koziel et al., J. Clin. Investig. 102:1332-1344, 1998). Experiments were performed to determine whether this defect is specific for P. carinii organisms. The results showed that these macrophages were unable to phagocytose both P. carinii organisms and fluorescein isothiocyanate (FITC)-conjugated latex beads, indicating that alveolar macrophages from P. carinii-infected hosts have a general defect in phagocytosis. To determine whether this defect correlates with the recently discovered down-regulation of the GATA-2 transcription factor gene during P. carinii infection, alveolar macrophages from dexamethasone-suppressed or healthy rats were treated with anti-GATA-2 oligonucleotides and then assayed for phagocytosis. Aliquots of the alveolar macrophages were also treated with the sense oligonucleotides as the control. Cells treated with the antisense oligonucleotides were found to have a 46% reduction in phagocytosis of P. carinii organisms and a 65% reduction in phagocytosis of FITC-latex beads compared to those treated with the sense oligonucleotides. To determine whether the defect in phagocytosis in alveolar macrophages from P. carinii-infected hosts can be corrected by overexpression of GATA-2, a plasmid containing the rat GATA-2 gene in the sense orientation driven by the cytomegalovirus (CMV) promoter was introduced into alveolar macrophages from P. carinii-infected rats. Aliquots of the same cells transfected with a plasmid containing GATA-2 in the antisense orientation relative to the CMV promoter served as the control. Alveolar macrophages treated with the sense GATA-2 expression construct were found to increase their phagocytic activity by 66% in phagocytosis of P. carinii organisms and by 280% in phagocytosis of FITC-latex beads compared to those that received the antisense GATA-2

  19. Efficacy of caspofungin, a 1,3-β-D-glucan synthase inhibitor, on Pneumocystis carinii pneumonia in rats.

    PubMed

    Sun, Peipei; Tong, Zhaohui

    2014-11-01

    Pneumocystis carinii pneumonia (PcP) is a common and potentially fatal opportunistic infection in immunosuppressed patients, and the standard trimethoprim-sulfamethoxazole (TMP-SMZ) treatment has serious side effects. The cell wall of the causative fungal pathogen is enriched in 1-3-β-D-glucan, providing an alternative therapeutic target. We directly compared the efficacy of the 1,3-β-D-glucan synthase inhibitor caspofungin to TMP-SMZ for promoting survival and reducing lung cyst number during the early phase of treatment in a rat model of PcP. Rats were immunosuppressed using dexamethasone for 8 weeks and PcP infection confirmed in test animals by lung print smear. The remaining rats were randomly divided into three control groups, a baseline group and two observed for 7 or 14 days, two caspofungin groups treated intravenously for 7 or 14 days (1 mg/kg/d), and 2 TMP-SMZ positive control groups treated by oral gavage for 7 or 14 days (300 mg/kg/d). Mortality was markedly reduced by both caspofungin and TMP-SMZ after 14 days (caspofungin: 20.0%, TMP-SMZ: 13.3%, Control: 40.0%). Body weight gain in caspofungin-treated rats after 7 (3.04 ± 3.54%) and 14 (4.27 ± 2.79%) days was similar to that in TMP-SMZ-treated rats (3.35 ± 1.88% and 5.85 ± 2.78%, respectively), whereas untreated controls showed weight loss. Lung weight to body weight ratio, and mean cyst number per 50 microscopic fields were significantly lower (all P < 0.05) in caspofungin-treated rats than untreated controls at both 7 and 14 days, and similar to those in the TMP-SMZ-treated rats (all P > 0.05 vs. caspofungin). Caspofungin exhibited similar efficacy to TMP-SMZ for enhancing survival and reducing lung edema and cyst load in a rat model of PcP, suggesting potential clinical utility against PcP.

  20. Clinical significance of quantifying Pneumocystis jirovecii DNA by using real-time PCR in bronchoalveolar lavage fluid from immunocompromised patients.

    PubMed

    Botterel, Françoise; Cabaret, Odile; Foulet, Françoise; Cordonnier, Catherine; Costa, Jean-Marc; Bretagne, Stéphane

    2012-02-01

    Quantitative PCR (qPCR) is more sensitive than microscopy for detecting Pneumocystis jirovecii in bronchoalveolar lavage (BAL) fluid. We therefore developed a qPCR assay and compared the results with those of a routine immunofluorescence assay (IFA) and clinical data. The assay included automated DNA extraction, amplification of the mitochondrial large-subunit rRNA gene and an internal control, and quantification of copy numbers with the help of a plasmid clone. We studied 353 consecutive BAL fluids obtained for investigation of unexplained fever and/or pneumonia in 287 immunocompromised patients. No qPCR inhibition was observed. Seventeen (5%) samples were both IFA and qPCR positive, 63 (18%) were IFA negative and qPCR positive, and 273 (77%) were both IFA and qPCR negative. The copy number was significantly higher for IFA-positive/qPCR-positive samples than for IFA-negative/qPCR-positive samples (4.2 ± 1.2 versus 1.1 ± 1.1 log(10) copies/μl; P < 10(-4)). With IFA as the standard, the qPCR assay sensitivity was 100% for ≥2.6 log(10) copies/μl and the specificity was 100% for ≥4 log(10) copies/μl. Since qPCR results were not available at the time of decision-making, these findings did not trigger cotrimoxazole therapy. Patients with systemic inflammatory diseases and IFA-negative/qPCR-positive BAL fluid had a worse 1-year survival rate than those with IFA-negative/qPCR-negative results (P < 10(-3)), in contrast with solid-organ transplant recipients (P = 0.88) and patients with hematological malignancy (P = 0.26). Quantifying P. jirovecii DNA in BAL fluids independently of IFA positivity should be incorporated into the investigation of pneumonia in immunocompromised patients. The relevant threshold remains to be determined and may vary according to the underlying disease.

  1. Detection of Pneumocystis carinii and characterization of mutations associated with sulfa resistance in bronchoalveolar lavage samples from human immunodeficiency virus-infected subjects.

    PubMed

    Zingale, Anna; Carrera, Paola; Lazzarin, Adriano; Scarpellini, Paolo

    2003-06-01

    One hundred ninety-four bronchoalveolar specimens were evaluated by microscopic examination and by amplification of a sequence of a Pneumocystis carinii dihidropteroate synthase gene for identification of mutations linked to sulfa resistance. PCR sensitivity and specificity were 100 and 86.7%, respectively, compared to results of microscopic examination. However, 7 out of 19 microscopy-negative, PCR-positive samples were collected from subjects with a clinically high probability of P. carinii pneumonia, suggesting that PCR may be more sensitive than microscopic examination, although the absolute performance of PCR cannot be determined. Mutations were identified in 28 out of 70 (40%) PCR-positive specimens and were significantly more common in patients exposed to sulfa drugs (21 out of 29 [72.4%]) than in those not exposed to sulfa drugs (4 out of 35 [11.4%]).

  2. [Comparison of the methenamine silver staining, direct fluorescent antibody and nested-polymerase chain reaction methods in the diagnosis of Pneumocystis carinii pneumonia].

    PubMed

    Güneş, Ilkay; Kalkanci, Ayşe; Kuştimur, Semra; Ergüven, Sibel; Ozet, Gülsüm; Ekim, Numan

    2004-01-01

    Pneumocystis carinii is one of the most common causative agents of pneumonia in immunocompromised patients, but the problems in the laboratory diagnosis of the disease frequently leads to diagnosis according to the response to medical treatment. In this study, the presence of P. carinii was investigated in immunocompromised patients who were presenting with the clinical symptoms of atypical pneumonia, by Gomori methenamine silver staining (GMS), direct fluorescent antibody (DFA) test and nested-polymerase chain reaction (nPCR) methods. Fifty-three samples of 49 patients were included in the study. Twelve of the samples (22.6%) were found to be positive by nPCR, 6 of them (11.3%) were found to be positive by DFA, while only one of them (1.8%) was positive by GMS staining method. As a result, for the appropriate treatment and prophylaxis of P. carinii infections, PCR which is a rapid and reliable diagnostic test should be used for diagnosis.

  3. Sterols of Saccharomyces cerevisiae erg6 Knockout Mutant Expressing the Pneumocystis carinii S-Adenosylmethionine:Sterol C-24 Methyltransferase (SAM:SMT)

    PubMed Central

    Kaneshiro, Edna S.; Johnston, Laura Q.; Nkinin, Stephenson W.; Romero, Becky I.; Giner, José-Luis

    2014-01-01

    The AIDS-associated lung pathogen Pneumocystis is classified as a fungus although Pneumocystis has several distinct features such as the absence of ergosterol, the major sterol of most fungi. The P. carinii S-adenosylmethionine:sterol C24-methyltransferase (SAM:SMT) enzyme, coded by the erg6 gene, transfers either one or two methyl groups to the C-24 position of the sterol side chain producing both C28 and C29 24-alkylsterols in approximately the same proportions whereas most fungal SAM:SMT transfer only one methyl group to the side chain. The sterol compositions of wild type Sacchromyces cerevisiae, the erg6 knockout mutant (Δerg6), and Δerg6 expressing the P. carinii or the S. cerevisiae erg6 gene were analyzed by a variety of chromatographic and spectroscopic procedures to examine functional complementation in the yeast expression system. Detailed sterol analyses were obtained using high performance liquid chromatography (HPLC) and proton nuclear magnetic resonance spectroscopy (1H-NMR). The P. carinii SAM:SMT in the Δerg6 restored its ability to produce the C28 sterol ergosterol as the major sterol, and also resulted in low levels of C29 sterols. This indicates that while the P. carinii SAM:SMT in the yeast Δerg6 cells was able to transfer a second methyl group to the side chain, the action of Δ24(28)-sterol reductase (coded by the erg4 gene) in the yeast cells prevented the formation and accumulation of as many C29 sterols as that found in P. carinii. PMID:25230683

  4. 2,4-Diamino-6,7-dihydro-5H-cyclopenta[d]pyrimidine analogues of trimethoprim as inhibitors of Pneumocystis carinii and Toxoplasma gondii dihydrofolate reductase.

    PubMed

    Rosowsky, A; Papoulis, A T; Queener, S F

    1998-03-12

    Three previously unreported (R,S)-2,4-diamino-5-[(3,4,5-trimethoxyphenyl) alkyl]-6,7-dihydro-5H-cyclopenta[d]pyrimidines 15a-c were synthesized as analogues of trimethoprim (TMP) and were tested as inhibitors of Pneumocystis carinii, Toxoplasma gondii, and rat liver dihydrofolate reductase (DHFR). The length of the alkyl bridge between the cyclopenta[d]pyrimidine and trimethoxyphenyl moiety ranged from one in 15a to three carbons in 15c. The products were tested as competitive inhibitors of the reduction of dihydrofolate by Pneumocystis carinii, Toxoplasma gondii, and rat liver DHFR. Compounds 15a-c had IC50 values of > 32, 1.8 and 1.3 microM, respectively, against P. carinii DHFR, as compared to 12 microM for TMP. Against the T. gondii enzyme, 15a-c had IC50 values of 21, 0.14 and 0.14 microM, respectively, as compared to 2.7 microM for TMP. Inhibitors 15b and 15c with two- and three-carbon bridges were significantly more potent than 15a against all three enzymes. Unlike TMP, 15b and 15c were better inhibitors of the rat liver enzyme than of the microbial enzymes. The potency of 15b and 15c against rat liver DHFR was less than has been reported for the corresponding 6,7-dihydro-5H-cyclopenta[d]pyrimidines with a classical p-aminobenzoyl-L-glutamate side chain as inhibitors of bovine, murine, and human DHFR.

  5. Development and evaluation of a real-time PCR assay for detection of Pneumocystis jirovecii on the fully automated BD MAX platform.

    PubMed

    Dalpke, Alexander H; Hofko, Marjeta; Zimmermann, Stefan

    2013-07-01

    Pneumocystis jirovecii is an opportunistic pathogen in immunocompromised and AIDS patients. Detection by quantitative PCR is faster and more sensitive than microscopic diagnosis yet requires specific infrastructure. We adapted a real-time PCR amplifying the major surface glycoprotein (MSG) target from Pneumocystis jirovecii for use on the new BD MAX platform. The assay allowed fully automated DNA extraction and multiplex real-time PCR. The BD MAX assay was evaluated against manual DNA extraction and conventional real-time PCR. The BD MAX was used in the research mode running a multiplex PCR (MSG, internal control, and sample process control). The assay had a detection limit of 10 copies of an MSG-encoding plasmid per PCR that equated to 500 copies/ml in respiratory specimens. We observed accurate quantification of MSG targets over a 7- to 8-log range. Prealiquoting and sealing of the complete PCR reagents in conical tubes allowed easy and convenient handling of the BD MAX PCR. In a retrospective analysis of 54 positive samples, the BD MAX assay showed good quantitative correlation with the reference PCR method (R(2) = 0.82). Cross-contamination was not observed. Prospectively, 278 respiratory samples were analyzed by both molecular assays. The positivity rate overall was 18.3%. The BD MAX assay identified 46 positive samples, compared to 40 by the reference PCR. The BD MAX assay required liquefaction of highly viscous samples with dithiothreitol as the only manual step, thus offering advantages for timely availability of molecular-based detection assays.

  6. Pneumocystis Pneumonia (For Parents)

    MedlinePlus

    ... Growth & Development Infections Diseases & Conditions Pregnancy & Baby Nutrition & Fitness Emotions & Behavior School & Family Life First Aid & Safety ... the baby's chest muscles may begin to retract (pull in abnormally) with each breath. The child's lips, ...

  7. Dihydropteroate synthase gene mutation rates in Pneumocystis jirovecii strains obtained from Iranian HIV-positive and non-HIV-positive patients.

    PubMed

    Sheikholeslami, Maryam-Fatemeh; Sadraei, Javid; Farnia, Parisa; Forozandeh Moghadam, Mehdi; Emadikochak, Hamid

    2015-05-01

    The dihydropteroate sulfate (DHPS) gene is associated with resistance to sulfa/sulfone drugs in Pneumocystis jirovecii. We investigated the DHPS mutation rate in three groups of Iranian HIV-positive and HIV-negative patients by polymerase chain reaction-restricted fragment length polymorphism analysis. Furthermore, an association between P. jirovecii DHPS mutations and strain typing was investigated based on direct sequencing of internal transcribed spacer region 1 (ITS1) and ITS2. The overall P. jirovecii DHPS mutation rate was (5/34; 14.7%), the lowest rate identified was in HIV-positive patients (1/16; 6.25%) and the highest rate was in malignancies patients (3/11; 27.3%). A moderate rate of mutation was detected in chronic obstructive pulmonary disease (COPD) patients (1/7; 14.3%). Most of the isolates were wild type (29/34; 85.3%). Double mutations in DHPS were detected in patients with malignancies, whereas single mutations at codons 55 and 57 were identified in the HIV-positive and COPD patients, respectively. In this study, two new and rare haplotypes were identified with DHPS mutations. Additionally, a positive relationship between P. jirovecii strain genotypes and DHPS mutations was identified. In contrast, no DHPS mutations were detected in the predominant (Eg) haplotype. This should be regarded as a warning of an increasing incidence of drug-resistant P. jirovecii strains.

  8. Mutations in the dihydropteroate synthase gene of human-derived Pneumocystis carinii isolates from Italy are infrequent but correlate with prior sulfa prophylaxis.

    PubMed

    Ma, Liang; Kovacs, Joseph A; Cargnel, Antonietta; Valerio, Antonella; Fantoni, Giovanna; Atzori, Chiara

    2002-05-15

    Mutations in the human-derived Pneumocystis carinii dihydropteroate synthase (DHPS) gene have been reported with increasing frequency and have been linked to prior sulfa prophylaxis and possible emergence of sulfa resistance. This study was done to examine the prevalence and clinical significance of P. carinii DHPS mutations in Italian patients. A previously described single-strand conformation polymorphism technique was used to identify P. carinii DHPS mutations in 107 patients with acquired immunodeficiency syndrome. Overall prevalence (8%) was low compared with that in other reports. Mutations were observed in 19% (6/31) of patients exposed to sulfa prophylaxis, compared with 4% (3/76) of patients not exposed to sulfa prophylaxis (P=.017). No significant association was observed between the presence of DHPS mutations and mortality, CD4 cell count, or demographic factors. The study confirms the association between DHPS mutations and prior sulfa prophylaxis and shows that the prevalence of DHPS mutations in an Italian patient population is lower than that in other populations.

  9. Both immunity and hyperresponsiveness to Pneumocystis carinii result from transfer of CD4+ but not CD8+ T cells into severe combined immunodeficiency mice.

    PubMed

    Roths, J B; Sidman, C L

    1992-08-01

    The opportunistic pathogen Pneumocystis carinii (Pc) is considered to be the leading cause of morbidity in patients with AIDS. It is important, therefore, to determine the immunological mechanisms of resistance to Pc. We have taken advantage of the lack of both T and B lymphocytes in severe combined immunodeficiency (scid) mice to determine the critical factors in resistance to spontaneously acquired Pc pneumonia. Using adoptive transfer of unfractionated or fractionated lymphocyte subsets or hyperimmune serum from congenic normal donors, we have demonstrated that effective immunity to Pc results from the action of CD4+ but not CD8+ T cells (in the absence of antibody) or from humoral immunity (in the absence of T cells). However, responses of CD4+ T cells (but not antibody) to already well-established burdens of Pc are often accompanied by a fatal hyperinflammatory reaction. The activity of CD4+ T cells against Pc thus illustrates a broadly applicable principle that T cell immunity represents a critical balance between consequences beneficial and harmful to the host.

  10. Prophylaxis for Pneumocystis jiroveci pneumonia: is it a necessity in pulmonary patients on high-dose, chronic corticosteroid therapy without AIDS?

    PubMed

    Liebling, Maryjane; Rubio, Edmundo; Ie, Susanti

    2015-04-01

    The benefit of prophylaxis for Pneumocystis jirovecii pneumonia (PJP) is well documented in immunocompromised patients, particularly those with HIV and/or AIDS; therefore, guidelines dictate this as standard of care. However, there is a paucity of literature regarding those without HIV and/or AIDS who are potentially predisposed to PJP, including patients with sarcoidosis, cryptogenic organizing pneumonia, interstitial lung disease, asthma and chronic obstructive pulmonary disease, who may require high dose of prolonged corticosteroids for disease maintenance or to prevent relapses. In this review, the authors examine the available literature regarding prophylaxis in these groups, elaborate on the pathogenesis of PJP, when to suspect PJP in these patients, as well as explore current recommendations that guide clinical practice regarding implementation of PJP prophylaxis, namely with trimethoprim/sulfamethoxazole being the preferred agent. In summary, the role of PJP prophylaxis in non-HIV patients on chronic steroids remains controversial. The authors present a review of the literature to provide better guidance to the clinician regarding the need to initiate PJP prophylaxis in this patient population.

  11. A multiplex real-time PCR assay for identification of Pneumocystis jirovecii, Histoplasma capsulatum, and Cryptococcus neoformans/Cryptococcus gattii in samples from AIDS patients with opportunistic pneumonia.

    PubMed

    Gago, Sara; Esteban, Cristina; Valero, Clara; Zaragoza, Oscar; Puig de la Bellacasa, Jorge; Buitrago, María José

    2014-04-01

    A molecular diagnostic technique based on real-time PCR was developed for the simultaneous detection of three of the most frequent causative agents of fungal opportunistic pneumonia in AIDS patients: Pneumocystis jirovecii, Histoplasma capsulatum, and Cryptococcus neoformans/Cryptococcus gattii. This technique was tested in cultured strains and in clinical samples from HIV-positive patients. The methodology used involved species-specific molecular beacon probes targeted to the internal transcribed spacer regions of the rDNA. An internal control was also included in each assay. The multiplex real-time PCR assay was tested in 24 clinical strains and 43 clinical samples from AIDS patients with proven fungal infection. The technique developed showed high reproducibility (r(2) of >0.98) and specificity (100%). For H. capsulatum and Cryptococcus spp., the detection limits of the method were 20 and 2 fg of genomic DNA/20 μl reaction mixture, respectively, while for P. jirovecii the detection limit was 2.92 log10 copies/20 μl reaction mixture. The sensitivity in vitro was 100% for clinical strains and 90.7% for clinical samples. The assay was positive for 92.5% of the patients. For one of the patients with proven histoplasmosis, P. jirovecii was also detected in a bronchoalveolar lavage sample. No PCR inhibition was detected. This multiplex real-time PCR technique is fast, sensitive, and specific and may have clinical applications.

  12. Genotyping of Pneumocystis jirovecii isolates from Chinese HIV-infected patients based on nucleotide sequence variations in the internal transcribed spacer regions of rRNA genes.

    PubMed

    Li, Kai; He, Ai; Cai, Wei Ping; Tang, Xiao Ping; Zheng, Xiao Ying; Li, Zhuo Ya; Zhan, Xi Mei

    2013-01-01

    Genetic diversity of Pneumocystis jirovecii isolates based on internal transcribed spacer (ITS) of the nuclear rRNA locus has previously been reported. The information about ITS genotype and epidemiology of this organism in Chinese human immunodeficiency virus-infected patients has not been available. In this study, 12 bronchoalveolar lavage fluid specimens obtained from HIV-infected patients were analyzed by PCR followed by cloning, sequencing and typing. Three ITS1 genotypes (E, B and 'H') and four ITS2 genotypes (b, g, i and r) as previously reported were identified, the most common of which were E, b and i. Five ITS haplotypes (Eg, Eb, Bi, Er and 'H'r) and 19 new combination types were also identified with the most common types being Eg (four of 12 patients, 10 of 60 clones), Eb (three of 12 patients, 11 of 60 clones) and Bi (three of 12 patients, 10 of 60 clones). Nine patients were found to be co-infected with more than one ITS genotype of P. jirovecii. The prevalence of ITS genotypes in HIV patients from one Chinese hospital did not seem to be significantly different when compared to reports from other countries.

  13. Comparison of PCR and standard cytological staining for detection of Pneumocystis carinii from respiratory specimens from patients with or at high risk for infection by human immunodeficiency virus.

    PubMed Central

    Leibovitz, E; Pollack, H; Moore, T; Papellas, J; Gallo, L; Krasinski, K; Borkowsky, W

    1995-01-01

    The detection of Pneumocystis carinii DNA by PCR was compared with routine cytologic staining techniques (CYT). A total of 284 clinical respiratory specimens, including 137 bronchoalveolar lavage (BAL), 63 bronchoalveolar washing, 63 sputum, and 21 induced sputum samples, obtained from patients with or at high risk for human immunodeficiency virus infection were evaluated. Eighty specimens were positive by PCR, and 69 were positive by CYT. PCR was able to detect P. carinii in more bronchoalveolar washing specimens (15 versus 11) and in comparable BAL specimens (53 versus 54) compared with CYT. PCR was particularly more sensitive than CYT in detecting P. carinii in expectorated sputum (12 versus 4 samples). Of the 19 patients whose respiratory specimens were positive for P. carinii by PCR but negative by CYT, 5 had P. carinii pneumonia (PCP) confirmed by subsequent BAL and transbronchial or mediastinal lymph node biopsy and 9 had a clinical course highly suggestive of acute PCP. Eleven (58%) of the 19 patients with discordant PCR and CYT results had received prior anti-PCP prophylaxis. In this clinical setting in particular and in the evaluation of sputum specimens, the ability of PCR to detect a low parasitic load suggests that this technique may become an important additional tool, along with current cytological methods, for the detection of P. carinii. PMID:8576362

  14. Utility of /sup 67/Ga scintigraphy and bronchial washings in the diagnosis and treatment of Pneumocystis carinii pneumonia in patients with the acquired immune deficiency syndrome

    SciTech Connect

    Tuazon, C.U.; Delaney, M.D.; Simon, G.L.; Witorsch, P.; Varma, V.M.

    1985-11-01

    Twenty patients with the acquired immune deficiency syndrome (AIDS) and suspected Pneumocystis carinii pneumonia were evaluated by /sup 67/Ga scintigraphy and fiberoptic bronchoscopy for initial diagnosis and response to therapy. Lung uptake of /sup 67/Ga was demonstrated in 100% of AIDS patients with P. carinii pneumonia, including those with subclinical infection. Fiberoptic bronchoscopy identified P. carinii in the bronchial washings of 100% of cases (19 patients), whereas only 13 of 16 (81%) patients had P. carinii in lung tissue obtained by transbronchial biopsy. Repeat fiberoptic bronchoscopy was performed in 16 of 20 patients. After 2 to 4 wk of therapy, P. carinii was identified in bronchial washings in 8 of 16 (50%) patients and in transbronchial biopsy in 1 of 10 (10%) patients examined. Bronchial washing has a higher yield than transbronchial biopsy in demonstrating P. carinii in patients with AIDS and may evolve as the procedure of choice in such patients. Based on the clinical course and results of /sup 67/Ga scintigraphy and fiberoptic bronchoscopy in AIDS patients with P. carinii pneumonia, optimal therapy may require at least 3 wk of treatment.

  15. Pneumocysterol [(24Z)-ethylidenelanost-8-en-3beta-ol], a rare sterol detected in the opportunistic pathogen Pneumocystis carinii hominis: structural identity and chemical synthesis.

    PubMed

    Kaneshiro, E S; Amit, Z; Swonger, M M; Kreishman, G P; Brooks, E E; Kreishman, M; Jayasimhulu, K; Parish, E J; Sun, H; Kizito, S A; Beach, D H

    1999-01-05

    Pneumocystis carinii pneumonia (PcP) remains among the most prevalent opportunistic infections among AIDS patients. Currently, drugs used clinically for deep mycosis act by binding ergosterol or disrupting its biosynthesis. Although classified as a fungus, P. carinii lacks ergosterol. Instead, the pathogen synthesizes a number of distinct Delta7, 24-alkylsterols, despite the abundance of cholesterol, which it can scavenge from the lung alveolus. Thus, the pathogen-specific sterols appear vital for organism survival and proliferation. In the present study, high concentrations of a C32 sterol were found in human-derived P. carinii hominis. The definitive structural identities of two C-24 alkylated lanosterol compounds, previously not reported for rat-derived P. carinii carinii, were determined by using GLC, MS, and NMR spectroscopy together with the chemical syntheses of authentic standards. The C31 and C32 sterols were identified as euphorbol (24-methylenelanost-8-en-3beta-ol) and pneumocysterol [(24Z)-ethylidenelanost-8-en-3beta-ol], respectively. The identification of these and other 24-alkylsterols in P. carinii hominis suggests that (i) sterol C-24 methyltransferase activities are extraordinarily high in this organism, (ii) 24-alkylsterols are important components of the pathogen's membranes, because the addition of these side groups onto the sterol side chain requires substantial ATP equivalents, and (iii) the inefficacy of azole drugs against P. carinii can be explained by the ability of this organism to form 24-alkysterols before demethylation of the lanosterol nucleus. Because mammals cannot form 24-alkylsterols, their biosyntheses in P. carinii are attractive targets for the development of chemotherapeutic strategies against this opportunistic infection.

  16. 2,4-Diaminothieno[2,3-d]pyrimidine lipophilic antifolates as inhibitors of Pneumocystis carinii and Toxoplasma gondii dihydrofolate reductase.

    PubMed

    Rosowsky, A; Papoulis, A T; Queener, S F

    1997-10-24

    Ten previously unreported 2,4-diaminothieno[2,3-d]pyrimidine lipophilic dihydrofolate reductase inhibitors were synthesized as potential inhibitors of Pneumocystis carinii and Toxoplasma gondii dihydrofolate reductase. Pivaloylation of 2,4-diamino-5-methylthieno[2,3-d]pyrimidine followed by dibromination with N-bromosuccinimide in the presence of benzoyl peroxide gave 2,4-bis(pivaloylamino)-6-bromo-5-(bromomethyl)thieno[2,3-d]pyrimid ine, which after condensation with substituted anilines or N-methylanilines and deprotection with base yielded 2,4-diamino-6-bromo-5-[(substituted anilino)methyl]thieno[2,3-d]pyrimidines. Removal of the 6-bromo substituent was accomplished with sodium borohydride and palladium chloride. The reaction yields were generally good to excellent. The products were tested as inhibitors of dihydrofolate reductase (DHFR) from P. carinii, T. gondii, and rat liver. Although the IC50 could not be reached for the 6-unsubstituted compounds because of their extremely poor solubility, three of the five 6-bromo derivatives were soluble enough to allow the IC50 to be determined against all three enzymes. 2,4-Diamino-5-[3,5-dichloro-4-(1-pyrrolo)anilino]methyl]- 6-bromothieno[2,3-d]pyrimidine was the most active of the 6-bromo derivatives, with an IC50 of 7.5 microM against P. carinii DHFR, but showed no selectivity for either P. carinii or T. gondii DHFR relative to the enzyme from rat liver.

  17. Clinical Relevance of Multiple Single-Nucleotide Polymorphisms in Pneumocystis jirovecii Pneumonia: Development of a Multiplex PCR-Single-Base-Extension Methodology▿

    PubMed Central

    Esteves, F.; Gaspar, J.; De Sousa, B.; Antunes, F.; Mansinho, K.; Matos, O.

    2011-01-01

    Pneumocystis jirovecii pneumonia (PcP) is a major cause of respiratory illness in patients with AIDS. The identification of multiple single-nucleotide polymorphisms (SNPs) at three distinct P. jirovecii loci encoding dihydrofolate reductase (DHFR), mitochondrial large-subunit rRNA (mtLSU rRNA), and superoxide dismutase (SOD) was achieved using multiplex-PCR (MPCR) followed by direct sequencing and two single-base extension (SBE) techniques. Four SNPs (DHFR312, mt85, SOD215, and SOD110), correlated previously with parameters of disease, were amplified and genotyped simultaneously. The concordance of results between the standard sequencing technique (direct sequencing) and SBE analysis was 96.9% for the acrylamide gel electrophoresis and 98.4% for the capillary electrophoresis. The cross-genetic analysis established several statistical associations among the SNPs studied: mt85C-SOD110T, SOD110T-SOD215C, and SOD110C-SOD215T. These results were confirmed by cluster analysis. Data showed that among the isolates with low to moderate parasite burden, the highest percentages of DHFR312C, mt85C, SOD110T, and SOD215C were detected, whereas for high parasite burden cases the highest frequencies were observed among isolates with DHFR312T, mt85T, SOD110C, and SOD215T. The polymorphisms studied were shown to be suitable genetic targets potentially correlated with PcP clinical data that can be used as predictors of outcome in further studies to help clinical decision-making in the management of PcP. The MPCR/SBE protocol described for the first time in the present study was shown to be a rapid, highly accurate method for genotyping P. jirovecii SNPs encoded by different loci that could be used for epidemiological studies and as an additional procedure for the prognostic classification and diagnosis of PcP. PMID:21389160

  18. Plasma IL-6/IL-10 Ratio and IL-8, LDH, and HBDH Level Predict the Severity and the Risk of Death in AIDS Patients with Pneumocystis Pneumonia

    PubMed Central

    Sun, Jia; Su, Junwei; Xie, Yirui; Yin, Michael T.; Huang, Ying; Xu, Lijun; Zhou, Qihui

    2016-01-01

    Objective. To identify blood biomarkers to predict severity and mortality in AIDS PCP patients. Methods. Biomarkers including clinical parameters and plasma inflammatory cytokines were assessed in 32 HIV-infected patients with Pneumocystis pneumonia (PCP) at time of admission. Predictive value of the biomarkers for clinical severity and in-hospital mortality was evaluated by corresponding ROC curve. Results. Levels of CRP, WBC, LDH, HBDH, and Ferritin were significantly higher in the severe and nonsurvivor AIDS PCP patients. These important biochemical indicators have inverse correlation with oxygenation index, especially levels of LDH (P = 0.008, R2 = 0.258), HBDH (P = 0.001, R2 = 0.335), and Ferritin (P = 0.005, R2 = 0.237). Plasma IL-8 and IL-6 levels were significantly higher in patients with PaO2/FiO2 ≤ 200 mmHg and nonsurvivors than in those with PaO2/FiO2 > 200 mmHg and survivors. Severe and nonsurvival groups showed higher ratio of mean IL-6/IL-10 level (1.78 ± 1.56, P < 0.001; 1.11 ± 0.72, P = 0.043), larger AUC (95% CI 0.781–1.000, P < 0.001; 95% CI 0.592–0.917, P = 0.043), and more significantly inverse correlation with the oxygenation index. Conclusion. Plasma IL-8, LDH, and HBDH levels and IL-6/IL-10 ratio could be helpful for early evaluation of the severity and predicting fatal outcomes in AIDS PCP patients. PMID:27579328

  19. Preliminary in vitro studies on two potent, water-soluble trimethoprim analogues with exceptional species selectivity against dihydrofolate reductase from Pneumocystis carinii and Mycobacterium avium.

    PubMed

    Forsch, Ronald A; Queener, Sherry F; Rosowsky, Andre

    2004-04-05

    2,4-Diamino-5-[3',4'-dimethoxy-5'-(5-carboxy-1-pentynyl)]benzylpyrimidine (6) and 2,4-diamino-5-[3',4'-dimethoxy-5'-(4-carboxyphenylethynyl)benzylpyrimidine (7) were synthesized from 2,4-diamino-5-(5'-iodo-3',4'-dimethoxybenzyl)pyrimidine (9) via a Sonogashira reaction with appropriate acetylenic esters followed by saponification, and were tested as inhibitors of dihydrofolate reductase (DHFR) from Pneumocystis carinii (Pc), Toxoplasma gondii (Tg), Mycobacterium avium (Ma), and rat in comparison with the widely used antibacterial agent 2,4-diamino-5-(3',4',5'-trimethoxybenzyl)pyrimidine (trimethoprim, TMP). The selectivity index (SI) for each compound was calculated by dividing its 50% inhibitory concentration (IC(50)) against rat DHFR by its IC(50) against Pc, Tg, or Ma DHFR. The IC(50) of 6 against Pc DHFR was 1.0 nM, with an SI of 5000. Compound 7 had an IC(50) of 8.2 nM against Ma DHFR, with an SI of 11000. By comparison, the IC(50) of TMP was 12000 nM against Pc, 300 nM against Ma, and 180000 against rat DHFR. The potency and selectivity values of 6 and 7 were not as high against Tg as they were against Pc or Ma DHFR, but nonetheless exceeded those of TMP. Because of the outstanding selectivity of 6 against Pc and of 7 against Ma DHFR, these novel analogues may be viewed as promising leads for further structure-activity optimization.

  20. Plasma IL-6/IL-10 Ratio and IL-8, LDH, and HBDH Level Predict the Severity and the Risk of Death in AIDS Patients with Pneumocystis Pneumonia.

    PubMed

    Sun, Jia; Su, Junwei; Xie, Yirui; Yin, Michael T; Huang, Ying; Xu, Lijun; Zhou, Qihui; Zhu, Biao

    2016-01-01

    Objective. To identify blood biomarkers to predict severity and mortality in AIDS PCP patients. Methods. Biomarkers including clinical parameters and plasma inflammatory cytokines were assessed in 32 HIV-infected patients with Pneumocystis pneumonia (PCP) at time of admission. Predictive value of the biomarkers for clinical severity and in-hospital mortality was evaluated by corresponding ROC curve. Results. Levels of CRP, WBC, LDH, HBDH, and Ferritin were significantly higher in the severe and nonsurvivor AIDS PCP patients. These important biochemical indicators have inverse correlation with oxygenation index, especially levels of LDH (P = 0.008, R (2) = 0.258), HBDH (P = 0.001, R (2) = 0.335), and Ferritin (P = 0.005, R (2) = 0.237). Plasma IL-8 and IL-6 levels were significantly higher in patients with PaO2/FiO2 ≤ 200 mmHg and nonsurvivors than in those with PaO2/FiO2 > 200 mmHg and survivors. Severe and nonsurvival groups showed higher ratio of mean IL-6/IL-10 level (1.78 ± 1.56, P < 0.001; 1.11 ± 0.72, P = 0.043), larger AUC (95% CI 0.781-1.000, P < 0.001; 95% CI 0.592-0.917, P = 0.043), and more significantly inverse correlation with the oxygenation index. Conclusion. Plasma IL-8, LDH, and HBDH levels and IL-6/IL-10 ratio could be helpful for early evaluation of the severity and predicting fatal outcomes in AIDS PCP patients.

  1. Reduced binding and phagocytosis of Pneumocystis carinii by alveolar macrophages from persons infected with HIV-1 correlates with mannose receptor downregulation.

    PubMed Central

    Koziel, H; Eichbaum, Q; Kruskal, B A; Pinkston, P; Rogers, R A; Armstrong, M Y; Richards, F F; Rose, R M; Ezekowitz, R A

    1998-01-01

    The macrophage mannose receptor, a pattern recognition molecule and component of innate immunity, mediates binding and phagocytosis of Pneumocystis carinii and likely represents an important clearance mechanism in the lungs of immunocompetent hosts. The purpose of this study was to examine the ability of alveolar macrophages from HIV-infected individuals to bind and phagocytose P. carinii, and to investigate the role of the macrophage mannose receptor in mediating this interaction. Compared with healthy individuals, alveolar macrophage phagocytosis of P. carinii from HIV+ persons was reduced up to 74% (P = 0.02), primarily reflecting a reduction in the number of organisms associated with each macrophage (P = 0.019). Furthermore, macrophages from HIV+ individuals demonstrated up to an 80% (P < 0.05) reduction in mannose receptor surface expression and endocytosis. Mannose receptor affinity was unaltered, and mRNA levels were modestly reduced (P < 0.05). Cells from HIV+ individuals with CD4(+) counts < 200 cells/mm3 (representing individuals at high clinical risk for P. carinii pneumonia) demonstrated the lowest levels of P. carinii phagocytosis and mannose receptor endocytosis. In vitro HIV infection of alveolar macrophages from healthy individuals reduced mannose receptor endocytosis to 53.2% (P < 0.05) and P. carinii binding and phagocytosis to 67.4% (P < 0.05) of control. Our studies suggest that HIV infection may alter innate immunity in the lungs, and that impaired alveolar macrophage mannose receptor-mediated binding and phagocytosis of P. carinii may contribute to the susceptibility of HIV-infected individuals to this opportunistic pulmonary pathogen. PMID:9769325

  2. Correlation Between Pneumocystis jirovecii Mitochondrial Genotypes and High and Low Fungal Loads Assessed by Single Nucleotide Primer Extension Assay and Quantitative Real-Time PCR.

