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  1. Pneumocystis jiroveci pneumonia

    MedlinePlus

    Pneumocystis pneumonia can be life threatening, causing respiratory failure that can lead to death. People with this condition need early and effective treatment. For moderate to severe pneumocystis pneumonia in people with ...

  2. Pneumocystis jiroveci pneumonitis complicating ruxolitinib therapy

    PubMed Central

    Lee, Samantha C; Feenstra, John; Georghiou, Paul R

    2014-01-01

    Ruxolitinib is a novel inhibitor of the Janus kinase (JAK) pathway that has become available for the treatment of myelofibrosis. There are increasing reports of opportunistic infections associated with ruxolitinib therapy. We present a case of Pneumocystis jiroveci pneumonitis complicating ruxolitinib therapy. Clinicians should consider the use of pneumocystis prophylaxis when using ruxolitinib. PMID:24891492

  3. Systemic inflammation in patients with chronic obstructive pulmonary disease who are colonized with Pneumocystis jiroveci.

    PubMed

    Calderón, Enrique J; Rivero, Laura; Respaldiza, Nieves; Morilla, Rubén; Montes-Cano, Marco A; Friaza, Vicente; Muñoz-Lobato, Fernando; Varela, José M; Medrano, Francisco J; Horra, Carmen de la

    2007-07-15

    In chronic obstructive pulmonary disease, high levels of airway and systemic inflammatory markers are associated with a faster decrease in lung function. Our study shows that patients colonized by Pneumocystis jiroveci have higher proinflammatory cytokine levels than do noncolonized patients. This suggests that Pneumocystis may play a role in disease progression. PMID:17578770

  4. Pneumocystis jiroveci dihydropteroate synthase gene mutations among colonized individuals and Pneumocystis pneumonia patients from Spain.

    PubMed

    Friaza, Vicente; Morilla, Rubén; Respaldiza, Nieves; de la Horra, Carmen; Calderón, Enrique J

    2010-11-01

    Cotrimoxazole, an association of trimethoprim and sulfamethoxazole, and dapsone, are mainstays for the prophylaxis and treatment of Pneumocystis pneumonia (PcP). The inability to culture Pneumocystis prevents routine susceptibility testing and detection of drug resistance. Instead, molecular techniques have been used to detect Pneumocystis jiroveci dihydropteroate synthase (DHPS) mutations that cause sulfa resistance in other microorganisms. The most frequent DHPS mutations occur at nucleotide positions 165 and 171, which lead to an amino acid change at positions 55 and 57. Several studies suggest that these mutations are associated with the failure of chemoprophylaxis for PcP. The aim was to establish the frequency and characteristics of P jiroveci DHPS mutations among colonized individuals and PcP patients from Spain. A total of 50 colonized individuals and 25 PcP patients were studied. DHPS polymorphisms were identified by restriction fragment length polymorphism assay. The analysis provided a rate of 28% of DHPS gene mutations in our population, with the presence of all possible polymorphisms described. The presence of mutations was higher in PcP patients than in colonized subjects (40% vs 22%), probably because of the chemoprophylaxis used in PcP patients. The comparison between patients with and without DHPS mutations did not show statistical differences due to age, sex, steroid use, sulfa drug exposure, or smoking. A high rate of DHPS mutations in our area of Spain, not only confined to patients previously exposed to sulfa drugs, is shown in this study. As well as PcP patients, colonized individuals who harbor P jiroveci strains with DHPS mutations could play a major role in the transmission cycle of these mutations, representing a reservoir and source of infection for susceptible individuals. Further research is thus warranted to assess the true scope of the problem and to design rational preventive strategies. PMID:21084778

  5. An epidemic of Pneumocystis jiroveci pneumonia in a renal transplantation center: role of T-cell lymphopenia.

    PubMed

    Brunot, V; Pernin, V; Chartier, C; Garrigue, V; Vetromile, F; Szwarc, I; Delmas, S; Portalès, P; Basset, D; Mourad, G

    2012-11-01

    Although only 2 cases of Pneumocystis jiroveci pneumonia were observed in our center between 2004 and 2009, we diagnosed 9 cases in 2010. Each patient had been in contact in the hospital with at least 1 other patient suffering P jiroveci pneumonia. Genotyping of P jiroveci pneumonia strains demonstrates a total homogeneity of the DNA sequences in the 7 patients already analyzed. CD4+ lymphocyte count was significantly lower at M3 in P jiroveci pneumonia patients than in controls. Our clinical and molecular data confirm that interhuman transmission of P jiroveci is possible, particularly to lymphopenic transplant recipients. PMID:23146531

  6. Mixed Pulmonary Infection with Penicillium notatum and Pneumocystis jiroveci in a Patient with Acute Myeloid Leukemia

    PubMed Central

    Tehrani, Shabnam; Hemmatian, Marjan

    2016-01-01

    Penicillium notatum is a fungus that widely exists in the environment and is often non-pathogenic to humans. However, in immunocompromised hosts it may be recognized as a cause of systemic mycosis. A 44-year-old man with acute myeloid leukemia (AML) was admitted to our hospital with fever and neutropenia. Due to no improvement after initial treatment, he underwent bronchoscopy. The patient was found to have P. notatum and Pneumocystis jiroveci infection, and therefore was given voriconazole, primaquine and clindamycin. The patient was successfully treated and suffered no complications. Conclusion: This case highlights P. notatum as a cause of infection in immunocompromised patients. To the best of our knowledge, mixed lung infection with P. notatum and P. jiroveci in a patient with AML has not been previously reported. PMID:27403180

  7. Pneumomediastinum, pneumorrhachis, and subcutaneous emphysema in Pneumocystis jiroveci pneumonia in AIDS

    PubMed Central

    Saleem, Nasir; Parveen, Sanober; Iroegbu, Nkemakolam

    2016-01-01

    Pneumomediastinum, the presence of free air within the mediastinal cavity, is sometimes accompanied by subcutaneous emphysema and pneumorrhachis (air within the spinal canal). We report the case of a 28-year-old man with previously undiagnosed HIV who was diagnosed with extensive pneumomediastinum, pneumorrhachis, and subcutaneous emphysema secondary to Pneumocystis jiroveci pneumonia after presenting with chest pain, dyspnea, and central cyanosis. Surgical consultation was requested, but a conservative approach of observation proved sufficient as the free air was resorbed into the surrounding tissues. PMID:27034565

  8. Pneumomediastinum, pneumorrhachis, and subcutaneous emphysema in Pneumocystis jiroveci pneumonia in AIDS.

    PubMed

    Saleem, Nasir; Parveen, Sanober; Odigwe, Chibuzo; Iroegbu, Nkemakolam

    2016-04-01

    Pneumomediastinum, the presence of free air within the mediastinal cavity, is sometimes accompanied by subcutaneous emphysema and pneumorrhachis (air within the spinal canal). We report the case of a 28-year-old man with previously undiagnosed HIV who was diagnosed with extensive pneumomediastinum, pneumorrhachis, and subcutaneous emphysema secondary to Pneumocystis jiroveci pneumonia after presenting with chest pain, dyspnea, and central cyanosis. Surgical consultation was requested, but a conservative approach of observation proved sufficient as the free air was resorbed into the surrounding tissues. PMID:27034565

  9. Pneumocystis jiroveci Dihydropteroate Synthase Genotypes in Immunocompetent Infants and Immunosuppressed Adults, Amiens, France

    PubMed Central

    Totet, Anne; Latouche, Sophie; Lacube, Philippe; Pautard, Jean-Claude; Jounieaux, Vincent; Raccurt, Christian; Roux, Patricia

    2004-01-01

    To date, investigations of Pneumocystis jiroveci circulation in the human reservoir through the dihydropteroate synthase (DHPS) locus analysis have only been conducted by examining P. jirovecii isolates from immunosuppressed patients with Pneumocystis pneumonia (PCP). Our study identifies P. jirovecii genotypes at this locus in 33 immunocompetent infants colonized with P. jirovecii contemporaneously with a bronchiolitis episode and in 13 adults with PCP; both groups of patients were monitored in Amiens, France. The results have pointed out identical features of P. jirovecii DHPS genotypes in the two groups, suggesting that in these two groups, transmission cycles of P. jirovecii infections are linked. If these two groups represent sentinel populations for P. jirovecii infections, our results suggest that all persons parasitized by P. jirovecii, whatever their risk factor for infection and the form of parasitism they have, act as interwoven circulation networks of P. jirovecii. PMID:15200857

  10. Pneumocystis jiroveci pneumonia in patients treated with systemic immunosuppressive agents for dermatologic conditions: a systematic review with recommendations for prophylaxis.