    PubMed

    Alanio, Alexandre; Olivi, Martine; Cabaret, Odile; Foulet, Françoise; Bellanger, Anne-Pauline; Millon, Laurence; Berceanu, Ana; Cordonnier, Catherine; Costa, Jean-Marc; Bretagne, Stéphane

    2015-01-01

    We designed a single nucleotide primer extension (SNaPshot) assay for Pneumocystis jirovecii genotyping, targeting mt85 SNP of the mitochondrial large subunit ribosomal RNA locus, to improve minority allele detection. We then analyzed 133 consecutive bronchoalveolar lavage (BAL) fluids tested positive for P. jirovecii DNA by quantitative real-time PCR, obtained from two hospitals in different locations (Hospital 1 [n = 95] and Hospital 2 [n = 38]). We detected three different alleles, either singly (mt85C: 39.1%; mt85T: 24.1%; mt85A: 9.8%) or together (27%), and an association between P. jirovecii mt85 genotype and the patient's place of hospitalization (p = 0.011). The lowest fungal loads (median = 0.82 × 10(3) copies/μl; range: 15-11 × 10(3) ) were associated with mt85A and the highest (median = 1.4 × 10(6) copies/μl; range: 17 × 10(3) -1.3 × 10(7) ) with mt85CTA (p = 0.010). The ratios of the various alleles differed between the 36 mixed-genotype samples. In tests of serial BALs (median: 20 d; range 4-525) from six patients with mixed genotypes, allele ratio changes were observed five times and genotype replacement once. Therefore, allele ratio changes seem more frequent than genotype replacement when using a SNaPshot assay more sensitive for detecting minority alleles than Sanger sequencing. Moreover, because microscopy detects only high fungal loads, the selection of microscopy-positive samples may miss genotypes associated with low loads.

  3. Diagnosis of pneumocystis pneumonia using serum (1-3)-β-D-Glucan: a bivariate meta-analysis and systematic review

    PubMed Central

    Li, Wei-Jie; Guo, Ya-Ling; Liu, Tang-Juan

    2015-01-01

    Background The (1-3)-β-D-Glucan (BG) assay has been approved for making a diagnosis of invasive fungal disease. However, the role of serum-BG assay for the diagnosis of pneumocystis pneumonia (PCP) is controversial, especially between patients with human immunodeficiency virus (HIV) and non-HIV. We conducted a meta-analysis to determine the difference of the overall accuracy of serum-BG assay for the diagnosis of PCP in immunocompromised patients with and without HIV. Methods After a systematic review of English-language studies and manual researching, sensitivity (Se), specificity (Sp), and other measures of accuracy of serum-BG for the diagnosis of PCP were pooled using random-effects models for bivariate meta-analysis. Summary receiver operating characteristic (SROC) curve was used to summarize overall test performance. Subgroup analyses were performed to explore the heterogeneity in Se and Sp. Results Thirteen studies met our inclusion criteria. The summary estimates for serum-BG assay for definite PCP were as follows: Se, 0.91 [95% confidence interval (CI), 0.88–0.93]; Sp, 0.75 (95% CI, 0.68–0.81). As for the patients with and without HIV, the Se and Sp were 0.92 and 0.78, 0.85 and 0.73, respectively. Significant heterogeneity between Se was presented (P=0.04). Conclusions Contrary to the results of the previous meta-analysis, a negative result of serum-BG determination is sufficient for ruling out PCP only in HIV cases. For non-HIV patients, the results should be interpreted in parallel with clinical and radiological findings. Besides, further prospective studies with larger sample size are needed to confirm the diagnosis strategy of BG detection. PMID:26793343

  4. Routine analysis of induced sputum is not an effective strategy for screening persons infected with human immunodeficiency virus for Mycobacterium tuberculosis or Pneumocystis carinii. Pulmonary Complications of HIV Infection Study Group.

    PubMed

    Kvale, P A; Hansen, N I; Markowitz, N; Rosen, M J; Jordan, M C; Meiselman, L; Glassroth, J; Reichman, L B; Wallace, J M; Stansell, J D

    1994-09-01

    A prospective multicenter cohort study comprising 1,171 individuals who were seropositive for human immunodeficiency virus (HIV) but did not have AIDS at the time of enrollment and 182 HIV-seronegative controls, was studied by means of routine induced-sputum analysis in an attempt to detect occult tuberculosis or Pneumocystis carinii pneumonia. One occult case of tuberculosis was discovered upon the patient's enrollment (at baseline); none were discovered during follow-up. Two additional Mycobacterium tuberculosis isolates were recovered (one at baseline, one during follow-up) from subjects with symptoms or abnormalities evident on chest roentgenograms. Three specimens were false-positive (one for M. tuberculosis, two for P. carinii). Five pathogenic nontuberculous mycobacteria isolates were recovered during follow-up. Nonpathogenic, nontuberculous mycobacteria were recovered from 51 (4.6%) of 1,113 baseline specimens and 56 (3.7%) of 1,518 follow-up specimens, primarily at a center where the water supply was contaminated. We conclude that routine induced-sputum analysis is not an effective strategy for screening HIV-infected asymptomatic subjects for tuberculosis or P. carinii pneumonia before the onset of clinically recognizable disease activity.

  5. Primary prophylaxis of bacterial infections and Pneumocystis jirovecii pneumonia in patients with hematological malignancies and solid tumors : guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO).

    PubMed

    Neumann, S; Krause, S W; Maschmeyer, G; Schiel, X; von Lilienfeld-Toal, M

    2013-04-01

    Bacterial infections are the most common cause for treatment-related mortality in patients with neutropenia after chemotherapy. Here, we discuss the use of antibacterial prophylaxis against bacteria and Pneumocystis pneumonia (PCP) in neutropenic cancer patients and offer guidance towards the choice of drug. A literature search was performed to screen all articles published between September 2000 and January 2012 on antibiotic prophylaxis in neutropenic cancer patients. The authors assembled original reports and meta-analysis from the literature and drew conclusions, which were discussed and approved in a consensus conference of the Infectious Disease Working Party of the German Society of Hematology and Oncology (AGIHO). Antibacterial prophylaxis has led to a reduction of febrile events and infections. A significant reduction of overall mortality could only be shown in a meta-analysis. Fluoroquinolones are preferred for antibacterial and trimethoprim-sulfamethoxazole for PCP prophylaxis. Due to serious concerns about an increase of resistant pathogens, only patients at high risk of severe infections should be considered for antibiotic prophylaxis. Risk factors of individual patients and local resistance patterns must be taken into account. Risk factors, choice of drug for antibacterial and PCP prophylaxis and concerns regarding the use of prophylactic antibiotics are discussed in the review.

  6. An evaluation of the performance of the Dynamiker® Fungus (1-3)-β-D-Glucan Assay to assist in the diagnosis of invasive aspergillosis, invasive candidiasis and Pneumocystis pneumonia.

    PubMed

    White, P Lewis; Price, Jessica S; Posso, Raquel B; Barnes, Rosemary A

    2017-03-03

    Invasive fungal disease (IFD) can be caused by a range of pathogens. Conventional diagnosis has the capacity to detect most causes of IFD, but poor performance limits impact. The introduction of non-culture diagnostics, including the detection of (1-3)-β-D-Glucan (BDG), has shown promising performance for the detection of IFD in variety of clinical settings. Recently, the Dynamiker® Fungus (1-3)-β-D-Glucan assay (D-BDG) was released as an IFD diagnostic test. This article describes an evaluation of the D-BDG assay for the diagnosis of invasive aspergillosis (IA), invasive candidiasis (IC) and Pneumocystis pneumonia (PCP) across several high-risk patient cohorts and provides comparative data with the Associates of Cape Cod Fungitell® and BioRad Platelia™ Aspergillus Ag (GM) assays. There were 163 serum samples from 121 patients tested, from 21 probable IA cases, 28 proven IC cases, six probable PCP cases, one probable IFD case, 14 possible IFD cases and 64 control patients. For proven/probable IFD the mean BDG concentration was 209pg/ml, significantly greater than the control population (73pg/ml; P: <.0001). The sensitivity, specificity, and diagnostic odds ratio for proven/probable IFD was 81.4%, 78.1%, and 15.5, respectively. Significant BDG false positivity (9/13) was associated post abdominal surgery. D-BDG showed fair and good agreement with the Fungitell®, and GM assays, respectively. In conclusion, the D-BDG provides a useful adjunct test to aid the diagnosis of IFD, with technical flexibility that will assist laboratories processing low sample numbers. Further, large scale, prospective evaluation is required to confirm the clinical validity and determine clinical utility.

  7. Pneumocystis Infections: MedlinePlus Health Topic

    MedlinePlus

    ... with bilateral ankle pain (microangiopathy) and complicated... Article: Comparison of a commercial real-time PCR assay, RealCycler® ... the sharing features on this page, please enable JavaScript. About MedlinePlus Site Map FAQs Customer Support Get ...

  8. Updates on Aspergillus, Pneumocystis and other opportunistic pulmonary mycoses.

    PubMed

    Curbelo, Jose; Galván, Jose María; Aspa, Javier

    2015-12-01

    Mycoses are serious diseases with potentially fatal outcome. The introduction of immunosuppressive treatments and life support techniques has led to a growing prevalence of different degrees of immunosuppression. Compromised immune response is the primary risk factor for the development of opportunistic mycoses. Early diagnosis and treatment are crucial for improving prognosis. However, isolation in cultures or identification using antigen detection techniques cannot distinguish between colonization and invasive infection, and the clinical status of the patient often prevents biopsy sampling. Clinicians thus find themselves in an uncertain position, requiring them to quickly recognize clinical and radiological signs and interpret microbiological results in context. The aim of this review is to provide a general overview of the profile of patients susceptible to these infections, the role of the immune system and, in more detail, the major diagnostic developments that have gained most acceptance and recognition among the scientific community.

  9. The changing face of Pneumocystis carinii pneumonia in AIDS patients.

    PubMed

    Boiselle, P M; Crans, C A; Kaplan, M A

    1999-05-01

    The classic presentation of PCP is a bilateral interstitial pattern, which may be characterized as finely granular, reticular, or ground-glass opacities. When chest radiographic findings are normal or equivocal, high-resolution CT may be helpful because it is more sensitive than chest radiography for detecting PCP. The typical CT finding is extensive ground-glass attenuation. The face of PCP is changing. The classic radiographic presentation is being encountered less frequently. Increasingly recognized characteristic patterns of PCP include cystic lung disease, spontaneous pneumothorax, and an upper lobe distribution of parenchymal opacities. The spectrum of abnormalities associated with PCP is broadening and now includes abnormalities of the lung parenchyma, airways, lymph nodes, and pleura. An awareness of the varied presentations of PCP is important because the radiologist is often the first to suggest the diagnosis of PCP.

  10. Intravenous pentamidine for Pneumocystis carinii/jiroveci pneumonia prophylaxis in pediatric transplant patients.

    PubMed

    Clark, Abigail; Hemmelgarn, Trina; Danziger-Isakov, Lara; Teusink, Ashley

    2015-05-01

    SMX/TMP is the current gold standard for prophylaxis against PCP in immunocompromised pediatric patients. Currently, there are several second-line options for prophylaxis but many, including intravenous (IV) pentamidine, have not been reported to be as effective or as safe as SMX/TMP in the pediatric transplant population. This study is to determine the efficacy and safety of IV pentamidine in preventing PCP in pediatric transplant patients. A retrospective chart review was conducted to evaluate all transplant patients that received at least one dose of IV pentamidine from January 2010 to July 2013. The primary outcome, IV pentamidine efficacy, was evaluated by the incidence of PCP diagnosis for 28 days after the last dose of IV pentamidine if patient was transitioned to another agent for PCP prophylaxis. Patients on IV pentamidine for entire course of PCP prophylaxis were followed at least six months after discontinuation of IV pentamidine. The safety of IV pentamidine was assessed by the incidence of adverse events leading to pentamidine discontinuation. All data were analyzed using descriptive statistics. All transplant patients at CCHMC who had received IV pentamidine were reviewed, and 333 patients met inclusion criteria. The overall incidence of PCP was found to be 0.3% for pediatric transplant patients on pentamidine. Pentamidine was found to be safe, and the incidence of adverse events leading to discontinuation was 6% with the most common reason being tachycardia 2.1%. IV pentamidine is safe and effective as PCP prophylaxis in pediatric transplant patients with a PCP breakthrough rate of 0.3% (1 of 333 patients), and only 20 adverse events led to discontinuation. We recommend that IV pentamidine be considered as a second-line option in pediatric transplant patients who cannot tolerate SMX/TMP.

  11. Is Aerosolized Pentamidine for Pneumocystis Pneumonia Prophylaxis in Renal Transplant Recipients Not as Safe as We Might Think?

    PubMed

    Macesic, N; Urbancic, K; Ierino, F; Grayson, M L

    2016-04-01

    Outbreaks ofPneumocystispneumonia have been described in renal transplant recipients. Aerosolized pentamidine is frequently used for prophylaxis in this setting. We report our experience with aerosolized pentamidine use in 56 renal transplant recipients. We found high rates of adverse reactions in patients with chronic respiratory disease.

  12. Roundtable for the Development of Drugs and Vaccines Against Acquired Immuno Deficiency Syndrome (AIDS).

    DTIC Science & Technology

    1991-05-01

    effectiveness of the therapy as prophylaxis for Pneumocystis carini pneumonia . San Francisco investigators presented a formal abstract describing...who had a history of cytologically confirmed Pneumocystis carinii pneumonia (PCP) or an absolute CD4 lymphocyte count of less than 200 per cubic...Jacobson, P. A. Voiberding, D. Abrams, and the San Francisco County Community Consortium, "Aerosolized pentamidine for prophylaxis against Pneumocystis

  13. Hierarchical Bayes Models for the Progression of HIV Infection Using Longitudinal CD4+ Counts.

    DTIC Science & Technology

    1992-11-27

    the risk of an AIDS-related disease ( Pneumocystis carinii pneumonia , or PCP) involving 1665 HIV-infected subjects. For additional results on...335. Centers for Disease Control (1989). Guidelines for prophylaxis against Pneumocystis carinii pneumonia for persons infected with human...Growth curve prediction. Sankhyll, Series A, 34, 393-412. Leibovitz, E., Rigaud, M., Pollack, H. et al. (1990). Pneumocystis carinii pneumonia in

  14. Variability of Serial Absolute and Percent CD4+ Lymphocyte Counts in Healthy Children Born to Human Immunodeficiency Virus 1-Infected Parents

    DTIC Science & Technology

    1994-01-01

    Pneumocystis carinii pneumonia prophy- laxis and antiretroviral therapy.’"’ Although age-specific normal values for T cell phenotypes have been...regarding in z scores over time, the mean of the absolute value of • the institution of Pneumocystis carinii pneumonia prophy- changes between...icant. The Centers for Disease Control currently recoin- Pneumocystis carinii pneumonia for children infected with hu- man immunodeficiency virus. MMWR

  15. Risk Factors for Prevalent Human Immunodeficiency Virus (HIV) Infection in Active Duty Army Men Who Initially Report No Identified Risk: A Case-Control Study

    DTIC Science & Technology

    1990-01-01

    Washington, D.C.; Ms. Robin Pomerantz, SRA Technol- Pneumocystis pneumonia among homosexual men. New s AYork and California. MMWR 1981 ;30:305-8.ogies...and Dr. sarcoma and Pneumocystis pneumonia . MMWR 1981;30: Steven Piantadosi, Johns Hopkins School of Medicine, 409-10. Baltimore, MD for data...National case-control ment of Defense. Milit Med 1986;151:623-7. study of Kaposi’s sarcoma and Pneumocystis carinii pneu- 2. Alexander LL, Renzullo PO

  16. Pediatric Pulmonary and Cardiovascular Complications of Vertically Transmitted HIV Infection (P2C2)

    ClinicalTrials.gov

    2016-04-13

    Acquired Immunodeficiency Syndrome; Lung Diseases; Cardiovascular Diseases; Heart Diseases; Heart Failure; HIV Infections; Cytomegalovirus Infections; Pneumocystis Carinii Infections; Ebstein-Barr Virus Infections

  17. Fatal pneumonia associated with temozolomide therapy in patients with malignant glioma.

    PubMed

    Hayashi, Hiroki; Saito, Yoshinobu; Kokuho, Nariaki; Morimoto, Taisuke; Kobayashi, Kenichi; Tanaka, Toru; Abe, Shinji; Fujita, Kazue; Azuma, Arata; Gemma, Akihiko

    2012-07-01

    This report presents the cases of three patients with fatal pneumonia that was highly suspected to be Pneumocystis pneumonia (PCP) based on serological diagnosis. Their chest radiographs showed bilateral pneumonia and each had presented with severe respiratory failure requiring mechanical ventilation when they arrived at the hospital. Although bronchoscopical sampling could not be performed, their chest computed tomography imaging and a marked elevation of serum KL-6 and β-D-glucan levels were characteristic of Pneumocystis pneumonia. All three were found to have been treated with temozolomide after surgery for malignant glioma. Temozolomide can cause Pneumocystis pneumonia. The three patients did not receive prophylactic medication against Pneumocystis pneumonia during treatment with temozolomide, and their histories suggested that all had delayed seeking treatment. It may be difficult to diagnose Pneumocystis pneumonia because the symptoms are not specific for Pneumocystis pneumonia and they tend to be similar to those of common respiratory infectious diseases. Therefore, patients who receive temozolomide therapy have the potential to develop fatal pneumonia and should be carefully observed. The patients should also be adequately informed about Pneumocystis pneumonia, and prophylaxis against Pneumocystis pneumonia should be considered proactively before treatment with temozolomide is initiated.

  18. AIDS (Acquired Immunodeficiency Syndrome) Prevention: Views on the Administration’s Budget Proposals.

    DTIC Science & Technology

    1987-08-12

    protozoal, or fungal infections. The two most common infections contracted by AIDS patients are pneumocystis carinii pneumonia and Kaposi’s sarcoma. CDC...according to CDC, the proportion of AIDS patients with Kaposi’s sarcoma may decrease while pneumocystis carinii pneumonia may increase. Since the latter

  19. Pentamidine Injection

    MedlinePlus

    Pentamidine injection is used to treat pneumonia caused by a fungus called Pneumocystis carinii. It is in a class of medications called antiprotozoals. It works by stopping the growth of protozoa that can cause pneumonia.

  20. Simple pulmonary eosinophilia

    MedlinePlus

    ... Pneumocystis jirovecii A parasite, including the roundworms Ascariasis lumbricoides , or Necator americanus , or the hookworm Ancylostoma duodenale ... contents ( gastric lavage ) may show signs of the Ascaris worm or another parasite. Treatment If you are ...

  1. The 30th Anniversary of the First Reported Cases of AIDS | NIH MedlinePlus the Magazine

    MedlinePlus

    ... 1981, an article concerning five previously healthy, young gay men in Los Angeles diagnosed with Pneumocystis carinii ... cases like these appeared, at first mainly in gay men, but then also in injection drug users, ...

  2. Saccharomycotina and Taphrinomycotina: the yeasts and yeast-like fungi of the Ascomycota

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The phylum Ascomycota has been resolved into three major phylogenetic lineages: the subphyla Saccharomycotina (e.g., Saccharomyces, Pichia, Candida), Taphrinomycotina (e.g., Protomyces, Taphrina, Pneumocystis), and the Pezizomycotina (e.g., Aspergillus, Neurospora, Peziza). We discuss the ecology, ...

  3. Otic and ophthalmic pneumocystosis in acquired immunodeficiency syndrome. Report of a case and review of the literature.

    PubMed

    Wasserman, L; Haghighi, P

    1992-05-01

    A case of primary Pneumocystis carinii infection involving the left middle ear of a patient with acquired immunodeficiency syndrome is described, and the literature on the otic and ophthalmic pneumocystosis is reviewed. Otic pneumocystosis typically presents as a unilateral polypoid mass, and it is clinically manifested as otalgia, hearing loss, or, sometimes, otorrhea without evidence of current respiratory disease or previous Pneumocystis pneumonia. In contrast, choroidal pneumocystosis usually occurs in a patient with acquired immunodeficiency syndrome with at least one previous episode of Pneumocystis pneumonia and aerosolized pentamidine treatment, it is usually asymptomatic and bilateral, and it may be discovered only because of other concurrent human immunodeficiency virus-related ophthalmic disease. The diagnosis is made clinically, and intravenous antiparasite treatment is successful.

  4. Pulmonary pneumocystosis in nonhuman primates.

    PubMed

    Chandler, F W; McClure, H M; Campbell, W G; Watts, J C

    1976-03-01

    Pulmonary infection with Pneumocystis carinii was detected in two aged owl monkeys (Aotus trivirgatus) and two young chimpanzees (Pan troglodytes). The clinical histories of the owl monkeys were similar and included progressive weight loss, anorexia, failure to thrive, and death. One of the owl monkeys had no concurrent disease, whereas the other had been experimentally inoculated with Treponema pallidum 44 months before death. In both chimpanzees, an underlying myeloproliferative malignant neoplasm was associated with Pneumocystis infection. Pneumocystis organisms were found in alveolar spaces and alveolar lining cells by light and electron microscopy. Pathologic features of these untreated cases and a case in a chimpanzee treated with pentamidine isethionate were similar to those described in humans. To our knowledge, this is the first report of pulmonary pneumocystosis associated with death in nonhuman primates.

  5. Maintenance of foals with combined immunodeficiency: causes and control of secondary infections.

    PubMed

    Perryman, L E; McGuire, T C; Crawford, T B

    1978-06-01

    Sixty-six cases of combined immunodeficiency (CID) in foals were studied to determine the most prevalent causes of infection and death. Lesions of the respiratory system were observed in 59 of the foals and were attributable to infection with equine adenovirus. Pneumocystis carinii, and bacteria. Significant lesions were also observed in liver, pancreas, intestines, heart, and kidneys. Maintenance of foals with CID for experimental purposes is directed at the prevention and control of these secondary infections. Adenovirus can be controlled by administration of horse plasma containing high titers of antiadenovirus antibody. Bacteria are controlled by appropriate antibiotic therapy. Pneumocystis carinii infection remains a significant problem in the maintenance of foals with CID.

  6. [Advances in research of dihydroartemisinin against parasitic diseases].

    PubMed

    Li, Hong-Jun; Wang, Wei; Liang, You-Sheng

    2011-08-01

    Dihydroartemisinin, the main metabolite of artemisinin and two artemisinin derivatives, artemether and artesunate, is a broad-spectrum anti-parasitic drug. The present paper systematically reviews the advances in research of dihydroartemisinin against Plasmodium, Schistosoma, Pneumocystis, Toxoplasma, Trichomonas vaginalis, Leishmania, Giardia lamblia.

  7. Oral osteomyelitis: pre-AIDS manifestation or strange coincidence?

    PubMed

    Harel-Raviv, M; Gorsky, M; Lust, I; Raviv, E

    1996-01-01

    A bizarre and unexplained localized osteomyelitis was discovered in the mandible of an otherwise apparently healthy 36-year-old man. This strange oral manifestation was followed 2 years later by a diagnosis of Pneumocystis carinii pneumonia, which indicated full-blown AIDS. Could osteomyelitis of the mandible be an alarming oral manifestation of AIDS before the disease is manifested in other ways?

  8. A Quantitative Model to Estimate Drug Resistance in Pathogens

    PubMed Central

    Baker, Frazier N.; Cushion, Melanie T.; Porollo, Aleksey

    2016-01-01

    Pneumocystis pneumonia (PCP) is an opportunistic infection that occurs in humans and other mammals with debilitated immune systems. These infections are caused by fungi in the genus Pneumocystis, which are not susceptible to standard antifungal agents. Despite decades of research and drug development, the primary treatment and prophylaxis for PCP remains a combination of trimethoprim (TMP) and sulfamethoxazole (SMX) that targets two enzymes in folic acid biosynthesis, dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS), respectively. There is growing evidence of emerging resistance by Pneumocystis jirovecii (the species that infects humans) to TMP-SMX associated with mutations in the targeted enzymes. In the present study, we report the development of an accurate quantitative model to predict changes in the binding affinity of inhibitors (Ki, IC50) to the mutated proteins. The model is based on evolutionary information and amino acid covariance analysis. Predicted changes in binding affinity upon mutations highly correlate with the experimentally measured data. While trained on Pneumocystis jirovecii DHFR/TMP data, the model shows similar or better performance when evaluated on the resistance data for a different inhibitor of PjDFHR, another drug/target pair (PjDHPS/SMX) and another organism (Staphylococcus aureus DHFR/TMP). Therefore, we anticipate that the developed prediction model will be useful in the evaluation of possible resistance of the newly sequenced variants of the pathogen and can be extended to other drug targets and organisms. PMID:28018911

  9. AIDS (Acquired Immune Deficiency Syndrome) and Employment Discrimination

    DTIC Science & Technology

    1987-09-30

    Protozoal and helminthic infections 1. Cryptosporidiosis 2. Pneumocystis carinii pneumonia (most common disease in AIDS victims) 3. Strongyloidosis 4...diagnosed with either a rare opportunistic infection (01), or cancer2 typically occurring only in individuals with severely compromised immune systems...disorder of the human immune system leading to enhanced susceptibility to particular opportunistic infections and certain cancers.5 In the immune

  10. CD4 Lymphocyte Decline and Survival in Human Immunodeficiency Virus Infection

    DTIC Science & Technology

    1992-01-01

    assess the association of CD4 cell decline (half-life), race, age, gender, initial CD4-cell count, and treatment (anti- Pneumocystis carinii pneumonia ...with a median interval of 2.65 mo between tests. (AZT), anti-Pneumnocystis cariniI pneumonia (PCP) prophy- The decline of CD4 cell count over time for

  11. Cutting edge: critical role of intracellular osteopontin in antifungal innate immune responses.

    PubMed

    Inoue, Makoto; Moriwaki, Yasuhiro; Arikawa, Tomohiro; Chen, Yu-Hsun; Oh, Young Joo; Oliver, Timothy; Shinohara, Mari L

    2011-01-01

    We found that absence of osteopontin (OPN) in immunocompromised Rag2(-/-) mice, which lack T and B cells, made the mice extremely susceptible to an opportunistic fungus Pneumocystis, although immunocompetent OPN-deficient mice could clear Pneumocystis as well as wild-type mice. OPN has been studied as an extracellular protein, and the role of an intracellular isoform of OPN (iOPN) is still largely unknown. In this study, we elucidated the mechanism by which iOPN was involved in antifungal innate immunity. First, iOPN was essential for cluster formation of fungal receptors that detect Pneumocystis, including dectin-1, TLR2, and mannose receptor. Second, iOPN played a role as an adaptor molecule in TLR2 and dectin-1 signaling pathways and mediated ERK activation and cytokine production by zymosan, which simultaneously activates TLR2 and dectin-1 pathways. Third, iOPN enhanced phagocytosis and clearance of Pneumocystis. Our study suggests the critical involvement of iOPN in antifungal innate immunity.

  12. Adult Respiratory Distress Syndrome in a Previously Healthy Young Male *

    PubMed Central

    Sigal, Stephen L.; Kliger, Alan; Smith, G.J. Walker

    1982-01-01

    Infection with pneumocystis carinii and cytomegalovirus was found in a young male suspected of having miliary tuberculosis. Problems of diagnosis and predisposing factors for these infections in the patient are discussed. The patient's clinical course and management are reviewed. Autopsy findings are presented. Alternative modes of therapy are considered. ImagesFIG. 1FIG. 2FIG. 3FIG. 4FIG. 5 PMID:6305041

  13. Cavitary Lung Disease in an HIV-Positive Patient

    DTIC Science & Technology

    2009-04-01

    effusion or pneumothorax visualized. Diagnosis Aspergillus niducans Report Documentation Page Form ApprovedOMB No. 0704-0188 Public...positive for Aspergillus niducans. Other assays performed ruled out Pneumocystis jiroveci (carinii), Legionella, coccidiomycosis, histoplasmosis... Aspergillus niducans. Pulmonary aspergilloma are cavitary lesions with a pathognomonic “halo sign” on computed tomography scan, or, more commonly

  14. Grouped Cases of Pulmonary Pneumocystosis After Solid Organ Transplantation: Advantages of Coordination by an Infectious Diseases Unit for Overall Management and Epidemiological Monitoring.

    PubMed

    Wintenberger, Claire; Maubon, Daniele; Charpentier, Elena; Rendu, John; Pavese, Patricia; Augier, Caroline; Malvezzi, Paolo; Camara, Boubou; Mallaret, Marie-Reine; Bouillet, Laurence; Epaulard, Olivier

    2017-02-01

    OBJECTIVE To determine the origin of grouped cases of Pneumocystis pneumonia in solid-organ transplant recipients at our institution. DESIGN A case series with clinical examinations, genotyping, and an epidemiological survey. SETTING A university hospital in France. PATIENTS We report 12 solid-organ transplant recipients with successive cases of Pneumocystis pneumonia that occurred over 3 years; 10 of these cases occurred in a single year. METHODS We used molecular typing of P. jirovecii strains by multilocus sequence typing and clinical epidemiological survey to determine potential dates and places of transmission. RESULTS Between May 2014 and March 2015, 10 solid-organ transplant recipients (5 kidney transplants, 4 heart transplants, and 1 lung transplant) presented with Pneumocystis pneumonia. Molecular genotyping revealed the same P. jirovecii strain in at least 6 patients. This Pneumocystis strain was not identified in control patients (ie, nontransplant patients presenting with pulmonary pneumocystosis) during this period. The epidemiological survey guided by sequencing results provided information on the probable or possible dates and places of contamination for 5 of these patients. The mobile infectious diseases unit played a coordination role in the clinical management (adaptation of the local guidelines) and epidemiological survey. CONCLUSION Our cardiac and kidney transplant units experienced grouped cases of pulmonary pneumocystosis. Genotyping and epidemiological surveying results suggested interhuman contamination, which was quickly eliminated thanks to multidisciplinary coordination. Infect Control Hosp Epidemiol 2017;38:179-185.

  15. Role of vaccinations and prophylaxis in rheumatic diseases.

    PubMed

    Papadopoulou, Despoina; Tsoulas, Christos; Tragiannidis, Athanassios; Sipsas, Nikolaos V

    2015-04-01

    Targeted strategies for reducing the increased risk of infection in patients with autoimmune rheumatic diseases include vaccinations as well as antibiotic prophylaxis in selected patients. However, there are still issues under debate: Is vaccination in patients with rheumatic diseases immunogenic? Is it safe? What is the impact of immunosuppressive drugs on vaccine immunogenicity and safety? Does vaccination cause disease flares? In which cases is prophylaxis against Pneumocystis jirovecii required? This review addresses these important questions to which clinicians and researchers still do not have definite answers. The first part includes immunization recommendations and reviews current data on vaccine efficacy and safety in patients with rheumatic diseases. The second part discusses prophylaxis for Pneumocystis pneumonia.

  16. Safety issues in vasculitis: infections and immunizations in the immunosuppressed host.

    PubMed

    Isada, Carlos M

    2012-11-01

    Infectious diseases are a significant cause of morbidity and mortality in immunosuppressed patients, including those with connective tissue diseases. Both disease and treatment contribute to a predisposition to infection in immunocompromised patients. Significant infection and morbidity occur in 25% to 50% of these patients with a median mortality of 5.2% due to common bacterial infections, such as pneumonia or bacteremia, and opportunistic fungal infections such as Pneumocystis. The lungs, skin, urinary tract, blood, and central nervous system are commonly affected. Pathogens such as Pneumocystis jirovecii, Histoplasma capsulatum, Aspergillus species, herpes zoster, JC virus, Nocardia asteroides, and Nocardia species are increasingly prevalent in immunocompromised patients. Improved recognition, diagnosis, and prevention of these infections are needed to enhance outcomes in these patients.

  17. Gender-related differences in the spectrum of HIV disease in the Bayamón area, Puerto Rico.

    PubMed

    Miniño, A; Gómez, M A; Velazquez, M; Hunter, R

    1997-11-01

    We compare prevalence (by actual presence or history of condition) rates of selected AIDS-defining conditions across genders in a sample of 1,498 HIV-infected participants who visited our health service facilities between mid 1992 and early 1996. The comparisons were performed globally (considering all subjects) and on a subsample of participants whose most probable mode of infection with HIV was through (self-reported) use of injecting drugs. Global analysis revealed no significant differences across genders for any of the conditions considered; the most prevalent condition being Pneumocystis carinii pneumonia. Subsample-specific analysis (injecting drug users), however, revealed that women from this subgroup were likelier to have (present or by history) at least one AIDS-defining condition; they were also significantly likelier to specifically report candidiasis and Pneumocystis carinii pneumonia.

  18. [Extrapulmonary pneumocystosis: a case report].

    PubMed

    Valdebenito, Carlos; Bonacic, Macarena; Matamala, Jennifer; Wolff, Marcelo

    2015-06-01

    We report a case of a middle-age male patient, with newly HIV infection in AIDS stage diagnosis, no comorbitidies, who was hospitalized for subacute malaise, fever, self-limited unproductive cough and no bloody chronic diarrea. The diagnosis of Pneumocystis jiroveci pneumonia was performed by imagenological suspicion and stains of cysts of this pathogen with bronchoalveolar lavage samples. Treatment was initiated with oral cotrimoxazole and starting HAART with good clinical outcome. Concomitantly, an etiologic study was conducted for chronic diarrhea and through histopathological examination of colonic mucosa, numerous extracellular cystic structures Pneumocystis characteristics were observed, performing the diagnosis of extrapulmonary pneumocystosis. Extrapulmonary pneumocystosis is a rare cause of P. jiroveci infection, requires a high index of suspicion and should be approached in HIV patients with severe AIDS which is common in co-infection of various infections and is peremptory to make an etiologic diagnosis and early treatment.

  19. Pulmonary complications of AIDS: radiologic features. [AIDS

    SciTech Connect

    Cohen, B.A.; Pomeranz, S.; Rabinowitz, J.G.; Rosen, M.J.; Train, J.S.; Norton, K.I.; Mendelson, D.S.

    1984-07-01

    Fifty-two patients with pulmonary complications of acquired immunodeficiency syndrome (AIDS) were studied over a 3-year period. The vast majority of the patients were homosexual; however, a significant number were intravenous drug abusers. Thirteen different organisms were noted, of which Pneumocystis carinii was by far the most common. Five patients had neoplasia. Most patients had initial abnormal chest films; however, eight patients subsequently shown to have Pneumocystis carinii pneumonia had normal chest films. A significant overlap in chest radiographic findings was noted among patients with different or multiple organisms. Lung biopsy should be an early consideration for all patients with a clinical history consistent with the pulmonary complications of AIDS. Of the 52 patients, 41 had died by the time this report was completed.

  20. Towards New Antifolates Targeting Eukaryotic Opportunistic Infections

    SciTech Connect

    Liu, J.; Bolstad, D; Bolstad, E; Wright, D; Anderson, A

    2009-01-01

    Trimethoprim, an antifolate commonly prescribed in combination with sulfamethoxazole, potently inhibits several prokaryotic species of dihydrofolate reductase (DHFR). However, several eukaryotic pathogenic organisms are resistant to trimethoprim, preventing its effective use as a therapeutic for those infections. We have been building a program to reengineer trimethoprim to more potently and selectively inhibit eukaryotic species of DHFR as a viable strategy for new drug discovery targeting several opportunistic pathogens. We have developed a series of compounds that exhibit potent and selective inhibition of DHFR from the parasitic protozoa Cryptosporidium and Toxoplasma as well as the fungus Candida glabrata. A comparison of the structures of DHFR from the fungal species Candida glabrata and Pneumocystis suggests that the compounds may also potently inhibit Pneumocystis DHFR.

  1. Antifungal activity of 10 Guadeloupean plants.

    PubMed

    Biabiany, Murielle; Roumy, Vincent; Hennebelle, Thierry; François, Nadine; Sendid, Boualem; Pottier, Muriel; Aliouat, El Moukhtar; Rouaud, Isabelle; Lohézic-Le Dévéhat, Françoise; Joseph, Henry; Bourgeois, Paul; Sahpaz, Sevser; Bailleul, François

    2013-11-01

    Screening of the antifungal activities of ten Guadeloupean plants was undertaken to find new extracts and formulations against superficial mycoses such as onychomycosis, athlete's foot, Pityriasis versicolor, as well as the deep fungal infection Pneumocystis pneumonia. For the first time, the CMI of these plant extracts [cyclohexane, ethanol and ethanol/water (1:1, v/v)] was determined against five dermatophytes, five Candida species, Scytalidium dimidiatum, a Malassezia sp. strain and Pneumocystis carinii. Cytotoxicity tests of the most active extracts were also performed on an HaCat keratinocyte cell line. Results suggest that the extracts of Bursera simaruba, Cedrela odorata, Enterolobium cyclocarpum and Pluchea carolinensis have interesting activities and could be good candidates for developing antifungal formulations.

  2. Pulmonary complications of AIDS: radiologic features.

    PubMed

    Cohen, B A; Pomeranz, S; Rabinowitz, J G; Rosen, M J; Train, J S; Norton, K I; Mendelson, D S

    1984-07-01

    Fifty-two patients with pulmonary complications of acquired immunodeficiency syndrome (AIDS) were studied over a 3-year period. The vast majority of the patients were homosexual; however, a significant number were intravenous drug abusers. Thirteen different organisms were noted, of which Pneumocystis carinii was by far the most common. Five patients had neoplasia. Most patients had initial abnormal chest films; however, eight patients subsequently shown to have Pneumocystis carinii pneumonia had normal chest films. A significant overlap in chest radiographic findings was noted among patients with different or multiple organisms. Lung biopsy should be an early consideration for all patients with a clinical history consistent with the pulmonary complications of AIDS. Repeat biopsy is also indicated to ascertain the progression of radiographic findings. Unfortunately, even with documentation of the nature of the pulmonary process, treatment often is ineffective. Of the 52 patients, 41 had died by the time this report was completed.

  3. Acquired immunodeficiency syndrome associated with blood-product transfusions

    SciTech Connect

    Jett, J.R.; Kuritsky, J.N.; Katzmann, J.A.; Homburger, H.A.

    1983-11-01

    A 53-year-old white man had fever, malaise, and dyspnea on exertion. His chest roentgenogram was normal, but pulmonary function tests showed impaired diffusion capacity and a gallium scan showed marked uptake in the lungs. Results of an open-lung biopsy documented Pneumocystis carinii pneumonia. Immunologic test results were consistent with the acquired immunodeficiency syndrome. The patient denied having homosexual contact or using intravenous drugs. Twenty-nine months before the diagnosis of pneumocystis pneumonia was made, the patient had had 16 transfusions of whole blood, platelets, and fresh-frozen plasma during coronary artery bypass surgery at another medical center. This patient is not a member of any currently recognized high-risk group and is believed to have contracted the acquired immunodeficiency syndrome from blood and blood-product transfusions.