    PubMed

    Gonzalez Santiago, Tania M; Wetter, David A; Kalaaji, Amer N; Limper, Andrew H; Lehman, Julia S

    2016-08-01

    Pneumocystis jiroveci pneumonia is an opportunistic infection associated with substantial rates of mortality in immunosuppressed patients. Prophylaxis recommendations are mostly targeted toward patients with non-dermatologic diagnoses. This study was conducted to determine when dermatology patients treated with immunosuppressive medications should be offered P. jiroveci pneumonia prophylaxis. We searched the literature from January 1, 1993, to December 31, 2013, using terms relating to P. jiroveci pneumonia and dermatologic diagnoses to analyze the clinical characteristics of previously affected patients. Guidelines for P. jiroveci pneumonia prophylaxis from other medical fields were also analyzed. Of 17 dermatology patients reported to have contracted P. jiroveci pneumonia, eight (47.1%) died of the pneumonia. Risk factors included lack of prophylaxis, systemic corticosteroid therapy, lymphopenia, hypoalbuminemia, low serum CD4 counts, comorbid pulmonary or renal disease, malignancy, and prior organ transplantation. The present conclusions are limited by heterogeneity among the selected studies and limitations in their identification and selection. However, P. jiroveci pneumonia in dermatology patients is associated with a high mortality rate. Based on our analysis, we propose that prophylaxis be considered in dermatology patients in whom treatment with systemic corticosteroids at doses exceeding 20 mg/day or treatment with corticosteroid-sparing immunosuppressive agents is anticipated for at least 4 weeks, and in patients with additional risk factors for P. jiroveci pneumonia. PMID:27009930

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

    PubMed

    Williams, K M; Ahn, K W; Chen, M; Aljurf, M D; Agwu, A L; Chen, A R; Walsh, T J; Szabolcs, P; Boeckh, M J; Auletta, J J; Lindemans, C A; Zanis-Neto, J; Malvezzi, M; Lister, J; de Toledo Codina, J S; Sackey, K; Chakrabarty, J L H; Ljungman, P; Wingard, J R; Seftel, M D; Seo, S; Hale, G A; Wirk, B; Smith, M S; Savani, B N; Lazarus, H M; Marks, D I; Ustun, C; Abdel-Azim, H; Dvorak, C C; Szer, J; Storek, J; Yong, A; Riches, M R

    2016-04-01

    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 Center for International Blood and Marrow Transplant Research 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, the 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

  12. 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

  13. Congenital rubella pneumonitis complicated by Pneumocystis jiroveci infection with positive long term respiratory outcome: a case report and literature review.

    PubMed

    Sanchez, M O; Chang, A B

    2009-12-01

    Rubella remains to be a significant illness in the developing countries because of limited access to immunizations. In congenital rubella syndrome, lung involvement becomes evident within the few months of life, as a manifestation of the "late onset rubella syndrome." The lungs and other organs become involved secondary to immunopathologic mechanisms and immunodeficiency predisposes affected patients to opportunistic pathogens. We report the clinical, respiratory and immunologic data of a young boy who developed rubella pneumonitis and concomitant infection with Pneumocystis jiroveci. Despite the complicated clinical course, the child survived. At follow-up he has a normal pulmonary examination, mild hyperinflation only on his chest radiograph, normal immunology and normal respiratory reactance and resistance. PMID:19911369

  14. Pneumocystis Pneumonia (For Parents)

    MedlinePlus

    ... 5 Things to Know About Zika & Pregnancy Pneumocystis Pneumonia KidsHealth > For Parents > Pneumocystis Pneumonia Print A A A Text Size What's in ... article? About PCP Diagnosing PCP Treating PCP Pneumocystis pneumonia (PCP) is an infection caused by Pneumocystis jiroveci , ...

  15. Pneumocystis jiroveci pneumonia

    MedlinePlus

    ... a weakened immune system due to AIDS, cancer, transplantation, or corticosteroid use, call your provider if ... transplant recipients Organ transplant recipients People who take long-term, high- ...

  16. Correlation between imaging features of Pneumocystis Jiroveci Pneumonitis (PCP), CD4+ T lymphocyte count, and plasma HIV viral load: A study in 50 consecutive AIDS patients

    PubMed Central

    Deng, Ying-Ying; Liu, Shui-Teng; Liu, Yan; Liu, Ying-Xia; Wang, Yi-Xiang J; Zhu, Wen-Ke; Le, Xiao-Hua; Yu, Wei-Ye; Zhou, Bo-Ping

    2012-01-01

    Purpose To investigate the imaging manifestations of Pneumocystis Jiroveci Pneumonitis (PCP) in AIDS patients, and the correlation between imaging features, CD4+ lymphocyte count, and plasma HIV viral load. Materials and methods A total of consecutive 50 AIDS patients with PCP were reviewed retrospectively. Chest CT manifestations, CD4+ lymphocyte count, and plasma HIV viral load were analyzed to investigate their correlation. Results PCP chest CT manifestations included ground-glass opacities dominated in 28 cases (28/50, 56%), lung cysts dominated in 10 cases (10/50, 20%), consolidation dominated in 6 cases (6/50, 12%), interstitial lesion dominated in 3 cases (3/50, 6%), and mixed lesions in 3 cases (3/50, 6%). In these 50 patients, CD4+ lymphocyte count ranged from 2 to 373 cells/µL. Plasma HIV viral load ranged from 500 to 5.28×107 copies/mL. CD4+ lymphocyte count in ground-glass opacities dominated patients was higher than that of lung cyst dominated patients (P<0.05). Plasma virus load of lung cysts dominated PCP patients was higher than that of consolidation dominated patients (P<0.05). Conclusions The typical chest imaging features of PCP in AIDS patients included lung ground-glass opacities and lung cysts. The chest imaging features were correlated with CD4+ T lymphocyte count and plasma HIV viral load. PMID:23256070

  17. Acute microbiologically negative hypoxic interstitial pneumonia on HAART: Immune Reconstitution Inflammatory Syndrome unmasking Pneumocystis Jiroveci infection with an atypical presentation

    PubMed Central

    Sovaila, S; de Raigniac, A; Picard, C; Taulera, O; Lascoux-Combe, C; Sereni, D; Bourgarit, A

    2012-01-01

    Highly active antiretroviral therapy for AIDS sometimes engenders inflammatory manifestations resulting from an inappropriate and unbalanced immune-system restoration, called Immune Reconstitution inflammatory Syndrome, which, in turn, can unmask a subclinical infection/pathology. Despite our patient’s evident syndrome, the atypical clinical, microbiologic and radiologic feature of Pneumocystis pneumonia made its diagnosis difficult. PMID:22802889

  18. Diagnostic Accuracy of Serum 1,3-β-d-Glucan for Pneumocystis jiroveci Pneumonia, Invasive Candidiasis, and Invasive Aspergillosis: Systematic Review and Meta-Analysis

    PubMed Central

    Onishi, Akira; Kogata, Yoshinori; Saegusa, Jun; Sugimoto, Takeshi; Kawano, Seiji; Morinobu, Akio; Nishimura, Kunihiro; Kumagai, Shunichi

    2012-01-01

    Serum 1,3-β-d-glucan (BG) assay may be helpful as a marker for the diagnosis of Pneumocystis jiroveci pneumonia (PJP) and invasive fungal infection (IFI). We conducted a systematic review to assess the diagnostic accuracy of this assay. We searched MEDLINE, Web of Science, Cochrane Collaboration databases, Ichushi-Web, reference lists of retrieved studies, and review articles. Our search included studies of serum BG assay that used (i) positive cytological or direct microscopic examination of sputum or bronchoalveolar lavage fluid for PJP and (ii) European Organization for Research and Treatment of Cancer or similar criteria for IFI as a reference standard and provided data to calculate sensitivity and specificity. Only major fungal infections such as invasive candidiasis and invasive aspergillosis were included in the IFI group. Twelve studies for PJP and 31 studies for IFI were included from January 1966 to November 2010. The pooled sensitivity, specificity, diagnostic odds ratio (DOR), and area under the summary receiver operating characteristic curve (AUC-SROC) for PJP were 96% (95% confidence interval [95% CI], 92% to 98%), 84% (95% CI, 83% to 86%), 102.3 (95% CI, 59.2 to 176.6) and 0.96 (95% CI, 0.94 to 0.99), respectively. No heterogeneity was found. For IFI, the values were 80% (95% CI, 77% to 82%), 82% (95% CI, 81% to 83%), 25.7 (95% CI, 15.0 to 44.1), and 0.88 (95% CI, 0.82 to 0.93). Heterogeneity was significant. The diagnostic accuracy of the BG assay is high for PJP and moderate for IFI. Because the sensitivity for PJP is particularly high, the BG assay can be used as a screening tool for PJP. PMID:22075593

  19. 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. PMID:25771943

  20. [Pnemocystis jiroveci pneumonia: Comparison between conventional PCR and staining techniques].

    PubMed

    Kaouech, E; Kallel, K; Anane, S; Belhadj, S; Abdellatif, S; Mnif, K; Ben Othmane, T; Ben Lakhal, S; Kilani, B; Ben Châabane, T; Chaker, E

    2009-07-01

    Diagnosis of pneumocystis pneumonia is usually based on clinical features and X-rays photography and confirmed in the laboratory by visualisation of Pneumocystis organisms in stained preparations of respiratory specimens using several techniques (Gomori-Grocott, May-Grünwald Giemsa, bleu de toluidine O). Actually, PCR has considerably increased sensitivity of detection of Pneumocystis. The aim of this study is to compare conventional PCR results to those of staining techniques (Gomori-Grocott, May-Grünwald Giemsa) in addition to the X-ray and clinical findings in order to evaluate the contribution of each method. Sixty-four respiratory specimens were collected from 54 immuno-compromised patients with clinical symptoms of pulmonary infection. We diagnosed pneumocystis pneumonia in 16 patients according to staining techniques and/or typical clinical and radiological findings and/or response to treatment. Of the 15 patients, 14 were positive by PCR and only five were positive by direct examination, yielding a sensitivity and specificity of 93.3 and 87.1% for PCR and 33.3 and 100% for staining techniques. Conventional PCR provides a sensitive and objective method for the detection Pneumocystis jiroveci from less invasive sample. PMID:19038508

  1. MedlinePlus: Pneumocystis Infections

    MedlinePlus

    ... With CD4 and CD8 (American Association for Clinical Chemistry) Related Issues Pneumocystis Pneumonia (PCP) and HIV (American Academy of Family Physicians) Also in Spanish Statistics and Research Pneumocystis Pneumonia Statistics (Centers for Disease Control and ...

  2. [Human reservoirs of Pneumocystis].

    PubMed

    Wissmann, Gustavo; Morilla, Ruben; Friaza, Vicente; Calderón, Enrique; Varela, Jose M

    2010-01-01

    Pneumocystis jirovecii, the fungal agent that causes Pneumocystis pneumonia (PCP), is known to exclusively infect humans. Molecular studies have enabled detection of this fungus in individuals who have been colonized by P. jirovecii. Such colonization, found in several populations, seems to act as a human reservoir for the fungus. Various studies have reported mutations associated with sulfa resistance in P. jirovecii strains isolated from colonized patients, who can transmit the mutant genotype to PCP-susceptible individuals. The growing interest in P. jirovecii colonization may prompt the design of new prevention and management strategies for PCP. PMID:19403207

  3. Chitinases in Pneumocystis carinii pneumonia

    PubMed Central

    Villegas, Leah R.; Kottom, Theodore J.

    2014-01-01

    Pneumocystis pneumonia remains an important complication of immune suppression. The cell wall of Pneumocystis has been demonstrated to potently stimulate host inflammatory responses, with most studies focusing on β-glucan components of the Pneumocystis cell wall. In the current study, we have elaborated the potential role of chitins and chitinases in Pneumocystis pneumonia. We demonstrated differential host mammalian chitinase expression during Pneumocystis pneumonia. We further characterized a chitin synthase gene in Pneumocystis carinii termed Pcchs5, a gene with considerable homolog to the fungal chitin biosynthesis protein Chs5. We also observed the impact of chitinase digestion on Pneumocystis-induced host inflammatory responses by measuring TNFα release and mammalian chitinase expression by cultured lung epithelial and macrophage cells stimulated with Pneumocystis cell wall isolates in the presence and absence of exogenous chitinase digestion. These findings provide evidence supporting a chitin biosynthetic pathway in Pneumocystis organisms and that chitinases modulate inflammatory responses in lung cells. We further demonstrate lung expression of chitinase molecules during Pneumocystis pneumonia. PMID:22535444

  4. Pathological and Protective Immunity to Pneumocystis Infection

    PubMed Central

    Eddens, Taylor; Kolls, Jay K.

    2014-01-01

    Pneumocystis jirovecii is a common opportunistic infection in the HIV-positive population and is re-emerging as a growing clinical concern in the HIV-negative immunosuppressed population. Newer targeted immunosuppressive therapies and the discovery of rare genetic mutations have furthered our understanding of the immunity required to clear Pneumocystis infection. The immune system can also mount a pathologic response against Pneumocystis following removal of immunosuppression and result in severe damage to the host lung. The current review will examine the most recent epidemiologic studies about the incidence of Pneumocystis in the HIV-positive and HIV-negative populations in the developing and developed world and will detail methods of diagnosis for Pneumocystis pneumonia. Finally, this review aims to summarize the known mediators of immunity to Pneumocystis and detail the pathologic immune response leading to Pneumocystis-related immune reconstitution inflammatory syndrome. PMID:25420451

  5. 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

  6. 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

  7. 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.

  8. Competitive coexistence of two Pneumocystis species.

    PubMed

    Icenhour, Crystal R; Arnold, Jonathan; Medvedovic, Mario; Cushion, Melanie T

    2006-05-01

    Pneumocystis are fungal pathogens of mammalian lungs that can cause lethal pneumonia in immunocompromised hosts. In some mammals, coinfections of genetically distinct Pneumocystis populations have been identified, but the nature of their interaction and its significance are unknown. Two species that infect rats, Pneumocystis carinii and Pneumocystis wakefieldiae, were studied over a 6-year period, representing approximately 700 generations of Pneumocystis. Population densities of each species were analyzed within the framework of the Lotka-Volterra competition model, which revealed the two species were in competition and predicted competitive exclusion of one species. However, stable coexistence was observed in 460 replicate populations. Selected extrinsic factors that might mitigate the extinction were evaluated. Logistic-regression analyses showed that higher relative humidity and higher organism lung burdens were associated with infections comprised of P. carinii alone, while lower temperatures and an increased rat census were associated with the presence of P. wakefieldiae. PCR and immunofluorescent analysis of rat lung tissue showed that both species were present within the same alveoli, excluding habitat heterogeneity as a mechanism of coexistence. These data suggest that P. carinii and P. wakefieldiae were in competitive coexistence, which was influenced in part by extrinsic factors. To our knowledge, this is the first report to evaluate interactions of pathogenic fungal species within a mammalian host using ecological models. PMID:15949973

  9. Barcoding markers for Pneumocystis species in wildlife.

    PubMed

    Danesi, Patrizia; da Rold, Graziana; Rizzoli, Annapaola; Hauffe, Heidi C; Marangon, Stefano; Samerpitak, Kittipan; Demanche, Cristine; Guillot, Jacques; Capelli, Gioia; de Hoog, Sybren G

    2016-02-01

    Lung specimens (n = 216) from six wildlife species were examined for occurrence of Pneumocystis species in pulmonary tissues. Among small mammals the shrew Sorex antinorii (80 %) were most frequently colonized. In contrast, foxes and badgers did not yield positive amplification. Host-specificity was noted, at least at the level of the host genus. Phylogenetic trees based on partial mtLSU and mtSSU showed high diversity of species corresponding to animal host diversity. Nuclear rDNA ITS data confirmed unambiguous separation of species. In conclusion, ITS is an excellent marker to distinguish species of the genus Pneumocystis. PMID:26781376

  10. Pneumatoceles and pneumothorax after Pneumocystis carinii pneumonia.

    PubMed

    Sauleda, J; Aran, X; Gea, J; Aguar, M C; Sanz, M; Broquetas, J M

    1993-01-01

    Pneumocystis carinii pneumonia (PCP) is common in patients with AIDS. The usual chest X-ray pattern is a diffuse interstitial pulmonary infiltrate. Nevertheless, unusual roentgenographic forms can appear. A patient with PCP that resulted in pneumatoceles and a further pneumothorax is described. PMID:8284529

  11. [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. PMID:26572261

  12. Phylogenetic status of Pneumocystis from corticosteroid-treated gerbils.

    PubMed

    Feng, XianMin; Wei, ChaoJun; Adam, Rodney D; Li, ZiHui; Lu, Siqi

    2010-10-01

    Pneumocystis spp. infect the lungs of multiple mammalian species and cause disease in immunosuppressed individuals. The Pneumocystis isolates that have been studied to date fall into two major clades, those from primates and those from rodents. Within each of these clades, different species have been described on the basis of host specificity and differences in sequence and morphology. Here, we demonstrate that dexamethasone immunosuppression consistently results in histologically apparent lung infection in gerbils (28/35 animals). Sequence analysis of the 18S, 5.8S and internal transcribed spacer regions of the rDNA and a portion of the mitochondrial large subunit rDNA demonstrated that this gerbil Pneumocystis is grouped with other rodent Pneumocystis spp., but is distinct from them. Our results suggest that gerbil Pneumocystis differs sufficiently from Pneumocystis species found in other rodents to be considered a separate species. PMID:20953947

  13. 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. PMID:26864029

  14. 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. PMID:24733475

  15. 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

  16. Lymphocyte apoptosis in murine Pneumocystis pneumonia

    PubMed Central

    Shi, Xin; LeCapitaine, Nicole J; Rudner, Xiaowen L; Ruan, Sanbao; Shellito, Judd E

    2009-01-01

    Background Apoptosis of lymphocytes is important in the termination of an immune response to infection but has also been shown to have detrimental effects in animal models of systemic infection and sepsis. We sought to characterize lymphocyte apoptosis in an animal model of pneumonia due to Pneumocystis murina, an infection localized to the lungs. Methods Control mice and mice depleted of CD4+ lymphocytes were inoculated with Pneumocystis. Apoptosis of lung and spleen lymphocytes was assayed by flow cytometry and PCR assay of apoptotic proteins. Results In control mice, apoptosis of lung lymphocytes was maximal just after the infection was cleared from lung tissue and then declined. However, in CD4-depleted mice, apoptosis was also upregulated in recruited lymphocytes in spite of progressive infection. In splenic lymphocytes, apoptosis was observed early at 1 week after inoculation and then declined. Apoptosis of lung lymphocytes in control mice was associated with a decrease in mRNA for Bcl-2 and an increase in mRNA for Bim. In CD4-depleted mice, lavaged CD8+ cells did change intracellular Bcl-2 but showed increased mRNA for Bim. Conclusion Apoptosis of both pulmonary and extrapulmonary lymphocytes is part of the normal host response to Pneumocystis but is also triggered in CD4-deficient animals with progressive infection. In normal mice apoptosis of pulmonary lymphocytes may serve to terminate the immune response in lung tissue. Apoptosis of lung lymphocytes takes place via both the intrinsic and extrinsic apoptotic pathways and is associated with changes in both pro- and anti-apoptotic proteins. PMID:19558669