  4. Immunologic Intervention in HIV Infection: Anti-Polymerase Responses and Hormonal Regulation

    DTIC Science & Technology

    1993-09-01

    cluster of Pneumocystis carinii pneumonia in adults without predisposing illnesses. N. Engl. J. Med. 324:246- 250. 20. Laurence J, Siegal FP, Schattner E... first model for investigation of control of HIV infection in B cells. This work also has implications for the pathogenesis of B cell lymphomas in AIDS...together with its anabolic properties, is of great interest in HIV disease. We have discovered that not only is growth hormone a potent T cell stimulant

  5. Medical problems in refugee children evacuated from South Vietnam.

    PubMed

    Hodson, E M; Springthorpe, B J

    1976-11-13

    One hundred and fourteen refugee children from South Vietnam showed similar disease prevalences to refugee children from Bangladesh. Common diseases were malnutrition, gastroenteritis, pneumonia and bronchitis, scabies and furunculosis. Seven children died, five from pneumonia complicated by malnutrition. Increased awareness of the high incidence of Pneumocystis pneumonia and more careful assessment of nutritional status may reduce mortality in future groups of refugee children evacuated to Australia.

  6. ‘Occam's Scissors’: opportunistic infections in advanced HIV infection

    PubMed Central

    Shah, Nirav; Owen, Leah; Bhagani, Sanjay

    2013-01-01

    The authors report the case of a new diagnosis of advanced HIV-1 infection with a blood CD4 cell count of 0.003×109/L (2%), presenting with weight loss, night sweats, diarrhoea and anorexia. Symptoms were due to disseminated histoplasmosis (confirmed pulmonary and colonic disease), Pneumocystis pneumonia and oral candidiasis highlighting the limitations of ‘Occam's razor’ with advanced HIV infection. PMID:23833087

  7. Reversal of Multidrug Resistance in Breast Cancer

    DTIC Science & Technology

    1994-08-23

    will receive Acyclovir 500 mg/M2 intravenously every eight hours beginning on the last day of high-dose chemotherapy (day -3) until seventeen days post...bone marrow reinfusion (day +17). Patients who are CMV negative but have positive herpes simplex virus titers will receive Acyclovir 250 mg/M2...negative cytomegalovirus titers and negative herpes simplex virus titers will not receive prophylactic Acyclovir . 5.458 Anti-Pneumocystis carinii

  8. Lung parasites of least weasels in Finland.

    PubMed

    Laakkonen, J; Sundell, J; Soveri, T

    1998-10-01

    Because of their constant exposure to normal rodent definitive hosts, least weasels (Mustela nivalis) were trapped in southern Finland in late fall 1994 and examined for lung parasites. Histological examination showed that 46% of the weasels (n = 46) were infected with adiaspores identified as Chrysosporium sp. Granulomas surrounding the adiaspores consisted of mostly unorganized layers of mononuclear cells. The adiaspores from least weasels were much smaller than those reported from their prey animals. Infection with Pneumocystis carinii also was found in two weasels.

  9. A multiplexed nucleic acid microsystem for point-of-care detection of HIV co-infection with MTB and PCP.

    PubMed

    Xu, Lingjia; Kong, Jilie

    2013-12-15

    Many individuals infected with the human immunodeficiency virus (HIV), especially children in African countries, die of co-infections with Mycobacterium tuberculosis (MTB) (coinfection rate: 50%) or Pneumocystis carinii pneumonia (PCP) (coinfection rate: 81%). The present proposal describes a rapid, portable, low-cost, multiplexed point-of-care diagnostic technique for simultaneously detecting HIV, MTB, and PCP. This technique incorporates a creative micro-device (hardware) and a loop-mediated isothermal amplification strategy (software).

  10. Radiogallium scan in P. carinii pneumonia

    SciTech Connect

    Parthasarathy, K.L.; Bakshi, S.P.; Bender, M.A.

    1982-02-01

    A gallium scan performed on a patient with fever of unknown origin (FUO) revealed an abnormal uptake of radiotracer in the lungs despite negative chest roentgenographic examination and other routine diagnostic studies. Subsequent lung biopsy results confirmed the presence of Pneumocystis (P.) carinii infection. A repeat gallium scan obtained following appropriate antibiotic therapy was essentially normal. The importance of radiogallium scanning in an immunosuppressed patient with FUO is emphasized.

  11. Unusual onset of venous thromboembolism and heparin-induced thrombocytopenia in a patient with essential thrombocythemia.

    PubMed

    Lapecorella, Mario; Lucchesi, Alessandro; Di Ianni, Mauro; Napolitano, Mariasanta; Coletti, Gino; Di Leonardo, Gabriella; Dell'Orso, Luigi; Barnabei, Remo; Mariani, Guglielmo

    2010-01-01

    Essential thrombocythemia is a hematological disorder characterized by clonal hemopoiesis in the bone marrow and increased number of circulating platelets. It is usually discovered accidentally at the time of routine blood examinations or can become clinically evident with either thrombotic or hemorrhagic complications. In the present article, we describe the case of a 66-year-old woman with pneumonia due to Pneumocystis carinii, who experienced deep vein thrombosis and pulmonary embolism during hospitalization with a subsequent heparin-induced thrombocytopenia. Bone marrow examination performed after clinical improvement revealed the patient to be affected by essential thrombocythemia.

  12. The causes of death in patients with human immunodeficiency virus infection: a clinical and pathologic study with emphasis on the role of pulmonary diseases.

    PubMed

    McKenzie, R; Travis, W D; Dolan, S A; Pittaluga, S; Feuerstein, I M; Shelhamer, J; Yarchoan, R; Masur, H

    1991-09-01

    The clinical records and autopsy data of 75 patients dying with AIDS were reviewed to determine the frequency of individual diseases diagnosed premortem and postmortem, the significance of pulmonary processes found in the lungs at autopsy, and the clinical and pathologic causes of death. Cytomegalovirus (CMV) infection was identified histologically either premortem or postmortem in 81% of patients. The lungs and adrenal glands were infected most commonly. Only one-half of CMV infections were recognized premortem. Pneumocystis pneumonia and Kaposi sarcoma occurred in 68% and 59% of patients, respectively, but were not unsuspected premortem in any patient. Visceral involvement with Kaposi sarcoma, however, was frequently recognized only at autopsy. While disseminated M. avium-intracellulare infection was common (31% of patients), histologically documented pulmonary disease was uncommon (3% of patients). Cryptococcal infection, diagnosed in 10 patients, was confined to the central nervous system in only 1 patient. Toxoplasma, in contrast, infected the brain of only 6 patients. All 75 patients had one or more disease processes identified in their lungs or pleurae at autopsy. These processes included opportunistic infections in 76% of patients, neoplasms in 37% (Kaposi sarcoma in 36% and lymphoma in 3%), and other processes in 60%. The most prevalent pathogen, CMV was found in pulmonary tissue from 44 patients and caused significant disease in 21 patients. Five patients died due to CMV pneumonia. Pneumocystis carinii was found at autopsy in 24 patients. In spite of treatment, pneumocystis pneumonia was fatal in 11 patients. One patient died with concomitant CMV and pneumocystis pneumonia. Kaposi sarcoma, identified in the lungs of 23 patients, led to death in 5 patients via upper airway obstruction, hemorrhage, or parenchymal destruction. Other fatal pulmonary processes included bacterial pneumonia in 9 patients, idiopathic diffuse alveolar damage in 5, cryptococcosis

  13. [Parasites of the respiratory system: research and significance (author's transl)].

    PubMed

    De Carneri, I; Trane, F

    1976-01-01

    A review is made of the methods of diagnosing both autochthonous and exotic protozoal and helminthic diseases of the respiratory system. Referring to protozooses, recent findings on respiratory pathology due to amoebae of the genus Acanthamoeba are commented, and modern methods are discussed of checking for Pneumocystis carinii in the patient, not just on autopsy material. Referring to helminthiases, in addition to pulmonary echinococcosis which is of prevalent interest in Italy, attention is also given to the pathology of migrant larvae of nematodes. Finally, the role of some microscopic mites in the pathogenesis of respiratory allergic disease from house dust is discussed.

  14. Autopsy findings in AIDS--a histopathological analysis of fifty cases.

    PubMed

    Falk, S; Schmidts, H L; Müller, H; Berger, K; Schneider, M; Schlote, W; Helm, E B; Stille, W; Hübner, K; Stutte, H J

    1987-07-15

    Fifty consecutive AIDS autopsy cases were evaluated. All subjects showed one or more opportunistic infections and malignancies included in the AIDS case definition with cytomegalovirus and Kaposi's sarcoma being most prevalent. Mycobacterial and cryptococcal infections occurred only infrequently. Most patients of our series after successful treatment of Pneumocystis carinii pneumonia or cerebral toxoplasmosis later succumbed to less treatable conditions like disseminated cytomegalovirus or fungal infections or malignant lymphoma. In the absence of specific treatment for the HIV infection leading to these lethal complications special emphasis must be put on the prevention of HIV transmission and spread.

  15. [Infections after organ transplantation].

    PubMed

    Kern, W V; Wagner, D; Hirsch, H H

    2005-06-01

    Early postoperative infections after transplantation vary according to the transplanted organ. During the subsequent course opportunistic infections such as cytomegalovirus reactivation, Pneumocystis jiroveci pneumonia, invasive pneumococcal infection and mould infections predominate. Reactivated tuberculous infection appears to become more prevalent. Some of the opportunistic infections are preventable by chemoprophylaxis; others can be managed very effectively by monitoring and early preemptive therapy. Physicians caring for patients after organ transplantation need to early consider in the differential diagnosis rare pathogens which are often overlooked with standard diagnostic procedures.

  16. Delayed presentation of severe combined immunodeficiency due to prolonged maternal T cell engraftment

    PubMed Central

    Al-Muhsen, Saleh Z.

    2010-01-01

    Severe combined immunodeficiency (SCID) is a primary immunodeficiency disorder with heterogenous genetic etiologies. We describe a typical case in a 9-year-old boy that was masked by a clinically functional maternal T cell engraftment leading to late presentation with Pneumocystis jiroveci pneumonia and cytomegalovirus infection, probably following exhaustion of maternally engrafted cells. Based on immunological findings, he had a T- B+SCID phenotype. This report suggests that in rare cases, engrafted maternal T cell might persist for long time leading to partial constitution of immune function and delayed clinical presentation of SCID. PMID:20427943

  17. Administration of aerosol pentamidine: a program design.

    PubMed

    O'Hara, C M; Anton, W R; Gormley, F X; Brazell, C

    1994-01-01

    Aerosol pentamidine (AP) is an FDA-approved prophylaxis against pneumocystis carinii pneumonia (PCP) in HIV-infected individuals who have a CD4+ lymphocyte count less than 200/mm3, constitutional symptoms, or a previous history of the pneumonia. The University of Washington Medical Center, a 450-bed tertiary care center, established a successful aerosol pentamidine treatment program, providing treatment in its special procedure nit. The authors present an overview of AP and discuss the role of interdisciplinary teamwork, staff training, patient teaching, and the provision of safety measures for patients and healthcare providers.

  18. Vitamin B3 confers resistance to sulfa drugs in Saccharomyces cerevisiae.

    PubMed

    Kornfeld, Olga; Nichols, Brian P

    2005-10-01

    Sulfa drugs are ubiquitous antibiotics used to treat bacterial infections and diseases caused by eukaryotes, such as Pneumocystis carinii, the leading cause of pneumonia (PCP) in HIV patients. A daily regimen of sulfonamides and multivitamins including vitamin B3 is also recommended for persons with HIV. We show that exogenous vitamin B3 (nicotinate) confers resistance to sulfa drugs in Saccharomyces cerevisiae, a model for P. carinii. We propose a model of metabolic rerouting in which increased nicotinate leads to increased intracellular concentration of p-aminobenzoate, thus leading to sulfonamide resistance.

  19. Sulfa drug screening in yeast: fifteen sulfa drugs compete with p-aminobenzoate in Saccharomyces cerevisiae.

    PubMed

    Castelli, L A; Nguyen, N P; Macreadie, I G

    2001-05-30

    Sulfa drugs have been used as antimicrobials for decades but resistance is now a problem. For major eukaryotic pathogens, including Plasmodium and Pneumocystis, sulfa drug testing is difficult or impossible. We have shown that the eukaryote yeast can be used as a model for the study of sulfa drugs within certain parameters. Fifteen sulfa drugs inhibited yeast growth in a manner indicating competition with p-aminobenzoate (pABA). Such competition resulted from direct addition of pABA or through increased expression of the pABA synthase gene (ABZ1). The model system predicts that overexpression of the pABA synthase gene can lead to drug resistance.

  20. Dapsone-induced pure red cell aplasia and cholestatic jaundice: A new experience for diagnosis and management

    PubMed Central

    Sawlani, Kamal Kumar; Chaudhary, Shyam Chand; Singh, Jitendra; Raja, Deep Chandh; Mishra, Sanjay; Goel, Madhu Mati

    2016-01-01

    Dapsone (4,4’- diaminodiphenylsulfone) is the parent compound of the sulfones, and it has potent antiparasitic, anti-inflammatory, and immunomodulatory effects. It is used in the treatment of leprosy, dermatitis herpetiformis, and prophylactically to prevent Pneumocystis pneumonia and toxoplasmosis in patients unable to tolerate trimethoprim with sulfamethoxazole. We hereby report a case of dapsone toxicity who developed pure red cell aplasia and cholestatic jaundice in a suspected case of dermatitis herpetiformis. Patient had an excellent response to corticosteroids after withdrawal of dapsone. PMID:27512715

  1. Abdominal miliary tuberculosis in a patient with AIDS: a case report.

    PubMed

    Pop, Monica; Pop, Cezar; Homorodean, Daniela; Itu, Corina; Man, Milena; Goron, Monica; Gherasim, Ruxandra; Coroiu, Georgiana

    2003-09-01

    We present a 34 year old patient, intravenous drug user, hospitalized with fever, distortion of general status, dry irritating cough, abdominal colicative pains, and we established the diagnosis of HIV infection advanced stage/AIDS; his antecedents revealed (August 2000) abdominal tuberculosis not treated during the last 3 months. He presented a pneumonia with Pneumocystis carinii during hospitalization. Death was due to a colon perforation with secundary peritonitis. Miliary tuberculous lesions in liver, spleen and colon were revealed at necropsy and cytomegalovirus was identified in necrotic samples also.

  2. Beware the lymphopenia: a case of severe combined immunodeficiency.

    PubMed

    Mehr, Sam; Kakakios, Alyson; Shaw, Peter; Webster, Richard; Kemp, Andrew

    2011-08-01

    We present a case of a 2-month-old boy with partially treated meningitis and suspected Pneumocystis carinii pneumonia. A full blood count revealed profound lymphopenia. The child was diagnosed with adenosine deaminase deficiency, a rare cause of severe combined immunodeficiency (SCID). SCID is an immunological emergency and must be considered in any lymphopaenic infant with opportunistic infection. We discuss adenosine deaminase-deficient SCID, which can involve multiple systems and in which other treatment options apart from bone marrow transplant are available.

  3. Patterns of gallium-67 scintigraphy in patients with acquired immunodeficiency syndrome and the AIDS related complex

    SciTech Connect

    Bitran, J.; Bekerman, C.; Weinstein, R.; Bennett, C.; Ryo, U.; Pinsky, S.

    1987-07-01

    Thirty-two patients with AIDS related complex (ARC) or acquired immunodeficiency syndrome (AIDS) underwent /sup 67/Ga scans as part of their evaluation. Three patterns of /sup 67/Ga biodistribution were found: lymph node uptake alone; diffuse pulmonary uptake; normal scan. Gallium-67 scans were useful in identifying clinically occult Pneumocystis carinii pneumonia in seven of 15 patients with ARC who were asymptomatic and had normal chest radiographs. Gallium scans are a useful ancillary procedure in the evaluation of patients with ARC or AIDS.

  4. Gallium scanning in lymphoid interstitial pneumonitis of children with AIDS

    SciTech Connect

    Schiff, R.G.; Kabat, L.; Kamani, N.

    1987-12-01

    Lymphoid interstitial pneumonitis (LIP) is a frequent pulmonary complication in the child with the acquired immune deficiency syndrome (AIDS) and human immunodeficiency virus (HIV) infection. We report the gallium scan findings in two children with AIDS and LIP. Gallium scintigraphy in both children demonstrated increased radionuclide concentration throughout the lungs, a pattern indistinguishable scintigraphically from that of Pneumocystis carinii pneumonia (PCP). This should alert nuclear medicine practitioners and referring physicians to another cause of diffusely increased gallium uptake in the lungs of patients with AIDS.

  5. [Liver injury and hepatic encephalopathy induced by the herbal medicine Hochuekkito].

    PubMed

    Negishi, Ryoju; Ichikawa, Takeshi; Tawa, Yoshiyuki; Fujimura, Akira; Tanaka, Sayo; Tenmoku, Akira; Akazawa, Kimika; Kanno, Masataka; Sasaki, Hiroshi; Okubo, Sae; Machida, Nobuaki; Fukuda, Yuh; Oi, Itaru; Fujino, Masayuki A

    2014-06-01

    A 57-year-old man was admitted with pruritus and jaundice following treatment for fatigue with the herbal medicine Hochuekkito. The patient was prescribed prednisolone and ursodeoxycholic acid, but he developed progressive cholestasis that required intravenous methylprednisolone pulse therapy. After treatment with plasma exchange for prolonged prothrombin time, the patient recovered; however, his liver function deteriorated because of liver injury induced by trimethoprim-sulfamethoxazole for pneumocystis pneumonia. After reduction of trimethoprim-sulfamethoxazole, his liver function almost returned to normal by day 130 of admission. It has remained normal for 10 months since then. Therefore, when prescribing Hochuekkito, the possibility of drug-induced liver injury should be taken in account.

  6. Sloth biology: an update on their physiological ecology, behavior and role as vectors of arthropods and arboviruses.

    PubMed

    Gilmore, D P; Da Costa, C P; Duarte, D P

    2001-01-01

    This is a review of the research undertaken since 1971 on the behavior and physiological ecology of sloths. The animals exhibit numerous fascinating features. Sloth hair is extremely specialized for a wet tropical environment and contains symbiotic algae. Activity shows circadian and seasonal variation. Nutrients derived from the food, particularly in Bradypus, only barely match the requirements for energy expenditure. Sloths are hosts to a fascinating array of commensal and parasitic arthropods and are carriers of various arthropod-borne viruses. Sloths are known reservoirs of the flagellate protozoan which causes leishmaniasis in humans, and may also carry trypanosomes and the protozoan Pneumocystis carinii.

  7. [EPIDEMIOLOGY OF VISCERAL FUNGAL INFECTION IN FRANCE AND IN THE WORLD].

    PubMed

    Blot, Mathieu; Lanternier, Fanny; Lortholary, Olivier

    2015-12-01

    Invasive fungal infections are severe infections and constantly rising in developed countries. Indeed, advances in hematology, oncology, transplantation and intensive care medicine, are responsible for a longer and deeper immunodepression, in patients which are increasingly older. Only HIV-associated cryptococcosis and Pneumocystis pneumonia are decreasing, in countries where HAART are available and have been able to restore immunity. An increase in the antifungal therapies exposure lead to the emergence of less susceptible species/isolates to usual treatments, and other fungi (Mucorales, Scedosporium, Fusarium). However, in developing countries where access to HAART is limited, cryptococcosis remains a major public health. To a lesser degree, some endemic mycoses are on the rise.

  8. Bubble continuous positive airway pressure in a human immunodeficiency virus-infected infant

    PubMed Central

    McCollum, E. D.; Smith, A.; Golitko, C. L.

    2014-01-01

    SUMMARY World Health Organization-classified very severe pneumonia due to Pneumocystis jirovecii infection is recognized as a life-threatening condition in human immunodeficiency virus (HIV) infected infants. We recount the use of nasal bubble continuous positive airway pressure (BCPAP) in an HIV-infected African infant with very severe pneumonia and treatment failure due to suspected infection with P. jirovecii. We also examine the potential implications of BCPAP use in resource-poor settings with a high case index of acute respiratory failure due to HIV-related pneumonia, but limited access to mechanical ventilation. PMID:21396221

  9. Cutaneous gallium uptake in patients with AIDS with mycobacterium avium-intracellulare septicemia

    SciTech Connect

    Allwright, S.J.; Chapman, P.R.; Antico, V.F.; Gruenewald, S.M.

    1988-07-01

    Gallium imaging is increasingly being used for the early detection of complications in patients with AIDS. A 26-year-old homosexual man who was HIV antibody positive underwent gallium imaging for investigation of possible Pneumocystis carinii pneumonia. Widespread cutaneous focal uptake was seen, which was subsequently shown to be due to mycobacterium avium-intracellulare (MAI) septicemia. This case demonstrates the importance of whole body imaging rather than imaging target areas only, the utility of gallium imaging in aiding the early detection of clinically unsuspected disease, and shows a new pattern of gallium uptake in disseminated MAI infection.

  10. Detection of thoracic infections by nuclear medicine techniques in the acquired immunodeficiency syndrome

    SciTech Connect

    Kramer, E.L.; Sanger, J.J. )

    1989-11-01

    The challenge of the acquired immunodeficiency syndrome (AIDS) for nuclear medicine has been the early detection of related intrathoracic opportunistic infections, inflammatory conditions, and neoplasms. Gallium-67 citrate scanning has proved a sensitive test not only for Pneumocystis carinii pneumonia but for many of the other opportunistic infections and malignancies, including mycobacterial infections and lymphoma. Patterns and intensity of gallium uptake may suggest more specific diagnoses. Indium-111-labeled white blood cells may also be a valuable diagnostic tool in the AIDS patient.41 references.

  11. Drug-induced Pneumonitis Following the Administration of TAS-102

    PubMed Central

    Hasegawa, Yoshikazu; Ota, Takayo; Tsukuda, Hiroshi; Suzumura, Tomohiro; Fukuoka, Masahiro

    2016-01-01

    A 59-year-old woman, diagnosed with advanced rectal cancer, presented with a low-grade fever and dyspnea on exertion after the 2nd cycle of TAS-102. TAS-102 has promising efficacy in patients with metastatic colorectal cancer. A CT scan revealed mosaic patterns with bilateral ground-glass opacities. The drug lymphocyte stimulation test for TAS-102 was strongly positive and serum β-D glucan level was elevated. The clinical course was compatible with TAS-102-induced pneumonitis combined with pneumocystis pneumonia (PCP). We herein report a rare case of drug-induced pneumonitis in a patient receiving TAS-102 in combination with PCP. PMID:27725548

  12. AIDS and UK respiratory physicians: attitudes to confidentiality, infection control, and management.

    PubMed Central

    Church, S; Owen, S; Woodcock, A A

    1990-01-01

    Respiratory physicians are concerned in the management of most patients with AIDS. Attitudes and practices of 463 respiratory physicians in the United Kingdom in relation to confidentiality, infection control, and treatment were sought by questionnaire from December 1987 to March 1988; 266 replies were received. Thirty eight per cent of respondents had not seen an HIV positive patient at the time of the survey. Respiratory physicians followed General Medical Council guidelines in relation to consent and confidentiality, except that if the patient's consent was withheld three quarters of the physicians would still inform an at risk hospital health care worker; only a quarter, however, would inform an at risk spouse. Routine infection control was frequently inadequate and "disease specific"--that is, substantially increased for known HIV positive patients. Given an HIV positive patient with respiratory symptoms and an abnormal chest radiograph, two thirds of respiratory physicians said that they would treat empirically for Pneumocystis carinii pneumonia as opposed to immediate bronchoscopy for accurate diagnosis. If a patient with AIDS who had pneumocystis pneumonia developed respiratory failure, half the physicians said at that time that they would elect not to ventilate the patient. PMID:2321178

  13. Cloning and nucleotide sequence of a specific DNA fragment from Paracoccidioides brasiliensis.

    PubMed

    Goldani, L Z; Maia, A L; Sugar, A M

    1995-06-01

    We cloned and sequenced a species-specific 110-bp DNA fragment from Paracoccidioides brasiliensis. The DNA fragment was generated by PCR with primers complementary to the rat beta-actin gene under a low annealing temperature. Comparison of the nucleotide sequence, after excluding the primers, with those in the GenBank database identified approximately 60% homology with an exon of a major surface glycoprotein gene from Pneumocystis carinii and a fragment of unknown function in Saccharomyces cerevisiae chromosome VIII. By Southern hybridization analysis, the 32P-labelled fragment detected 1.0- and 1.9-kb restriction fragments within whole-cell genomic DNA of P. brasiliensis digested with HindIII and PstI, respectively, but failed to hybridize to genomic DNAs from Candida albicans, Blastomyces dermatitidis, Cryptococcus neoformans, Aspergillus fumigatus, Saccharomyces cerevisiae, Pneumocystis carinii, rat tissue, or humans under low-stringency hybridization conditions. Additionally, the specific DNA fragment from three different P. brasiliensis isolates (Pb18, RP18, RP17) was amplified by PCR with primers mostly complementary to nonactin sequences of the 110-bp DNA fragment. In contrast, there were no amplified products from other fungus genomic DNAs previously tested, including Histoplasma capsulatum. To date, this is the first species-specific DNA fragment cloned from P. brasiliensis which might be useful as a diagnostic marker for the identification and classification of different P. brasiliensis isolates.

  14. Diagnostic fiberoptic bronchoscopy: Techniques and results of biopsy in 600 patients.

    PubMed

    Zavala, D C

    1975-07-01

    Six hundred patients underwent diagnostic flexible fiberoptic bronchoscopy (FFB). The two diseases most frequently encountered were bronchogenic carcinoma in 330 patients (55 percent) and bacterial infection in 94 (16 percent). A positive cytology on biopsy material was obtained in 279 of 330 patients (85 percent) with primary lung cancer. Fluoroscopy was a valuable aid in diagnosing bronchogenic carcinoma, since 42 percent of the tumors were not visible endoscopically and required fluoroscopic control for placement of the biopsy instrument. Of the 55 patients with hemoptysis and negative chest x-ray films, nine (15 percent) had fiberoptically visible endobronchial carcinomas! In addition, two patients with carcinoma of the larynx and one with carcinoma of the nasopharynx were discovered. Transbronchial biopsy (TBB) in 68 patinets with diffuse and localized disease achieved an overall 69 percent diagnostic success, including a correct diagnosis in each of four patients with Pneumocystis carinii pneumonia. Brush biopsy provided additional valuable laboratory data in bacterial, mycobacterial and cytomegalovirsu infectious but had a poor yield in Pneumocystis infection. Complications as a result of forceps biopsy were minimal, except for brisk bleeding in six patients.

  15. Epidemiology and clinical features of HIV infection/AIDS in Korea.

    PubMed

    Kim, June Myung; Cho, Goon Jae; Hong, Sung Kwan; Chang, Kyung Hee; Chung, Joo Sup; Choi, Young Hwa; Song, Young Goo; Huh, Aejung; Yeom, Joon Sup; Lee, Kkot Sil; Choi, Jun Yong

    2003-06-30

    HIV infection/AIDS shows characteristic epidemiological and clinical patterns according to the region, country, and race. The epidemiological and clinical patterns of HIV infection/ AIDS in Korea was investigated by retrospectively analyzing the medical records of 176 HIV-infected persons who visited two major referral hospitals of AIDS in Korea from 1985 to April 2000. The most common transmission route was heterosexual contact (52.3%), followed by homosexual contact (23.9%). Among the opportunistic diseases, candidiasis was the most prevalent (21.6%), followed by Pneumocystis carinii pneumonia (15.9%), tuberculosis (12.5%), and CMV infection (9.1%). The most common initial AIDS-defining opportunistic disease was tuberculosis (33.3%). The most common causes of death were tuberculosis (25.7%) and Pneumocystis carinii pneumonia (25.7%). This study describes the epidemiological and clinical patterns of HIV infection/AIDS in Korea, which not only enables us to accurately understand HIV infection/ AIDS in this country, but eventually to aid in establishing effective preventive measures and treatment guidelines in Korea.

  16. PCR Improves Diagnostic Yield from Lung Aspiration in Malawian Children with Radiologically Confirmed Pneumonia

    PubMed Central

    Carrol, Enitan D.; Mankhambo, Limangeni A.; Guiver, Malcolm; Banda, Daniel L.; Denis, Brigitte; Dove, Winifred; Jeffers, Graham; Molyneux, Elizabeth M.; Molyneux, Malcolm E.; Graham, Stephen M.

    2011-01-01

    Background Accurate data on childhood pneumonia aetiology are essential especially from regions where mortality is high, in order to inform case-management guidelines and the potential of prevention strategies such as bacterial conjugate vaccines. Yield from blood culture is low, but lung aspirate culture provides a higher diagnostic yield. We aimed to determine if diagnostic yield could be increased further by polymerase chain reaction (PCR) detection of bacteria (Streptococcus pneumoniae and Haemophilus influenzae b) and viruses in lung aspirate fluid. Methods A total of 95 children with radiological focal, lobar or segmental consolidation had lung aspirate performed and sent for bacterial culture and for PCR for detection of bacteria, viruses and Pneumocystis jirovecii. In children with a pneumococcal aetiology, pneumococcal bacterial loads were calculated in blood and lung aspirate fluid. Results Blood culture identified a bacterial pathogen in only 8 patients (8%). With the addition of PCR on lung aspirate samples, causative pathogens (bacterial, viral, pneumocystis) were identified singly or as co-infections in 59 children (62%). The commonest bacterial organism was S.pneumoniae (41%), followed by H. influenzae b (6%), and the commonest virus identified was adenovirus (16%), followed by human bocavirus (HBoV) (4%), either as single or co-infection. Conclusions In a select group of African children, lung aspirate PCR significantly improves diagnostic yield. Our study confirms a major role of S.pneumoniae and viruses in the aetiology of childhood pneumonia in Africa. PMID:21695128

  17. Nonspecific interstitial pneumonitis: a common cause of pulmonary disease in the acquired immunodeficiency syndrome

    SciTech Connect

    Suffredini, A.F.; Ognibene, F.P.; Lack, E.E.; Simmons, J.T.; Brenner, M.; Gill, V.J.; Lane, H.C.; Fauci, A.S.; Parrillo, J.E.; Masur, H.

    1987-07-01

    During a 4.4-year period, nonspecific interstitial pneumonitis was seen in 41 of 110 (38%) patients with the acquired immunodeficiency syndrome and accounted for 32% (48/152) of all episodes of clinical pneumonitis. Diffuse alveolar damage was typically a feature of nonspecific interstitial pneumonitis, but neither lung biopsy nor bronchoalveolar lavage detected a pathogen. Of these 41 patients, 13 had no associated pulmonary tumor and had not been exposed to pulmonary toxins, whereas 28 patients had either concurrent pulmonary Kaposi sarcoma, previous experimental therapies, or a history of pneumocystis pneumonia or drug abuse. Of these 41, 23 had normal chest radiographs. The clinical features of patients with nonspecific interstitial pneumonitis were similar to those of patients with pneumocystis pneumonia, although histologic findings showed less severe alveolar damage in patients with nonspecific interstitial pneumonitis (p less than 0.001). Pathologic evaluation and clinical follow-up suggest that many clinical episodes of pneumonitis in patients with the acquired immunodeficiency syndrome are due to nonspecific interstitial pneumonitis of unknown cause.

  18. Cloning and nucleotide sequence of a specific DNA fragment from Paracoccidioides brasiliensis.

    PubMed Central

    Goldani, L Z; Maia, A L; Sugar, A M

    1995-01-01

    We cloned and sequenced a species-specific 110-bp DNA fragment from Paracoccidioides brasiliensis. The DNA fragment was generated by PCR with primers complementary to the rat beta-actin gene under a low annealing temperature. Comparison of the nucleotide sequence, after excluding the primers, with those in the GenBank database identified approximately 60% homology with an exon of a major surface glycoprotein gene from Pneumocystis carinii and a fragment of unknown function in Saccharomyces cerevisiae chromosome VIII. By Southern hybridization analysis, the 32P-labelled fragment detected 1.0- and 1.9-kb restriction fragments within whole-cell genomic DNA of P. brasiliensis digested with HindIII and PstI, respectively, but failed to hybridize to genomic DNAs from Candida albicans, Blastomyces dermatitidis, Cryptococcus neoformans, Aspergillus fumigatus, Saccharomyces cerevisiae, Pneumocystis carinii, rat tissue, or humans under low-stringency hybridization conditions. Additionally, the specific DNA fragment from three different P. brasiliensis isolates (Pb18, RP18, RP17) was amplified by PCR with primers mostly complementary to nonactin sequences of the 110-bp DNA fragment. In contrast, there were no amplified products from other fungus genomic DNAs previously tested, including Histoplasma capsulatum. To date, this is the first species-specific DNA fragment cloned from P. brasiliensis which might be useful as a diagnostic marker for the identification and classification of different P. brasiliensis isolates. PMID:7650207

  19. Design, synthesis and molecular modeling of novel pyrido[2,3-d]pyrimidine analogs as antifolates: Application of Buchwald-Hartwig aminations of heterocycles

    PubMed Central

    Gangjee, Aleem; Namjoshi, Ojas A.; Raghavan, Sudhir; Queener, Sherry F.; Kisliuk, Roy L.; Cody, Vivian

    2013-01-01

    Opportunistic infections caused by Pneumocystis jirovecii (P. jirovecii, pj), Toxoplasma gondii (T. gondii, tg) and Mycobacterium avium (M. avium, ma) are the principal causes of morbidity and mortality in patients with acquired immunodeficiency syndrome (AIDS). The absence of any animal models for human Pneumocystis jirovecii pneumonia and the lack of crystal structures of pjDHFR and tgDHFR make the design of inhibitors challenging. A novel series of pyrido[2,3-d]pyrimidines as selective and potent DHFR inhibitors against these opportunistic infections are presented. Buchwald-Hartwig coupling reaction of substituted anilines with pivaloyl protected 2,4-diamino-6-bromo-pyrido[2,3-d]pyrimidine was successfully explored to synthesize these analogs. Compound 26 was the most selective inhibitor with excellent potency against pjDHFR. Molecular modeling studies with a pjDHFR homology model explained the potency and selectivity of 26. Structural data are also reported for 26 with pcDHFR and 16 and 22 with variants of pcDHFR. PMID:23627352

  20. Atovaquone for Prophylaxis of Toxoplasmosis after Allogeneic Hematopoietic Stem Cell Transplantation.

    PubMed

    Mendorf, Alexander; Klyuchnikov, Evgeny; Langebrake, Claudia; Rohde, Holger; Ayuk, Francis; Regier, Marc; Christopeit, Maximilian; Zabelina, Tatjana; Bacher, Adelbert; Stübig, Thomas; Wolschke, Christine; Bacher, Ulrike; Kröger, Nicolaus

    2015-01-01

    Toxoplasmosis and infections by other opportunistic agents such as Pneumocystis jirovecii constitute life-threatening risks for patients after allogeneic hematopoietic stem cell transplantation. Trimethoprim/sulfamethoxazole (TMP-SMX) has been well established for post-transplant toxoplasmosis and pneumocystis prophylaxis, but treatment may be limited due to toxicity. We explored atovaquone as an alternative and compared it with TMP-SMX regarding toxicity and efficacy during the first 100 days after transplantation in 155 consecutive adult stem cell recipients. Eight patients with a prior history of TMP-SMX intolerance received atovaquone as first-line prophylaxis. TMP-SMX was used for 141 patients as first-line strategy, but 13 patients (9.2%) were later switched to atovaquone due to TMP-SMX toxicity or gastrointestinal symptoms. No active toxoplasmosis or active P. jirovecii infection developed under continued prophylaxis with either TMP-SMX or atovaquone. However, for reasons of TMP-SMX and/or atovaquone toxicity, 7 patients were unable to tolerate any efficacious toxoplasmosis prophylaxis and therefore obtained inhalative pentamidine as P. jirovecii prophylaxis but no toxoplasmosis prophylaxis. Importantly, 2 of these patients developed severe toxoplasmosis. In summary, atovaquone appears as a valid alternative for at least some post-transplant patients who cannot tolerate TMP-SMX. This should be further confirmed by multicenter trials.

  1. Design of anti-parasitic and anti-fungal hydroxy-naphthoquinones that are less susceptible to drug resistance

    PubMed Central

    Hughes, Louise M.; Lanteri, Charlotte A.; O’Neil, Michael T.; Johnson, Jacob D.; Gribble, Gordon W.; Trumpower, Bernard L.

    2016-01-01

    Atovaquone is a hydroxy-naphthoquinone that is used to treat parasitic and fungal infections including Plasmodium falciparum (malaria), Pneumocystis jivorecii (pneumonia) and Toxoplasma gondii (toxoplasmosis). It blocks mitochondrial oxidation of ubiquinol in these organisms by binding to the ubiquinol oxidation site of the cytochrome bc1 complex. Failure of atovaquone treatment has been linked to the appearance of mutations in the mitochondrially encoded gene for cytochrome b. In order to determine the optimal parameters required for inhibition of respiration in parasites and pathogenic fungi and overcome drug resistance, we have synthesized and tested the inhibitory activity of novel hydroxy-naphthoquinones against blood stage P. falciparum and liver stage P. berghei and against cytochrome bc1 complexes isolated from yeast strains bearing mutations in cytochrome b associated with resistance in Plasmodium, Pneumocystis, and Toxoplasma. One of the new inhibitors is highly effective against an atovaquone resistant Plasmodium and illustrates the type of modification to the hydroxy-naphthoquinone ring of atovaquone that might mitigate drug resistance. PMID:21251932

  2. THE UTILITY OF BRONCHOALVEOLAR LAVAGE BETA-D-GLUCAN TESTING FOR THE DIAGNOSIS OF INVASIVE FUNGAL INFECTIONS

    PubMed Central

    Rose, Stacey R.; Vallabhajosyula, Saraschandra; Velez, Miguel G.; Fedorko, Daniel P.; VanRaden, Mark J.; Gea-Banacloche, Juan C.; Lionakis, Michail S.