  17. 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

  18. Pneumocystis jirovecii in the air surrounding patients with Pneumocystis pulmonary colonization.

    PubMed

    Le Gal, Solène; Pougnet, Laurence; Damiani, Céline; Fréalle, Emilie; Guéguen, Paul; Virmaux, Michèle; Ansart, Séverine; Jaffuel, Sylvain; Couturaud, Francis; Delluc, Aurélien; Tonnelier, Jean-Marie; Castellant, Philippe; Le Meur, Yann; Le Floch, Gaétan; Totet, Anne; Menotti, Jean; Nevez, Gilles

    2015-06-01

    In this study, Pneumocystis jirovecii was detected and characterized in the air surrounding patients with Pneumocystis pulmonary colonization. Air samples were collected in the rooms of 10 colonized patients using Coriolis® μ air sampler at 1m and 5m from the patient's head. P. jirovecii DNA was amplified and genotyped in pulmonary and air samples at the mitochondrial large subunit ribosomal RNA gene. P. jirovecii DNA was detected in 5 of the 10 air samples collected at 1m and in 5 of the 10 other air samples collected at 5m. P. jirovecii genotyping was successful in 4 pairs or triplets of air and pulmonary samples. Full genotype matches were observed in 3 of the 4 pairs or triplets of air and pulmonary samples. These results provide original data supporting P. jirovecii exhalation from colonized patients and emphasize the risk of P. jirovecii nosocomial transmission from this patient population. PMID:25801779

  19. [Pneumocystis pneumonia in 3 non HIV patients].

    PubMed

    Battikh, R; M'sadek, F; Ben Abdelhafidh, N; Louzir, B; Labidi, J; Ajili, F; Jemli, B; Gargouri, S; Cheikh, R; Othmani, S

    2007-09-01

    We report 3 cases of pneumocystis pneumonia (PCP) in 2 female and 1 male patients (mean age=50 years) free of human immunodeficiency virus (HIV) infection. One female patient presented with breast neoplasm the other with Wegener's granulomatosis, the male patient with lymphoma. All patients were taking immunosuppressive treatment at the time of infection. Persistent cough, dyspnea, and severe hypoxemia were the most characteristic clinical signs. All patients presented with lymphopenia (average CD4-cell count=275/mm3), two with hypoalbuminemia, and one with renal failure. In all cases, the microscopic analysis of bronchoalveolar lavage was used to establish the diagnosis. All patients were treated with trimethoprim and sulfamethoxazole and a tapering dose of corticosteroids. Outcome was favorable for 1 patient, 1 was transferred to the intensive care unit for acute respiratory failure, and 1 died. PMID:17306485

  20. Pneumocystis: A Novel Pathogen in Chronic Obstructive Pulmonary Disease?

    PubMed Central

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

    2008-01-01

    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. PMID:18259974

  1. Biological profile and response to anti-pneumocystis agents of Pneumocystis carinii in cell culture.

    PubMed Central

    Pifer, L L; Pifer, D D; Woods, D R

    1983-01-01

    Although the growth characteristics of Pneumocystis carinii have been described in several cell culture systems, the response of this organism to the drugs of choice, trimethoprim-sulfamethoxazole and pentamidine isethionate, have not been described in vitro. The effect of various concentrations of drugs against P. carinii on the growth of this potentially hazardous opportunistic organism as well as the methodology for in vitro assay of these agents have been detailed. Fluorescence profiles illustrating size ranges of trophozoites and cysts derived from cell culture are described. PMID:6607029

  2. Strain Typing Methods and Molecular Epidemiology of Pneumocystis Pneumonia

    PubMed Central

    Roux, Patricia; Nevez, Gilles; Hauser, Philippe M.; Kovacs, Joseph A.; Unnasch, Thomas R.; Lundgren, Bettina

    2004-01-01

    Pneumocystis pneumonia (PCP) caused by the opportunistic fungal agent Pneumocystis jirovecii (formerly P. carinii) continues to cause illness and death in HIV-infected patients. In the absence of a culture system to isolate and maintain live organisms, efforts to type and characterize the organism have relied on polymerase chain reaction–based approaches. Studies using these methods have improved understanding of PCP epidemiology, shedding light on sources of infection, transmission patterns, and potential emergence of antimicrobial resistance. One concern, however, is the lack of guidance regarding the appropriateness of different methods and standardization of these methods, which would facilitate comparing results reported by different laboratories. PMID:15504257

  3. 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.

  4. Pneumocystis jirovecii Transmission from Immunocompetent Carriers to Infant

    PubMed Central

    Rivero, Laura; de la Horra, Carmen; Montes-Cano, Marco A.; Rodríguez-Herrera, Alfonso; Respaldiza, Nieves; Friaza, Vicente; Morilla, Rubén; Gutiérrez, Sonia; Varela, José M.; Medrano, Francisco J.

    2008-01-01

    We report a case of Pneumocystis jirovecii transmission from colonized grandparents to their infant granddaughter. Genotyping of P. jirovecii showed the same genotypes in samples from the infant and her grandparents. These findings support P. jirovecii transmission from immunocompetent carrier adults to a susceptible child. PMID:18598635

  5. Pneumocystis jirovecii transmission from immunocompetent carriers to infant.

    PubMed

    Rivero, Laura; de la Horra, Carmen; Montes-Cano, Marco A; Rodríguez-Herrera, Alfonso; Respaldiza, Nieves; Friaza, Vicente; Morilla, Rubén; Gutiérrez, Sonia; Varela, José M; Medrano, Francisco J; Calderón, Enrique J

    2008-07-01

    We report a case of Pneumocystis jirovecii transmission from colonized grandparents to their infant granddaughter. Genotyping of P. jirovecii showed the same genotypes in samples from the infant and her grandparents. These findings support P. jirovecii transmission from immunocompetent carrier adults to a susceptible child. PMID:18598635

  6. Attachment of Pneumocystis carinii to rat pneumocytes.

    PubMed

    Long, E G; Smith, J S; Meier, J L

    1986-06-01

    Male Sprague-Dawley rats were immunosuppressed by subcutaneous injections of cortisone acetate for 8 weeks to induce Pneumocystis carinii pneumonia. Rats were killed with ether, their lungs were filled in situ with cold glutaraldehyde, and sections were examined by transmission electron microscopy. P. carinii trophozoites were observed in lungs for as long as 6 weeks after cessation of corticosteroid injections. Trophozoites were attached most frequently to type I pneumocytes but were seen on several occasions to be attached to type II pneumocytes. In attachment, trophozoites in contact with alveolar epithelial cells produced cytoplasmic modifications of three basic forms: one was an invagination of parasite surface to pinch cytoplasmic extensions on the surface of the epithelial cells. A second was an extension that was inserted into a crevice of the host surface and enlarged at the tip to form an anchor. The third was an extension that remained pointed at the tip and was recurved to form a hook. None of these modifications was seen on the surface of the trophozoites. Filopodia did not appear to be involved in attachment but were seen on both attached and lumenal surfaces of the trophozoites. Trophozoites and cysts were also observed to be partially or completely enveloped by extensions of the host cell's cytoplasm. In these instances, parasites had rounded surfaces but appeared viable. No fusion of cell membranes between parasite and host cells was ever seen. These observations may help explain why P. carinii can attach tenaciously to lung epithelium without cell-membrane fusion, production of a glycocalyx, or invasion of host cells. PMID:3487003

  7. Molecular phylogeny of pneumocystis based on 5.8S rRNA gene and the internal transcribed spacers of rRNA gene sequences.

    PubMed

    Li, ZiHui; Feng, XianMin; Lu, SiQi; Zhang, Fan; Wang, FengYun; Huang, Song

    2008-05-01

    To clarify the phylogenetic relationships and species status of Pneumocystis, the 5.8S rRNA gene and the internal transcribed spacers (ITS, 1 and 2) of Pneumocystis rRNA derived from rat, gerbil and human were amplified, cloned and sequenced. The genetic distance matrix of six Pneumocystis species compared with other fungi like Taphrina and Saccharomyces indicated that the Pneumocystis genus contained multiple species including Pneumocystis from gerbil. The phylogenetic tree also showed that Pneumocystis from human and monkey formed one group and four rodent Pneumocystis formed another group. Among the four members, Pneumocystis wakefieldiae was most closely related to Pneumocystis murina and Pneumocystis carinii, and was least related to gerbil Pneumocystis. PMID:18785590

  8. 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. PMID:27242785

  9. 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

  10. 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. PMID:27324243

  11. A protracted course of Pneumocystis pneumonia in the setting of an immunosuppressed child with GMS-negative bronchoalveolar lavage

    PubMed Central

    Eddens, Taylor; Song, Eunkyung; Ardura, Monica I.; Kolls, Jay K.

    2016-01-01

    We report a case of Pneumocystis pneumonia in a 5-year-old male with Trisomy 21 and acute lymphoblastic leukemia. The lack of response to trimethoprim-sulfamethoxazole raised concerns for antimicrobial resistance. Further, diagnosis of Pneumocystis in this patient was complicated by a GMS-negative bronchoalveolar lavage despite molecular evidence of Pneumocystis infection. PMID:27182485

  12. Pneumocystis jirovecii pneumonia in Latin America. A public health problem?

    PubMed

    Calderón, Enrique J; de Armas, Yaxsier; Panizo, Maria Mercedes; Wissmann, Gustavo

    2013-06-01

    Pneumocystis jirovecii pneumonia (PcP) is a well-recognized major opportunistic infection in HIV-infected patients. During the 1980s, the HIV pandemic turned PcP into a major worldwide medical and public health problem. With the introduction of Pneumocystis chemoprophylaxis and the development of highly active antiretroviral therapy (ART) for the treatment of HIV infection, there has been a decrease in PcP incidence in developed countries. However, the prevalence of AIDS-related PcP in developing countries remains high because a lot of people do not have access to ART or ignore their HIV infection status. This article discusses the information available about PcP among Latin American countries where there is a great regional heterogeneity in the prevalence of HIV infection and in ART coverage, as well as in the observed frequencies of PcP that range from 5.9 to 55% in this area. PMID:23750728

  13. Pulmonary paracoccidioidomycosis misdiagnosed as Pneumocystis pneumonia in an immunocompromised host.

    PubMed Central

    Silletti, R P; Glezerov, V; Schwartz, I S

    1996-01-01

    Yeast cells of Paracoccidioides brasiliensis can resemble the cysts of Pneumocystis carinii in smears stained with Grocott's modification of the Gomori methanamine silver stain. Furthermore, P. brasiliensis can cross-react in material stained with a widely used P. carinii immunofluorescent stain which uses monoclonal antibodies. The need to differentiate P. brasiliensis and P. carinii will become more important as the increasing incidence of immunosuppression results in the reactivation of latent P. brasiliensis infections. PMID:8862614

  14. Colonization by Pneumocystis jirovecii and Its Role in Disease

    PubMed Central

    Norris, Karen A.

    2012-01-01

    Summary: Although the incidence of Pneumocystis pneumonia (PCP) has decreased since the introduction of combination antiretroviral therapy, it remains an important cause of disease in both HIV-infected and non-HIV-infected immunosuppressed populations. The epidemiology of PCP has shifted over the course of the HIV epidemic both from changes in HIV and PCP treatment and prevention and from changes in critical care medicine. Although less common in non-HIV-infected immunosuppressed patients, PCP is now more frequently seen due to the increasing numbers of organ transplants and development of novel immunotherapies. New diagnostic and treatment modalities are under investigation. The immune response is critical in preventing this disease but also results in lung damage, and future work may offer potential areas for vaccine development or immunomodulatory therapy. Colonization with Pneumocystis is an area of increasing clinical and research interest and may be important in development of lung diseases such as chronic obstructive pulmonary disease. In this review, we discuss current clinical and research topics in the study of Pneumocystis and highlight areas for future research. PMID:22491773

  15. 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

  16. Histopathology of Pneumocystis carinii pneumonia in immunocompetent laboratory rats

    PubMed Central

    KIM, HYUN-SOO; DO, SUNG-IM; KIM, YOUN WHA

    2014-01-01

    The occurrence of idiopathic pulmonary lesions in laboratory rats, characterized by lymphohistiocytic interstitial pneumonia with dense perivascular lymphoid cuffs, has been reported over the past decade. Although the term rat respiratory virus (RRV) was adopted to confer a putative viral etiology to the idiopathic pulmonary lesions, the etiology of this disease remains to be elucidated. Recently, inflammatory lesions have been observed in the lungs of immunocompetent laboratory rats similar to those previously described. Based on the latest evidence indicating that Pneumocystis carinii (P. carinii), and not putative RRV, causes infectious interstitial pneumonia in laboratory rats, the present study investigated whether the pulmonary lesions observed were caused by P. carinii infection. Male Sprague-Dawley rats, free of known pathogens, were introduced into a rat colony positive for RRV-type lesions. Routine histopathological examinations were performed on the rat lung tissues following exposure. The presence of Pneumocystis organisms was confirmed using Grocott’s methenamine silver (GMS) staining. At week 3 following introduction, a few small lymphoid aggregates were located adjacent to the edematous vascular sheath. By week 5, foci of dense perivascular lymphoid cuffing were observed. Multifocal lymphohistiocytic interstitial pneumonia and prominent lymphoid perivascular cuffs were observed between week 7 and 10. GMS staining confirmed the presence of Pneumocystis cysts. Thus, the results of the present study demonstrated that P. carinii caused lymphohistiocytic interstitial pneumonia in a group of laboratory rats. The observations strongly support the conclusion that P. carinii infection in immunocompetent laboratory rats causes the lung lesions that were previously attributed to RRV. PMID:25009598

  17. Inhibition of Pneumocystis carinii dihydropteroate synthetase by sulfa drugs.

    PubMed Central

    Merali, S; Zhang, Y; Sloan, D; Meshnick, S

    1990-01-01

    A new reversed-phase high-pressure liquid chromatography assay procedure for dihydropteroate synthetase (DHPS) that involves the elution of the enzyme incubation solution with a series of three solvents of decreasing polarity (ammonium phosphate buffer, 10% methanol, and 50% methanol) was designed. By this procedure DHPS was detected in Escherichia coli and Pneumocystis carinii with specific activities of 450 and 14 U/mg, respectively. A comparison of the effects of five sulfa drugs on P. carinii DHPS activity revealed that dapsone is the most potent of these drugs. PMID:2203302

  18. Efficacy of lasalocid against murine Pneumocystis carinii pneumonitis.

    PubMed Central

    OZ, H S; Hughes, W T; Rehg, J E

    1997-01-01

    The efficacy of the ionophore lasalocid against Pneumocystis carinii pneumonitis in corticosteroid-immunosuppressed Sprague-Dawley rats was investigated. Lasalocid was effective in the prevention of the pneumonitis in a dose-dependent manner. At dosages of 0, 5, 10, and 20 mg/kg/day, P. carinii infection rates were 92, 60, 20, and 0%, respectively, during dexamethasone immunosuppression. Also, lasalocid compared favorably with other drugs known to have anti-P. carinii activity, including trimethoprim-sulfamethoxazole, atovaquone, and dapsone-trimethoprim. PMID:8980779

  19. Combined Quantification of Pulmonary Pneumocystis jirovecii DNA and Serum (1→3)-β-d-Glucan for Differential Diagnosis of Pneumocystis Pneumonia and Pneumocystis Colonization

    PubMed Central

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

    2013-01-01

    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 × 107 versus 3.4 × 103 copies/μl, P < 0.05). A lower cutoff value (1.6 × 103 copies/μl) achieving 100% sensitivity for PCP diagnosis and an upper cutoff value (2 × 104 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 × 103 and 2 × 104 copies/μl, and serum BG detection, applying a 100 pg/ml threshold, can differentiate PCP and colonization diagnoses. PMID:23903553

  20. 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

  1. Pentamidine in Pneumocystis jirovecii prophylaxis in heart transplant recipients.

    PubMed

    Diken, Adem Ilkay; Diken, Ozlem Erçen; Hanedan, Onur; Yılmaz, Seyhan; Ecevit, Ata Niyazi; Erol, Emir; Yalçınkaya, Adnan

    2016-03-24

    Despite advances in transplantation techniques and the quality of post-transplantation care, opportunistic infections remain an important cause of complications. Pneumocystis jirovecii (P. jirovecii) is an opportunistic organism, represents an important cause of infections in heart transplantation patients. Almost 2% to 10% of patients undergoing cardiac transplantation have Pneumocystis pneumonia. Prophylaxis is essential after surgery. Various prophylaxis regimes had been defined in past and have different advantages. Trimethoprim/sulfamethoxazole (TMP/SMX) has a key role in prophylaxis against P. jirovecii. Generally, although TMP/SMX is well tolerated, serious side effects have also been reported during its use. Pentamidine is an alternative prophylaxis agent when TMP/SMX cannot be tolerated by the patient. Structurally, pentamidine is an aromatic diamidine compound with antiprotozoal activity. Since it is not effectively absorbed from the gastrointestinal tract, it is frequently administered via the intravenous route. Pentamidine can alternatively be administered through inhalation at a monthly dose in heart transplant recipients. Although, the efficiency and safety of this drug is well studied in other types of solid organ transplantations, there are only few data about pentamidine usage in heart transplantation. We sought to evaluate evidence-based assessment of the use of pentamidine against P. jirovecii after heart transplantation. PMID:27011917

  2. Pentamidine in Pneumocystis jirovecii prophylaxis in heart transplant recipients

    PubMed Central

    Diken, Adem Ilkay; Diken, Ozlem Erçen; Hanedan, Onur; Yılmaz, Seyhan; Ecevit, Ata Niyazi; Erol, Emir; Yalçınkaya, Adnan