    2014-01-01

    SUMMARY Objectives To investigate the utility of beta-D-glucan (BDG) testing in bronchoalveolar lavage (BAL) fluid for the diagnosis of invasive fungal infection (IFI), as compared to BAL galactomannan (GM). Methods We retrospectively reviewed medical records of 132 consecutive patients at the National Institutes of Health (NIH) in whom BAL BDG testing was performed for diagnosis of pneumonia. Using the European Organization for Research and Treatment of Cancer/Mycoses Study Group guidelines, we determined which patients had proven or probable IFI, and assessed the diagnostic performance of BAL BDG testing, relative to BAL GM. We also determined the reproducibility of the BDG assay in BAL via repeat testing of patient samples. Results Ten patients had Pneumocystis pneumonia, and 34 patients had proven/probable IFI, including 14 with invasive aspergillosis (IA). BAL BDG was 100% sensitive for Pneumocystis. Although BAL BDG had similar sensitivity to BAL GM for the diagnosis of IA and IFI, it exhibited inferior specificity. Repeat testing demonstrated poor reproducibility of the BDG assay in BAL but not in serum. Conclusions BDG testing exhibits poor specificity and reproducibility in BAL. Identification of the BAL-specific factors that may interfere with the performance of the assay could improve the clinical usefulness of BAL BDG testing. PMID:24797077

  3. The pharmacoeconomics of HIV disease.

    PubMed

    Lynn, L A; Schulman, K A; Eisenberg, J M

    1992-03-01

    Human immunodeficiency virus (HIV) infection is a major public health problem in all parts of the world. For the United States, federal spending on HIV disease for 1982 to 1989 was $US5.5 billion. Projections indicate that AIDS spending may reach 1.6% of total health expenditures in 1992, while the indirect costs of HIV infection may be 5 times as great as the direct costs. In the developing world, the cost per person with HIV infection may be 0.8- to 9-fold greater than the per capita gross national product (GNP). Pharmacoeconomic analysis has been used to assess 2 important therapeutic options in caring for HIV patients: zidovudine therapy for asymptomatic illness, and prophylaxis for Pneumocystis carinii pneumonia (PCP). The cost-effectiveness ratio for zidovudine therapy, $US6553 to $US70 526 per year of life saved, compares favourably with ratios for other medical therapies. Prophylaxis against Pneumocystis carinii pneumonia has been shown to be most efficient using oral dapsone or cotrimoxazole (trimethoprim-sulfamethoxazole). Pharmacological therapy for HIV is costly, however, and may limit the access to new therapies for patients in the developing world. Concurrent economic assessment of therapies during phase III trials may serve as an essential part of the research that will advance international efforts to combat this disease.

  4. Emerging trends in the epidemiology of invasive mycoses in England and Wales (1990-9).

    PubMed

    Lamagni, T L; Evans, B G; Shigematsu, M; Johnson, E M

    2001-06-01

    Invasive fungal infections are becoming an increasing public health problem owing to the growth in numbers of susceptible individuals. Despite this, the profile of mycoses remains low and there is no surveillance system specific to fungal infections currently existing in England and Wales. We analysed laboratory reports of deep-seated mycoses made to the Communicable Disease Surveillance Centre between 1990 and 1999 from England and Wales. A substantial rise in candidosis was seen during this period (6.76-13.70 reports per million population/year), particularly in the older age groups. Rates of cryptococcosis in males fluctuated over the decade but fell overall (1.05-0.66 per million population/year), whereas rates of female cases gradually rose up until 1998 (0.04-0.41 per million population/year). Reports of Pneumocystis carinii in men reduced substantially between 1990 and 1999 (2.77-0.42 per million population/year) but showed little change in women. Reports of aspergillosis fluctuated up until 1996, after which reports of male and female cases rose substantially (from 0.08 for both in 1996 to 1.92 and 1.69 per million population/year in 1999 for males and females respectively), largely accounted for by changes in reporting practice from one laboratory. Rates of invasive mycoses were generally higher in males than females, with overall male-to-female rate ratios of 1.32 (95% CI 1.25-1.40) for candidosis, 1.30 (95% CI 1.05-1.60) for aspergillosis, 3.99 (95% CI 2.93-5.53) for cryptococcosis and 4.36 (95% CI 3.47-5.53) for Pneumocystis carinii. The higher male than female rates of reports is likely to be a partial reflection of HIV epidemiology in England and Wales, although this does not fully explain the ratio in infants and older age groups. Lack of information on underlying predisposition prevents further identification of risk groups affected. Whilst substantial under-reporting of Pneumocystis carinii and Cryptococcus species was apparent, considerable

  5. Incidence of acquired immunodeficiency syndrome-associated opportunistic diseases and the effect of treatment on a cohort of 1115 patients infected with human immunodeficiency virus, 1989-1997.

    PubMed

    San-Andrés, Francisco-Javier; Rubio, Rafael; Castilla, Jesús; Pulido, Federico; Palao, Guillermo; de Pedro, Inmaculada; Costa, José-Ramón; del Palacio, Angel

    2003-05-01

    Temporal trends in the incidence of opportunistic diseases (ODs) related to acquired immunodeficiency syndrome (AIDS) were studied during 1989-1997 in 1115 outpatients infected with human immunodeficiency virus (331 of whom had AIDS) in a hospital in Madrid, Spain. We analyzed the effect of adherence to antiretroviral therapy and Pneumocystis carinii pneumonia (PCP) prophylaxis on the incidence of OD. Diseases that showed a significant decreasing trend were esophageal candidiasis, pulmonary and extrapulmonary tuberculosis, and cerebral toxoplasmosis. Patients who adhered to antiretroviral therapy had a smaller risk of OD. Patients who adhered to PCP prophylaxis had a reduced risk of cerebral toxoplasmosis and PCP. A reduction in the incidence of AIDS-related ODs was observed, mainly in patients who underwent prophylaxis. Adherence to antiretroviral treatment and PCP prophylaxis was associated with a reduction in the risk of disease.

  6. [General epidemiology of invasive fungal disease].

    PubMed

    Pemán, Javier; Salavert, Miguel

    2012-02-01

    Invasive mycoses associated with high morbidity and mortality rates are increasing among immunocompromised or severely ill patients. Candida, Cryptococcus, Pneumocystis and Aspergillus are most prevalent agents with varying distribution as regards geography, patient condition and hospital units. The latest multicentre candidaemia survey conducted in Spain, showed C. albicans as the most frequently isolated species followed by C. parapsilosis, C. glabrata, C. tropicalis and C. krusei in contrast with other European or American studies where C. glabrata was second in rank. Aspergillus spp. is the leading agent causing invasive mycoses among filamentous fungi followed by Fusarium spp., Scedosporium spp. and zygomycetes. Aspergillus fumigatus is the most common agent in invasive aspergillosis (and azole-resistant isolates have been reported) but in the last few years Aspergillus flavus, Aspergillus nidulans and Aspergillus terreus have been isolated with increasing frequency variable with geographical factors, patients' underlying conditions or previous antifungal treatments.

  7. [Czech eponyms in pathology].

    PubMed

    Steiner, Ivo

    2013-01-01

    The 24th European Congress of Pathology taking place in Prague is an opportunity to remind our society of the Czech names appearing as eponyms in pathological terminology: Karel Rokitanský - R. protuberance in dermoid cyst; R. thrombogenic theory of atherosclerosis; Mayer - R. - Küster - Hauser - Winckel syndrome (congenital malformation of the vagina and uterus); Václav Treitz - T. duodenal ligament; T. retroperitoneal hernia; T. uremic colitis; Vilém Dušan Lambl - L. excrescences of heart valves; Lamblia (Giardia) intestinalis, and also the foundation of urological cytology; Stanislav Provázek - Prowazek - Halberstädter bodies (trachoma), Rickettsia Prowazeki (typhus fever); Josef Vaněk - V. tumor (gastric inflammatory fibroid polyp), and also discovery of the etiology of pneumocystic pneumonia; Otto Jírovec - Pneumocystis Jiroveci; Blahoslav Bednář - B. tumor (pigmented dermatofibrosarcoma protuberans).

  8. Preventative and therapeutic vaccines for fungal infections: from concept to implementation.

    PubMed

    Deepe, George S

    2004-12-01

    Many challenges confront the development of fungal vaccines for humans including differences in host susceptibility, varied pathogenic mechanisms employed by the different species of fungi and mechanisms of host resistance. Hence, no single antigen can be expected to serve as a pan fungal vaccine. Instead, it is likely that progress for fungal vaccines will have to be made at the level of each individual organism. In recent years, tremendous strides have been made in understanding the immunopathogenesis of medically important fungal infections and identifying putative vaccine candidates. Such discoveries will facilitate the introduction of fungal vaccines into the therapeutic armamentarium of clinicians. The fungi under discussion in this review include Candida spp., Aspergillus spp., Cryptococcus neoformans, Coccidioides spp., Histoplasma capsulatum, Blastomyces dermatitidis, Paracoccidioides brasiliensis and Pneumocystis jirovecii.

  9. Excessive naked megakaryocyte nuclei in myelodysplastic syndrome mimicking idiopathic thrombocytopenic purpura: a complicated pre- and post-transplantation course.

    PubMed

    Olcay, Lale; Tuncer, A Murat; Okur, Hamza; Erdemli, Esra; Uysal, Zumrut; Cetin, Mualla; Duru, Feride; Cetinkaya, Duygu Uckan

    2009-09-01

    A boy 3 years 7 months old with thrombocytopenia and history of intracranial hemorrhage who underwent bone marrow transplantation is presented. He was refractory to steroids, immunoglobulin G, vincristine, azathioprine, cyclosporine A, interleukin-11, chemotherapy, and splenectomy. Idiopathic thrombocytopenic purpura was excluded by light /electron microscopic and flow cytometric findings; the diagnosis of refractory cytopenia, a subgroup of pediatric myelodysplastic syndrome, was made. Naked megakaryocyte nuclei were 55.38 +/- 28.2% vs. 31.67 +/- 23.22% of all megakaryocytes in the patient and the control group of 9 patients with idiopathic thrombocytopenic purpura, respectively (p = .016). The posttransplatation course was complicated by delayed platelet engraftment, bronchiolitis obliterans associated with pneumocystis carinii pneumonia, which resolved completely.

  10. 'Infectious web'.

    PubMed

    Kotra, L P; Ojcius, D M

    2000-07-01

    Infections by Helicobacter pylori are responsible for duodenal and gastric ulcers and are a significant risk factor for the development of gastric adenocarcinoma. H. pylori was discovered in 1983, but many institutes in Canada, Europe, and the United States are already involved in programs to understand and treat the infections, as reflected by the growing number of internet sites devoted to this bacterium. Most AIDS patients and about 20% of children with acute lymphoblastic leukemia develop Pneumocystis carinii pneumoniae. Information on clinical symptoms and treatment, as well as the P. carinii genome sequencing project, are described at several web sites. Students and researchers wishing to understand the correlation between telomere length and AIDS may turn to web sites of the University of Colorado and Washington University School of Medicine for the latest on telomeres and telomerase, and their function in aging and cancer.

  11. The prevalence and management of pain in patients with AIDS: a review of 134 cases.

    PubMed

    Lebovits, A H; Lefkowitz, M; McCarthy, D; Simon, R; Wilpon, H; Jung, R; Fried, E

    1989-09-01

    In light of the lack of any prior systematic evaluations of the prevalence and types of pain syndromes and treatments found in patients with AIDS, a chart review study was undertaken to evaluate this issue. Fifty-two of 96 charts reviewed (54%) had at least one note on nonprocedural pain or analgesic prescription. Although chest pain was the most prevalent pain location (22%), presumably because of the high incidence of Pneumocystis carinii pneumonia, other possible AIDS-related entities, such as peripheral neuropathy and thrombophlebitis, were also found. No specific AIDS syndromes could be identified that were related to a higher incidence of pain. Nearly one-third of patients with pain received codeine (31%), others received acetaminophen (27%), and 17% of patients received acetaminophen and oxycodone HCl. Specific pain management interventions must be evaluated and applied to control the nontrivial occurrence of pain in patients who have AIDS symptoms that may be overlooked by the physician given the overwhelming disease process.

  12. Human immunodeficiency virus infection in Singapore--the first 50 cases.

    PubMed

    Chew, S K; Chan, R; Monteiro, E H; Sng, E H

    1990-12-01

    As at 31 May 1990, fifty Singaporeans with the Human Immunodeficiency Virus (HIV) infection had been detected. Of these, nineteen had the Acquired Immunodeficiency Syndrome (AIDS). The majority of infected persons had been infected through sexual contact (homosexual 52%; bisexual 24%; heterosexual 20%) with men and women from countries where HIV infection was prevalent. The majority of infected patients (88%) were in the age range 20-39 years. There was one case of blood transfusion-associated AIDS. There were no infected paediatric or haemophiliac cases or intravenous drug use in any of the patients. A spectrum of AIDS-related opportunistic infections and cancers was observed, and Pneumocystis carinii pneumonia was the most frequent presentation. Thirteen patients with AIDS had died and the median survival time was about seven months.

  13. The respiratory presentation of severe combined immunodeficiency in two Mennonite children at a tertiary centre highlighting the importance of recognizing this pediatric emergency

    PubMed Central

    Lam, Simon; Kavadas, Fotini D; Haider, Seemab; Noseworthy, Mary E

    2014-01-01

    Severe combined immunodeficiency (SCID) is considered to be a pediatric emergency, with respiratory distress being the most common presenting symptom. The authors present two cases of SCID in children <4 months of age with respiratory distress at a tertiary care centre due to a recently described homozygous CD3 delta mutation found only in the Mexican Mennonite population. Failure to respond to broad-spectrum antibiotics prompted investigation for possible SCID. Bronchial alveolar lavage fluid from both patients grew Pneumocystis jiroveci, and flow cytometry revealed absent T cells. The CD3 delta gene is believed to be important in T cell differentiation and maturation. The present article reminds pediatricians and pediatric respirologists that the key to diagnosing SCID is to have a high index of suspicion if there is poor response to conventional therapies. PMID:24288697

  14. Supreme Court says suit against insurer can continue.

    PubMed

    1996-04-05

    The Oregon Supreme Court is allowing the estate of [name removed], a restaurant worker, to seek damages against an insurance company that refused to cover his employer when it was determined that [name removed] had Pneumocystis carinii pneumonia, an AIDS-defining condition. [Name removed]'s lawsuit charges that the PAAC Health Plan Inc. denied the application for insurance filed by employer [name removed] [name removed] of the Old Wives' Tales Restaurant. [Name removed] sued PAAC, [name removed], and the insurance broker. Before [name removed]'s death in August 1993, an appeals court voted 2-1 to affirm a trial judge's decision to dismiss claims against the broker, but reversed an order granting summary judgment to PAAC. State Supreme Court Justice Wallace P. Carson, Jr., heard PAAC's appeal and ruled that [name removed]'s estate could proceed with claims against PAAC.

  15. Delivering on Antimicrobial Resistance Agenda Not Possible without Improving Fungal Diagnostic Capabilities

    PubMed Central

    Perlin, David S.; Muldoon, Eavan G.; Colombo, Arnaldo Lopes; Chakrabarti, Arunaloke; Richardson, Malcolm D.; Sorrell, Tania C.

    2017-01-01

    Antimicrobial resistance, a major public health concern, largely arises from excess use of antibiotic and antifungal drugs. Lack of routine diagnostic testing for fungal diseases exacerbates the problem of antimicrobial drug empiricism, both antibiotic and antifungal. In support of this contention, we cite 4 common clinical situations that illustrate this problem: 1) inaccurate diagnosis of fungal sepsis in hospitals and intensive care units, resulting in inappropriate use of broad-spectrum antibacterial drugs in patients with invasive candidiasis; 2) failure to diagnose chronic pulmonary aspergillosis in patients with smear-negative pulmonary tuberculosis; 3) misdiagnosis of fungal asthma, resulting in unnecessary treatment with antibacterial drugs instead of antifungal drugs and missed diagnoses of life-threatening invasive aspergillosis in patients with chronic obstructive pulmonary disease; and 4) overtreatment and undertreatment of Pneumocystis pneumonia in HIV-positive patients. All communities should have access to nonculture fungal diagnostics, which can substantially benefit clinical outcome, antimicrobial stewardship, and control of antimicrobial resistance. PMID:27997332

  16. Case of Steven-Johnson Syndrome in a male with breast cancer secondary to docetaxel/cyclophosphamide therapy.

    PubMed

    Jarrett, Benjamin; Ghazala, Sehem; Chao, Joseph; Chaudhary, Sachin

    2016-11-15

    The mortality rate for Stevens-Johnson syndrome (SJS) is estimated to be ∼12% and for toxic epidermal necrolysis (TEN) it is around 30%. It continues to be a severe life-threatening drug reaction. We present a 60-year-old Caucasian man with a medical history significant for breast cancer status post mastectomy and chemotherapy with docetaxel and cyclophosphamide who presented with severe mucositis and a progressing skin rash consistent with SJS. He was started on high-dose corticosteroids and IVIG but continued to have worsening mucosal ulcerations and severe bleeding from the oral, conjunctival and genital mucosa. He underwent several rounds of plasmapheresis and additional high-dose steroids with mild improvement in the mucocutaneous manifestations. He subsequently developed respiratory failure, which required mechanical ventilation, as well as disseminated intravascular coagulation, diffuse alveolar haemorrhage, with Pneumocystis jirovecii pneumonia which led to his demise on hospital day 15.

  17. Trimethoprim-sulfamethoxazole-induced Steven Johnson syndrome in an HIV-infected patient.

    PubMed

    Taqi, Syed Ahmed; Zaki, Syed Ahmed; Nilofer, Angadi Rajasab; Sami, Lateef Begum

    2012-01-01

    Trimethoprim-sulfamethoxazole (TMP/SMX) is a widely prescribed antimicrobial for the management of several uncomplicated infections. It is commonly used for the treatment and prophylaxis of Pneumocystis jirovecii pneumonia (PCP) in the HIV-infected population. The adverse reaction to TMP/SMX is more frequent and severe in HIV-infected patients as compared to the general population. Here, we report a case of Stevens-Johnson syndrome (SJS) secondary to TMP/SMX. The patient had a generalized cutaneous reaction with involvement of the eyes, oral cavity, and genitals. He had elevated hepatic alanine aminotransferase and aspartate aminotransferase enzyme. TMP/SMX therapy was stopped and supportive treatment was started. His condition improved after eight days of stopping TMP/SMX therapy.

  18. The 2015 Clinical Guidelines for the Treatment and Prevention of Opportunistic Infections in HIV-Infected Koreans: Guidelines for Opportunistic Infections

    PubMed Central

    2016-01-01

    The Committee for Clinical Guidelines for the Treatment and Prevention of Opportunistic Infections of the Korean Society for AIDS was founded in 2011. The first edition of the Korean guidelines was published in 2012. The guideline recommendations contain important information for physicians working with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) in the clinical field. It has become necessary to revise the guidelines due to new data in this field. These guidelines aim to provide up-to-date, comprehensive information regarding the treatment and prevention of opportunistic infections in HIV-infected Koreans. These guidelines deal with several common opportunistic infections, including pneumocystis pneumonia, tuberculosis, cryptococcal meningitis, etc. A brief summary of the revised guidelines is provided below. Recommendations are rated using the same system used in the previous guidelines. PMID:27104018

  19. Tetrahydrobiopterin biosynthesis as an off-target of sulfa drugs.

    PubMed

    Haruki, Hirohito; Pedersen, Miriam Grønlund; Gorska, Katarzyna Irena; Pojer, Florence; Johnsson, Kai

    2013-05-24

    The introduction of sulfa drugs for the chemotherapy of bacterial infections in 1935 revolutionized medicine. Although their mechanism of action is understood, the molecular bases for most of their side effects remain obscure. Here, we report that sulfamethoxazole and other sulfa drugs interfere with tetrahydrobiopterin biosynthesis through inhibition of sepiapterin reductase. Crystal structures of sepiapterin reductase with bound sulfa drugs reveal how structurally diverse sulfa drugs achieve specific inhibition of the enzyme. The effect of sulfa drugs on tetrahydrobiopterin-dependent neurotransmitter biosynthesis in cell-based assays provides a rationale for some of their central nervous system-related side effects, particularly in high-dose sulfamethoxazole therapy of Pneumocystis pneumonia. Our findings reveal an unexpected aspect of the pharmacology of sulfa drugs and might translate into their improved medical use.

  20. Sulfa hypersensitivity in patients with HIV infection: onset, treatment, critical review of the literature.

    PubMed

    Ryan, C; Madalon, M; Wortham, D W; Graziano, F M

    1998-05-01

    Trimethoprim/Sulfamethoxazole is the most effective medication used in both the treatment and prevention of Pneumocystis carinii pneumonia (PCP) in patients with HIV/AIDS. Its use, however, is accompanied by a high incidence of adverse reactions, especially fever, myalgia and rash (sulfa hypersensitivity). In a group of our patients, we have examined the clinical parameters at the time of onset of sulfa hypersensitivity, and the success of a desensitization protocol for this adverse event. We also have performed a comprehensive review of the literature on sulfa hypersensitivity and have compared our results to those previously reported in the literature. Our findings indicate that the sulfa hypersensitivity reaction is more likely to develop in patients with advanced disease and that desensitization can restore tolerability to the drug in approximately two thirds of those who attempt it.

  1. Pulmonary effects of AIDS: nosocomial transmission.

    PubMed

    Garay, S M; Plottel, C S

    1988-09-01

    This review provides an overview of the risk of nosocomial infection in the "AIDS era." Airborne spread of Mycobacterium tuberculosis from affected patients has re-emerged as a hazard to hospital personnel. The risk of acquiring clinical illness due to Pneumocystis carinii or cytomegalovirus is, in contrast, a function of the immunocompetence of the health care worker. Methods of transmission as well as the epidemiology of human immunodeficiency virus-related infection in the health care worker will be discussed. The increase in the number of immunocompromised patients (AIDS and non-AIDS) requires careful attention to infection control methodology with respect to the cleansing of the fiberoptic bronchoscope, the intensive care unit's respiratory equipment (such as mechanical ventilators and nebulizers), and the pulmonary function laboratory.

  2. Red fist and muscle weakness with a rare complication

    PubMed Central

    van Groeningen, Iris; Arnoldus, Joyce; Perenboom, Roos; Voskuyl, Alexandre

    2014-01-01

    A 64-year-old man was referred to our hospital, for a second opinion, with fever, skin lesions and general muscle pain. He has been treated in another hospital with antibiotics on suspicion of erysipelas. A week later skin lesions developed on the metacarpophalangeal and proximal carpophalangeal joints of the hands and nose. His mobility was impaired due to muscle pain and muscle weakness. He also showed proximal muscle atrophy and most importantly a typical heliotrope rash in the eyes. Based on these clinical observations, the most likely diagnosis was dermatomyositis. The diagnosis was confirmed by the presence of increased serum creatine kinase levels and abnormalities in skin and muscle biopsy. Prednisone (70 mg/kg) was initiated, but after  19 days the patient developed a Pneumocystis jiroveci pneumonia. He died of respiratory failure a few days later. PMID:24557476

  3. Infrapatellar bursitis with Mycobacterium malmoense related to immune reconstitution inflammatory syndrome in an HIV-positive patient.

    PubMed

    Leth, Steffen; Jensen-Fangel, Søren

    2012-11-27

    The immune reconstitution inflammatory syndrome (IRIS) after starting antiretroviral treatment for HIV infection can be caused by a great variety of pathogens. Among these are non-tuberculous mycobacteria (NTM), with Mycobacterium avium complex being the most commonly described finding. Antimycobacterial treatment of NTM in cases of IRIS is controversial. We report the case of a 39-year-old man diagnosed with HIV-1 infection during admission to hospital with Pneumocystis jirovecii pneumonia (PCP) and a CD4 cell count of 60/μl. The patient started antiretroviral treatment and made an uneventful recovery from the PCP diagnosis, but was readmitted after 2.5 months with a purulent infrapatellar bursitis on the left knee. A surgical procedure was performed and Mycobacterium malmoense was grown from the pus from the bursa. The patient recovered without supplemental antimycobacterial treatment. To our knowledge, this is the first report on IRIS caused by M malmoense.

  4. Acquired immune deficiency in Haitians: opportunistic infections in previously healthy Haitian immigrants.

    PubMed

    Vieira, J; Frank, E; Spira, T J; Landesman, S H

    1983-01-20

    We describe acquired immune deficiency manifested by opportunistic infections in 10 previously healthy heterosexual Haitian men. The opportunistic pathogens included Toxoplasma gondii (in four patients), Cryptococcus neoformans (in one), Pneumocystis carinii (in four patients), and Candida albicans (in three). Six of the patients also had Mycobacterium tuberculosis. Immunologic studies of three patients showed a decrease in the numbers and activity of helper T cells, with normal or increased populations of suppressor T cells. Serologic markers for previous infections from hepatitis A, cytomegalovirus, and herpes simplex virus were detected in several patients. Six of the patients died despite specific antimicrobial therapy. The clinical and immunologic findings in these 10 Haitians are similar to those reported in drug addicts and homosexuals with the acquired immune-deficiency syndrome.

  5. The respiratory presentation of severe combined immunodeficiency in two Mennonite children at a tertiary centre highlighting the importance of recognizing this pediatric emergency.

    PubMed

    Lam, Simon; Kavadas, Fotini Dimitriou; Haider, Seemab; Noseworthy, Mary Elizabeth

    2014-01-01

    Severe combined immunodeficiency (SCID) is considered to be a pediatric emergency, with respiratory distress being the most common presenting symptom. The authors present two cases of SCID in children <4 months of age with respiratory distress at a tertiary care centre due to a recently described homozygous CD3 delta mutation found only in the Mexican Mennonite population. Failure to respond to broad-spectrum antibiotics prompted investigation for possible SCID. Bronchial alveolar lavage fluid from both patients grew Pneumocystis jiroveci, and flow cytometry revealed absent T cells. The CD3 delta gene is believed to be important in T cell differentiation and maturation. The present article reminds pediatricians and pediatric respirologists that the key to diagnosing SCID is to have a high index of suspicion if there is poor response to conventional therapies.

  6. Gallium-67 scans of the chest in patients with acquired immunodeficiency syndrome

    SciTech Connect

    Kramer, E.L.; Sanger, J.J.; Garay, S.M.; Greene, J.B.; Tiu, S.; Banner, H.; McCauley, D.I.

    1987-07-01

    Eighty-six (/sup 67/Ga)citrate chest scans were performed in 71 adult patients with the acquired immunodeficiency syndrome. Forty-five of these patients also had Kaposi's sarcoma. Only 29 of 57 abnormal scans were correlated with abnormal chest radiographs. Chest radiographs were negative for 27 scans and unavailable for one. Several scan patterns were seen. Diffusely increased lung uptake was seen most commonly with Pneumocystis carinii pneumonia, but also other infections and noninfectious inflammatory conditions. Focal uptake corresponding to regional lymph node groups occurred most often with Mycobacterium avium-intracellulare but aslo with lymphoma. Localized intrapulmonary uptake was seen in bacterial pneumonias. Perihilar activity occurred in two cases. When chest radiographs were abnormal and /sup 67/Ga scans negative, the most common diagnosis was pulmonary Kaposi's sarcoma.

  7. Significance of diffuse pulmonary uptake in radiogallium scans: concise communication

    SciTech Connect

    Gupta, S.M.; Sziklas, J.J.; Spencer, R.P.; Rosenberg, R.

    1980-04-01

    Diffuse pulmonary uptake of radiogallium was observed in 50 out of 510 scans (9.8%) performed in a general hospital over a period of 1 y. Of the 50 cases, 80% had bilateral, diffuse distribution, and 20% unilateral. A variety of clinical conditions produced a similar picture on the pulmonary images. The most common cause of the diffuse uptake was infectious disease (48%) followed by infiltrative disorders (30%) and neoplastic conditions (22%). On a repeat study there was significant reduction in the intensity of pulmonary radiogallium uptake following drug therapy in three patients - sarcoidosis on corticosteroid therapy, pneumocystis carinii treated with trimethoprim and sulfamethoxozole, and interstitial pulmonary fibrosis on corticosteroids. No close correlation was observed between the underlying clinical disorder and the pattern or intensity of pulmonary uptake of radiogallium.

  8. [Pulmonary complications in children with human immunodeficiency virus infection].

    PubMed

    Brockmann V, Pablo; Viviani S, Támara; Peña D, Anamaría

    2007-08-01

    Pulmonary complications in children infected by human immunodeficiency virus (HIV) are common and may be the first manifestation of acquired immunodeficiency syndrome (AIDS). The aim of our study was to review pulmonary diseases and complications in pediatric patients with HIV infection in a large tertiary hospital in Santiago, Chile. We performed a retrospective, descriptive analysis of 17 patients with HIV infection controlled at the Hospital Dr. Sótero del Rio. Respiratory complications/diseases were: overall pneumonia (n: 14), recurrent pneumonia (n: 10), citomegalovirus associated pneumonia (n: 4), Pneumocystis jiroveci associated pneumonia (n: 1) pulmonary tuberculosis (n: 1), lymphoid interstitial pneumonia (n: 3) and chronic pulmonary disease (n: 7). Microorganisms isolated were mostly atypical and frequently associated with severe and chronic pulmonary damage. A high degree of suspicion is required to detect atypical microorganisms promptly, in order to rapidly implement pathogen targeted therapy that could potentially decrease the possibility of sequelae.

  9. Small intestinal lymphoma in three patients with acquired immune deficiency syndrome.

    PubMed

    Steinberg, J J; Bridges, N; Feiner, H D; Valensi, Q

    1985-01-01

    Three cases of small bowel lymphoma in young homosexual men are presented. All three had acquired immune deficiency syndrome as demonstrated by demography, sexual history, cachexia, opportunistic infections by Cytomegalovirus, Pneumocystis carinii, atypical Mycobacterium, Candida, and/or evidence of immune deficiency, such as skin test anergy, lymphopenia, inversion of T-helper/T-suppressor ratio, and diminished lymphocyte response to either phytohemmaglutinin or pokeweed mitogen. All had peripheral and/or abdominal lymphadenopathy, and gastrointestinal symptoms, e.g., diarrhea, spasms, constipation, and oral candidiasis. The diagnosis of lymphoma was made at laparotomy in all cases. All three had complete removal of localized tumor (stage Ie or IIe), yet died within 6 months of surgery and/or chemotherapy. Thus gastrointestinal complaints may not always be related to "gay bowel" syndrome, or other infectious diseases in patients with acquired immune deficiency syndrome. Small intestinal lymphoma should be added to the list of neoplasms to which this group is susceptible.

  10. The burden of serious fungal diseases in Russia.

    PubMed

    Klimko, N; Kozlova, Y; Khostelidi, S; Shadrivova, O; Borzova, Y; Burygina, E; Vasilieva, N; Denning, D W

    2015-10-01

    The incidence and prevalence of fungal infections in Russia is unknown. We estimated the burden of fungal infections in Russia according to the methodology of the LIFE program (www.LIFE-worldwide.org). The total number of patients with serious and chronic mycoses in Russia in 2011 was three million. Most of these patients (2,607,494) had superficial fungal infections (recurrent vulvovaginal candidiasis, oral and oesophageal candidiasis with HIV infection and tinea capitis). Invasive and chronic fungal infections (invasive candidiasis, invasive and chronic aspergillosis, cryptococcal meningitis, mucormycosis and Pneumocystis pneumonia) affected 69,331 patients. The total number of adults with allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitisation was 406,082.

  11. Bacterial Respiratory Infections Complicating Human Immunodeficiency Virus.

    PubMed

    Feldman, Charles; Anderson, Ronald

    2016-04-01

    Opportunistic bacterial and fungal infections of the lower respiratory tract, most commonly those caused by Streptococcus pneumoniae (the pneumococcus), Mycobacterium tuberculosis, and Pneumocystis jirovecii, remain the major causes of mortality in those infected with human immunodeficiency virus (HIV). Bacterial respiratory pathogens most prevalent in those infected with HIV, other than M. tuberculosis, represent the primary focus of the current review with particular emphasis on the pneumococcus, the leading cause of mortality due to HIV infection in the developed world. Additional themes include (1) risk factors; (2) the predisposing effects of HIV-mediated suppression on pulmonary host defenses, possibly intensified by smoking; (3) clinical and laboratory diagnosis, encompassing assessment of disease severity and outcome; and (4) antibiotic therapy. The final section addresses current recommendations with respect to pneumococcal immunization in the context of HIV infection, including an overview of the rationale underpinning the current "prime-boost" immunization strategy based on sequential administration of pneumococcal conjugate vaccine 13 and pneumococcal polysaccharide vaccine 23.

  12. Chronic fatal pneumocystosis in nude mice.

    PubMed

    Ueda, K; Goto, Y; Yamazaki, S; Fujiwara, K

    1977-12-01

    A chronic pulmonary disease was encountered in nude mice of a barrier sustained colony, and Pneumocystis carinii was identified as the causative agent histopathologically as well as on impression smear preparations in the affected lungs. Fatal infection was seen only in old nude mice aged more than 6 months, while focal pulmonary lesions were developed without clinical signs in young adult nudes 2 to 3 months of age. The lesions produced in aged nude mice were characterized by propagation of mononuclear cells with the presence of foamy masses of P. carinii. Heterozygous littermates were much less susceptible to the infection but pneumocystic lesions could be produced readily by multiple treatment with immunosuppressants. The infection could be transmitted without immunosuppressant to non-infected nudes but not to heterozygous littermates after intranasal inoculation of affected tissue emulsion or by cage mating with severely affected nudes.

  13. Recovery of the human immunodeficiency virus from fibreoptic bronchoscopes.

    PubMed Central

    Hanson, P J; Gor, D; Clarke, J R; Chadwick, M V; Gazzard, B; Jeffries, D J; Gaya, H; Collins, J V

    1991-01-01

    Ten bronchoscopes that had been used on patients with the acquired immunodeficiency syndrome were sampled to determine the nature and extent of microbial contamination. Samples were taken by irrigating the suction biopsy channel with modified viral transport medium and by swabbing the insertion tube. Sampling was repeated after they had been cleaned in detergent and after two minutes' disinfection in 2% alkaline glutaraldehyde. Before being cleaned the seven bronchoscopes tested by polymerase chain reaction were contaminated with the human immunodeficiency virus, though infectivity and antigen assays gave negative results. Other organisms identified were hepatitis B virus (1), commensal bacteria (9), and Pneumocystis carinii (4). Mean bacterial contamination was 2.27 log colony forming organisms per millilitre. Cleaning the bronchoscope before disinfection removed all detectable contaminants with a reduction in bacterial growth of up to 8 log colony forming units/ml. PMID:1858078

  14. Delivering on Antimicrobial Resistance Agenda Not Possible without Improving Fungal Diagnostic Capabilities.

    PubMed

    Denning, David W; Perlin, David S; Muldoon, Eavan G; Colombo, Arnaldo Lopes; Chakrabarti, Arunaloke; Richardson, Malcolm D; Sorrell, Tania C

    2017-02-01

    Antimicrobial resistance, a major public health concern, largely arises from excess use of antibiotic and antifungal drugs. Lack of routine diagnostic testing for fungal diseases exacerbates the problem of antimicrobial drug empiricism, both antibiotic and antifungal. In support of this contention, we cite 4 common clinical situations that illustrate this problem: 1) inaccurate diagnosis of fungal sepsis in hospitals and intensive care units, resulting in inappropriate use of broad-spectrum antibacterial drugs in patients with invasive candidiasis; 2) failure to diagnose chronic pulmonary aspergillosis in patients with smear-negative pulmonary tuberculosis; 3) misdiagnosis of fungal asthma, resulting in unnecessary treatment with antibacterial drugs instead of antifungal drugs and missed diagnoses of life-threatening invasive aspergillosis in patients with chronic obstructive pulmonary disease; and 4) overtreatment and undertreatment of Pneumocystis pneumonia in HIV-positive patients. All communities should have access to nonculture fungal diagnostics, which can substantially benefit clinical outcome, antimicrobial stewardship, and control of antimicrobial resistance.

  15. Fungal infection involvement in primary biliary cirrhosis: A review of 2 cases

    PubMed Central

    Wang, Yanyan; Zhao, Zheng; Lu, Hui; Zhang, Jianglin; Huang, Feng

    2017-01-01

    The present study aimed to analyze the imaging, clinical and pathological features of fungal infection involvement in primary biliary cirrhosis (PBC) by retrospectively analyzing and reviewing the features of two patients with fungal infection involvement in PBC. Both patients were female. One patient had a confirmed diagnosis of PBC. The other patient had confirmed Sjogren syndrome and PBC. The two cases of PBC were infected with fungal infection after treatment with hormonal and immunosuppressive agents. RCR of sputum confirmed Pneumocystis spp. infection in the patient with PBC alone. The mucormycosis infection was confirmed in the other patient after pathological examination of a renal biopsy. The state of the illnesses progressed quickly and both patients ultimately succumbed to their conditions. The patient prognosis of fungal infection involvement PBC is poor. Patients treated with long-term hormone and immunosuppressive agents should be monitored. PMID:28352320

  16. [Disseminated infection due to Penicillium marneffei related to HIV infection: first observation in Argentina].

    PubMed

    Santiso, Gabriela; Chediak, Viviana; Maiolo, Elena; Mujica, María T; San Juan, Jorge; Arechavala, Alicia; Negroni, Ricardo

    2011-01-01

    The first case observed in Argentina of AIDS-related human penicillosis is herein presented. The patient was a six- teen year-old young man coming from a rural area of southern China. He was admitted at the F. J. Muñiz Hospital of Buenos Aires city with severe pneumonia and adult respiratory distress. Penicillium marneffei was isolated from bronchoalveolar lavage fuid and was microscopically observed in a skin cytodiagnosis. P. marneffei identification was confirmed by rRNA amplification and its phenotypic characteristics. The patient suffered an advanced HIV infection and also presented several AIDS-related diseases due to CMV, nosocomial bacterial infections and Pneumocystis jirovecii which led to a fatal outcome.

  17. Pneumocystosis in wild small mammals from California

    USGS Publications Warehouse

    Laakkonen, Juha; Fisher, Robert N.; Case, Ted J.

    2001-01-01

    Cyst forms of the opportunistic fungal parasite Pneumocystis carinii were found in the lungs of 34% of the desert shrew, Notiosorex crawfordi (n = 59), 13% of the ornate shrew, Sorex ornatus (n = 55), 6% of the dusky-footed wood rat, Neotoma fuscipes (n = 16), 2.5% of the California meadow vole,Microtus californicus (n = 40), and 50% of the California pocket mouse, Chaetodipus californicus (n= 2) caught from southern California between February 1998 and February 2000. Cysts were not found in any of the harvest mouse, Reithrodontomys megalotis (n = 21), California mouse,Peromyscus californicus (n = 20), brush mouse, Peromyscus boylii (n = 7) or deer mouse, Peromyscus maniculatus (n = 4) examined. All infections were mild; extrapulmonary infections were not observed. Other lung parasites detected were Hepatozoon sp./spp. from M. californicus andNotiosorex crawfordi, Chrysosporium sp. (Emmonsia) from M. californicus, and a nematode from S. ornatus.

  18. Acquired immunodeficiency syndrome: Ga-67 citrate imaging

    SciTech Connect

    Woolfenden, J.M.; Carrasquillo, J.A.; Larson, S.M.; Simmons, J.T.; Masur, H.; Smith, P.D.; Shelhamer, J.H.; Ognibene, F.P.

    1987-02-01

    All gallium-67 citrate scans obtained in patients with acquired immunodeficiency syndrome (AIDS) at the Clinical Center, National Institutes of Health (Bethesda, Md.) were retrospectively analyzed and correlated with the results of bronchoscopy, chest radiography, and endoscopy. There were 164 scans of 95 patients. Twenty scans were from patients with Pneumocystis carinii pneumonia; 19 were abnormal, for a sensitivity of 95%. Ga-67 uptake tended to be less in patients receiving therapy for P. carinii pneumonia. Chest radiographs were normal at least initially in three patients with abnormal scans and P. carinii pneumonia. Unusually prominent colonic activity was associated with infection in some patients. No lesions of Kaposi sarcoma showed tracer uptake. Gallium scanning is useful for detecting P. carinii pneumonia and other opportunistic infections in patients with AIDS, but it is not useful for localizing Kaposi sarcoma.

  19. Impact of folate therapy on combined immunodeficiency secondary to hereditary folate malabsorption.

    PubMed

    Kishimoto, Kenji; Kobayashi, Ryoji; Sano, Hirozumi; Suzuki, Daisuke; Maruoka, Hayato; Yasuda, Kazue; Chida, Natsuko; Yamada, Masafumi; Kobayashi, Kunihiko

    2014-07-01

    Hereditary folate malabsorption (HFM) is a rare autosomal recessive disorder. Severe folate deficiency in HFM can result in immunodeficiency. We describe a female infant with HFM who acquired severe Pneumocystis pneumonia. The objective of the present study was to elucidate her immunological phenotype and to examine the time course of immune recovery following parenteral folate therapy. The patient demonstrated a combined immunodeficiency with an impaired T cell proliferation response, pan-hypogammaglobulinemia, and an imbalanced pro-inflammatory cytokine profile. She had normal white blood cell count, normal lymphocyte subsets, and normal complement levels. Two novel mutations were identified within the SLC46A1 gene to produce a compound heterozygote. We confirmed full recovery of her immunological and neurophysiological status with parenteral folate replacement. The time course of recovery of her immunological profile varied widely, however. HFM should be recognized as a unique form of immunodeficiency.

  20. Enteric pathogens associated with gastrointestinal dysfunction in children with HIV infection.

    PubMed

    Ramos-Soriano, A G; Saavedra, J M; Wu, T C; Livingston, R A; Henderson, R A; Perman, J A; Yolken, R H

    1996-04-01

    Infants and young children with HIV infection commonly suffer from gastrointestinal manifestations of their disease. Many HIV infected children have evidence of persistent diarrhoea, malabsorption, malnutrition or growth failure. The aetiology and pathogenesis of gastrointestinal dysfunction in HIV infected children have not been well defined. We performed immunocytochemical analyses on intestinal tissue from 19 HIV-infected children with gastrointestinal dysfunction or growth failure. None of these 19 children had microbial pathogens identified in faecal samples using standard microbiological methods. Intestinal tissues were obtained from the children by biopsy and were examined for antigens from Pneumocystis carinii, cytomegalovirus (CMV) and herpes simplex virus (HSV) using the avidin-biotin-complex immunohistochemical technique and monoclonal or monospecific antibodies. We detected at least one of these pathogens in samples from eight (42%) of 19 HIV infected children. P. carinii was the most prevalent pathogen, found in five of the eight HIV infected children. All of the children with intestinal pneumocystis infection were receiving prophylaxis directed at the prevention of pulmonary disease with this organism and none of them were undergoing active pulmonary infection. We also identified CMV antigens in intestinal tissues from four children and HSV antigens in intestinal tissues from one child. Two children were infected with more than one pathogen. On the other hand, none of these pathogens were found in the tissues obtained from 10 HIV-uninfected patients who had intestinal tissues obtained for chronic non-infectious diarrheal and inflammatory diseases (P < 0.01, Fisher's exact test). Our findings indicate that some children with HIV infection and gastrointestinal dysfunction may be infected with opportunistic pathogens despite negative analyses employing standard microbiological methods. Our study also indicates that HIV infected children can undergo

  1. Treatment of infectious complications of acquired immunodeficiency syndrome.

    PubMed

    Furio, M M; Wordell, C J

    1985-01-01

    The infectious complications of the acquired immunodeficiency syndrome (AIDS) are discussed, and the conventional and nonconventional therapies used for these infections are reviewed. The infections most commonly encountered in patients with AIDS are Pneumocystis carinii pneumonia (58%), Candida esophagitis (31%), toxoplasmosis (21%), cytomegalovirus infections (15%), and herpes-simplex virus infections (12%). Pneumocystis carinii pneumonia is the most common life-threatening process in these patients. Trimethoprim-sulfamethoxazole (TMP-SMZ) is considered the drug of choice for its treatment. Oral candidiasis often indicates the progression to AIDS in the high-risk populations of homosexual or bisexual men, intravenous drug abusers, and individuals with hemophilia. Nystatin suspension is commonly used to treat oral candidiasis, while Candida esophagitis demands systemic therapy with ketoconazole. Toxoplasmosis most commonly manifests itself in patients with AIDS as a cerebral mass lesion. The recommended therapy includes sulfadiazine and pyrimethamine. AIDS patients frequently experience protozoal invasion of the intestinal tract with Giardia lamblia, Isospora belli, and Cryptosporidium muris. Various drugs have been tried for these infections, including quinacrine hydrochloride, metronidazole, TMP-SMZ, and spiramycin. Cytomegalovirus (CMV) infections commonly involve the lungs, gastrointestinal tract, eyes, brain, and nervous system. Attempts to treat these disseminated CMV infections with antiviral agents, including acyclovir, have not been successful. However, acyclovir has been found beneficial in the treatment of herpes-simplex virus infections. Multiple infectious complications may occur in patients with AIDS as a result of the cellular-immune deficiency associated with this disease. Until more research is done with AIDS patients, therapy must be based on the data available from the treatment of these infections in immunosuppressed patients without AIDS.

  2. Diagnosis and antimicrobial therapy of lung infiltrates in febrile neutropenic patients (allogeneic SCT excluded): updated guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO)†

    PubMed Central

    Maschmeyer, G.; Carratalà, J.; Buchheidt, D.; Hamprecht, A.; Heussel, C. P.; Kahl, C.; Lorenz, J.; Neumann, S.; Rieger, C.; Ruhnke, M.; Salwender, H.; Schmidt-Hieber, M.; Azoulay, E.

    2015-01-01

    Up to 25% of patients with profound neutropenia lasting for >10 days develop lung infiltrates, which frequently do not respond to broad-spectrum antibacterial therapy. While a causative pathogen remains undetected in the majority of cases, Aspergillus spp., Pneumocystis jirovecii, multi-resistant Gram-negative pathogens, mycobacteria or respiratory viruses may be involved. In at-risk patients who have received trimethoprim–sulfamethoxazole (TMP/SMX) prophylaxis, filamentous fungal pathogens appear to be predominant, yet commonly not proven at the time of treatment initiation. Pathogens isolated from blood cultures, bronchoalveolar lavage (BAL) or respiratory secretions are not always relevant for the etiology of pulmonary infiltrates and should therefore be interpreted critically. Laboratory tests for detecting Aspergillus galactomannan, β-d-glucan or DNA from blood, BAL or tissue samples may facilitate the diagnosis; however, most polymerase chain reaction assays are not yet standardized and validated. Apart from infectious agents, pulmonary side-effects from cytotoxic drugs, radiotherapy or pulmonary involvement by the underlying malignancy should be included into differential diagnosis and eventually be clarified by invasive diagnostic procedures. Pre-emptive treatment with mold-active systemic antifungal agents improves clinical outcome, while other microorganisms are preferably treated only when microbiologically documented. High-dose TMP/SMX is first choice for treatment of Pneumocystis pneumonia, while cytomegalovirus pneumonia is treated primarily with ganciclovir or foscarnet in most patients. In a considerable number of patients, clinical outcome may be favorable despite respiratory failure, so that intensive care should be unrestrictedly provided in patients whose prognosis is not desperate due to other reasons. PMID:24833776

  3. HIV infection/acquired immunodeficiency syndrome at Siriraj Hospital, 2002: time for secondary prevention.

    PubMed

    Anekthananon, Thanomsak; Ratanasuwan, Winai; Techasathit, Wichai; Rongrungruang, Yong; Suwanagool, Surapol

    2004-02-01

    The authors retrospectively reviewed the medical records of HIV/AIDS patients who were admitted to the medical service, Siriraj Hospital from January 1, 2002 through December 31, 2002. Demographics, CD4 lymphocyte counts, discharge diagnoses, the incidence of Pneumocystis carinii pneumonia (PCP), cerebral toxoplasmosis and cryptococcosis in patients who received and did not receive appropriate chemoprophylaxis against those opportunistic infections when indicated, and outcome of the patients were collected. Three hundred medical records of 286 HIV/AIDS patients were available for review. One hundred and seventy two patients (60.1%) were male. Mean age of the patients was 36.8 +/- 9.91 years (range 14-74). The mean CD4 lymphocyte count that was determined in 165 patients was 74.7 +/- 134.21 cells/mm3 (range 0-894). Of the 300 admissions, 36 per cent were newly diagnosed HIV infection. Only 23 (7.7%) patients had received antiretroviral drugs at the time of hospitalization. The leading HIV-related diseases were tuberculosis (29.3%), Pneumocystis carinii pneumonia (18.7%), and cryptococcosis (15.7%). The rest of them included cytomegalovirus diseases (6.3%), lymphoma (6.3%), Salmonella bacteremia (6%), cerebral toxoplasmosis (5.7%), cryptosporidiosis (5.3%), disseminated Mycobacterium avium complex infection (1.0%), extrapulmonary histoplasmosis (1.0%), Candida esophagitis (1.0%), progressive multifocal leukoencephalopathy (1.0%), and rhodococcosis (0.7%). Among those for whom HIV infection was established and chemoprophylaxis for PCP, cerebral toxoplasmosis and cryptococcosis were indicated, 9.8 per cent vs 28.2 per cent, 3.6 per cent vs 5.1 per cent, and 10 per cent vs 15.2 per cent of whom received and did not receive the appropriate chemoprophylaxis developed PCP, cerebral toxoplasmosis and cryptococcosis respectively. One hundred and ninety (63.3%) patients were alive at discharge, 84 (28.0%) had died, 21 (7%) were referred to other hospitals, and 5 (1.7%) left

  4. Structural analysis of a holoenzyme complex of mouse dihydrofolate reductase with NADPH and a ternary complex with the potent and selective inhibitor 2, 4-diamino-6-(2′-hydroxydibenz[b, f]azepin-5-yl)methylpteridine

    SciTech Connect

    Cody, Vivian; Pace, Jim; Rosowsky, Andre

    2008-09-01

    The structures of mouse DHFR holo enzyme and a ternary complex with NADPH and a potent inhibitor are described. It has been shown that 2, 4-diamino-6-arylmethylpteridines and 2, 4-diamino-5-arylmethylpyrimidines containing an O-carboxylalkyloxy group in the aryl moiety are potent and selective inhibitors of the dihydrofolate reductase (DHFR) from opportunistic pathogens such as Pneumocystis carinii, the causative agent of Pneumocystis pneumonia in HIV/AIDS patients. In order to understand the structure–activity profile observed for a series of substituted dibenz[b, f]azepine antifolates, the crystal structures of mouse DHFR (mDHFR; a mammalian homologue) holo and ternary complexes with NADPH and the inhibitor 2, 4-diamino-6-(2′-hydroxydibenz[b, f]azepin-5-yl)methylpteridine were determined to 1.9 and 1.4 Å resolution, respectively. Structural data for the ternary complex with the potent O-(3-carboxypropyl) inhibitor PT684 revealed no electron density for the O-carboxylalkyloxy side chain. The side chain was either cleaved or completely disordered. The electron density fitted the less potent hydroxyl compound PT684a. Additionally, cocrystallization of mDHFR with NADPH and the less potent 2′-(4-carboxybenzyl) inhibitor PT682 showed no electron density for the inhibitor and resulted in the first report of a holoenzyme complex despite several attempts at crystallization of a ternary complex. Modeling data of PT682 in the active site of mDHFR and P. carinii DHFR (pcDHFR) indicate that binding would require ligand-induced conformational changes to the enzyme for the inhibitor to fit into the active site or that the inhibitor side chain would have to adopt an alternative binding mode to that observed for other carboxyalkyloxy inhibitors. These data also show that the mDHFR complexes have a decreased active-site volume as reflected in the relative shift of helix C (residues 59–64) by 0.6 Å compared with pcDHFR ternary complexes. These data are consistent with the

  5. Structural Analysis of a Holoenzyme Complex of Mouse Dihydrofolate Reductase With NADPH And a Ternary Complex With the Potent And Selective Inhibitor 2,4-Diamino-6-(2'-Hydroxydibenz[b,F]azepin-5-YI)

    SciTech Connect

    Cody, V.; Pace, J.; Rosowsky, A.

    2009-05-12

    It has been shown that 2,4-diamino-6-arylmethylpteridines and 2,4-diamino-5-arylmethylpyrimidines containing an O-carboxylalkyloxy group in the aryl moiety are potent and selective inhibitors of the dihydrofolate reductase (DHFR) from opportunistic pathogens such as Pneumocystis carinii, the causative agent of Pneumocystis pneumonia in HIV/AIDS patients. In order to understand the structure-activity profile observed for a series of substituted dibenz[b,f]azepine antifolates, the crystal structures of mouse DHFR (mDHFR; a mammalian homologue) holo and ternary complexes with NADPH and the inhibitor 2,4-diamino-6-(2{prime}-hydroxydibenz[b,f]azepin-5-yl)methylpteridine were determined to 1.9 and 1.4 A resolution, respectively. Structural data for the ternary complex with the potent O-(3-carboxypropyl) inhibitor PT684 revealed no electron density for the O-carboxylalkyloxy side chain. The side chain was either cleaved or completely disordered. The electron density fitted the less potent hydroxyl compound PT684a. Additionally, cocrystallization of mDHFR with NADPH and the less potent 2{prime}-(4-carboxybenzyl) inhibitor PT682 showed no electron density for the inhibitor and resulted in the first report of a holoenzyme complex despite several attempts at crystallization of a ternary complex. Modeling data of PT682 in the active site of mDHFR and P. carinii DHFR (pcDHFR) indicate that binding would require ligand-induced conformational changes to the enzyme for the inhibitor to fit into the active site or that the inhibitor side chain would have to adopt an alternative binding mode to that observed for other carboxyalkyloxy inhibitors. These data also show that the mDHFR complexes have a decreased active-site volume as reflected in the relative shift of helix C (residues 59-64) by 0.6 A compared with pcDHFR ternary complexes. These data are consistent with the greater inhibitory potency against pcDHFR.

  6. Primary brain tumors treated with steroids and radiotherapy: Low CD4 counts and risk of infection

    SciTech Connect

    Hughes, Michael A.; Parisi, Michele; Grossman, Stuart; Kleinberg, Lawrence . E-mail: kleinla@jhmi.edu

    2005-08-01

    Purpose: Patients with primary brain tumors are often treated with high doses of corticosteroids for prolonged periods to reduce intracranial swelling and alleviate symptoms such as headaches. This treatment may lead to immunosuppression, placing the patient at risk of life-threatening opportunistic infections, such as Pneumocystis carinii pneumonia. The risk of contracting some types of infection may be reduced with prophylactic antibiotics. The purpose of this study was to determine the occurrence of low CD4 counts and whether monitoring CD4 counts during and after radiotherapy (RT) is warranted. Methods and Materials: CD4 counts were measured during RT in 70 of 76 consecutive patients with newly diagnosed Grade III and IV astrocytoma and anaplastic oligodendroglioma treated with corticosteroids and seen at the Johns Hopkins Hospital. Weekly CD4 measurements were taken in the most recent 25 patients. Prophylactic trimethoprim-sulfamethoxazole (160 mg/800 mg p.o. every Monday, Wednesday, and Friday) or dapsone (100 mg p.o. daily) in those with sulfa allergy was prescribed only if patients developed a low CD4 count. Carmustine chemotherapy wafers were placed at surgery in 23% of patients, evenly distributed between the groups. No patient received any other chemotherapy concurrent with RT. Results: CD4 counts decreased to <200/mm{sup 3} in 17 (24%) of 70 patients. For the 25 patients with weekly CD4 counts, all CD4 counts were >450/mm{sup 3} before RT, but 6 (24%) of 25 fell to <200/mm{sup 3} during RT. Patients with counts <200/mm{sup 3} were significantly more likely to be hospitalized (41% vs. 9%, p <0.01) and be hospitalized for infection (23% vs. 4%, p <0.05) during RT. Overall survival was not significantly different between the groups. All patients with low CD4 counts were treated with prophylactic antibiotics, and no patient developed Pneumocystis carinii pneumonia. No patients developed a serious adverse reaction to antibiotic therapy. The mean dose of

  7. The expanding role of co-trimoxazole in developing countries.

    PubMed

    Church, James A; Fitzgerald, Felicity; Walker, A Sarah; Gibb, Diana M; Prendergast, Andrew J

    2015-03-01

    Co-trimoxazole is an inexpensive, broad-spectrum antimicrobial drug that is widely used in developing countries. Before antiretroviral therapy (ART) scale-up, co-trimoxazole prophylaxis reduced morbidity and mortality in adults and children with HIV by preventing bacterial infections, diarrhoea, malaria, and Pneumocystis jirovecii pneumonia, despite high levels of microbial resistance. Co-trimoxazole prophylaxis reduces early mortality by 58% (95% CI 39-71) in adults starting ART. Co-trimoxazole provides ongoing protection against malaria and non-malaria infections after immune reconstitution in ART-treated individuals in sub-Saharan Africa, leading to a change in WHO guidelines, which now recommend long-term co-trimoxazole prophylaxis for adults and children in settings with a high prevalence of malaria or severe bacterial infections. Co-trimoxazole prophylaxis is recommended for HIV-exposed infants from age 4-6 weeks; however, the risks and benefits of co-trimoxazole during infancy are unclear. Co-trimoxazole prophylaxis reduces anaemia and improves growth in children with HIV, possibly by reducing inflammation, either through direct immunomodulatory activity or through effects on the intestinal microbiota leading to reduced microbial translocation. Ongoing trials are now assessing the ability of adjunctive co-trimoxazole to reduce mortality in children after severe anaemia or severe acute malnutrition. In this Review, we discuss the mechanisms of action, benefits and risks, and clinical trials of co-trimoxazole in developing countries.

  8. An appraisal of thoracic procedures performed in patients with HIV-positive serology.

    PubMed

    Canver, C C

    1995-08-01

    Patients who have contracted the human immunodeficiency virus (HIV) often require a diagnostic or therapeutic thoracic procedure. To determine the clinical benefits of a noncardiac pulmonary intervention in the treatment of HIV-positive individuals, 82 patients with HIV-positive serology who underwent a thoracic procedure for illnesses related to acquired immunodeficiency syndrome (AIDS) between 1987 and 1990 were reviewed. Pneumocystis carinii pneumonia was the most common opportunistic infection and was the initial manifestation for establishing the HIV-positive serology in 54 patients (66%). Fiberoptic bronchoscopy was performed in 74 patients (90%), closed tube thoracostomy in 9 (11%), thoracentesis in 3 (4%), thoracostomy and lung resection in 2 (2.4%), pericardial window in 1 (1.2%), and tracheostomy in 1 (1.2%). The operation was useful in 46 patients (56%) and improved the clinical short-term outcome of 53 patients (64%). Nonfatal complications occurred in only two patients (2.4%). There were no deaths directly caused by the thoracic procedure within the first 30 days. However, overall 8 patients (10%ZZ) succumbed to infectious complications of AIDS. We conclude that thoracic procedures directed toward pulmonary opportunistic infections and their complications in HIV-positive patients are beneficial and may offer an improved short-term outcome.

  9. The acquired immune deficiency syndrome: an international health problem of increasing importance.

    PubMed

    Wofsy, C B; Mills, J

    1984-06-01

    The Acquired Immune Deficiency Syndrome (AIDS) is a new disease which first appeared in human populations about 1979. The disease is defined by the development of unusual types of cancer (e.g. Kaposi's sarcoma), or severe cellular immunodeficiency manifested by opportunistic infections (e.g. Pneumocystis carinii infection), or both. Although the etiology of AIDS is unknown, the epidemiologic evidence is consistent with an infectious agent transmitted by blood (e.g. transfusion, needle sharing) or sexual intercourse. Over three-quarters of the cases have been in homosexual or bisexual males and in intravenous drug abusers; about 5% of cases do not have recognized risk factors. A small number of cases have resulted from transfusion of blood or blood products. The early clinical manifestations are non-specific, and may include asymptomatic skin lesions, dyspnea and dry cough, weight loss, chronic diarrhea, and focal and non-focal central nervous system findings. Treatment for the associated cancers and opportunistic infections may be successful in individual instances, but the underlying immunosuppression of AIDS appears to progress inexorably and the fatality rate approaches 100% within a few years from diagnosis. Although nosocomial transmission has not been documented, infection control guidelines have been developed by analogy with hepatitis B infection.

  10. Drug treatment of pneumonia in the hospital. What are the choices?

    PubMed

    Aoun, M; Klastersky, J

    1991-12-01

    Mortality and morbidity of nosocomial pneumonia remain high. Successful treatment of pulmonary infections depends on several factors including type of infection, offending pathogen, status of host defences, and adequate choice of antibiotic therapy. The physician's decision should aim at achieving antibiotic concentrations beyond the MIC at the site of infection. Gram-negative bacilli, notably Pseudomonos aeruginosa, Klebsiella pneumoniae and Escherichia coli, remain the most frequent agents in nosocomial pneumonia. Staphylococcus aureus and Streptococcus pneumoniae predominate among the Gram-positive cocci. Pneumocystis carinii predominates in immunocompromised patients. Protected sample bronchoscopy associated with quantitative cultures of samples, and quantification of intracellular microorganisms in cells recovered by broncho-alveolar lavage are two promising procedures which might replace previous, more aggressive methods. Penetration of antibiotics into lung tissue depends on physicochemical properties of the drug and the degree of inflammation of lung tissue. Quinolones, macrolides, tetracyclines and trimethoprim penetrate well into bronchial secretions. Penetration is moderate to low for aminoglycosides and beta-lactams. Fluoroquinolones and new beta-lactam agents, including third-generation cephalosporins imipenem, aztreonam and ticarcillin-clavulanate, showed comparative clinical efficacy in treatment of nosocomial pneumonia, with an efficacy rate close to 80%. Aminoglycosides should not be used alone. Combination therapy reduces but does not eliminate the risk of selection of Gram-negative resistant mutants. It should not be used routinely except for P. aeruginosa, Enterobacter cloacae and Serratia marcescens infections.

  11. Lessons learned about opportunistic infections in southeast Asia.

    PubMed

    Nissapatorn, Veeranoot

    2008-07-01

    Southeast Asia is a region where the number of people infected with HIV/AIDS is one of the fastest growing in the world. Tuberculosis (TB) has grown along with the HIV epidemic. TB is not only the most common AIDS-defining illness but is also the leading cause of morbidity and mortality in AIDS patients. Cryptococcosis (meningitis or disseminated) is one of the most common opportunistic infections in AIDS patients. Cryptococcal meningitis is the first in the differential diagnosis considered with meningeal irritation. Penicillosis, a unique systemic mycosis, is an important emerging public health problem and has been classified as an AIDS defining illness in endemic areas like Thailand. Pneumocystis carinii (jiroveci) pneumonia has been one of the most important opportunistic infections in AIDS patients. Among parasitic infections, cryptosporidiosis is the most common intestinal protozoan infection relating to diarrhea in AIDS patients and toxoplasmosis is the only parasitic infection of the nervous system with a substantial incidence, up to 14.8%. Cytomegalovirus (CMV) retinitis has a lower prevalence compared to other opportunistic infections. In the era of highly active antiretroviral therapy (HAART), the incidence of opportunistic infections has significantly reduced in the past few years. Subsequently, the phenomena of immune restoration inflammatory syndrome (IRIS) in AIDS patients has been reported in this region as a result of HAART.

  12. Treatment of Extra — Abdominal Desmoid Tumors with Chemotherapy

    PubMed Central

    Montgomery, Corey; Emory, Cynthia; Adams, Sheila; Cohen, Jonathan; Pitcher, John David; Potter, Benjamin Kyle; Temple, H. Thomas

    2011-01-01

    Fibromatosis, or extra-abdominal desmoid tumor, is a benign disease which often has an aggressive clinical course that can be difficult to treat. We performed a retrospective review of 16 patients (12 females and four males) with a mean age of 34.2 years treated with methotrexate and vinblastine for newly diagnosed or recurrent extra-abdominal desmoid tumor. The mean age of our patient cohort was 34.2 years (range 11–70), and the mean tumor size was 11.5 cm (range 2.5–21.2 cm). The mean duration of therapy was 12 months with an average follow-up of 43 months (range 1–149 months). Fourteen of 16 patients demonstrated a clinical response to treatment. Eight of 14 patients demonstrated a radiologic decrease in tumor size. Only one patient progressed on therapy. Six patients developed recurrent symptoms after discontinuation of treatment. Chemotherapy-related symptoms including neutropenia, nausea, and vomiting were common and observed in most patients, however these side effects were mild and transient. Five patients developed peripheral neuropathy that prompted a change from vinblastine to vinorelbine during treatment. One potentially life-threatening complication (pneumocystis pneumonia) occurred which was diagnosed early and successfully treated. The use of methotrexate and vinblastine/vinorelbine in the management of fibromatosis appears to be an effective treatment with minimal treatment-related side effects. PMID:24212959

  13. Acquired immune deficiency syndrome (AIDS) in Brazil. Necropsy findings.

    PubMed

    Michalany, J; Mattos, A L; Michalany, N S; Filie, A C; Montezzo, L C

    1987-01-01

    According to the 15 autopsies performed at the Department of Pathological Anatomy, Escola Paulista de Medicina, São Paulo, Brazil, it was confirmed that acquired immunodeficiency syndrome (AIDS) occurs preferably in young homosexual males, who die in a short period of time of the disease, which leads to a consumptive state verified by cachexia of the cadavers. The most affected organs of this series were the lungs and encephalum, exactly the ones responsible for the immediate cause of death. In this series of autopsies there were 9 types of microorganisms represented by virus, bacteria, fungi, protozoans and two types of tumors, Kaposi's sarcoma and lymphoma of the central nervous system. From the microorganisms, the most frequent was the Cytomegalovirus and, from the tumors, Kaposi's sarcoma. The various types of microorganisms were frequently associated, principally in the central nervous and digestive systems. There was also association of microorganisms with tumors. Besides the lesions produced by microorganisms there were other associated alterations as brown atrophy of neuronia, which was related to the infiltration of cerebral lymphoma, and the lymphocytic depletion of lymphoid organs due to immunological exhaustion. Cellular reaction to microorganisms was practically none, principally with Pneumocystis carinii and Cryptococcus neoformans, the first one behaving as an inert mould in the pulmonary alveoli and the second proliferating freely in tissues. In two cases there was no granulomatous reaction to Mycobacterium tuberculosis. The primary lymphoma of the central nervous system should be interpreted as a microglioma, i.e., a reticulosarcoma of this system according to Hortega's school.

  14. Transfusion-acquired AIDS in Taiwan.

    PubMed

    Yao, C; Wang, W W; Chung, Y M; Su, Y L; Liu, C Y; Chen, Y M

    1996-01-01

    Human immunodeficiency virus type 1 (HIV-1) can be transmitted through blood transfusion. The first transfusion-acquired immunodeficiency syndrome (AIDS) patient in Taiwan was a 46-year-old woman who received two units of whole blood during a hysterectomy at a provincial hospital in 1985. In 1991, she experienced a herpes zoster infection. In March 1993, she had extensive herpetic gingivostomatitis and another herpes zoster attack, and was treated at the same hospital. Two months later, she had oral candidiasis and was treated at a medical center. She was not tested for HIV-1 infection until she developed Pneumocystis carinii pneumonia in June 1993. In February 1994, and developed cytomegalovirus retinitis and died 6 months later. Donor blood given to the patients during the hysterectomy was HIV-1 positive. The donor's HIV infection was discovered in 1991 and he died of AIDS in 1993. As blood centers in Taiwan did not start screening for HIV-1 until January 1988, it is urgently recommended that any individual who received a blood transfusion between 1984 and 1987 in Taiwan and who currently experiences repeated episodes of opportunistic infections have an HIV-1 blood test. The receipt of a blood transfusion between 1984 and 1987 should be listed by the Department of Health as an indication for HIV-1 screening.

  15. Crystal structure of the anti-bacterial sulfonamide drug target dihydropteroate synthase.

    PubMed

    Achari, A; Somers, D O; Champness, J N; Bryant, P K; Rosemond, J; Stammers, D K

    1997-06-01

    Sulfonamides were amongst the first clinically useful antibacterial agents to be discovered. The identification of sulfanilamide as the active component of the dye Prontosil rubrum led to the synthesis of clinically useful analogues. Today sulfamethoxazole (in combination with trimethoprim), is used to treat urinary tract infections caused by bacteria such as Escherichia coli and is also a first-line treatment for pneumonia caused by the fungus Pneumocystis carinii, a common condition in AIDS patients. The site of action is the de novo folate biosynthesis enzyme dihydropteroate synthase (DHPS) where sulfonamides act as analogues of one of the substrates, para-aminobenzoic acid (pABA). We report here the crystal structure of E.coli DHPS at 2.0 A resolution refined to an R-factor of 0.185. The single domain of 282 residues forms an eight-stranded alpha/beta-barrel. The 7,8-dihydropterin pyrophosphate (DHPPP) substrate binds in a deep cleft in the barrel, whilst sulfanilamide binds closer to the surface. The DHPPP ligand site is highly conserved amongst prokaryotic and eukaryotic DHPSs.

  16. Human retroviruses and neoplastic disease.

    PubMed

    Kaplan, M H

    1993-11-01

    Human retroviral infections result in significant neoplastic disease. Human T cell lymphotropic virus I (HTLV-I), the first human retrovirus to be discovered, is associated with the development of acute T cell leukemia with characteristic hypercalcemia and skin lesions after many years of chronic infection of CD4+ cells. HTLV-I also produces myelopathy. A minor T cell immunodeficiency occurs in HTLV-I acute T cell leukemia with associated strongyloidiasis and Pneumocystis carinii pneumonia. Human T cell lymphotropic virus II (HTLV-II) is found to be endemic in Amerindians and intravenous drug users (IVDUs) and has been linked to some cases of hairy-cell leukemia. HTLV-II infects the CD8+ population, with significant cell-associated viremia. Clinical neurological disease is rare, with one patient with myelopathy having been described. Immunodeficiency does not seem to occur. Human immunodeficiency virus 1 (HIV-1) produces aggressive large cell and Burkitt's lymphoma in as many as 10% of HIV-1-infected patients. More than 20% of homosexual men infected with HIV-1 develop Kaposi's sarcoma (KS). The pathogenesis of KS is better understood through studying KS-like cell lines that induce angiogenic factors. In some patients HIV-1 and HTLV-I or HTLV-II infections occur concomitantly. HIV-1 accelerates the tumorigenesis of HTLV-I and produces unusual skin diseases when combined with HTLV-II. Immunodeficiency occurs in all HIV-1-infected patients.

  17. [HIV infection and acquired immunodeficiency syndrome].

    PubMed

    Takamatsu, J

    1997-05-01

    On June 4, 1981, MMWR published a report about Pneumocystis carinii pneumonia in homosexual men in Los Angeles. This was the first published report. A years later, this disease was named acquired immunodeficiency syndrome (AIDS). In the following year, Montangier et al in France discovered the causative agent, which they called lymphadenopathy virus (LAV), now known as human immunodeficiency virus (HIV). In 1985, solid-phase enzymeimmunoassay for the detection of the antibody to HIV was developed. Since then, other new techniques for the identification of HIV infection have been become available. These include more sensitive methods (for example; polymerase chain reaction techniques). Although these techniques facilitate early and definite diagnosis of infection, these tests may fail to detect the antibody in sera during window period of infection or overdiagnose infection in sera contaminated with genes not related to HIV. Although preventing blood exposure is the primary means of preventing occupationally acquired human immunodeficiency virus (HIV) infection, appropriate post-exposure management is an important element of workplace safety. Information suggesting that zidovudine (ZDV) postexposure prophylaxis (PEP) may reduce the risk for HIV transmission after occupational exposure to HIV infected blood prompted a Public Health Service (PHS) interagency working group, with expert consultation, and recommendations on PEP and management of occupational exposure to HIV in relation to these findings were discussed.

  18. The pathology of AIDS.

    PubMed Central

    Macher, A M

    1988-01-01

    The acquired immunodeficiency syndrome (AIDS) is a devastating new disease caused by the human immunodeficiency virus (HIV). This retrovirus causes profound immunoincompetence in its infected hosts, who are thereafter susceptible to develop myriad severe and relapsing protozoal, fungal, bacterial, viral, and arthropodal opportunistic infections, as well as unusual malignancies. The more than 50,000 patients who have developed AIDS in the United States have produced a sudden unexpected deluge of diagnostic dilemmas that are stressing laboratories of pathology everywhere. This paper describes the gross and microscopic pathology of the numerous complications in patients infected by HIV: (a) the prodromal AIDS-related complex with persistent generalized lymphadenopathy, (b) lymphoid infiltration of salivary gland and lung, including the complex of lymphoid interstitial pneumonitis-pulmonary lymphoid hyperplasia, (c) extranodal non-Hodgkin's lymphomas, (d) multifocal mucocutaneous and visceral Kaposi's sarcoma, (e) small cell undifferentiated (oat cell) carcinomas, (f) protozoal infections caused by Pneumocystis carinii, Toxoplasma gondii, Acanthamoeba, Cryptosporidium species (sp.), and Isospora belli, (g) the causes of chronic enteritis, (h) mycotic infections caused by Candida sp., Cryptococcus neoformans, Histoplasma capsulatum, Coccidioides immitis, and Sporothrix schenckii, (i) bacterial infections caused by Mycobacterium avium-intracellulare, M. tuberculosis, M. kansasii, Nocardia sp., Listeria monocytogenes, Legionella sp., Treponema pallidum, and others, (j) viral infections caused by cytomegalovirus, herpes simplex and zoster, polyomavirus (progressive multifocal leukoencephalopathy), hepatitis B, molluscum contagiosum, and papillomavirus, (k) oral hairy leukoplakia, (l) subacute encephalopathy, and (m) Norwegian scabies. PMID:2836878

  19. Preventing secondary infections among HIV-positive persons.

    PubMed Central

    Filice, G A; Pomeroy, C

    1991-01-01

    Secondary infectious diseases contribute substantially to morbidity and mortality of people infected with human immunodeficiency virus (HIV). The authors developed comprehensive, practical recommendations for prevention of infectious complications in HIV-infected people. Recommendations are concerned with the pathogens that are more common or more severe in HIV-infected people. Several infectious complications can be prevented by avoiding ingestion of contaminated food or water. Zoonoses can be prevented by precautions to be taken in contacts with animals. The risk of several fungal diseases can be reduced if activities likely to lead to inhalation of spores are avoided. HIV-infected people should be advised how to lower adverse health effects of travel, especially international travel. The potential for infectious complications of sexual activity and illicit drug use should be stressed, and recommendations to reduce the risk are discussed. Recommendations for use of vaccines in HIV-infected people are reviewed. Blood CD4+ lymphocyte concentrations, tuberculin skin testing, Toxoplasma serology, and sexually transmitted disease screening should be performed in certain subsets of HIV-infected people. Guidelines for chemoprophylaxis against Pneumocystis carinii and tuberculosis are presented. Recent data suggest that intravenous immunoglobulin therapy may prevent bacterial infections in HIV-infected children. PMID:1910184

  20. [Thoracic manifestations of AIDS (acquired immunodeficiency syndrome)].

    PubMed

    Bernasconi, A; Zompatori, M; Chiodo, F; Costigliola, P; Ricchi, E; Colangeli, V; Canini, R; Gavelli, G

    1989-11-01

    AIDS (acquired immunodeficiency syndrome) seems to be related to human immunodeficiency virus (HIV) and is characterized by severe T-helpers lymphocyte dysfunction. Many of the AIDS patients (47-70%) develop pulmonary manifestations, both infectious and neoplastic, in the course of their disease. In the Department of Infectious Diseases of our Hospital are studied many patients HIV+. Every year 246 seropositive new patients have been discovered. Among them we have studied 25 subjects with respiratory disease, by chest radiographs; successively, according to clinical picture, we have performed thoracic computed tomography, Gallium scintigraphy, fiberoptic bronchoscopy with transbronchial biopsy (TBB), bronchoalveolar lavage (BAL); the majority of these patients (68%) had AIDS, only 28% had ARC and 4% had PGL. In our experience, the diagnosed diseases were mainly infections (92%), and most frequently (52%) due to Pneumocystis carinii, alone or in association with other etiologic agents. We have not found pathognomonic radiographic abnormalities, but chest X-ray evaluated with clinical and laboratory data, may often be useful to obtain diagnostic indications and in order to determine a more specific and aggressive diagnostic approach.

  1. AIDS in the pre-AIDS era.

    PubMed

    Huminer, D; Rosenfeld, J B; Pitlik, S D

    1987-01-01

    A search of the medical literature published since 1950 disclosed 19 cases of probable AIDS reported before the start of the current epidemic. These cases retrospectively met the Centers for Disease Control's surveillance definition of the syndrome and had a clinical course suggestive of AIDS. The reports originated from North America, Western Europe, Africa, and the Middle East. The mean age of patients was 37 years, and the ratio of male to female patients was 1.7:1. Sixteen patients had opportunistic infections(s) without Kaposi's sarcoma. The remainder had disseminated Kaposi's sarcoma. The commonest opportunistic infection was Pneumocystis carinii pneumonia. Two patients were reported to be homosexual. Three others had been living in Africa, and one patient was born in Haiti. In two instances concurrent or subsequent opportunistic infection occurred in family members. All patients died 1 month to 6 years after the initial manifestation of disease. In view of the historical data, unrecognized cases of AIDS appear to have occurred sporadically in the pre-AIDS era.

  2. [Fever of unknown origin in a cohort of HIV-positive patients].

    PubMed

    Genné, D; Chave, J P; Glauser, M P

    1992-11-21

    The purpose of this study was to determine the prevalence of fever of unknown origin (FUO) in a cohort of HIV positive patients and to describe their evolution and the final diagnosis. The clinical records of 412 patients followed from January 1987 to December 1990 at our HIV outpatient clinic were reviewed: in 151 patients 255 episodes of fever had been observed of which 22 (in 21 patients) met the criteria for FUO. 19 patients (90%) presented with a CDC/WHO stage IV HIV infection and the mean CD4+ lymphocyte count was 0.160 G/l. The etiology was ultimately determined in 13/22 episodes (3 Pneumocystis carinii pneumonia, 3 invasive infections due to atypical mycobacteria, 2 bacterial pneumonia, 1 Cytomegalovirus colitis, 1 Isospora belli enteritis, 1 visceral leishmania, 1 candida septicemia and 1 lymphoma). In 6/22 episodes, the fever subsided after zidovudine was started and was therefore attributed to HIV itself. In 3/22 episodes no etiology was found. In conclusion, this series shows that FUO is usually seen in advanced HIV infection and that it often represents an early sign of opportunistic infection. This observation underlines the importance of follow-up, since it finally served to detect the etiology of FUO in 86% of cases. Trial treatment with zidovudine can be useful where no pathology has been discovered despite 3 weeks' follow-up and appropriate investigations.