    2016-01-01

    Despite advances in transplantation techniques and the quality of post-transplantation care, opportunistic infections remain an important cause of complications. Pneumocystis jirovecii (P. jirovecii) is an opportunistic organism, represents an important cause of infections in heart transplantation patients. Almost 2% to 10% of patients undergoing cardiac transplantation have Pneumocystis pneumonia. Prophylaxis is essential after surgery. Various prophylaxis regimes had been defined in past and have different advantages. Trimethoprim/sulfamethoxazole (TMP/SMX) has a key role in prophylaxis against P. jirovecii. Generally, although TMP/SMX is well tolerated, serious side effects have also been reported during its use. Pentamidine is an alternative prophylaxis agent when TMP/SMX cannot be tolerated by the patient. Structurally, pentamidine is an aromatic diamidine compound with antiprotozoal activity. Since it is not effectively absorbed from the gastrointestinal tract, it is frequently administered via the intravenous route. Pentamidine can alternatively be administered through inhalation at a monthly dose in heart transplant recipients. Although, the efficiency and safety of this drug is well studied in other types of solid organ transplantations, there are only few data about pentamidine usage in heart transplantation. We sought to evaluate evidence-based assessment of the use of pentamidine against P. jirovecii after heart transplantation. PMID:27011917

  3. Typing of Pneumocystis jirovecii by multilocus sequencing: evidence of outbreak?

    PubMed

    Depypere, M; Saegeman, V; Lagrou, K

    2016-06-01

    Different reports of Pneumocystis jirovecii pneumonia (PcP) outbreaks on oncology and transplant units suggest the possibility of a person-to-person transmission. Based on these reports, we searched retrospectively for possible PcP clusters in UZ Leuven in 2013. A movement and transmission map was established for all patients (n = 21) with a positive PcP PCR on BAL fluid. BAL fluid samples from all patients with a positive PCR on the mitochondrial large subunit mRNA of P. jirovecii and possible cross exposure were typed with multilocus sequence typing (MLST). Five patients with a positive PcP PCR could have contact with another PcP patient. Another five patients with a weak positive PcP PCR on BAL fluid during the same period were also included. Based on the MLST typing of the BAL samples of these ten patients, there was no evidence of a PcP outbreak in UZ Leuven in 2013. MLST has proven to be a useful tool in genotyping and outbreak detection. From this case series, it could be concluded that current infection control precautions for P. jirovecii are appropriate in UZ Leuven. However, there is need for an international Pneumocystis database and more clarity in the geographic distribution of different P. jirovecii genotypes. PMID:27038443

  4. Pneumocystis jirovecii Pneumonia in Human Immunodeficiency Virus Infection.

    PubMed

    Siegel, Marc; Masur, Henry; Kovacs, Joseph

    2016-04-01

    The presentation of Pneumocystis pneumonia (PCP) in previously healthy men having sex with men (MSM) in San Francisco and New York City in 1981 heralded the beginning of the human immunodeficiency virus (HIV) pandemic. Despite a decreasing incidence of PCP among patients with HIV/AIDS (acquired immunodeficiency syndrome) since the advent of combination antiretroviral therapy in the mid-1990s, PCP remains one of the most common AIDS-defining opportunistic infections in the United States and Western Europe. Newer molecular diagnostic tests in conjunction with standard immunofluorescent or colorimetric tests have allowed for more rapid and accurate diagnosis. Although several effective oral and intravenous therapies exist to treat PCP, mortality rates in HIV-infected individuals remain unacceptably high, especially in those with advanced AIDS. The identification of specific mutations in Pneumocystis genes targeted by trimethoprim-sulfamethoxazole has raised concerns about the development of resistance to the drug of choice and may ultimately lead to greater utilization of alternative therapies to treat PCP in the future. PMID:26974301

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

    PubMed

    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

  6. 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

  7. Recent advances in the diagnosis, treatment, and prevention of Pneumocystis carinii pneumonia.

    PubMed Central

    Davey, R T; Masur, H

    1990-01-01

    In summary, recent advances in our ability to diagnose, treat, and prevent recurrences of pneumocystis pneumonia have significantly improved the clinical management of this infection, especially in HIV-1-infected individuals. As current investigations allow our therapeutic armamentarium in this disease to be strengthened even further, it is likely that pneumocystis pneumonia will pose a diminishing threat to those patients currently most susceptible to this infection. PMID:2140495

  8. 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

  9. Analysis of Current Antifungal Agents and Their Targets within the Pneumocystis carinii Genome

    PubMed Central

    Porollo, Aleksey; Meller, Jaroslaw; Joshi, Yogesh; Jaiswal, Vikash; Smulian, A. George; Cushion, Melanie T.

    2013-01-01

    Pneumocystis pneumonia (PCP) remains a leading opportunistic infection in patients with weakened immune system. The fungus causing the infection belongs to the genus, Pneumocystis, and its members are found in a large variety of mammals. Adaptation to the lung environment of a host with an intact immune system has been a key to its successful survival. Unfortunately, the metabolic strategies used by these fungi to grow and survive in this context are largely unknown. There were considerable impediments to standard approaches for investigation of this unique pathogen, the most problematic being the lack of a long term in vitro culture system. The absence of an ex vivo cultivation method remains today, and many fundamental scientific questions about the basic biology, metabolism, and life cycle of Pneumocystis remain unanswered. Recent progress in sequencing of the Pneumocystis carinii genome, a species infecting rats, permitted a more informative search for genes and biological pathways within this pathogen that are known to be targets for existing antifungal agents. In this work, we review the classes of antifungal drugs with respect to their potential applicability to the treatment of PCP. Classes covered in the review are the azoles, polyenes, allylamines, and echinocandins. Factors limiting the use of standard antifungal treatments and the currently available alternatives (trimethoprim-sulfamethoxazole, atovaquone, and pentamidine) are discussed. A summary of genomic sequences within Pneumocystis carinii associated with the corresponding targeted biological pathways is provided. All sequences are available via Pneumocystis Genome Project at http://pgp.cchmc.org/. PMID:22934582

  10. 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. PMID:23903553

  11. Monodrug efficacies of sulfonamides in prophylaxis for Pneumocystis carinii pneumonia.

    PubMed Central

    Hughes, W T; Killmar, J

    1996-01-01

    A remarkably high rate of adverse events is associated with the use of trimethoprim-sulfamethoxazole in patients with human immunodeficiency virus type 1 infection. We examined the efficacies of sulfonamides alone in the prevention of Pneumocystis carinii pneumonitis, with the assumption that at least some of the adverse events with the drug combination might be due to trimethoprim. With the immunosuppressed rat model, eight sulfonamides were studied at 100, 10, and 1.0 mg/kg/day (10 rats per dosage and drug). P. carinii infection was prevented in all animals (100%) receiving dosages of as little as 1.0 mg of sulfamethoxazole, sulfamethoxypyridazine, and sulfadimethoxine per kg per day, as little as 10 mg of sulfameter, sulfachlorpyridazine, and sulfaquinoxaline per kg per day; and 100 mg of sulfaguanidine and sulfanilamide per kg per day. These studies suggest that a sulfonamide, such as sulfamethoxazole, might provide effective prophylaxis for P. carinii pneumonitis without trimethoprim. PMID:8849260

  12. Increasing Pneumocystis Pneumonia, England, UK, 2000–2010

    PubMed Central

    Maini, Rishma; Sheridan, Elizabeth A.; Lamagni, Theresa; Nichols, Gordon; Delpech, Valerie; Phin, Nick

    2013-01-01

    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. PMID:23622345

  13. 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.

  14. 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

  15. 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. PMID:25630458

  16. 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

  17. PCR Diagnosis of Pneumocystis Pneumonia: a Bivariate Meta-Analysis ▿

    PubMed Central

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

    2011-01-01

    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. PMID:22012008

  18. Virtual Screening of Phytochemicals to Novel Target (HAT) Rtt109 in Pneumocystis Jirovecii using Bioinformatics Tools

    PubMed Central

    Adithavarman, Abhinand Ponneri; Dakshinamoorthi, Anusha; David, Darling Chellathai; Ragunath, Padmavathi Kannan

    2016-01-01

    Introduction Pneumocystis jirovecii is a fungus that causes Pneumocystis pneumonia in HIV and other immunosuppressed patients. Treatment of Pneumocystis pneumonia with the currently available antifungals is challenging and associated with considerable adverse effects. There is a need to develop drugs against novel targets with minimal human toxicities. Histone Acetyl Transferase (HAT) Rtt109 is a potential therapeutic target in Pneumocystis jirovecii species. HAT is linked to transcription and is required to acetylate conserved lysine residues on histone proteins by transferring an acetyl group from acetyl CoA to form e-N-acetyl lysine. Therefore, inhibitors of HAT can be useful therapeutic options in Pneumocystis pneumonia. Aim To screen phytochemicals against (HAT) Rtt109 using bioinformatics tool. Materials and Methods The tertiary structure of Pneumocystis jirovecii (HAT) Rtt109 was modeled by Homology Modeling. The ideal template for modeling was obtained by performing Psi BLAST of the protein sequence. Rtt109-AcCoA/Vps75 protein from Saccharomyces cerevisiae (PDB structure 3Q35) was chosen as the template. The target protein was modeled using Swiss Modeler and validated using Ramachandran plot and Errat 2. Comprehensive text mining was performed to identify phytochemical compounds with antipneumonia and fungicidal properties and these compounds were filtered based on Lipinski’s Rule of 5. The chosen compounds were subjected to virtual screening against the target protein (HAT) Rtt109 using Molegro Virtual Docker 4.5. Osiris Property Explorer and Open Tox Server were used to predict ADME-T properties of the chosen phytochemicals. Results Tertiary structure model of HAT Rtt 109 had a ProSA score of -6.57 and Errat 2 score of 87.34. Structure validation analysis by Ramachandran plot for the model revealed 97% of amino acids were in the favoured region. Of all the phytochemicals subjected to virtual screening against the target protein (HAT) Rtt109, baicalin

  19. Pneumocystis jirovecii Pneumonia in a Patient with Rheumatoid Arthritis Treated with Abatacept

    PubMed Central

    Ospina, Fabio E.; Agualimpia, Andrés; Cañas, Carlos A.; Tobón, Gabriel J.