  3. Cystic Lung Diseases: Algorithmic Approach.

    PubMed

    Raoof, Suhail; Bondalapati, Praveen; Vydyula, Ravikanth; Ryu, Jay H; Gupta, Nishant; Raoof, Sabiha; Galvin, Jeff; Rosen, Mark J; Lynch, David; Travis, William; Mehta, Sanjeev; Lazzaro, Richard; Naidich, David

    2016-10-01

    Cysts are commonly seen on CT scans of the lungs, and diagnosis can be challenging. Clinical and radiographic features combined with a multidisciplinary approach may help differentiate among various disease entities, allowing correct diagnosis. It is important to distinguish cysts from cavities because they each have distinct etiologies and associated clinical disorders. Conditions such as emphysema, and cystic bronchiectasis may also mimic cystic disease. A simplified classification of cysts is proposed. Cysts can occur in greater profusion in the subpleural areas, when they typically represent paraseptal emphysema, bullae, or honeycombing. Cysts that are present in the lung parenchyma but away from subpleural areas may be present without any other abnormalities on high-resolution CT scans. These are further categorized into solitary or multifocal/diffuse cysts. Solitary cysts may be incidentally discovered and may be an age related phenomenon or may be a remnant of prior trauma or infection. Multifocal/diffuse cysts can occur with lymphoid interstitial pneumonia, Birt-Hogg-Dubé syndrome, tracheobronchial papillomatosis, or primary and metastatic cancers. Multifocal/diffuse cysts may be associated with nodules (lymphoid interstitial pneumonia, light-chain deposition disease, amyloidosis, and Langerhans cell histiocytosis) or with ground-glass opacities (Pneumocystis jirovecii pneumonia and desquamative interstitial pneumonia). Using the results of the high-resolution CT scans as a starting point, and incorporating the patient's clinical history, physical examination, and laboratory findings, is likely to narrow the differential diagnosis of cystic lesions considerably.

  4. Pulmonary disease at autopsy in patients with the acquired immunodeficiency syndrome.

    PubMed

    Wallace, J M; Hannah, J B

    1988-08-01

    To characterize the postmortem pulmonary disease and analyze the effectiveness of antemortem diagnosis, we examined the clinical records and autopsy material from 54 patients who died of the acquired immunodeficiency syndrome. At autopsy, all patients had pulmonary disease. One or more specific diagnoses were made in 53, including opportunistic infection, nonopportunistic infection, and Kaposi's sarcoma. Multiple postmortem pulmonary diagnoses were established in 37. Respiratory failure was the most common cause of death. Of the 97 pulmonary disorders discovered at autopsy, only 31 were diagnosed before death. The frequency with which infections were diagnosed during life varied according to the organism, and was significantly higher for Pneumocystis carinii than for cytomegalovirus or bacterial agents. Pulmonary Kaposi's sarcoma was diagnosed in only 7% of patients with autopsy documentation. The yield of diagnostic procedures also varied according to the disease present. Sputum culture was relatively effective in detecting Cryptococcus neoformans and Mycobacterium avium-intracellulare, fiber-optic bronchoscopy was extremely useful for diagnosing P Carinii, and one or more diagnoses were provided in 4 of 7 patients who underwent thoracotomy, but significant disease including cytomegalovirus infection and pulmonary Kaposi's sarcoma was frequently missed. Although the spectrum of lung disease found at autopsy is similar to that observed during life, the frequency of some pathologic processes including cytomegalovirus infection and Kaposi's sarcoma may be underrepresented in antemortem series.

  5. Preventing opportunistic infections in human immunodeficiency virus-infected persons: implications for the developing world.

    PubMed

    Kaplan, J E; Hu, D J; Holmes, K K; Jaffe, H W; Masur, H; De Cock, K M

    1996-07-01

    More than 18 million persons in the world are estimated to have been infected with human immunodeficiency virus (HIV), the cause of the acquired immunodeficiency syndrome (AIDS). As immunodeficiency progresses, these persons become susceptible to a wide variety of opportunistic infections (OIs) The spectrum of OIs varies among regions of the world. Tuberculosis is the most common serious OI in sub-Saharan Africa and is also more common in Latin America and in Asia than in the United States. Bacterial and parasitic infections are prevalent in Africa; protozoal infections such as toxoplasmosis, cryptosporidiosis, and isosporiasis are also common in Latin America. Fungal infections, including cryptococcosis and Penicillium marneffei infection, appear to be prevalent in Southeast Asia. Despite limited health resources in these regions, some measures that are recommended to prevent OIs in the United States may be useful for prolonging and improving the quality of life of HIV-infected persons. These include trimethoprim-sulfamethoxazole to prevent Pneumocystis carinii pneumonia, toxoplasmosis, and bacterial infections; isoniazid to prevent tuberculosis; and 23-valent pneumococcal vaccine to prevent disease due to Streptococcus pneumoniae. Research is needed to determine the spectrum of OIs and the efficacy of various prevention measures in resource-poor nations, and health officials need to determine a minimum standard of care for HIV-infected persons. An increasing problem in the developing world, HIV/AIDS should receive attention comparable to other tropical diseases.

  6. Gender differences in reported AIDS-indicative diagnoses.

    PubMed

    Fleming, P L; Ciesielski, C A; Byers, R H; Castro, K G; Berkelman, R L

    1993-07-01

    To compare AIDS-defining conditions in women and men, US adult AIDS cases diagnosed between January 1988 and June 1991 and reported to the Centers for Disease Control and Prevention through June 1992 were examined. For most AIDS-defining conditions, the prevalence was similar for women and men when differences in race/ethnicity and mode of transmission were accounted for. Pneumocystis carinii pneumonia was the most prevalent condition (> 50%) regardless of gender, race/ethnicity, or mode of transmission. By logistic regression analysis, among injection drug users, conditions reported significantly more frequently in women than in men include esophageal candidiasis (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.40-1.62), herpes simplex virus (HSV) disease (OR, 1.68; CI, 1.46-1.94), and cytomegalovirus (CMV) disease (OR, 1.43; CI, 1.18-1.73). More knowledge of the interrelationships in women between HIV infection and secondary opportunistic infections, including candidiasis and sexually transmitted disease (e.g., HSV and CMV) is needed.

  7. Severe and protracted hypoglycaemia associated with co-trimoxazole use.

    PubMed

    Strevel, Elizabeth L; Kuper, Ayelet; Gold, Wayne L

    2006-03-01

    Co-trimoxazole (trimethoprim-sulfamethoxazole) is a commonly prescribed antimicrobial agent. Although it is well tolerated in most patients, serious adverse events related to its use have been described. Hypoglycaemia is a rare but potentially life-threatening complication of therapy. We describe a case of refractory hypoglycaemia complicated by seizure associated with co-trimoxazole for the treatment of Pneumocystis carinii pneumonia in a patient with AIDS. We also review 13 previously reported cases of co-trimoxazole-induced hypoglycaemia. Among this patient population, renal insufficiency was the most prevalent predisposing risk factor (93%). The mean daily dose of co-trimoxazole was 4.5 double strength (160 mg trimethoprim/800 mg sulfamethoxazole) tablets per day. Serum insulin levels were raised or inappropriately normal in 88% of cases in which they were measured, suggesting a sulfonylurea-like effect of co-trimoxazole as the mechanism of hypoglycaemia. All cases required intravenous glucose administration, and 43% experienced protracted (>12 hours) hypoglycaemia. Dosage adjustments should be made when prescribing co-trimoxazole to patients with renal dysfunction.

  8. Potential Impact of Co-Infections and Co-Morbidities Prevalent in Africa on Influenza Severity and Frequency: A Systematic Review.

    PubMed

    Cohen, Adam L; McMorrow, Meredith; Walaza, Sibongile; Cohen, Cheryl; Tempia, Stefano; Alexander-Scott, Marissa; Widdowson, Marc-Alain

    2015-01-01

    Infectious diseases and underlying medical conditions common to Africa may affect influenza frequency and severity. We conducted a systematic review of published studies on influenza and the following co-infections or co-morbidities that are prevalent in Africa: dengue, malaria, measles, meningococcus, Pneumocystis jirovecii pneumonia (PCP), hemoglobinopathies, and malnutrition. Articles were identified except for influenza and PCP. Very few studies were from Africa. Sickle cell disease, dengue, and measles co-infection were found to increase the severity of influenza disease, though this is based on few studies of dengue and measles and the measles study was of low quality. The frequency of influenza was increased among patients with sickle cell disease. Influenza infection increased the frequency of meningococcal disease. Studies on malaria and malnutrition found mixed results. Age-adjusted morbidity and mortality from influenza may be more common in Africa because infections and diseases common in the region lead to more severe outcomes and increase the influenza burden. However, gaps exist in our knowledge about these interactions.

  9. The spectrum of pathological changes in the lung in children with the acquired immunodeficiency syndrome: an autopsy study of 36 cases.

    PubMed

    Moran, C A; Suster, S; Pavlova, Z; Mullick, F G; Koss, M N

    1994-09-01

    We present the pulmonary findings in 36 autopsies of children affected by the acquired immunodeficiency syndrome (AIDS). Twenty-three patients were male and 13 were female, ranging in age between 3 days and 13 years. Twenty children had human immunodeficiency virus (HIV)-positive parents or parents who were at high risk of exposure (intravenous drug abusers and prostitutes), five had a history of transfusion, and one had a history of renal transplantation and blood transfusion. Clinically, the patients presented with recurrent infections, failure to thrive, hepatosplenomegaly, fever, cough, and/or hemoptysis. Histologically, specific infectious processes were the most common finding (75% of cases), with Pneumocystis carinii pneumonia being the most prevalent type of infection, followed by bacterial pneumonia. Neoplastic conditions and lymphoid interstitial pneumonia were less frequent (approximately 10% of cases). In addition, in approximately 10% of the cases the pulmonary findings were non-specific (ie, pulmonary edema and atelectasis) and probably unrelated to HIV infection. Our findings suggest that specific infectious conditions constitute the most common type of pulmonary pathology in children with AIDS. However, because there is a small percentage of children with nonspecific findings, a transbronchial biopsy is important for proper evaluation before institution of therapy.

  10. Interpretation of chest radiographs in AIDS patients: usefulness of CD4 lymphocyte counts.

    PubMed

    Shah, R M; Kaji, A V; Ostrum, B J; Friedman, A C

    1997-01-01

    Specific infections and neoplasms that are complications of acquired immunodeficiency syndrome (AIDS) occur within various CD4 lymphocyte count ranges. Knowledge of how these counts correlate with radiographic appearances of these entities can limit the differential diagnosis because certain conditions are uncommon above a specific count. In patients with CD4 lymphocyte counts above 200 cells/mm3 and radiographic findings of cavitary and noncavitary consolidation, bacterial pneumonia and Mycobacterium tuberculosis are the major diagnostic considerations. As the CD4 lymphocyte count falls, these infections are still common; however, cavitation is seen less frequently with Mycobacterium tuberculosis, and unusual bacterial infections, including those caused by Rhodococcus equi and Nocardia asteroides, should be considered. In patients with counts below 200 cells/mm3, Pneumocystis carinii pneumonia is the most common infection, usually manifesting radiographically as a reticular interstitial pattern. At CD4 lymphocyte counts of 50-200 cells/mm3, disseminated fungal infection and Kaposi sarcoma become prevalent. In patients with advanced AIDS and counts below 50 cells/mm3, radiographic nodular or reticular patterns may indicate AIDS-related lymphoma and cytomegalovirus and Mycobacterium avium-intracellulare infections. When CD4 lymphocyte counts are applied to interpretation of chest radiographs in AIDS patients, the working differential diagnosis of a radiographic pattern can be tailored to the clinical situation of a given patient.

  11. Pulmonary complications of HIV-1 infection among adults living in Sub-Saharan Africa.

    PubMed

    Murray, J F

    2005-08-01

    Sub-Saharan Africa, which has just over 10% of the world's population, is home to more than 25 million people living with HIV/AIDS-two thirds of the global total. Opportunistic pulmonary infections are major causes of morbidity and mortality among HIV-infected adults in the subcontinent. Of these diseases, tuberculosis (TB) is by far the most prevalent and serious, and in some countries it causes one third or more of all AIDS-related deaths. Because it is so frequent and a major public health problem, TB tops the list of differential diagnoses of people-with or without coexisting HIV infection-who present to the health care system with chronic cough and other pulmonary symptoms. As HIV-induced immunosuppression worsens, the clinical and radiographic manifestations of TB become increasingly atypical. Second among HIV/AIDS-associated pulmonary complications is community-acquired pneumonia, most commonly caused by Streptococcus pneumoniae, which usually responds to standard beta-lactam antimicrobial agents. The prevalence of Pneumocystis jirovecii pneumonia is increasing, due to both improved recognition of its characteristic clinical and radiographic features and aggressive diagnostic interventions. Treatment outcome in most countries, however, has been poor. Combined infections, usually including TB, are common. Pulmonary nocardiosis, cryptococcosis, Kaposi's sarcoma, and (possibly) histoplasmosis appear to be infrequent, but probably underdiagnosed. Improved diagnosis, treatment, and prevention of all these diseases are urgently needed, but a greatly expanded antiretroviral treatment program will help most of all.

  12. Epidemiology of HIV-Associated Lung Disease in the United States.

    PubMed

    Fitzpatrick, Meghan; Brooks, John T; Kaplan, Jonathan E

    2016-04-01

    The epidemiology of HIV infection and its pulmonary complications in the United States has evolved significantly over nearly 20 years since the advent of combination antiretroviral therapy. While infectious complications are less of a threat to patients whose immune systems have been restored, many HIV-infected persons in the United States remain at high risk for opportunistic infection because they are unaware of their HIV infection, have difficulty maintaining linkage to care, or maintain inadequate viral control. Bacterial pneumonia and Pneumocystis pneumonia remain significantly more prevalent among HIV-infected persons, and together with seasonal influenza are areas where public health efforts to increase antiretroviral therapy, appropriate prophylaxis, and vaccination may decrease burden of disease. Noninfectious pulmonary complications of chronic HIV infection are increasingly recognized in the United States and elsewhere. Chronic obstructive pulmonary disease, asthma, pulmonary hypertension, sleep-disordered breathing, and primary lung cancer may all be more common among persons with HIV; of concern, disease burden in U.S. HIV-infected persons may be underestimated due to lack of diagnostic testing for these conditions. Smoking is among the most prevalent preventable causes of morbidity and mortality affecting persons living with HIV infection, and has particular import to pulmonary disease. As of 2009, 42% of HIV-infected adults in medical care in the United States smoked tobacco (over twice the national rate in the general population). Successful efforts to promote smoking cessation among HIV-infected persons are of critical importance to decrease the burden of chronic pulmonary disease.

  13. A study of chest infections in HIV seropositive patients in Kuala Lumpur.

    PubMed

    Wood, E; Cheong, I; Lee, C

    1998-01-01

    A retrospective study of 144 adults with HIV infection was conducted to investigate the prevalence of upper and lower respiratory tract infections (URTIs and LRTIs). The patients were divided into two groups: those with acquired HIV through intravenous drug abuse (IVDA), and those who had acquired HIV through 'other' risk behaviours. LRTIs were more prevalent than URTIs overall, and LRTIs were significantly more common (p < 0.001) in IVDAs than in the other-risk group. Tuberculosis (40%) and bacterial pneumonias (33%) comprised the majority of LRTIs among IVDAs, while Pneumocystis carinii pneumonia (40%) was the commonest LRTI in the other-risk group. Analysis of CD4 T-lymphocyte counts indicated that HIV-seropositive IVDAs are at greater risk of developing chest infections at higher CD4 counts than other-risk patients. The IVDAs were also found to have a much higher rate of co-infection with hepatitis C and B, which may be a factor accelerating the progression from HIV infection to AIDS. The mean time averaged for the two groups from known seroconversion to development of respiratory tract infection is only 1.37 years, which suggests HIV-infected patients are presenting late for treatment in Malaysia.

  14. Major complications following hematopoietic stem cell transplantation.

    PubMed

    Afessa, Bekele; Peters, Steve G

    2006-06-01

    Tens of thousands of patients undergo hematopoietic stem cell transplantation (HSCT) annually, 15 to 40% of whom are admitted to the intensive care unit. Pulmonary complications are the most life threatening conditions that develop in HSCT recipients. Both infectious and noninfectious complications occur more frequently in allogeneic HSCT. The management of HSCT recipients requires knowledge of their immune status, appropriate diagnostic evaluation, and early treatment. During the pre-engraftment phase (0 to 30 days after transplant), the most prevalent pathogens causing infection are bacteria and Candida species and, if the neutropenia persists, Aspergillus species. The early post-engraftment phase (30 to 100 days) is characterized by cytomegalovirus (CMV), Pneumocystis jiroveci, and Aspergillus infections. During the late posttransplant phase (> 100 days), allogeneic HSCT recipients are at risk for CMV, community-acquired respiratory virus, and encapsulated bacterial infections. Antigen and polymerase chain reaction assays are important for the diagnosis of CMV and Aspergillus infections. Diffuse alveolar hemorrhage (DAH) and peri-engraftment respiratory distress syndrome occur in both allogeneic and autologous HSCT recipients, usually during the first 30 days. Bronchiolitis obliterans occurs exclusively in allogeneic HSCT recipients with graft versus host disease. Idiopathic pneumonia syndrome occurs at any time following transplant. Bronchoscopy is usually helpful for the diagnosis of the infectious pulmonary complications and DAH.

  15. [The AIDS patient in anesthesia].

    PubMed

    Jalowy, A; Flesche, C W; Lorenz, C

    1997-02-01

    Treatment of a patient with Acquired Immune Deficiency Syndrome (AIDS) is very challenging, and makes great demands on the anaesthesiologist. Any of an AIDS patient's vital organ systems may be compromised, either by the human immunodeficiency virus (HIV) itself, opportunistic infections, by tumours, or as a result of AIDS-related drug therapies. Infections of the lungs (e.g., Pneumocystis carinii pneumonia) are prevalent, and cardiac impairment can be found in as many as 50% of AIDS patients. In addition, disorders of the central and peripheral nervous system and water and electrolyte imbalances are often seen. Perioperatively, the AIDS patient is especially prone to infections as a result of a compromised immune system. The choice of anaesthetic procedure for the AIDS patient-aside from the type of operation-depends on the severity of the illness and progression of organ impairment. All anaesthesia personnel must be careful to avoid infection, as they frequently come in contact with the blood or body fluids of their patients. However, the risk of being infected by an AIDS patient is very low, provided hygiene regulations are followed strictly. The rate of seroconversion after accidental needle-stick injury is below 1%. If exposure does occur, regular serologic controls should be continued for one year. Prophylactic treatment with azidothymidine after exposition to HIV is recommended.

  16. AIDS-defining opportunistic illnesses in the HAART era in New York City.

    PubMed

    Hanna, D B; Gupta, L S; Jones, L E; Thompson, D M; Kellerman, S E; Sackoff, J E

    2007-02-01

    Despite widespread availability of HAART, opportunistic illnesses (OIs) still occur and result in an increased risk of mortality among persons with AIDS. We estimated the incidence of OIs among all new adult AIDS cases in New York City in 2000 overall and in demographic and clinical subgroups and identified factors associated with occurrence of an AIDS-defining OI versus AIDS diagnosis based on low CD4+ values only. In 2000, 5,451 new AIDS cases were reported to the New York City Department of Health and Mental Hygiene. Of these 27.4% (95% CI: 22.8-32.6) had at least one OI, most frequent being Pneumocystis jiroveci pneumonia (12.2%) and M. tuberculosis (5.3%); 47.1% (41.7-52.5) had a late HIV diagnosis (i.e.< or =6 months before AIDS diagnosis). Persons with a late HIV diagnosis not in recent care had a 3.5-fold increased odds (1.29-9.63) of an OI, compared to non-late testers in care. Other predictors of an OI were injection drug use and older age. We conclude that OIs remain prevalent in the HAART era and late testers not in care are especially likely to develop an OI. Our results support comprehensive HIV programs promoting early HIV testing and linkage to care to prevent OI-related morbidity and mortality.

  17. Reversible severe combined immunodeficiency phenotype secondary to a mutation of the proton-coupled folate transporter

    PubMed Central

    Borzutzky, Arturo; Crompton, Brian; Bergmann, Anke K.; Giliani, Silvia; Baxi, Sachin; Martin, Madelena; Neufeld, Ellis J.; Notarangelo, Luigi D.

    2009-01-01

    Hereditary folate malabsorption is a rare inborn error of metabolism due to mutations in the proton-coupled folate transporter (PCFT). Clinical presentation of PCFT deficiency may mimic severe combined immune deficiency (SCID). We report a 4-month-old female who presented with failure to thrive, normocytic anemia, Pneumocystis jirovecii pneumonia and systemic cytomegalovirus infection. Immunological evaluation revealed hypogammaglobulinemia, absent antibody responses, and lack of mitogen-induced lymphocyte proliferative responses. However, the absolute number and distribution of lymphocyte subsets, including naïve T cells and recent thymic emigrants, were normal, arguing against primary SCID. Serum and cerebrospinal fluid folate levels were undetectable. A homozygous 1082-1G>A mutation of the PCFT gene was found, resulting in skipping of exon 3. Parenteral folinic acid repletion resulted in normalization of anemia, humoral and cellular immunity, and full clinical recovery. PCFT mutations should be considered in infants with SCID-like phenotype, as the immunodeficiency is reversible with parenteral folinic acid repletion. PMID:19740703

  18. Cytomegalovirus pneumonia as the first manifestation of severe combined immunodeficiency

    PubMed Central

    Jończyk-Potoczna, Katarzyna; Ossowska, Lidia; Bręborowicz, Anna; Bartkowska-Śniatkowska, Alicja; Wachowiak, Jacek

    2014-01-01

    Severe combined immunodeficiency (SCID) is characterized by the absence of functional T lymphocytes and impairment of adaptive immunity. While heterogeneity of the genetic background in SCID leads to the variability of immune phenotypes, most of affected newborns appear healthy but within the first few months they develop life-threatening opportunistic respiratory or gastrointestinal tract infections. The objective of the study was to define the presenting features and etiology of infections in children with SCID. We retrospectively reviewed five children in whom the diagnosis of SCID had been established in our pediatric immunology clinic over the last 10-year period. A viral respiratory tract infection was the first manifestation of SCID in all the children studied. Cytomegalovirus (CMV) pneumonia was recognized in as many as 4 cases and coronavirus pulmonary infection was diagnosed in one case, whereas Pneumocystis jiroveci was identified as a co-pathogen in one CMV-infected patient. Severe combined immunodeficiency is a pediatric emergency condition and given the significant impact of pulmonary CMV infection in SCID children, establishing an accurate etiological diagnosis is of essential importance in instituting the specific treatment and improving the outcome. PMID:26155153

  19. The Spectrum of Infectious Diseases in Kidney Transplantation: A Review of the Classification, Pathogens and Clinical Manifestations.

    PubMed

    Anastasopoulos, Nikolaos-Andreas; Duni, Anila; Peschos, Dimitrios; Agnantis, Niki; Dounousi, Evangelia

    2015-01-01

    Kidney transplantation is the treatment-of-choice for a significant number of patients with end-stage renal disease. Renal transplant recipients (RTRs) benefit from a longer life expectancy, with a better quality of life. Despite, recent accomplishments in the field of kidney transplantation, both short- and long-term, surgical and medical complications still exist. Among these complications, cardiovascular disease, carcinogenesis and infections are the most important. Infectious diseases constitute the most common complications after renal transplantation and the second most common cause of death among RTRs with a functioning graft. Theoretically, all infectious pathogens could cause disease in immunocompromised RTRs, yet among these, one could identify more important ones, such as the Enterobacteriaceae, causing urinary tract infections; pneumonia due to Pneumocystis jirovecii; Candida species which cause invasive fungal infections; herpes viruses; hepatitis viruses and parasites. Early diagnosis and effective treatment are key elements in salvaging both the allograft and the patient. However, clinical manifestations and diagnosis of such infectious diseases are not easily identified due to the altered state of immune response of the RTR. Thus, apart from possessing a deep knowledge of the etiology and the treatment options in each case, transplant physicians should also always remain alert when dealing with RTRs.

  20. sup 111 In-labeled nonspecific immunoglobulin scanning in the detection of focal infection

    SciTech Connect

    Rubin, R.H.; Fischman, A.J.; Callahan, R.J.; Khaw, B.A.; Keech, F.; Ahmad, M.; Wilkinson, R.; Strauss, H.W. )

    1989-10-05

    We performed radionuclide scanning after the intravenous injection of human IgG labeled with indium-111 in 128 patients with suspected focal sites of inflammation. Localization of 111In-labeled IgG correlated with clinical findings in 51 infected patients (21 with abdominal or pelvic infections, 11 with intravascular infections, 7 with pulmonary infections, and 12 with skeletal infections). Infecting organisms included gram-positive bacteria, gram-negative bacteria, Pneumocystis carinii, Mycoplasma pneumoniae, and Candida albicans. No focal localization of 111In-labeled IgG was observed in 63 patients without infection. There were five false negative results, and nine results were unusable. Serial scans were carried out in eight patients: continued localization correctly predicted relapse in six, and the absence of localization indicated resolution in two. To determine whether 111In-labeled IgG localization was specific for inflammation, we studied 16 patients with cancer. Focal localization occurred in 13 of these patients (5 with melanomas, 5 with gynecologic cancers, and 1 each with lymphoma, prostate cancer, and malignant fibrous histiocytoma). No localization was seen in patients with renal or colon cancer or metastatic medullary carcinoma of the thyroid. We conclude that 111In-labeled IgG imaging is effective for the detection of focal infection and that serial scans may be useful in assessing therapeutic efficacy. This technique may also be helpful in the evaluation of certain cancers.

  1. International NeuroAIDS: prospects of HIV-1 associated neurological complications.

    PubMed

    Trujillo, J Roberto; Jaramillo-Rangel, Gilberto; Ortega-Martinez, Marta; Penalva de Oliveira, Augusto C; Vidal, Jose E; Bryant, Joseph; Gallo, Robert C

    2005-01-01

    Neurological complications associated with HIV-1/AIDS are being recognized with a high frequency that parallels the increased number of AIDS cases. The early infiltration by HIV-1 into the nervous system can cause primary and/or secondary neurological complications. The most common neurocognitive disorder is AIDS Dementia Complex (ADC). In developing countries of Asia the three most opportunistic infections are tuberculosis (TB), cryptococcosis, and Pneumocystis carinii pneumonia. Therefore, it is expected that secondary neurological complications due to TB and cryptococcosis will be the most common cause of morbility and mortality in HIV-1/AIDS cases in China. Research of NeuroAIDS in China is necessary to understand the impact and the biology of HIV-1 in the nervous system. Future studies would include, the molecular epidemiology and the description of opportunistic infections associated to HIV-1; the neuropathological description of primary and secondary HIV-1 complications in different groups; the HIV-1 neurotropism and immune response studies for China's unique HIV-1 strains and recombinant forms derived from the nervous system, including experimental models such as the use of transgenic rats; and the study of potential resistant virus, primarily when the anti-retroviral therapy (ART) has not full access in the brain.

  2. Characterization of nebulized buparvaquone nanosuspensions--effect of nebulization technology.

    PubMed

    Hernández-Trejo, Norma; Kayser, Oliver; Steckel, Hartwig; Müller, Rainer H

    2005-01-01

    The poorly soluble drug buparvaquone is proposed as an alternative treatment of Pneumocystis carinii pneumonia (PCP) lung infections. Physically stable nanosuspensions were formulated in order to deliver the drug at the site of infection using nebulization. The aerosolization characteristics of two buparvaquone nanosuspensions were determined with commercial jet and ultrasonic nebulizer devices. Aerosol droplet size distribution was determined with laser diffractometry (LD). Nebulization of the nanosuspensions and dispersion media surfactant solutions produced aerosol droplets diameters in the range from 3 to 5 microm for Respi-jet Kendall, Pari Turbo Boy system and Multisonic nebulizers and particles around 9-10 microm with Omron U1. Fractions of the nanosuspensions from the nebulizer reservoir and of aerosol produced were collected to investigate changes in the size of the drug nanocrystals influenced by the nebulization technology. Comparisons were performed measuring the drug nanocrystals with photon correlation spectroscopy (PCS) and LD of the samples. Drug particle aggregates were detected in the fractions of aerosol collected from jet nebulizers. Nebulizer technology (jet vs. ultrasonic) showed influence on the stability of the drug particle size distribution of buparvaquone nanocrystals during the nebulization time evaluated.

  3. Proceedings of the 2013 National Toxicology Program Satellite Symposium

    PubMed Central

    Elmore, Susan A.; Boyle, Michael C.; Boyle, Molly H.; Cora, Michelle C.; Crabbs, Torrie A.; Cummings, Connie A.; Gruebbel, Margarita M.; Johnson, Crystal L.; Malarkey, David E.; McInnes, Elizabeth F.; Nolte, Thomas; Shackelford, Cynthia C.; Ward, Jerrold M.

    2014-01-01

    The 2013 annual National Toxicology Program (NTP) Satellite Symposium, entitled “Pathology Potpourri” was held in Portland, Oregon in advance of the Society of Toxicologic Pathology's 32nd annual meeting. The goal of the NTP Symposium is to present current diagnostic pathology or nomenclature issues to the toxicologic pathology community. This article presents summaries of the speakers' presentations, including diagnostic or nomenclature issues that were presented, along with select images that were used for audience voting and discussion. Some lesions and topics covered during the symposium included a caudal tail vertebra duplication in mice; nephroblastematosis in rats; ectopic C cell tumor in a hamster; granular cell aggregates/tumor in the uterus of a hamster; Pneumocystis carinii in the lung of a rat; iatrogenic chronic inflammation in the lungs of control rats; hepatoblastoma arising within an adenoma in a mouse; humoral hypercalcemia of benignancy in a transgenic mouse; acetaminophen induced hepatoxicity in rats; electron microscopy images of iatrogenic intraerythrocytic inclusions in transgenic mice; questionable hepatocellular degeneration/cell death/artifact in rats; atypical endometrial hyperplasia in rats; malignant mixed Müllerian tumors/carcinosarcomas in rats; differential diagnoses of proliferative lesions the intestine of rodents; and finally obstructive nephropathy caused by melamine poisoning in a rat. PMID:24334674

  4. Pharmacokinetics of hyperimmune anti-human immunodeficiency virus immunoglobulin in persons with AIDS.

    PubMed Central

    Fletcher, C V; Goodroad, B K; Cummins, L M; Henry, K; Balfour, H H; Rhame, F S

    1997-01-01

    Hyperimmune anti-human immunodeficiency virus immunoglobulin (HIVIG) is an intravenous immunoglobulin prepared from HIV-infected asymptomatic donors with a CD4 cell count greater than 400 cells/microl and a high titer of antibody to HIV-1 p24 protein. Twelve persons with AIDS received four doses of HMG (two at 50 mg/kg of body weight and then two at 200 mg/kg) every 28 days. Pharmacokinetics were evaluated by measurement of anti-p24 antibody. HIVIG was well tolerated, and all participants completed the study. Three subjects who were not receiving Pneumocystis carinii pneumonia (PCP) prophylaxis developed PCP. The mean value for HIVIG clearance was 3.02 ml/kg/day at 50 mg/kg and 3.65 ml/kg/day at 200 mg/kg (P = 0.027); the mean trough antibody titers (reciprocal units) were 1,442 and 4,428, respectively. This study indicates that high titers of anti-p24 antibody can be maintained with a monthly administration schedule of HIVIG and that short-term safety is acceptable. Comparisons to evaluate the therapeutic potential of HIVIG are justified. PMID:9210687

  5. The 13th International Workshops on Opportunistic Protists (IWOP13)

    PubMed Central

    CALDERON, ENRIQUE J.; CUSHION, MELANIE T.; XIAO, LIHUA; LORENZO-MORALES, JACOB; MATOS, OLGA; KANESHIRO, EDNA S.; WEISS, LOUIS M.

    2015-01-01

    The 13th International Workshops on Opportunistic Protists (IWOP-13) was held November 13 to 15, 2014 in Seville, Spain. The objectives of the IWOP meetings are to: (1) Serve as a forum for exchange of new information among active researchers concerning the basic biology, molecular genetics, immunology, biochemistry, pathogenesis, drug development, therapy, and epidemiology of these immunodeficiency associated pathogenic eukaryotic microorganisms that are seen in patients with AIDS; and (2) to foster the entry of new and young investigators into these underserved research areas. The IWOP meeting focuses on opportunistic protists; e.g. the free-living amoebae, Pneumocystis, Cryptosporidium, Toxoplasma, the Microsporidia, and kinetoplastid flagellates. This conference represents the major conference which brings together research groups working on these opportunistic pathogens. Progress has been achieved on understanding the biology of these pathogenic organisms, their involvement in disease causation in both immune deficient and immune competent hosts and is providing important insights into these emerging and reemerging pathogens. A continuing concern of the participants is the ongoing loss of scientific expertise and diversity in this research community. This decline is due to the small size of these research communities and an ongoing lack of understanding by the broader scientific community of the challenges and limitations faced by researchers working on these organisms, which makes these research communities very sensitive to declines in research funding. PMID:25923469

  6. The prevalence and clinical course of HIV-associated pulmonary cryptococcosis in Uganda

    PubMed Central

    Yoo, Samuel D; Worodria, William; Davis, JL; Cattamanchi, Adithya; den Boon, Saskia; Kyeyune, Rachel; Kisembo, Harriet; Huang, Laurence

    2010-01-01

    Background The prevalence and clinical course of pulmonary cryptococcosis in Sub-Saharan Africa are not well-described. Methods Consecutive HIV-infected adults hospitalized at Mulago Hospital (Kampala, Uganda) between September 2007 and July 2008 with cough ≥ 2 weeks were enrolled. Patients with negative sputum smears for acid-fast bacilli were referred for bronchoscopy with bronchoalveolar lavage (BAL). BAL fluid was examined for mycobacteria, Pneumocystis jirovecii, and fungi. Patients were followed two and six months after hospital discharge. Results Of 407 patients enrolled, 132 (32%) underwent bronchoscopy. Of 132 BAL fungal cultures, 15 (11%) grew Cryptococcus neoformans. None of the patients were suspected to have pulmonary cryptococcosis on admission. The median CD4 count among those with pulmonary cryptococcosis was 23 cells/µL (IQR 7–51). Of 13 patients who completed six-month follow-up, four died and nine were improved, including five who had started antiretroviral therapy (ART) but had not received antifungal medication. Conclusions Pulmonary cryptococcosis is common in HIV-infected TB suspects in Uganda. Early initiation of ART in those with isolated pulmonary infection may improve outcomes, even without anti-fungal therapy. This finding suggests that some HIV-infected patients with C. neoformans isolated from respiratory samples may have colonization or localized infection. PMID:20150818

  7. Causes of death in renal transplant recipients: a study of 102 autopsies from 1968 to 1991.

    PubMed Central

    Reis, M A; Costa, R S; Ferraz, A S

    1995-01-01

    A study was conducted on 102 patients submitted to renal transplant who died and were autopsied at the University Hospital, Faculty of Medicine of Ribeirão Preto, Brazil, from 1968 to 1991. The cause of death, based on a review of medical records and autopsy reports, was assigned to one of the following categories: infectious (69.6%); cardiovascular (12.7%); gastrointestinal (7.8%); graft rejection (6.9%); tumoral (2.0%); and undetermined (1.0%). Among the 71 cases of death caused by infection, 28 (39.4%) showed disseminated agents involving two or more organs. Isolated pneumonia involved 17 patients (23.9%), followed by acute pyelonephritis in the transplanted kidney in 10 patients (14.1%). The most frequent agents were: bacteria (58.0%), divided into 'non-classified' (83.0%), Nocardia (10.6%) and Mycobacterium (6.4%); fungi (27.5%) represented by Cryptococcus (22.7%), Aspergillus, Candida and Pneumocystis carinii (18.1% each), Histoplasma (13.6%), Mucor and Paracoccidioides brasiliensis (4.5% each); viruses (6.2%) represented by Herpes simplex (60.0%); metazoa (5.0%, S. stercoralis), and protozoa (2.5%, T. cruzi). Cytomegalovirus (CMV) was identified in the lungs of 12 patients and was not directly correlated with death but was associated with other agents. In conclusion, immunodepressed patients such as renal transplant recipients should be carefully monitored for infection due to the high mortality rate. PMID:7884765

  8. Reversible myoclonus, asterixis, and tremor associated with high dose trimethoprim-sulfamethoxazole: a case report

    PubMed Central

    Foo, Dominic

    2016-01-01

    Case Diagnosis Reversible myoclonus, tremor, and asterixis induced by high dose trimethoprim-sulfamethoxazole. Case Description The patient was a 66-year-old male with T9 AIS1 C quadriplegia secondary to spinal cord compression by a tumor due to large B cell lymphoma. Subsequent to tumor resection and chemotherapy, the patient was discovered to have Pneumocystis jiroveci pneumonia (PJP). Once started on high dose trimethoprim-sulfamethoxazole (TMP-SMX) therapy (15.6 mg/kg/day of trimethoprim) for the treatment of PJP, he displayed bilateral upper extremity myoclonic jerks at rest, asterixis, and postural tremor. Symptoms resolved once TMP-SMX therapy was discontinued. Discussion Myoclonus, asterixis, and tremor have been linked to high dose TMP-SMX therapy as a toxic side effect. Our patient's symptoms did improve with levetiracetam therapy, but did not fully resolve until TMP-SMX was discontinued. Conclusions This is thought to be the first reported case of reversible myoclonus, tremor, and asterixis induced by high dose TMP-SMX in the spinal cord injury population. Early recognition of TMP-SMX induced complications were of key importance as they negatively impacted the rehabilitation process. We also recommend consideration of symptomatic treatment with levetiracetam for the duration of required TMP-SMX therapy as it appeared to mitigate the severity of our patient's movement disorders. PMID:26111222

  9. Pentamidine analogs as inhibitors of [3H]MK-801 and [3H]ifenprodil binding to rat brain NMDA receptors

    PubMed Central

    Berger, Michael L.; Maciejewska, Dorota; Vanden Eynde, Jean Jacques; Mottamal, Madhusoodanan; Żabiński, Jerzy; Kaźmierczak, Paweł; Rezler, Mateusz; Jarak, Ivana; Piantanida, Ivo; Karminski-Zamola, Grace; Mayence, Annie; Rebernik, Patrick; Kumar, Arvind; Ismail, Mohamed A.; Boykin, David W.; Huang, Tien L.