    2014-01-01

    Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial membrane inflammation and joint cartilage destruction. Abatacept is a biologic agent that blocks the costimulation signals, preventing antigen presentation and proliferation of T lymphocytes. It is approved for the treatment of patients with RA. Pneumocystis jirovecii pneumonia (PJP) is an infectious disease complicating several immunosuppressive drugs. PJP associated with abatacept has not been reported yet in the medical literature. Various factors, such as the mechanism of action of abatacept, may contribute to predisposing to  Pneumocystis jirovecii infection. In this paper, we report a patient with RA who developed PJP under abatacept treatment. PMID:25313341

  20. Pneumocystis jirovecii Pneumonia in a Patient with Rheumatoid Arthritis Treated with Abatacept.

    PubMed

    Ospina, Fabio E; Agualimpia, Andrés; Bonilla-Abadía, Fabio; Cañas, Carlos A; Tobón, Gabriel J

    2014-01-01

    Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial membrane inflammation and joint cartilage destruction. Abatacept is a biologic agent that blocks the costimulation signals, preventing antigen presentation and proliferation of T lymphocytes. It is approved for the treatment of patients with RA. Pneumocystis jirovecii pneumonia (PJP) is an infectious disease complicating several immunosuppressive drugs. PJP associated with abatacept has not been reported yet in the medical literature. Various factors, such as the mechanism of action of abatacept, may contribute to predisposing to  Pneumocystis jirovecii infection. In this paper, we report a patient with RA who developed PJP under abatacept treatment. PMID:25313341

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

    PubMed Central

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

    1995-01-01

    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. PMID:7486915

  2. Outbreaks of Pneumocystis carinii pneumonia in colonies of immunodeficient mice.

    PubMed

    Walzer, P D; Kim, C K; Linke, M J; Pogue, C L; Huerkamp, M J; Chrisp, C E; Lerro, A V; Wixson, S K; Hall, E; Shultz, L D

    1989-01-01

    Outbreaks of Pneumocystis carinii pneumonia occurred in colonies of nu/nu and scid/scid mice at four different institutions. The disease, which was characterized by chronic wasting and respiratory insufficiency, was more severe in older mice and in animals housed in cages with special protective tops. Histopathologic features included alveolar filling with the typical foamy honeycomb material and a mild, nonspecific host inflammatory response. Immunofluorescence and immunoblotting studies suggested the P. carinii isolate was of mouse rather than of rat or human origin, and the outbreaks could be related to each other by common vendor or source of breeding animals. Once P. carinii became established in a mouse colony, the organism tended to persist for long periods of time. The principal control measure was depopulation of the colony, although limited experience with the administration of trimethoprim-sulfamethoxazole was encouraging. Thus, outbreaks of pneumocystosis are a serious problem among colonies of immunodeficient mice, with important implications for the use of these animals in biomedical research. Data obtained by studying these outbreaks should enhance understanding of the pathogenesis of P. carinii pneumonia and be helpful in formulating improved methods of detection and control. PMID:2642471

  3. 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. PMID:22308234

  4. 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

  5. Pneumocystis Carinii Pneumonia—Problems in Diagnosis and Therapy in 24 Cases

    PubMed Central

    Gentry, Layne O.; Ruskin, Joel; Remington, Jack S.

    1972-01-01

    Twenty-four instances of Pneumocystis carinii pneumonia were recognized in 23 patients at the Stanford University Hospitals between 1962 and 1970. The affected persons could be broadly characterized as “compromised” hosts. All but one were receiving immunosuppressive drug therapy for such underlying disease as hematopoietic malignant disease, collagen vascular disorder, and organ transplant rejection. The one patient not receiving immunosuppressant medication had congenital dysgammaglobulinemia and suffered two discrete bouts of pneumocystis pneumonia. Most of the patients were concomitantly infected with other “opportunistic” pathogens. Open lung biopsy remained the most reliable method of antemortem diagnosis of pneumocystis infection during this eight-year period. It resulted in little morbidity. Unfortunately, direct examination of appropriately stained sputum specimens for cysts was almost uniformly nonproductive. The majority of patients received specific antipneumocystis drug treatment (pentamidine isethionate or pyrimethamine and sulfadiazine). “Cure” was achieved when institution of therapy was prompt and duration of therapy approached the empirically recommended two-week course. The fact that pneumocystis pneumonia can be controlled if recognized early is compelling reason to pursue diagnosis of pneumocystosis in an appropriate clinical setting, namely, in patients with impaired host defenses who have pulmonary infection unresponsive to conventional therapy. There is hope that a noninvasive (serological) technique will be developed shortly to simplify identification of this not uncommon cause of diffuse interstitial pneumonitis. PMID:4537021

  6. Molecular Identification of Tritrichomonas foetus-Like Organisms as Coinfecting Agents of Human Pneumocystis Pneumonia

    PubMed Central

    Duboucher, Christophe; Caby, Stéphanie; Dufernez, Fabienne; Chabé, Magali; Gantois, Nausicaa; Delgado-Viscogliosi, Pilar; Billy, Christophe; Barré, Eric; Torabi, Edith; Capron, Monique; Pierce, Raymond J.; Dei-Cas, Eduardo; Viscogliosi, Eric

    2006-01-01

    Trichomonads closely related to the bovid parasite Tritrichomonas foetus were identified in the bronchoalveolar lavage sample from a patient with AIDS in association with Pneumocystis pneumonia. This human case of T. foetus-like infection emphasizes the zoonotic potential of trichomonads, although the existence of a human-host-adapted T. foetus strain cannot be excluded. PMID:16517921

  7. 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. PMID:24966006

  8. Pneumocystis Jirovecii Pneumonia in a Patient with Anti-N-Methyl-D-Aspartate Receptor Postherpetic Encephalitis.

    PubMed

    García-Moreno, Jorge; Igartua Laraudogoitia, Jon; Montes Ros, Milagrosa

    2016-07-01

    Anti-N-methyl-D-aspartate receptor encephalitis is a neuroimmunologic disorder that has been increasingly diagnosed during the past 5 years. It provokes a predictable syndrome treated with several immunomodulatory agents, such as corticosteroids and/or biologics. We managed a child with this disease who developed Pneumocystis jirovecii pneumonia as a direct infectious complication of the use of rituximab. PMID:27093160

  9. [Investigation of Pneumocystis jirovecii in clinical specimens by different methods].

    PubMed

    Tekinşen, F Filiz; Koç, A Nedret

    2013-10-01

    Pneumocystis jirovecii causes pneumonia in premature, newborn or malnourished children, as well as in immunocompromised subjects such as chemotherapy receiving, transplant and AIDS patients. Since the mortality and morbidity rates of Pneumocystis pneumonia (PCP) in these patients were high, rapid and accurate diagnosis is important. The aim of this study was to evaluate the diagnostic value of Giemsa staining (GS), direct fluorescent antibody (DFA) assay, (1→3)-β-D-Glucan (BDG) test and real-time polymerase chain reaction (PCR) for the detection of P.jirovecii in clinical specimens. A total of 100 PCP-suspected patients with underlying diseases who were followed-up in outpatient and inpatient clinics of our hospital between December 2008-July 2010 were included in the study. All the patients (66 male, 34 female; mean age: 42.04 years) were under long-term immunosuppressive drug therapy due to their hematological malignancies, kidney transplantation, neutropenia or chronic diseases. Respiratory samples [86 bronchoalveolar lavage (BAL), 8 endotracheal aspirate, 1 nasotracheal aspirate, 3 pleural, 2 lung biopsy samples] obtained from the patients have been studied with GS (Merck, Germany), DFA (Pneumo Cel, Cellabs, Australia) and PCR (primers targeting MSG gene, LightCycler, Roche, USA), while serum samples (n= 100) with BDG (Fungitell, ACC Inc, USA) and PCR methods. In BAL samples two were found positive by GS, DFA and PCR, and six were positive only by PCR, yielding a total positivity in 8 (8%) samples. All of the sera were negative with PCR, however 29 of them were positive (> 80 pg/ml), five were equivocal (61-79 pg/ml) and 66 were negative (< 60 pg/ml) with BDG test. Eight patients with positive results in BAL-PCR were also positive with BDG test. Although the agreement between GS and DFA was high (κ= 1), it was observed as low between PCR and DFA (κ= 0.38), DFA and BDG (κ= 0.07), BAL-PCR and BDG (κ= 0.28). DFA taken as the gold standard, the sensitivity

  10. 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

  11. High Prevalence of Dihydropteroate Synthase Mutations in Pneumocystis jirovecii Isolated from Patients with Pneumocystis Pneumonia in South Africa▿

    PubMed Central

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

    2010-01-01

    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. PMID:20351205

  12. 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

  13. Opportunistic Infections and Other Conditions

    MedlinePlus

    ... toxo) Pneumocystis jiroveci pneumonia (PCP) Tuberculosis (TB) Vaginal yeast infections Treatments for HIV/AIDS Research and clinical ... fact sheet Urinary tract infections fact sheet Vaginal yeast infections fact sheet More information on opportunistic infections ...