    2016-01-01

    The anti-protozoal drug pentamidine is active against opportunistic Pneumocystis pneumonia, but in addition has several other biological targets, including the NMDA receptor (NR). Here we describe the inhibitory potencies of 76 pentamidine analogs at 2 binding sites of the NR, the channel binding site labeled with [3H]MK-801 and the [3H]ifenprodil binding site. Most analogs acted weaker at the ifenprodil than at the channel site. The spermine-sensitivity of NR inhibition by the majority of the compounds was reminiscent of other long-chain dicationic NR blockers. The potency of the parent compound as NR blocker was increased by modifying the heteroatoms in the bridge connecting the 2 benzamidine moieties and also by integrating the bridge into a seven-membered ring. Docking of the 45 most spermine-sensitive bisbenzamidines to a recently described acidic interface between the N-terminal domains of GluN1 and GluN2B mediating polyamine stimulation of the NR revealed the domain contributed by GluN1 as the most relevant target. PMID:26117647

  10. The Spectrum of Clinical and Pathological Manifestations of AIDS in a Consecutive Series of 236 Autopsied Cases in Mumbai, India

    PubMed Central

    Lanjewar, Dhaneshwar Namdeorao

    2011-01-01

    The HIV epidemic in the Asian subcontinent has a significant impact on India. The AIDS associated pathology has not been well evaluated in a representative study hence very little is known about the spectrum of HIV/AIDS associated diseases in Indian subcontinent. To determine the important postmortem findings in HIV infected individuals in Mumbai, autopsy study was carried out. The patient population included patients with AIDS who died at the tertiary care hospital over a 20 year period from 1988 to 2007. A total of 236 (182; 77% males and 54; 23%) females) patients with AIDS were autopsied. The main risk factor for HIV transmission was heterosexual contact (226 patients; 96%) and 223/236 (94%) patients died of HIV-related diseases. Tuberculosis was the prime cause of death in 149 (63%) patients, followed by bacterial pneumonia 33 (14%), cryptococcosis 18 (8%), toxoplasmosis of brain 15 (6%), pneumocystis jiroveci (PCJ) 1 (0.5%) and Non-Hodgkin's lymphoma 7 (3%) cases. The major underlying pathologies are either preventable or treatable conditions. There is an urgent need for attention towards the diagnosis, issue of therapy, and care of HIV disease in developing countries. Reducing mortality in patients with AIDS from infections must be highest public health policy in India. PMID:21660276

  11. CD4+ T cell–independent DNA vaccination against opportunistic infections

    PubMed Central

    Zheng, Mingquan; Ramsay, Alistair J.; Robichaux, Myles B.; Norris, Karen A.; Kliment, Corrine; Crowe, Christopher; Rapaka, Rekha R.; Steele, Chad; McAllister, Florencia; Shellito, Judd E.; Marrero, Luis; Schwarzenberger, Paul; Zhong, Qiu; Kolls, Jay K.

    2005-01-01

    Depletion or dysfunction of CD4+ T lymphocytes profoundly perturbs host defenses and impairs immunogenicity of vaccines. Here, we show that plasmid DNA vaccination with a cassette encoding antigen (OVA) and a second cassette encoding full-length CD40 ligand (CD40L), a molecule expressed on activated CD4+ T lymphocytes and critical for T cell helper function, can elicit significant titers of antigen-specific immunoglobulins in serum and Tc1 CD8+ T cell responses in CD4-deficient mice. To investigate whether this approach leads to CD4+ T cell–independent vaccine protection against a prototypic AIDS-defining infection, Pneumocystis (PC) pneumonia, we used serum from mice vaccinated with PC-pulsed, CD40L-modifed DCs to immunoprecipitate PC antigens. Kexin, a PC antigen identified by this approach, was used in a similar DNA vaccine strategy with or without CD40L. CD4-deficient mice receiving DNA vaccines encoding Kexin and CD40L showed significantly higher anti-PC IgG titers as well as opsonic killing of PC compared with those vaccinated with Kexin alone. Moreover, CD4-depleted, Kexin-vaccinated mice showed a 3-log greater protection in a PC challenge model. Adoptive transfer of CD19+ cells or IgG to SCID mice conferred protection against PC challenge, indicating a role of humoral immunity in the protection. The results of these studies show promise for CD4-independent vaccination against HIV-related or other opportunistic pathogens. PMID:16308571

  12. Severe combined immunodeficiency (SCID): from molecular basis to clinical management.

    PubMed

    Sponzilli, Ivonne; Notarangelo, Luigi D

    2011-04-01

    Primary immune deficiency diseases (PID) comprise a genetically heterogeneous group of disorders that affect distinct components of the innate and adaptive immune system, such as neutrophils, macrophages, dendritic cells, complement proteins, natural killer cells, as well as T and B lymphocytes. Severe combined immunodeficiency (SCID) is a group of disorders characterized by increased susceptibility to severe infections and early death. The diagnosis of SCID is supported by the demonstration of low absolute lymphocyte count and T cell lymphopenia (variably associated with numerical defects of B and NK cells). In the last two decades, advances in the characterization of the molecular pathophysiology of SCID, have permitted the development of novel diagnostic assays based on analysis of the expression of the disease-associated proteins and mutation analysis. More recently, pilot newborn screening programs for the identification of infants with SCID have been initiated in the United States. Prompt and aggressive treatment of infections, antimicrobial prophylaxis (in particular against Pneumocystis jiroveci) and regular administration of immunoglobulins are essential to reduce the risk of early death. However, survival ultimately depends on reconstitution of immune function, that is usually achieved by means of hematopoietic cell transplantation (HCT). Gene therapy and enzyme replacement therapy have also been used successfully is selected forms of SCID. Here we review the molecular and cellular pathophysiology and the mainstay of treatment of SCID.

  13. IKBKG (nuclear factor-κB essential modulator) mutation can be associated with opportunistic infection without impairing Toll-like receptor function

    PubMed Central

    Salt, Bryn H.; Niemela, Julie E.; Pandey, Rahul; Hanson, Eric P.; Deering, Raquel P.; Quinones, Ralph; Jain, Ashish; Orange, Jordan S.; Gelfand, Erwin W.

    2011-01-01

    Background Patients with hypomorphic nuclear factor-κB essential modulator (NEMO) mutations have extensive phenotypic variability that can include atypical infectious susceptibility. Objective This study may provide important insight into immunologic mechanisms of host defense. Methods Immunologic evaluation, including studies of Toll-like receptor (TLR) function, was performed in a 6-month-old boy with normal ectodermal development who was diagnosed with Pneumocystis pneumonia and cytomegalovirus sepsis. Results Genomic and cDNA sequencing demonstrated a novel NEMO missense mutation, 337G->A, predicted to cause a D113N (aspartic acid to asparagine) substitution in the first coiled-coil region of the NEMO protein. Quantitative serum immunoglobulins, lymphocyte subset numbers, and mitogeninduced lymphocyte proliferation were essentially normal. The PBMC responses to TLR ligands were also surprisingly normal, whereas natural killer cell cytolytic activity, T-cell proliferative responses to specific antigens, and T-cell receptor–induced NF-κB activation were diminished. Conclusion Unlike the unique NEMO mutation described here, the most commonly reported mutations are clustered at the 3′ end in the tenth exon, which encodes a zinc finger domain. Because specific hypomorphic variants of NEMO are associated with distinctive phenotypes, this particular NEMO mutation highlights a dispensability of the region including amino acid 113 for TLR signaling and ectodysplasin A receptor function. This region is required for certain immunoreceptor functions as demonstrated by his susceptibility to infections as well as natural killer cell and T-cell defects. PMID:18179816

  14. Review of zoonotic parasites in medical and veterinary fields in the Republic of Korea.

    PubMed

    Youn, Heejeong

    2009-10-01

    Zoonotic parasites are animal parasites that can infect humans. The major zoonotic protozoa in the Republic of Korea are Babesia bovis, Chilomastix mesnili, Cryptosporidium parvum, Endolimax nana, Entamoeba coli, Entamoeba hitolytica, Giardia lamblia, Iodamoeba bütschlii, Pneumocystis carinii, Sarcocystis cruzi, and Toxoplasma gondii. The major zoonotic helminths in Korea include trematodes, cestodes, and nematodes. Trematodes are Clonorchis sinensis, Echinostoma hortense, Echinostoma spp., Fasciola hepatica, Heterophyes nocens, Metagonimus yokogawai, and Paragonimus westermani. Cestodes are Diphyllobothrium latum, Dipylidium caninum, Echinococcus granulosus, Hymenolepis nana, Raillietina tetragona, sparganum (Spirometra spp.), Taenia saginata, T. solium, and T. asiatica. Nematodes are Ancylostoma caninum, Brugia malayi, Capillaria hepatica, Dirofilaria immitis, Gnathostoma dololesi, Gnathostoma spinigerum, Loa loa, Onchocerca gibsoni, Strongyloides stercoralis, Thelazia callipaeda, Trichinella spiralis, Trichostrongylus orientalis, Trichuris trichiura, and Trichuris vulpis. The one arthropod is Sarcoptes scabiei. Many of these parasites have disappeared or were in decline after the 1990's. Since the late 1990's, the important zoonotic protozoa have been C. parvum, E. nana, E. coli, E. hitolytica, G. lamblia, I. buetschlii, P. carinii and T. gondii. The important zoonotic helminths have been C. sinensis, H. nocens, M. yokogawai, P. westermani, D. latum, T. asiatica, sparganum, B. malayi, T. orientalis, T. callipaeda and T. spiralis. However, outbreaks of these parasites are only in a few endemic areas. The outbreaks of Enterobius vermicularis and head lice, human parasites, have recently increased in the kindergartens and primary schools in the Republic of Korea.

  15. Review of Zoonotic Parasites in Medical and Veterinary Fields in the Republic of Korea

    PubMed Central

    2009-01-01

    Zoonotic parasites are animal parasites that can infect humans. The major zoonotic protozoa in the Republic of Korea are Babesia bovis, Chilomastix mesnili, Cryptosporidium parvum, Endolimax nana, Entamoeba coli, Entamoeba hitolytica, Giardia lamblia, Iodamoeba bütschlii, Pneumocystis carinii, Sarcocystis cruzi, and Toxoplasma gondii. The major zoonotic helminths in Korea include trematodes, cestodes, and nematodes. Trematodes are Clonorchis sinensis, Echinostoma hortense, Echinostoma spp., Fasciola hepatica, Heterophyes nocens, Metagonimus yokogawai, and Paragonimus westermani. Cestodes are Diphyllobothrium latum, Dipylidium caninum, Echinococcus granulosus, Hymenolepis nana, Raillietina tetragona, sparganum (Spirometra spp.), Taenia saginata, T. solium, and T. asiatica. Nematodes are Ancylostoma caninum, Brugia malayi, Capillaria hepatica, Dirofilaria immitis, Gnathostoma dololesi, Gnathostoma spinigerum, Loa loa, Onchocerca gibsoni, Strongyloides stercoralis, Thelazia callipaeda, Trichinella spiralis, Trichostrongylus orientalis, Trichuris trichiura, and Trichuris vulpis. The one arthropod is Sarcoptes scabiei. Many of these parasites have disappeared or were in decline after the 1990's. Since the late 1990's, the important zoonotic protozoa have been C. parvum, E. nana, E. coli, E. hitolytica, G. lamblia, I. buetschlii, P. carinii and T. gondii. The important zoonotic helminths have been C. sinensis, H. nocens, M. yokogawai, P. westermani, D. latum, T. asiatica, sparganum, B. malayi, T. orientalis, T. callipaeda and T. spiralis. However, outbreaks of these parasites are only in a few endemic areas. The outbreaks of Enterobius vermicularis and head lice, human parasites, have recently increased in the kindergartens and primary schools in the Republic of Korea. PMID:19885329

  16. Technetium-99m DTPA aerosol and gallium scanning in acquired immune deficiency syndrome

    SciTech Connect

    Picard, C.; Meignan, M.; Rosso, J.; Cinotti, L.; Mayaud, C.; Revuz, J.

    1987-07-01

    In 11 non-smoking AIDS patients suspected of pneumocystis carinii pneumonia (PCP), the results of Tc-99m DTPA aerosol clearances, gallium scans, and arterial blood gases were compared with those of bronchoalveolar lavage (BAL). Nine patients had PCP. All had increased clearances five times higher than the normal (5.6 +/- 2.3% X min-1 vs 1.1 +/- 0.34% X min-1, N = 10, P less than 0.001), suggesting an increased alveolar permeability. Gallium scans were abnormal in six patients but normal or slightly abnormal in the three others. Four of these nine patients had normal chest x-rays. In two of these the gallium scan was abnormal, but in the two others, only the increased Tc-99m DTPA clearances showed evidence of lung disease. Two patients had normal BAL, with normal clearances and gallium scans. Four out of the nine patients with PCP were studied after treatment. Three recovered and had normal clearance and gallium scans. One still had PCP with increased clearance but normal gallium scan. Gallium scanning and Tc-99m DTPA clearance are useful for detecting lung disease in AIDS patients with suspected PCP and for prompting BAL when chest x-rays and PaO/sub 2/ levels are normal. Due to its high sensitivity, a normal Tc-99m DTPA clearance could avoid BAL.

  17. [In vitro antifungal activity of anidulafungin].

    PubMed

    Quindós, Guillermo; Eraso, Elena

    2008-06-01

    Anidulafungin is a new and very useful pharmacological tool for the treatment of invasive mycoses. The antifungal spectrum of anidulafungin reaches the most common pathogenic fungi. Anidulafungin is especially active against the genera Candida and Aspergillus. Its antifungal mechanism is based on the inhibition of the beta-1,3-D-glucan synthesis, an essential molecule for the cell wall architecture, with different consequences for Candida and Aspergillus, being anidulafungin fungicide for the former and fungistatic for the latter. This review describes the in vitro antifungal spectrum of anidulafungin based in the scientific and medical literature of recent years. We can underline that most than 99% of Candida isolates are susceptible to < or = 2 microg/ml of anidulafungin. MIC are very low (< or =0.125 microg/ml) for most clinical isolates of the species Candida albicans, Candida glabrata, Candida tropicalis and Candida krusei while Candida parapsilosis and Candida guilliermondii isolates are susceptible to anidulafungin concentrations < or = 2 microg/ml. An excellent activity of anidulafungin has been also described against Aspergillus, Pneumocystis and other fungi. However, its activity is very low against Cryptococcus and the Zygomycetes. The excellent activity of anidulafungin has made this antifungal a first line therapeutic indication for candidemia and invasive candidiasis in non-neutropenic patients.

  18. Late-Onset Cerebral Toxoplasmosis After Allogeneic Hematopoietic Stem Cell Transplantation.

    PubMed

    Khalaf, Ahmed M; Hashim, Mahmoud A; Alsharabati, Mohammed; Fallon, Kenneth; Cure, Joel K; Pappas, Peter; Mineishi, Shin; Saad, Ayman

    2017-03-10

    BACKGROUND Toxoplasmosis is an uncommon but potentially fatal complication following allogeneic hematopoietic stem cell transplantation (HCT). Post-transplant toxoplasmosis is often a reactivation of prior infection and typically occurs within the first 6 months of transplant. Herein, we report that cerebral toxoplasmosis may occur 22 months after allogeneic hematopoietic stem cell transplantation. CASE REPORT We describe a case of cerebral toxoplasmosis that occurred 22 months after an allogeneic HCT while the patient was on aerosolized pentamidine for Pneumocystis jiroveci pneumonia (PCP) prophylaxis. The disease was only diagnosed after brain biopsy because of atypical MRI appearance of the cerebral lesion and negative Toxoplasma gondii IgG antibody test result in the cerebrospinal fluid (CSF). The patient received pyrimethamine and sulfadiazine treatment, with dramatic improvement after several months. The patient is alive 2 years after infection diagnosis, with no evidence of disease and is off Toxoplasma prophylaxis. CONCLUSIONS Cerebral toxoplasmosis can occur late after allogeneic HCT while patients are on immunosuppression therapy, with atypical features on imaging studies and negative Toxoplasma gondii IgG antibody test result in the CSF. Pre-transplant serologic screening for T. gondii antibodies in allogeneic transplant candidates is warranted. Brain biopsy can be a helpful diagnostic tool for cerebral lesions.

  19. Omenn syndrome associated with a functional reversion due to a somatic second-site mutation in CARD11 deficiency

    PubMed Central

    Fuchs, Sebastian; Rensing-Ehl, Anne; Pannicke, Ulrich; Lorenz, Myriam R.; Fisch, Paul; Jeelall, Yogesh; Rohr, Jan; Speckmann, Carsten; Vraetz, Thomas; Farmand, Susan; Schmitt-Graeff, Annette; Krüger, Marcus; Strahm, Brigitte; Henneke, Philipp; Enders, Anselm; Horikawa, Keisuke; Goodnow, Christopher; Schwarz, Klaus

    2015-01-01

    Omenn syndrome (OS) is a severe immunodeficiency associated with erythroderma, lymphoproliferation, elevated IgE, and hyperactive oligoclonal T cells. A restricted T-cell repertoire caused by defective thymic T-cell development and selection, lymphopenia with homeostatic proliferation, and lack of regulatory T cells are considered key factors in OS pathogenesis. We report 2 siblings presenting with cytomegalovirus (CMV) and Pneumocystis jirovecii infections and recurrent sepsis; one developed all clinical features of OS. Both carried homozygous germline mutations in CARD11 (p.Cys150*), impairing NF-κB signaling and IL-2 production. A somatic second-site mutation reverting the stop codon to a missense mutation (p.Cys150Leu) was detected in tissue-infiltrating T cells of the OS patient. Expression of p.Cys150Leu in CARD11-deficient T cells largely reconstituted NF-κB signaling. The reversion likely occurred in a prethymic T-cell precursor, leading to a chimeric T-cell repertoire. We speculate that in our patient the functional advantage of the revertant T cells in the context of persistent CMV infection, combined with lack of regulatory T cells, may have been sufficient to favor OS. This first observation of OS in a patient with a T-cell activation defect suggests that severely defective T-cell development or homeostatic proliferation in a lymphopenic environment are not required for this severe immunopathology. PMID:26289640

  20. Infectious complications of antilymphocyte therapies in solid organ transplantation.

    PubMed

    Issa, Nicolas C; Fishman, Jay A

    2009-03-15

    Antilymphocyte therapies are widely used for immunosuppression in solid organ transplantation. These agents have varied mechanisms of action, with resulting differences in the intensity and duration of immunosuppression and in associated infectious complications. Induction therapy with antithymocyte globulins is associated with a greater incidence of cytomegalovirus, Epstein-Barr virus, and BK polyomavirus infections, compared with therapy with interleukin (IL)-2a receptor antagonists. However, long-term experience with the IL-2a receptor antagonists is lacking. By contrast, the treatment of graft rejection with T cell-depleting antibodies is associated with an increased risk of opportunistic infections. This is likely a reflection of the intensification of immunosuppression in the treatment of graft rejection and, often, a failure to link the use of antilymphocyte agents to prophylaxis for infection. The use of T cell-depleting agents, especially in the treatment of acute graft rejection, must be linked to monitoring and risk-adjusted prophylaxis for Pneumocystis, other fungi, Epstein-Barr virus, BK polyomavirus, and cytomegalovirus infection.

  1. From the classic concepts to modern practice.

    PubMed

    Fishman, J A

    2014-09-01

    Transplant infectious disease is a field in evolution. For most allograft recipients, immunosuppressive therapies are more potent and have reduced the incidence of acute allograft rejection. At the same time, these therapies have increased susceptibility to many opportunistic infections and virally-mediated malignancies. Immunological tolerance has been achieved in only small numbers of patients who avoid drug toxicities and infection for as long as tolerance persists. The traditional timeline of post-transplant infections remains useful in the development of a differential diagnosis for patients with infectious syndromes. However, patterns of infection in the post-transplant period have changed over the past decade. Recipients are derived from a broader range of socioeconomic and geographical backgrounds. Infections are diagnosed more often, with improved microbiological assays (e.g. nucleic acid testing, NAT) used routinely in the diagnosis and management of common infections and increasingly in the screening of organ donors. Patterns of opportunistic infection have been altered by the increased identification of organisms demonstrating antimicrobial resistance and by the broader use of strategies to prevent viral, bacterial and fungal (including Pneumocystis) infections. Newer techniques are being applied (e.g. HLA-linked tetramer binding, intracellular cytokine staining) to assess pathogen-specific immunity. These are being integrated into clinical practice to assess individual susceptibility to specific infections. Infection, inflammation and the human microbiome are recognized as playing a central role in shaping innate and adaptive immune responses, graft rejection and autoimmunity. The full impact of infection on transplantation is only beginning to be appreciated.

  2. Spectrum of opportunistic infections in AIDS cases.

    PubMed

    Singh, A; Bairy, I; Shivananda, P G

    2003-01-01

    Human Immunodeficiency viruses are the initial causative agents in AIDS, but most of the morbidity and mortality in AIDS cases result from opportunistic infections, Identification of such pathogen is very important for clinicians and health planners to tackle the AIDS epidemic in more effective manner. The present study describes the clinical and laboratory profile of 100 AIDS causes who presented to a referral hospital. Oral candidiasis (59.00%) was found to be the most common opportunistic infection, followed by tuberculosis (56.00%), Cryptosporidium infection (47.00%) and Pneumocystis carinii (7.00%). Presence of oral candidiasis and weight loss is highly predictive of low DC4 count and can be considered as a marker of HIV disease progression. The patients coinfected with HIV and tuberculosis are also on rise. Recognition of dual infection and taking adequate steps to deal with this epidemic is needed. As Cryptosporidium infection was detected in large number, provision of safe drinking water and maintaining good hygiene is important for prevention. Early diagnosis of opportunistic infection and prompt treatment, delays the progression towards AIDS. 91.00% of patients were infected with HIV1 and 4.00% had HIV2 infection and 5.00% were dully infected. 87.00% of patients were males and 13.00% were belonging to 21-40 years of age. Majority of them were belonging to lower socioeconomic status and heterosexual route of transmission was the commonest mode of spread.

  3. [Primary hepatic lymphoma in subjects with acquired immunodeficiency syndrome].

    PubMed

    Trinchieri, V; Causo, T; Fabietti, P; Bellagamba, R; Berardelli, G; Cirelli, A; Catania, S

    1992-02-01

    In this study the authors describe a non-Hodgkin's lymphoma histologically typed "large non-cleaved cell immunophenotype B cell", placed primitively into the liver. It affected a woman twenty seven years old, who contracted HIV infection due to heterosexual intercourse with at risk partner. At the time of diagnosis the woman was already considered AIDS patient on account of a previous Pneumocystis carinii pneumoniae and severe immunodeficiency (DC4 = 13 cells/mm3). The patient received cycles of chemotherapy (adriamycin 40 mg/iv, teniposide 50 mg/iv, cyclophosphamide 500 mg/iv, vincristine 2 mg/iv, bleomycin 15 mg/iv, betamethasone 4 mg/iv). At the 15th day of therapeutic cycle vincristine 2 mg/iv, bleomycin 15 mg/iv and betamethasone 4 mg/iv were given. After one cycle of therapy, hepatic echography showed signs that the lymphoma was reduced significantly. The authors stress the uncommon non-Hodgkin lymphoma localization, which is frequently underestimated in HIV-patients.

  4. Interstitial lung disease and profound hypoxaemia in a severely-malnourished child with very severe pneumonia and potential lymph-node tuberculosis: an uncommon but serious co-morbidity.

    PubMed

    Chisti, Mohammod J; Parvin, Irin; Ashraf, Hasan; Saha, Haimanti; Matin, Fariha B; Pietroni, Mark A C

    2013-03-01

    A nine-month old boy was initially admitted at the Acute Respiratory Infection Unit of Dhaka Hospital of icddr,b and soon after transferred to the Intensive Care Unit of the same hospital. The boy had problems of very severe pneumonia (confirmed by radiology), severe hypoxaemia, severe malnutrition, and Down's syndrome. The patient was treated according to the hospital protocol for the management of pneumonia and malnutrition. During the hospital stay, hypoxaemia was persistent with very little improvement of pneumonia; a number of differentials, such as pneumocystis jirovecii pneumonia, lymph-node tuberculosis, were added to the problems. Subsequently, the patient's hypoxaemia improved with the empirical use of antitubercular drugs. However, the patient again developed persistent hypoxaemia and, after unsuccessful treatment for a hospital-acquired pneumonia, the problems further expanded to include interstitial lung disease (ILD). This was confirmed by high-resolution computed tomography, and the patient was treated with prednisolone for 6 months, along with antitubercular drugs. He fully recovered from ILD, hypoxaemia, and pneumonia both clinically and radiologically. Therefore, severely-malnourished children having wet cough and pneumonia with persistent hypoxaemia should be assessed for the possible existence of interstitial lung disease. This may help provide a prompt and appropriate management to reduce morbidity and deaths in such patients.

  5. A review of the current status and techniques of allogeneic bone marrow transplantation for treatment of leukaemia.

    PubMed Central

    Prentice, H G

    1983-01-01

    Bone marrow transplantation is now an accepted component in the overall therapy of acute and chronic (myeloid) leukaemia for some selected patients. Some of the obstacles to success have been partially overcome. Many advances in supportive care have been made. Pneumocystis carinii and herpes simplex infections are preventable. Effective decontamination of the gastrointestinal tract for bacteria and fungi is now readily achievable and may have reduced the risk of serious systemic infections. New antibiotics which, in combination, are effective in life-threatening infections are under study. Recent developments in the prevention or amelioration of graft versus host disease (GvHD) have included T lymphocyte depletion in the donor marrow and the use of the fungal polypeptide cyclosporin A. Less than 10% of patients would now be expected to succumb to this complication. Outstanding problems remaining to be resolved are the improvement in the antileukaemic conditioning prior to transplantation and the prevention or treatment of cytomegalovirus infection in the seropositive recipient. This infection can cause pneumonitis and is currently the single most frequent transplant related cause of mortality. PMID:6355192

  6. Clinical features of HIV disease in developing countries.

    PubMed

    Grant, A

    2002-06-01

    HIV disease progresses from an asymptomatic period of variable duration, through mild symptoms, to severe disease characteristic of cellular immunodeficiency. The rate of progression from infection to severe disease is probably similar world-wide. However, individuals in developing countries have more symptomatic disease, in keeping with the high incidence of morbidity in the general population, and poor survival with advanced disease. The clinical manifestations of severe HIV-related immunosuppression vary with geographical region. Tuberculosis (TB) is the most important severe opportunistic disease in developing countries: the clinical presentation may differ from TB in the immunocompetent. Bacterial infections, particularly due to Streptococcus pneumoniae and non-typhoid Salmonella spp., are also important causes of morbidity and mortality. Fungal diseases such as Pneumocystis carinii pneumonia (PCP), cryptococcosis, histoplasmosis and penicilliosis vary in prevalence in different geographical regions. A high index of suspicion of HIV infection and knowledge of the local spectrum of HIV disease are important for early diagnosis and appropriate management of HIV-related disease.

  7. Changing patterns of infections in patients with AIDS: a study of 279 autopsies of prison inmates and nonincarcerated patients at a university hospital in eastern Texas, 1984-1993.

    PubMed

    Lyon, R; Haque, A K; Asmuth, D M; Woods, G L

    1996-08-01

    Reports on autopsies of 279 persons infected with human immunodeficiency virus (HIV) were reviewed retrospectively to determine changes in survival rates and infections and to identify differences between prison inmates and nonincarcerated patients. The 78 cases from 1984 through 1988 were compared with 201 from 1989 through 1993, on the basis of use of antiretroviral therapy and (after 1988) prophylaxis against Pneumocystis carinii pneumonia (PCP). Risk factors for HIV infection were homosexuality/bisexuality (30%), injection drug use (IDU; 22%), transfusion (5%), heterosexual contact (4%), and combinations of the above or unknown factors (38%); 95% of patients were males and 41% were state prison inmates in Texas. IDU was more common and homosexuality/ bisexuality was less common among inmates than among nonincarcerated patients. Mean survival time was 12 months in the first period studied and 23 months in the later period (P < .05). Cytomegalovirus infection was the most common type in both periods. The number of cases of PCP declined and the number of cases of bacterial infections increased significantly in the later period. Tuberculosis was significantly more common in inmates than in nonincarcerated patients. Tuberculosis and disseminated histoplasmosis (noted at autopsy) and deaths due to disseminated Mycobacterium avium complex and histoplasmosis were significantly more common among injection drug users than among homosexuals/bisexuals. Invasive candidiasis was more common in homosexuals/ bisexuals and in those who survived > 3 years. Antiretroviral therapy, prophylaxis for PCP, and risk factors for HIV infection appear to influence the mortality rate and prevalence of certain infections found at autopsy.

  8. Potential Impact of Co-Infections and Co-Morbidities Prevalent in Africa on Influenza Severity and Frequency: A Systematic Review

    PubMed Central

    Cohen, Adam L.; McMorrow, Meredith; Walaza, Sibongile; Cohen, Cheryl; Tempia, Stefano; Alexander-Scott, Marissa; Widdowson, Marc-Alain

    2015-01-01

    Infectious diseases and underlying medical conditions common to Africa may affect influenza frequency and severity. We conducted a systematic review of published studies on influenza and the following co-infections or co-morbidities that are prevalent in Africa: dengue, malaria, measles, meningococcus, Pneumocystis jirovecii pneumonia (PCP), hemoglobinopathies, and malnutrition. Articles were identified except for influenza and PCP. Very few studies were from Africa. Sickle cell disease, dengue, and measles co-infection were found to increase the severity of influenza disease, though this is based on few studies of dengue and measles and the measles study was of low quality. The frequency of influenza was increased among patients with sickle cell disease. Influenza infection increased the frequency of meningococcal disease. Studies on malaria and malnutrition found mixed results. Age-adjusted morbidity and mortality from influenza may be more common in Africa because infections and diseases common in the region lead to more severe outcomes and increase the influenza burden. However, gaps exist in our knowledge about these interactions. PMID:26068416

  9. Assessment of the Usefulness of Multiplex Real-Time PCR Tests in the Diagnostic and Therapeutic Process of Pneumonia in Hospitalized Children: A Single-Center Experience

    PubMed Central

    Bartkowska-Śniatkowska, Alicja; Jończyk-Potoczna, Katarzyna; Wysocka-Leszczyńska, Joanna; Bobkowski, Waldemar; Fichna, Piotr; Sobkowiak, Paulina; Mazur-Melewska, Katarzyna; Bręborowicz, Anna; Wysocki, Jacek; Januszkiewicz-Lewandowska, Danuta

    2017-01-01

    The aim of the study was assessment of the usefulness of multiplex real-time PCR tests in the diagnostic and therapeutic process in children hospitalized due to pneumonia and burdened with comorbidities. Methods. The study group included 97 children hospitalized due to pneumonia at the Karol Jonscher Teaching Hospital in Poznań, in whom multiplex real-time PCR tests (FTD respiratory pathogens 33; fast-track diagnostics) were used. Results. Positive test results of the test were achieved in 74 patients (76.3%). The average age in the group was 56 months. Viruses were detected in 61 samples (82% of all positive results); bacterial factors were found in 29 samples (39% of all positive results). The presence of comorbidities was established in 90 children (92.78%). On the basis of the obtained results, 5 groups of patients were established: viral etiology of infection, 34 patients; bacterial etiology, 7 patients; mixed etiology, 23 patients; pneumocystis, 9 patients; and no etiology diagnosed, 24 patients. Conclusions. Our analysis demonstrated that the participation of viruses in causing severe lung infections is significant in children with comorbidities. Multiplex real-time PCR tests proved to be more useful in establishing the etiology of pneumonia in hospitalized children than the traditional microbiological examinations. PMID:28182108

  10. ABO-Incompatible Kidney Transplantation

    PubMed Central

    Morath, Christian; Zeier, Martin; Döhler, Bernd; Opelz, Gerhard; Süsal, Caner

    2017-01-01

    ABO-incompatible (ABOi) kidney transplantation has long been considered a contraindication to successful kidney transplantation. During the last 25 years, increasing organ shortage enforced the development of strategies to overcome the ABO antibody barrier. In the meantime, ABOi kidney transplantation has become a routine procedure with death-censored graft survival rates comparable to the rates in compatible transplantations. Desensitization is usually achieved by apheresis and B cell-depleting therapies that are accompanied by powerful immunosuppression. Anti-A/B antibodies are aimed to be below a certain threshold at the time of ABOi kidney transplantation and during the first 2 weeks after surgery. Thereafter, even a rebound of anti-A/B antibodies does not appear to harm the kidney transplant, a phenomenon that is called accommodation, but is poorly understood. There is still concern, however, that infectious complications such as viral disease, Pneumocystis jirovecii pneumonia, and severe urinary tract infections are increased after ABOi transplantations. Recent data from the Collaborative Transplant Study show that during the first year after kidney transplantation, one additional patient death from an infectious complication occurs in 100 ABOi kidney transplant recipients. Herein, we review the recent evidence on ABOi kidney transplantation with a focus on desensitization strategies and respective outcomes. PMID:28321223

  11. Caveolae in the uptake and targeting of infectious agents and secreted toxins.

    PubMed

    Norkin, L C

    2001-07-28

    A variety of microbial pathogens, including viruses, intracellular bacteria, and prions, as well as certain secreted bacterial toxins, can now be added to the list of ligands that enter cells via caveolae or caveolae-like membrane domains. In general, the caveolae-mediated entry pathway results in transport of these microbes and toxins to intracellular destinations that are different from that of cargo entering by other means. As a result, the caveolae-mediated entry pathway can profoundly affect the host cell-pathogen interaction long after entry has occurred. Furthermore, some microbes such as SV40 that enter via cavolae will be valuable as probes to analyze certain poorly understood intracellular trafficking pathways, such as retrograde transport to the ER. Also, viruses that enter via caveolae may have unique potential as gene and drug delivery vectors. In addition, some extracellular microbial pathogens, such as Pneumocystis carinii, may also interact with host cells via caveolae. Finally, caveolae may play a role in host immune defense mechanisms.

  12. Assignment of the human macrophage mannose receptor gene (MRC1) to 10p13 by in situ hybridization and PCR-based somatic cell hybrid mapping

    SciTech Connect

    Eichbaum, Q.; Clerc, P.; Bruns, G.

    1994-08-01

    Tissue macrophages form a latticework beneath epithelial surfaces and play a pivotal role in first line host defense. The macrophage mannose receptor is highly expressed on these terminally differentiated cells, but is not expressed on circulating monocytes. Although originally defined as an endocytic receptor, the predominant physiological role for this 170-kDa transmembrane protein appears to be phagocytosis of microorganisms, such as Candida albicans and Pneumocystis carinii. The characterization of cDNAs that encode the human and mouse mannose receptors reveals that the ectodomain contains a cysteine-rich NH{sub 2} domain that appears to resemble the b subunit of ricin D. This domain is followed by a fibronectin type 2 domain. A tandem array of eight carbohydrate recognition domains bear approximately 30% homology to one another. A short hydrophobic region is followed by a 45-amino-acid cytoplasmic tail. Comparison of the human and mouse encoded proteins reveals an average homology of 80%. Of interest is the fact that the murine and human genes both span about 70 kb that contains 30 exons interrupted by 29 introns. The position of the introns and the size of the exons are identical in the mouse and human genes. 15 refs., 2 figs.

  13. Estimating the burden of fungal disease in Vietnam.

    PubMed

    Beardsley, J; Denning, D W; Chau, N V; Yen, N T B; Crump, J A; Day, J N

    2015-10-01

    Data regarding the prevalence of fungal infections in Vietnam are limited yet they are likely to occur more frequently as increasingly sophisticated healthcare creates more iatrogenic risk factors. In this study, we sought to estimate baseline incidence and prevalence of selected serious fungal infections for the year 2012. We made estimates with a previously described actuarial method, using reports on the incidence and prevalence of various established risk factors for fungal infections from Vietnam, or similar environments, supplemented by personal communications. Global data were used if local data were unavailable. We estimated 2,352,748 episodes of serious fungal infection occurred in Vietnam in 2012. Frequent conditions included recurrent vaginal candidiasis (3893/100,000 women annually), tinea capitis (457/100,000 annually) and chronic pulmonary aspergillosis (61/100,000/5 year period). We estimated 140 cases of cryptococcal meningitis, 206 of penicilliosis and 608 of Pneumocystis jirovecii pneumonia. This is the first summary of Vietnamese fungal infections. The majority of severe disease is due to Aspergillus species, driven by the high prevalence of pulmonary tuberculosis. The AIDS epidemic highlights opportunistic infections, such as penicilliosis and cryptococcosis, which may complicate immunosuppressive treatments. These estimates provide a useful indication of disease prevalence to inform future research and resource allocation but should be verified by further epidemiological approaches.

  14. Minimizing fungal disease deaths will allow the UNAIDS target of reducing annual AIDS deaths below 500 000 by 2020 to be realized

    PubMed Central

    2016-01-01

    Deaths from AIDS (1 500 000 in 2013) have been falling more slowly than anticipated with improved access to antiretroviral therapy. Opportunistic infections account for most AIDS-related mortality, with a median age of death in the mid-30s. About 360 000 (24%) of AIDS deaths are attributed to tuberculosis. Fungal infections deaths in AIDS were estimated at more than 700 000 deaths (47%) annually. Rapid diagnostic tools and antifungal agents are available for these diseases and would likely have a major impact in reducing deaths. Scenarios for reduction of avoidable deaths were constructed based on published outcomes of the real-life impact of diagnostics and generic antifungal drugs to 2020. Annual deaths could fall for cryptococcal disease by 70 000, Pneumocystis pneumonia by 162 500, disseminated histoplasmosis by 48 000 and chronic pulmonary aspergillosis by 33 500, with approximately 60% coverage of diagnostics and antifungal agents; a total of >1 000 000 lives saved over 5 years. If factored in with the 90–90–90 campaign rollout and its effect, AIDS deaths could fall to 426 000 annually by 2020, with further reductions possible with increased coverage. Action could and should be taken by donors, national and international public health agencies, NGOs and governments to achieve the UNAIDS mortality reduction target, by scaling up capability to detect and treat fungal disease in AIDS. This article is part of the themed issue ‘Tackling emerging fungal threats to animal health, food security and ecosystem resilience’. PMID:28080991

  15. Burden of serious fungal infections in the Czech Republic.

    PubMed

    Chrdle, Aleš; Mallátová, Nad'a; Vašáková, Martina; Haber, Jan; Denning, David W

    2015-10-01

    We have estimated the number of serious fungal infections in the Czech Republic. All published epidemiology papers reporting Czech fungal infection rates were identified. Where no data existed, we used specific populations at risk and fungal infection frequencies in those populations. Population statistics were obtained from the 2011 Census data, prevalence and incidence data for at-risk conditions were obtained from publicly accessible healthcare statistics and relevant surveys. We estimate that 152,840 Czech women suffer with recurrent vaginal thrush. Allergic bronchopulmonary aspergillosis is likely in 4739 adults and 6581 more have severe asthma with fungal sensitisation. Hypersensitivity pneumonitits secondary to fungi is estimated in 1050 cases and 365 people may have chronic pulmonary aspergillosis. Oesophageal candidiasis is estimated in 210 HIV-positive people. There are 12 cases of Pneumocystis pneumonia in HIV population and 60 more cases in non-HIV population. There are an estimated 526 cases of candidaemia, 79 cases of Candida peritonitis and 297 cases of invasive aspergillosis a year. About 176,000 (1.67%) Czech people suffer from severe fungal infections each year, predominantly from recurrent vaginitis and allergic respiratory conditions. Substantial uncertainty surrounds these estimates except for invasive aspergillosis in haematology and candidaemia in critical care.

  16. The burden of serious human fungal infections in Brazil.

    PubMed

    Giacomazzi, Juliana; Baethgen, Ludmila; Carneiro, Lilian C; Millington, Maria Adelaide; Denning, David W; Colombo, Arnaldo L; Pasqualotto, Alessandro C

    2016-03-01

    In Brazil, human fungal infections are prevalent, however, these conditions are not officially reportable diseases. To estimate the burden of serious fungal diseases in 1 year in Brazil, based on available data and published literature. Historical official data from fungal diseases were collected from Brazilian Unified Health System Informatics Department (DATASUS). For fungal diseases for which no official data were available, assumptions of frequencies were made by estimating based on published literature. The incidence (/1000) of hospital admissions for coccidioidomycosis was 7.12; for histoplasmosis, 2.19; and for paracoccidioidomycosis, 7.99. The estimated number of cryptococcal meningoencephalitis cases was 6832. Also, there were 4115 cases of Pneumocystis pneumonia in AIDS patients per year, 1 010 465 aspergillosis and 2 981 416 cases of serious Candida infections, including invasive and non-invasive diseases. In this study, we demonstrate that more than 3.8 million individuals in Brazil may be suffering from serious fungal infections, mostly patients with malignant cancers, transplant recipients, asthma, previous tuberculosis, HIV infection and those living in endemic areas for truly pathogenic fungi. The scientific community and the governmental agencies should work in close collaboration in order to reduce the burden of such complex, difficult-to-diagnose and hard to treat diseases.

  17. Cryptococcal disease and the burden of other fungal diseases in Uganda; Where are the knowledge gaps and how can we fill them?

    PubMed

    Parkes-Ratanshi, R; Achan, B; Kwizera, R; Kambugu, A; Meya, D; Denning, D W

    2015-10-01

    The HIV epidemic in Uganda has highlighted Cryptococcus and Candida infections as important opportunistic fungal infections. However, the burden of other fungal diseases is not well described. We aimed to estimate the burden of fungal infections in Uganda. All epidemiological papers of fungal diseases in Uganda were reviewed. Where there is no Ugandan data, global or East African data were used. Recurrent vaginal candidiasis is estimated to occur in 375 540 Uganda women per year; Candida in pregnant women affects up to 651,600 women per year. There are around 45,000 HIV-related oral and oesophageal candidosis cases per year. There are up to 3000 cases per year of post-TB chronic pulmonary aspergillosis. There are an estimated 40,392 people with asthma-related fungal conditions. An estimated 1,300,000 cases of tinea capitis occur in school children yearly in Uganda. There are approximately 800 HIV-positive adults with Pneumocystis jirovecii pneumonia (PJP) annually and up to 42 000 children with PJP per year. There are an estimated 4000 cryptococcal cases annually. There are an estimated 2.5 million fungal infections per year in Uganda. Cryptococcus and PJP cause around 28,000 deaths in adults and children per year. We propose replicating the model of research around cryptococcal disease to investigate and development management strategies for other fungal diseases in Uganda.

  18. Burden of serious fungal infections in Belgium.

    PubMed

    Lagrou, Katrien; Maertens, Johan; Van Even, Ellen; Denning, David W

    2015-10-01

    We aimed to estimate the total number of serious fungal infections occurring yearly in Belgium. The number of cryptococcal infections was retrieved from the National Reference Center for Mycosis. Populations at risk and fungal infections frequencies in these populations were used to estimate incidence or prevalence of other fungal infections. The Belgian population consists of 11.10 million people. Cryptococcal meningitis is rare. In all, 15 of the 1227 newly diagnosed HIV/AIDS cases presented with Pneumocystis jirovecii pneumonia. This accounts for ±14% of total PCP cases (n = 120). The incidence of candidaemia is estimated as 5/100,000 resulting in 555 cases and 213 deaths. A total number of 675 invasive aspergillosis cases and ≥169 deaths attributed to this infection were calculated. Chronic pulmonary aspergillosis is estimated to be prevalent in 662 cases. Allergic bronchopulmonary aspergillosis cases were estimated to be 23,119 applying a 2.5% and 15% rate in adult asthma and cystic fibrosis patients respectively. Severe asthma with fungal sensitisation cases was estimated to be 30,402. There were 174,760 women with recurrent Candida vaginitis assuming a 6% rate in women aged between 15 and 50. Approximately 233,000 people of the Belgian population (2.1%) are estimated to suffer from a fungal infection on a yearly basis.

  19. Burden of serious fungal infections in Tanzania.

    PubMed

    Faini, Diana; Maokola, Werner; Furrer, Hansjakob; Hatz, Christoph; Battegay, Manuel; Tanner, Marcel; Denning, David W; Letang, Emilio

    2015-10-01

    The incidence and prevalence of fungal infections in Tanzania remains unknown. We assessed the annual burden in the general population and among populations at risk. Data were extracted from 2012 reports of the Tanzanian AIDS program, WHO, reports, Tanzanian census, and from a comprehensive PubMed search. We used modelling and HIV data to estimate the burdens of Pneumocystis jirovecii pneumonia (PCP), cryptococcal meningitis (CM) and candidiasis. Asthma, chronic obstructive pulmonary disease and tuberculosis data were used to estimate the burden of allergic bronchopulmonary aspergillosis (ABPA) and chronic pulmonary aspergillosis (CPA). Burdens of candidaemia and Candida peritonitis were derived from critical care and/or cancer patients' data. In 2012, Tanzania's population was 43.6 million (mainland) with 1,500,000 people reported to be HIV-infected. Estimated burden of fungal infections was: 4412 CM, 9600 PCP, 81,051 and 88,509 oral and oesophageal candidiasis cases respectively. There were 10,437 estimated post-tuberculosis CPA cases, whereas candidaemia and Candida peritonitis cases were 2181 and 327 respectively. No reliable data exist on blastomycosis, mucormycosis or fungal keratitis. Over 3% of Tanzanians suffer from serious fungal infections annually, mostly related to HIV. Cryptococcosis and PCP are major causes of mycoses-related deaths. National surveillance of fungal infections is urgently needed.

  20. Burden of fungal infections in Senegal.

    PubMed

    Badiane, Aida S; Ndiaye, Daouda; Denning, David W

    2015-10-01

    Senegal has a high rate of tuberculosis and a low HIV seropositivity rate and aspergilloma, life-threatening fungal infections, dermatophytosis and mycetoma have been reported in this study. All published epidemiology papers reporting fungal infection rates from Senegal were identified. Where no data existed, we used specific populations at risk and fungal infection frequencies in each to estimate national incidence or prevalence. The results show that tinea capitis is common being found in 25% of children, ~1.5 million. About 191,000 Senegalese women get recurrent vaginal thrush, ≥4 times annually. We estimate 685 incident cases of chronic pulmonary aspergillosis (CPA) following TB and prevalence of 2160 cases. Asthma prevalence in adults varies from 3.2% to 8.2% (mean 5%); 9976 adults have allergic bronchopulmonary aspergillosis (ABPA) and 13,168 have severe asthma with fungal sensitisation (SAFS). Of the 59,000 estimated HIV-positive patients, 366 develop cryptococcal meningitis; 1149 develop Pneumocystis pneumonia and 1946 develop oesophageal candidiasis, in which oral candidiasis (53%) and dermatophytosis (16%) are common. Since 2008-2010, 113 cases of mycetoma were diagnosed. In conclusion, we estimate that 1,743,507 (12.5%) people in Senegal suffer from a fungal infection, excluding oral candidiasis, fungal keratitis, invasive candidiasis or aspergillosis. Diagnostic and treatment deficiencies should be rectified to allow epidemiological studies.

  1. Burden of serious fungal infections in Ukraine.

    PubMed

    Osmanov, Ali; Denning, David W

    2015-10-01

    Ukraine has high rates of TB, AIDS and cancer. We estimated the burden of fungal disease from epidemiology papers and specific populations at risk and fungal infection frequencies. HIV/AIDS cases and deaths (2012) and tuberculosis statistics were obtained from the State Service of Ukraine, while chronic obstructive pulmonary disease (COPD) cases were from M. Miravitlles et al., Thorax 64, 863-868 (2009). Annual estimates are 893,579 Ukrainian women get recurrent vaginal thrush (≥4× per year), 50,847 cases of oral candidiasis and 13,727 cases of oesophageal candidiasis in HIV, and 101 (1%) of 10,085 new AIDS cases develop cryptococcal meningitis, 6152 cases of Pneumocystis pneumonia (13.5 cases per 100,000). Of the 29,265 cases of active respiratory TB in 2012, it is estimated that 2881 new cases of chronic pulmonary aspergillosis (CPA) occurred and that the 5-year period prevalence is 7724 cases with a total CPA burden of 10,054 cases. Assuming adult asthma prevalence is ~2.9%, 28,447 patients with allergic bronchopulmonary aspergillosis (ABPA) are likely and 37,491 with severe asthma with fungal sensitisation. We estimate 2278 cases and 376 postsurgical intra-abdominal Candida infections. Invasive aspergillosis in immunocompromised patients is estimated at 303 patients annually; 930 cases in COPD patients. Ninety cases of mucormycosis (2 per 1,000,000) are estimated. In total, ~1,000,000 (2.2%) people in Ukraine develop serious fungal infections annually.

  2. Burden of serious fungal infections in Trinidad and Tobago.

    PubMed

    Denning, David W; Gugnani, Harish C

    2015-10-01

    The information on the prevalence of fungal infections in the Caribbean region including Trinidad and Tobago (population 1,339,000 million) is scanty. Tinea capitis is common in children, being predominant in those of African descent, with no definitive estimate. Asthma is also common affecting 77,000-139,000 adults with an estimated 1927-3491 affected by allergic bronchopulmonary aspergillosis (ABPA) and 2544-4608 with severe asthma and fungal sensitisation (SAFS). An estimated 23,763 women have ≥4 attacks of vaginal candidiasis annually. Among the estimated 14,000 HIV-infected patients, 750 cases of oesophageal candidiasis, 400 cases of Pneumocystis pneumonia (PCP) and 50 cases of cryptococcal meningitis are anticipated. Histoplasma capsulatum is endemic in the islands with a 49% skin positivity rate in those <60 years old. Three cases of cutaneous histoplasmosis in AIDS patients have been reported. Three cases of pulmonary histoplasmosis were reported among German biologists following exposure to bats in a cave in Trinidad. Using a low mean international incidence figure for candidaemia of 5/100,000, 67 cases of candidaemia are estimated. The burden of fungal infections in Trinidad and Tobago is considerable and requires appropriate diagnostic and clinical expertise.

  3. Prospective etiological investigation of community-acquired pulmonary infections in hospitalized people living with HIV

    PubMed Central

    Figueiredo-Mello, Claudia; Naucler, Pontus; Negra, Marinella D.; Levin, Anna S.

    2017-01-01

    Abstract The study of the etiological agents of community-acquired pulmonary infections is important to guide empirical therapy, requires constant updating, and has a substantial impact on the prognosis of patients. The objective of this study is to determine prospectively the etiology of community-acquired pulmonary infections in hospitalized adults living with HIV. Patients were submitted to an extended microbiological investigation that included molecular methods. The microbiological findings were evaluated according to severity of the disease and pneumococcal vaccine status. Two hundred twenty-four patients underwent the extended microbiological investigation of whom 143 (64%) had an etiology determined. Among the 143 patients with a determined etiology, Pneumocystis jirovecii was the main agent, detected in 52 (36%) cases and followed by Mycobacterium tuberculosis accounting for 28 (20%) cases. Streptococcus pneumoniae and Rhinovirus were diagnosed in 22 (15%) cases each and influenza in 15 (10%) cases. Among atypical bacteria, Mycoplasma pneumoniae was responsible for 12 (8%) and Chlamydophila pneumoniae for 7 (5%) cases. Mixed infections occurred in 48 cases (34%). S pneumoniae was associated with higher severity scores and not associated with vaccine status. By using extended diagnostics, a microbiological agent could be determined in the majority of patients living with HIV affected by community-acquired pulmonary infections. Our findings can guide clinicians in the choice of empirical therapy for hospitalized pulmonary disease. PMID:28121925

  4. Utility of bronchoalveolar lavage in diagnosing respiratory tract infections in patients with hematological malignancies: are invasive diagnostics still needed?

    PubMed Central

    Svensson, Tobias; Lundström, Kristina Lamberg; Höglund, Martin; Cherif, Honar

    2017-01-01

    Background Patients treated for hematological malignancies have an increased risk of serious infections. Diagnosis and prompt initiation of therapy are essential. Bronchoalveolar lavage (BAL) is a well-established investigation for identifying the cause of pulmonary infiltrates in immunocompromised patients. The aim of the study was to determine the diagnostic yield of BAL in patients treated for hematological malignancies and how often it contributed to a modification of the anti-infectious therapy. Methods We reviewed records from 151 consecutive BAL procedures in 133 adult patients with hematological malignancies, treated at a tertiary hematology unit from 2004 to 2013. Extensive microbiological work-ups on BAL samples had been performed according to a standardized protocol. Results A microbiological finding causing the infectious episode could be identified in 59 (39%) cases. In 44 (29%) of the cases, results from BAL had an impact on clinical management either by contributing to a specific diagnosis (25%) or by leading to cessation of ongoing microbiological therapy. The most common diagnoses were invasive pulmonary aspergillosis (IPA) and Pneumocystis jirovecii pneumonia (PJP). Diagnoses of IPA and PJP were based on results from BAL in 65% and 93% of cases, respectively. Several microbiological tests on BAL samples rendered no positive results. Complications were few and mainly mild. Conclusion BAL is still important for either verifying or excluding some of the most important respiratory tract pathogens in patients with hematological malignancies, particularly IPA and PJP. Standardized procedures for BAL sampling should be continually revised to exclude unnecessary microbiological tests. PMID:27739337

  5. Postmortem findings and opportunistic infections in HIV-positive patients from a public hospital in Peru.

    PubMed

    Eza, Dominique; Cerrillo, Gustavo; Moore, David A J; Castro, Cecilia; Ticona, Eduardo; Morales, Domingo; Cabanillas, Jose; Barrantes, Fernando; Alfaro, Alejandro; Benavides, Alejandro; Rafael, Arturo; Valladares, Gilberto; Arevalo, Fernando; Evans, Carlton A; Gilman, Robert H

    2006-01-01

    There is a paucity of HIV autopsy data from South America and none that document the postmortem findings in patients with HIV/AIDS in Peru. The purpose of this autopsy study was to determine the spectrum of opportunistic infections and the causes of mortality in HIV-positive patients at a public hospital in Lima. Clinico-epidemiological information regarding HIV infection in Peru is also reviewed. Sixteen HIV-related hospital postmortems, performed between 1999 and 2004, were included in this retrospective analysis. The primary cause of death was established in 12 patients: one died of neoplasia and 11 of infectious diseases, including 3 from pulmonary infection, 7 from disseminated infection, and 2 from central nervous system infection (one case had dual pathology). Opportunistic infections were identified in 14 cases, comprising cytomegalovirus, histoplasmosis, cryptococcosis, toxoplasmosis, Pneumocystis pneumonia, aspergillosis, tuberculosis, varicella zoster virus, and cryptosporidiosis. Fourteen patients had at least one AIDS-related disease that had been neither clinically suspected nor diagnosed premortem. Moreover, 82% of the diagnoses considered to be of important clinical significance had not been suspected antemortem. The spectrum and frequency of certain opportunistic infections differed from other South American autopsy studies, highlighting the importance of performing HIV/AIDS postmortems in resource-limited countries where locally specific disease patterns may be observed.

  6. Postmortem findings and opportunistic infections in HIV-positive patients from a public hospital in Peru

    PubMed Central

    Eza, Dominique; Cerrillo, Gustavo; Moore, David A.J.; Castro, Cecilia; Ticona, Eduardo; Morales, Domingo; Cabanillas, Jose; Barrantes, Fernando; Alfaro, Alejandro; Benavides, Alejandro; Rafael, Arturo; Valladares, Gilberto; Arevalo, Fernando; Evans, Carlton A.; Gilman, Robert H.

    2010-01-01

    There is a paucity of HIV autopsy data from South America and none that document the postmortem findings in patients with HIV/AIDS in Peru. The purpose of this autopsy study was to determine the spectrum of opportunistic infections and the causes of mortality in HIV-positive patients at a public hospital in Lima. Clinico-epidemiological information regarding HIV infection in Peru is also reviewed. Sixteen HIV-related hospital postmortems, performed between 1999 and 2004, were included in this retrospective analysis. The primary cause of death was established in 12 patients: one died of neoplasia and 11 of infectious diseases, including 3 from pulmonary infection, 7 from disseminated infection, and 2 from central nervous system infection (one case had dual pathology). Opportunistic infections were identified in 14 cases, comprising cytomegalovirus, histoplasmosis, cryptococcosis, toxoplasmosis, Pneumocystis pneumonia, aspergillosis, tuberculosis, varicella zoster virus, and cryptosporidiosis. Fourteen patients had at least one AIDS-related disease that had been neither clinically suspected nor diagnosed premortem. Moreover, 82% of the diagnoses considered to be of important clinical significance had not been suspected antemortem. The spectrum and frequency of certain opportunistic infections differed from other South American autopsy studies, highlighting the importance of performing HIV/AIDS postmortems in resource-limited countries where locally specific disease patterns may be observed. PMID:16979302

  7. A Case of Proliferative Diabetic Retinopathy with HIV Infection in Which HAART Possibly Influenced the Prognosis of Visual Function

    PubMed Central

    Kitagaki, Takakuni; Sato, Takaki; Hirai, Junko; Kimura, Daisaku; Kakurai, Keigo; Fukumoto, Masanori; Tajiri, Kensuke; Kobayashi, Takatoshi; Kida, Teruyo; Kojima, Shota; Ikeda, Tsunehiko

    2016-01-01

    Background We report on a patient with proliferative diabetic retinopathy (PDR) and human immunodeficiency virus (HIV) infection who exhibited extremely active PDR followed by a rapid onset of blindness in the right eye. The progression of visual disturbance in the patient's left eye was slowed after starting highly active anti-retroviral therapy (HAART), and vision in that eye was rescued after vitrectomy. Case Report A 72-year-old male developed pneumocystis carinii pneumonia stemming from an HIV infection and began HAART at the Department of Hematology, Osaka Medical College, Takatsuki City, Japan. Prior to HAART, the patient had shown rapidly progressing retinopathy in the right eye accompanied by vitreous hemorrhage, tractional retinal detachment, and neovascular glaucoma, ultimately leading to early-onset blindness. After starting HAART, the progression of the retinopathy in the left eye became slower compared to the right eye, with corrected visual acuity improving to 0.6 after vitrectomy, despite being accompanied by vitreous hemorrhage. The patient's overall condition has remained stable following the operation, and the condition of the ocular fundus in the left eye has also settled. Conclusion Significant differences were found in the progression rate of PDR with HIV infection between before and after starting HAART. Our findings suggest that early administration of HAART to HIV patients with diabetic retinopathy is crucial for maintaining visual function. PMID:27990117

  8. [Nosocomial infection: clinical aspects].

    PubMed

    Frottier, J

    1993-05-01

    Nosocomial infections develop within a hospital or are produced by microorganisms acquired during hospitalization. They may involve not only patients (2 to 10 percent) but also hospital personnel. They arise from complex interactions of multiple causal factors. Patients risk factors are these that reduce the patient's capacity for resisting the injurious effects of the microorganisms and impair natural host defense mechanisms: patients with malignant disorders or immunosuppressive therapy, poor nutritional status, extensive burn wounds ... The young and the elderly are generally more susceptible to infection. Other infections are preventable. Disease causation is often multifactorial. Nosocomial urinary tract infections had the highest rate, followed by lower respiratory tract infections, surgical infections and bacteremias. The emergence of other nosocomial infections, caused by bacteria (tuberculosis), virus (HIV, hepatitis B and C virus, cytomegalovirus...), Aspergillus species or Pneumocystis carinii appears to be recent in origin and is of importance to immunocompromised hosts, other patients and hospital personnel. Nosocomial infections and their social and economic impacts require for their prevention vigorous organized hospital-wide surveillance and control programs.

  9. Delayed opportunistic infections in hematopoietic stem cell transplantation patients: a surmountable challenge

    PubMed Central

    Marr, Kieren A.

    2015-01-01

    Changes in the transplantation procedure and the implementation of effective supportive care strategies have decreased the incidence of infectious complications early after conditioning therapy for allogeneic hematopoietic stem cell transplantation (HCT) and have extended the duration of risks later. Therefore, the types of infections that cause significant morbidity and the timing of risks have changed. These late infections are caused by all types of organisms, bacterial, viral, and fungal, but risks are predictable and surmountable with the use of tailored prevention strategies. Specifically, recent studies document prolonged risks for bacterial infections in the setting of GVHD, especially those caused by encapsulated organisms and those secondary to impaired Ab responses. Both prophylaxis and vaccination strategies can be used as a means to prevent infections, which typically manifest in the respiratory tract. Multiple viruses cause infection later after HCT, including several herpesviruses (eg, CMV and varicella zoster virus) and other respiratory viruses such as influenza and adenovirus. These infections can cause severe disease with diagnostic challenges, but prevention strategies using enhanced monitoring and/or prophylaxis may be effective. Finally, fungi also cause disease late after HCT, especially filamentous fungi (eg, Aspergillus species and Mucormycoses) and Pneumocystis jiroveci; prophylactic strategies may be used successfully to prevent invasive infection. Late infections and methods to prevent them are reviewed herein. PMID:23233590

  10. Clinical profile and factors associated with mortality in hospitalized patients with HIV/AIDS: a retrospective analysis from Tripoli Medical Centre, Libya, 2013.

    PubMed

    Shalaka, N S; Garred, N A; Zeglam, H T; Awasi, S A; Abukathir, L A; Altagdi, M E; Rayes, A A

    2015-10-02

    In Libya, little is known about HIV-related hospitalizations and in-hospital mortality. This was a retrospective analysis of HIV-related hospitalizations at Tripoli Medical Centre in 2013. Of 227 cases analysed, 82.4% were males who were significantly older (40.0 versus 36.5 years), reported injection drug use (58.3% versus 0%) and were hepatitis C virus co-infected (65.8% versus 0%) compared with females. Severe immunosuppression was prevalent (median CD4 count = 42 cell/μL). Candidiasis was the most common diagnosis (26.0%); Pneumocystis pneumonia was the most common respiratory disease (8.8%), while cerebral toxoplasmosis was diagnosed in 8.4% of patients. Current HAART use was independently associated with low risk of in-hospital mortality (OR 0.33), while central nervous system symptoms (OR 4.12), sepsis (OR 6.98) and low total lymphocyte counts (OR 3.60) were associated with increased risk. In this study, late presentation with severe immunosuppression was common, and was associated with significant in-hospital mortality.

  11. Soluble CD8 and CD25 in serum of patients after heart transplantation.

    PubMed Central

    Wijngaard, P L; Van der Meulen, A; Gmelig Meyling, F H; De Jonge, N; Schuurman, H J

    1994-01-01

    To evaluate the diagnostic value of serum cytokine levels and cytokine receptor levels in the diagnosis of acute rejection after heart transplantation, we measured soluble CD8 and soluble CD25 in the serum of heart transplant recipients. The results were compared with endomyocardial biopsy (EMB) histopathology, lymphocyte activation by morphologic inspection of peripheral blood cells (cytoimmunologic monitoring), clinically manifested infections, and the maintenance immunosuppressive therapy. Significantly increased levels were observed in cases of lymphocyte activation in cytoimmunologic monitoring indicative of either rejection or infection. In clinically documented cytomegalovirus (CMV), bacterial, and Pneumocystis carinii infections, increased levels of soluble CD25 were observed. Soluble CD8 was only increased in a single case of P. carinii infection. A statistically significant correlation was calculated between the levels of soluble CD8 and whole blood cyclosporin A level. Considering chemotherapy, the levels of soluble CD8 showed an inverse correlation with the daily dosage of azathioprine. In conclusion, the levels of soluble CD8 and CD25 are associated with lymphocyte activation in peripheral blood, but do not differentiate between lymphocyte activation indicative of rejection or infection. No relationship was observed between levels of soluble CD8 and CD25, and EMB histopathology. Therefore, the assessment of these two cell products has no diagnostic potential for monitoring acute rejection after heart transplantation. PMID:8082307

  12. Genome Sequencing of the Plant Pathogen Taphrina deformans, the Causal Agent of Peach Leaf Curl

    PubMed Central

    Cissé, Ousmane H.; Almeida, João M. G. C. F.; Fonseca, Álvaro; Kumar, Ajay Anand; Salojärvi, Jarkko; Overmyer, Kirk; Hauser, Philippe M.; Pagni, Marco

    2013-01-01

    ABSTRACT Taphrina deformans is a fungus responsible for peach leaf curl, an important plant disease. It is phylogenetically assigned to the Taphrinomycotina subphylum, which includes the fission yeast and the mammalian pathogens of the genus Pneumocystis. We describe here the genome of T. deformans in the light of its dual plant-saprophytic/plant-parasitic lifestyle. The 13.3-Mb genome contains few identifiable repeated elements (ca. 1.5%) and a relatively high GC content (49.5%). A total of 5,735 protein-coding genes were identified, among which 83% share similarities with other fungi. Adaptation to the plant host seems reflected in the genome, since the genome carries genes involved in plant cell wall degradation (e.g., cellulases and cutinases), secondary metabolism, the hallmark glyoxylate cycle, detoxification, and sterol biosynthesis, as well as genes involved in the biosynthesis of plant hormones. Genes involved in lipid metabolism may play a role in its virulence. Several locus candidates for putative MAT cassettes and sex-related genes akin to those of Schizosaccharomyces pombe were identified. A mating-type-switching mechanism similar to that found in ascomycetous yeasts could be in effect. Taken together, the findings are consistent with the alternate saprophytic and parasitic-pathogenic lifestyles of T. deformans. PMID:23631913

  13. Ayurvedic medicine and the lung.

    PubMed

    Lim, Chiao Yuen; Takano, Angela; Yang, Steve; Lee, Pyng

    2014-01-01

    A middle-aged Indian woman with knee pain had consumed ayurvedic medicine (Ostolief and Arthrella tablets) daily for 6 months. She presented to the respiratory clinic with worsening dyspnea, cough and weight loss of 2 months' duration. She was a homemaker, never-smoker and did not keep birds. Physical examination detected fine end-inspiratory crackles. There was no clubbing of the fingers, joint deformity or swelling, skin lesion or enlarged cervical lymphadenopathy. High-resolution computed tomography showed diffuse centrilobular nodules with ground-glass attenuation. Restrictive ventilatory defect (FVC 44% predicted, FEV1/FVC ratio 93%) was observed on spirometry, and the autoimmune screen was negative. Bronchoalveolar lavage fluid revealed lymphocytosis with an increased CD4/CD8 (T helper:T suppressor) ratio. Cultures for bacteria, mycobacteria, fungi, viruses and Pneumocystis carinii were negative. Alveolitis with infiltration of interstitium by lymphocytes and peribronchiolar noncaseating granulomas were observed on bronchoscopic lung biopsy. A diagnosis of hypersensitivity pneumonitis as a result of ayurvedic medicine was made. She was advised to stop the offending medicine; high-dose steroids and bactrim prophylaxis were commenced and tapered over 3 months with good response and radiological resolution. She was followed for 1 year without relapse.

  14. Late-Onset Cerebral Toxoplasmosis After Allogeneic Hematopoietic Stem Cell Transplantation

    PubMed Central

    Khalaf, Ahmed M.; Hashim, Mahmoud A.; Alsharabati, Mohammed; Fallon, Kenneth; Cure, Joel K.; Pappas, Peter; Mineishi, Shin; Saad, Ayman

    2017-01-01

    Patient: Male, 44 Final Diagnosis: Cerebral toxoplasmosis after HSCT Symptoms: Hemiparesis • muscle weakness Medication: — Clinical Procedure: — Specialty: Hematology Objective: Unusual clinical course Background: Toxoplasmosis is an uncommon but potentially fatal complication following allogeneic hematopoietic stem cell transplantation (HCT). Post-transplant toxoplasmosis is often a reactivation of prior infection and typically occurs within the first 6 months of transplant. Herein, we report that cerebral toxoplasmosis may occur 22 months after allogeneic hematopoietic stem cell transplantation. Case Report: We describe a case of cerebral toxoplasmosis that occurred 22 months after an allogeneic HCT while the patient was on aerosolized pentamidine for Pneumocystis jiroveci pneumonia (PCP) prophylaxis. The disease was only diagnosed after brain biopsy because of atypical MRI appearance of the cerebral lesion and negative Toxoplasma gondii IgG antibody test result in the cerebrospinal fluid (CSF). The patient received pyrimethamine and sulfadiazine treatment, with dramatic improvement after several months. The patient is alive 2 years after infection diagnosis, with no evidence of disease and is off Toxoplasma prophylaxis. Conclusions: Cerebral toxoplasmosis can occur late after allogeneic HCT while patients are on immunosuppression therapy, with atypical features on imaging studies and negative Toxoplasma gondii IgG antibody test result in the CSF. Pre-transplant serologic screening for T. gondii antibodies in allogeneic transplant candidates is warranted. Brain biopsy can be a helpful diagnostic tool for cerebral lesions. PMID:28280256

  15. Fungal infections: a growing threat.

    PubMed Central

    Dixon, D M; McNeil, M M; Cohen, M L; Gellin, B G; La Montagne, J R

    1996-01-01

    THE EMERGENCE OF newly identified fungal pathogens and the reemergence of previously uncommon fungal diseases is primarily related to increases in the numbers of susceptible persons: people with HIV infection, bone marrow and organ transplant recipients, cancer patients being treated with chemotherapy, critically ill persons, and very low birth weight ( < or = 1500 g) infants. These immunocompromised populations are at risk for infection not only with opportunistic pathogens (for example, Pneumocystis, Candida, Cryptococcus, Trichosporon, Malassezia, Aspergillus, Penicillium marneffei, and numerous other moulds or yeasts) but also with fungal pathogens that usually infect otherwise healthy persons not previously exposed to endemic fungi (for example, Coccidioides immitis, Histoplasma capsulatum, and Blastomyces dermatitidis) and Sporothrix schenckii. Morbidity, mortality, and health care costs associated with fungal infections are high. Addressing the emergence of fungal diseases will require increased surveillance coupled with the availability of rapid, noninvasive diagnostic tests; monitoring the development of resistance to antifungal agents; and research focused on the understanding, prevention, and control of fungal infections. Images p[227]-a p226-a p232-a PMID:8643813

  16. Infections in severe alcoholic hepatitis

    PubMed Central

    Karakike, Eleni; Moreno, Christophe; Gustot, Thierry

    2017-01-01

    Severe alcoholic hepatitis (sAH), defined by a modified discriminant function ≥32, is the most severe form of alcohol-induced liver disease and is associated with a 1-month mortality rate of around 30%. Corticosteroid treatment remains the only therapeutic option that improves short-term survival. Infectious complications, occurring in approximately 50% of patients, are the main causes of death, even in patients who benefit from corticosteroids. Liver failure, recent alcohol consumption and immunosuppressive drugs contribute to this infectious risk. Although infection is a well-described feature of cirrhosis, little is known about the characteristics of infections in sAH. Infection is mainly of bacterial origin and frequently affects the respiratory tract. Pathogens classically observed in cirrhosis, such as gram-negative bacilli, are frequently involved, but opportunistic pathogens, such as fungi (Aspergillus fumigatus, Pneumocystis jirovecii) or viruses (Cytomegalovirus, Herpes simplex) may appear, mainly related to corticosteroid treatment. A high level of suspicion with systematic screening and prompt, adequate treatment are warranted to improve outcomes in these patients. Prophylactic strategies in this high-risk population should be assessed in well-designed trials. PMID:28243035

  17. ABO-Incompatible Kidney Transplantation.

    PubMed

    Morath, Christian; Zeier, Martin; Döhler, Bernd; Opelz, Gerhard; Süsal, Caner

    2017-01-01

    ABO-incompatible (ABOi) kidney transplantation has long been considered a contraindication to successful kidney transplantation. During the last 25 years, increasing organ shortage enforced the development of strategies to overcome the ABO antibody barrier. In the meantime, ABOi kidney transplantation has become a routine procedure with death-censored graft survival rates comparable to the rates in compatible transplantations. Desensitization is usually achieved by apheresis and B cell-depleting therapies that are accompanied by powerful immunosuppression. Anti-A/B antibodies are aimed to be below a certain threshold at the time of ABOi kidney transplantation and during the first 2 weeks after surgery. Thereafter, even a rebound of anti-A/B antibodies does not appear to harm the kidney transplant, a phenomenon that is called accommodation, but is poorly understood. There is still concern, however, that infectious complications such as viral disease, Pneumocystis jirovecii pneumonia, and severe urinary tract infections are increased after ABOi transplantations. Recent data from the Collaborative Transplant Study show that during the first year after kidney transplantation, one additional patient death from an infectious complication occurs in 100 ABOi kidney transplant recipients. Herein, we review the recent evidence on ABOi kidney transplantation with a focus on desensitization strategies and respective outcomes.

  18. Human pathogens utilize host extracellular matrix proteins laminin and collagen for adhesion and invasion of the host.

    PubMed

    Singh, Birendra; Fleury, Christophe; Jalalvand, Farshid; Riesbeck, Kristian

    2012-11-01

    Laminin (Ln) and collagen are multifunctional glycoproteins that play an important role in cellular morphogenesis, cell signalling, tissue repair and cell migration. These proteins are ubiquitously present in tissues as a part of the basement membrane (BM), constitute a protective layer around blood capillaries and are included in the extracellular matrix (ECM). As a component of BMs, both Lns and collagen(s), thus function as major mechanical containment molecules that protect tissues from pathogens. Invasive pathogens breach the basal lamina and degrade ECM proteins of interstitial spaces and connective tissues using various ECM-degrading proteases or surface-bound plasminogen and matrix metalloproteinases recruited from the host. Most pathogens associated with the respiratory, gastrointestinal, or urogenital tracts, as well as with the central nervous system or the skin, have the capacity to bind and degrade Lns and collagen(s) in order to adhere to and invade host tissues. In this review, we focus on the adaptability of various pathogens to utilize these ECM proteins as enhancers for adhesion to host tissues or as a targets for degradation in order to breach the cellular barriers. The major pathogens discussed are Streptococcus, Staphylococcus, Pseudomonas, Salmonella, Yersinia, Treponema, Mycobacterium, Clostridium, Listeria, Porphyromonas and Haemophilus; Candida, Aspergillus, Pneumocystis, Cryptococcus and Coccidioides; Acanthamoeba, Trypanosoma and Trichomonas; retrovirus and papilloma virus.

  19. Extracorporeal membrane oxygenation: a breakthrough for respiratory failure.

    PubMed

    Frenckner, B

    2015-12-01

    Extracorporeal membrane oxygenation (ECMO) is a method for providing long-term treatment of a patient in a modified heart-lung machine. Desaturated blood is drained from the patient, oxygenated and pumped back to a major vein or artery. ECMO supports heart and lung function and may be used in severe heart and/or lung failure when conventional intensive care fails. The Stockholm programme started in 1987 with treatment of neonates. In 1995, the first adult patient was accepted onto the programme. Interhospital transportation during ECMO was started in 1996, which enabled retrieval of extremely unstable patients during ECMO. Today, the programme has an annual volume of about 80 patients. It has been characterized by, amongst other things, minimal patient sedation. By 31 December 2014, over 900 patients had been treated, the vast majority for respiratory failure, and over 650 patients had been transported during ECMO. The median ECMO duration was 5.3, 5.7 and 7.1 days for neonatal, paediatric and adult patients, respectively. The survival to hospital discharge rate for respiratory ECMO was 81%, 70% and 63% in the different age groups, respectively, which is significantly higher than the overall international experience as reported to the Extracorporeal Life Support Organization (ELSO) Registry (74%, 57% and 57%, respectively). The survival rate was significantly higher in the Stockholm programme compared to ELSO for meconium aspiration syndrome, congenital diaphragmatic hernia in neonates and pneumocystis pneumonia in paediatric patients.

  20. Effect of cimetidine on pentamidine induced hyperglycemia in rats.

    PubMed

    Arino, Toru; Karakawa, Seiji; Ishiwata, Yasuyoshi; Nagata, Masashi; Yasuhara, Masato

    2012-10-15

    The antiprotozoal agent pentamidine, used for the treatment of Pneumocystis jirovecii pneumonia (PCP), is known to cause abnormalities in blood glucose homeostasis, such as hypoglycemia and hyperglycemia. Pentamidine has been reported to be a substrate of organic cation transporter 1 (OCT1). We investigated the combination effects of cimetidine, an OCT1 inhibitor, on the pharmacokinetics of pentamidine and on pentamidine-induced hyperglycemia. Pentamidine was infused intravenously to rats for 20 min at a dose of 7.5 or 15 mg/kg and serum samples were obtained periodically. The serum concentration of glucose did not change significantly after pentamidine infusion at 7.5mg/kg, while it increased with pentamidine at 15 mg/kg, and the maximal concentration of glucose was 167 ± 36 mg/dl, 30 min after the start of pentamidine infusion. Cimetidine (50mg/kg) enhanced the pentamidine-induced elevation of glucose concentration and the maximal concentration of glucose was 208 ± 33 mg/dl in the pentamidine 15 mg/kg treated group. Cimetidine combination significantly reduced total body clearance of pentamidine and increased pentamidine concentrations in the liver, kidneys, and lungs. A significant correlation was found between changes in serum glucose concentrations and serum concentrations of pentamidine 30 min after the start of pentamidine infusion. These results suggest that the hyperglycemic effect of pentamidine is dependent on the concentration of pentamidine and can be enhanced by cimetidine combination.