  14. 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

  15. Genetic Diversity of Pneumocystis carinii Isolated from Human Immunodeficiency Virus-Positive Patients in Turin, Italy

    PubMed Central

    Volpe, Gisella; Sbaiz, Luca; Avanzini, Claudio; Caramello, Pietro; Savoia, Dianella

    2001-01-01

    By DNA sequence analysis we identified two new strain types and five novel sporadic variations among 25 isolates of Pneumocystis carinii f. sp. hominis obtained from 19 human immunodeficiency virus-positive patients. Of these, 13 were infected with a single strain and 6 were coinfected. Fifteen different combination types were identified among the 18 strains for which complete molecular typing was accomplished. PMID:11474032

  16. Activity of clindamycin with primaquine against Pneumocystis carinii in vitro and in vivo.

    PubMed Central

    Queener, S F; Bartlett, M S; Richardson, J D; Durkin, M M; Jay, M A; Smith, J W

    1988-01-01

    The combination of primaquine with clindamycin is effective in both in vitro and in vivo models of Pneumocystis infection. Primaquine alone at concentrations from 10 to 300 micrograms/ml reduced the numbers of organisms in cultures to less than 7% of control. Significant inhibition was observed down to 0.1 microgram/ml. Clindamycin at 5 micrograms/ml was ineffective alone. Combinations of clindamycin and primaquine in culture at various concentrations were effective, but there was no evidence of true synergy. In rats with established Pneumocystis pneumonia, clindamycin alone at 5 or 225 mg/kg was ineffective. Primaquine alone at 0.5 or 2 mg/kg did not significantly affect the numbers of organisms remaining. The combination of 0.5 mg of primaquine per kg and 225 mg of clindamycin per kg was effective for therapy, lowering the numbers of organisms in the lungs by about 90%. The combination of 2 mg of primaquine per kg and 225 mg of clindamycin per kg was more effective, lowering the numbers of organisms by almost 98%. In the in vivo prophylaxis model, primaquine at 0.1 or 0.2 mg/kg did not prevent the development of Pneumocystis pneumonia in immune-suppressed rats. Clindamycin at 50 mg/kg had a modest effect alone, but at 5 mg/kg all animals became heavily infected. At 0.5 mg/kg, primaquine alone reduced the severity of infection, but seven of eight rats were still infected. In contrast, the combination of 5 mg of clindamycin per kg and 0.5 mg of primaquine per kg prevented infection in 8 of 10 rats; 2 rats had minimal infection. These studies suggest that the combination of clindamycin and primaquine should be tested in therapy or prophylaxis of Pneumocystis infections in humans. Images PMID:3261959

  17. Intrabronchial valves for treatment of alveolar-pleural fistula in a patient with Pneumocystis jirovecii pneumonia.

    PubMed

    Vicencio, Alfin G; Tozzi, Meghan; Thompson, Cecilia; Satchell, Margaret; Delbello, David; Ting, Andrew; Harkin, Timothy J

    2014-10-01

    Alveolo-pleural fistula is a common complication of severe pulmonary infection. Some patients require long-term placement of chest tubes until spontaneous closure of the fistula takes place, whereas others require surgical intervention. We report a case of a patient with alveolo-pleural fistula secondary to Pneumocystis jirovecii pneumonia who was successfully treated with the use of intrabronchial unidirectional valves inserted using flexible bronchoscopy. PMID:25321456

  18. 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

  19. Validation of the MycAssay Pneumocystis kit for detection of Pneumocystis jirovecii in bronchoalveolar lavage specimens by comparison to a laboratory standard of direct immunofluorescence microscopy, real-time PCR, or conventional PCR.

    PubMed

    McTaggart, Lisa R; Wengenack, Nancy L; Richardson, Susan E

    2012-06-01

    Pneumocystis jirovecii pneumonia is a significant cause of morbidity and mortality in AIDS patients as well as those with non-HIV immunosuppressive diseases. To aid diagnosis, the commercial MycAssay Pneumocystis real-time PCR assay (Myconostica, Ltd., Manchester, United Kingdom) targeting the mitochondrial ribosomal large subunit (mtLSU) has been developed to detect P. jirovecii in bronchoalveolar lavage (BAL) specimens. Here, we validated this assay against a laboratory standard of direct immunofluorescence microscopy, a cdc2 real-time PCR assay, or conventional PCR and sequencing of mtLSU. While more sensitive than any of these three assays analyzed individually, the MycAssay Pneumocystis assay demonstrated 100% sensitivity, 100% specificity, a 100% negative predictive value, and a 100% positive predictive value for detecting the presence of P. jirovecii in BAL specimens compared to the laboratory standard. Of note, two samples with positive cycle threshold (C(T)) values according to the MycAssay Pneumocystis assay lacked exponential amplification curves and thus were deemed negative. Also negative according to the laboratory standard, these samples highlight the importance of examining the amplification curves, in addition to noting the C(T) values, when interpreting positive results. Comparison of the MycAssay Pneumocystis assay to a laboratory standard establishes this assay to be a highly sensitive and specific method for the detection of P. jirovecii in bronchoalveolar lavage specimens. The approach may also be useful for the clinical laboratory validation of other sensitive real-time PCR assays. PMID:22422855

  20. Type I IFNs Act upon Hematopoietic Progenitors To Protect and Maintain Hematopoiesis during Pneumocystis Lung Infection in Mice.

    PubMed

    Prigge, Justin R; Hoyt, Teri R; Dobrinen, Erin; Capecchi, Mario R; Schmidt, Edward E; Meissner, Nicole

    2015-12-01

    Although acquired bone marrow failure (BMF) is considered a T cell-mediated autoimmune disease, few studies have considered contributing roles of innate immune deviations following otherwise innocuous infections as a cause underlying the immune defects that lead to BMF. Type I IFN signaling plays an important role in protecting hematopoiesis during systemic stress responses to the opportunistic fungal pathogen Pneumocystis. During Pneumocystis lung infection, mice deficient in both lymphocytes and type I IFN receptor (IFrag(-/-)) develop rapidly progressing BMF associated with accelerated hematopoietic cell apoptosis. However, the communication pathway eliciting the induction of BMF in response to this strictly pulmonary infection has been unclear. We developed a conditional-null allele of Ifnar1 and used tissue-specific induction of the IFrag(-/-) state and found that, following Pneumocystis lung infection, type I IFNs act not only in the lung to prevent systemic immune deviations, but also within the progenitor compartment of the bone marrow to protect hematopoiesis. In addition, transfer of sterile-filtered serum from Pneumocystis-infected mice as well as i.p. injection of Pneumocystis into uninfected IFrag(-/-) mice induced BMF. Although specific cytokine deviations contribute to induction of BMF, immune-suppressive treatment of infected IFrag(-/-) mice ameliorated its progression but did not prevent loss of hematopoietic progenitor functions. This suggested that additional, noncytokine factors also target and impair progenitor functions; and interestingly, fungal β-glucans were also detected in serum. In conclusion, our data demonstrate that type 1 IFN signaling protects hematopoiesis within the bone marrow compartment from the damaging effects of proinflammatory cytokines elicited by Pneumocystis in the lung and possibly at extrapulmonary sites via circulating fungal components. PMID:26519535

  1. 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

  2. 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. PMID:26654847

  3. Pneumocystis Elicits a STAT6-Dependent, Strain-Specific Innate Immune Response and Airway Hyperresponsiveness

    PubMed Central

    Meissner, Nicole N.; Siemsen, Dan W.; McInnerney, Kate; Harmsen, Allen G.

    2012-01-01

    It is widely held that exposure to pathogens such as fungi can be an agent of comorbidity, such as exacerbation of asthma or chronic obstructive pulmonary disease. Although many studies have examined allergic responses to fungi and their effects on pulmonary function, the possible pathologic implications of the early innate responses to fungal pathogens have not been explored. We examined early responses to the atypical fungus Pneumocystis in two common strains of mice in terms of overall immunological response and related pathology, such as cell damage and airway hyperresponsiveness (AHR). We found a strong strain-specific response in BALB/c mice that included recruitment of neutrophils, NK, NKT, and CD4 T cells. This response was accompanied by elevated indicators of lung damage (bronchoalveolar lavage fluid albumin and LDH) and profound AHR. This early response was absent in C57BL/6 mice, although both strains exhibited a later response associated with the clearance of Pneumocystis. We found that this AHR could not be attributed exclusively to the presence of recruited neutrophils, NKT, NK, or CD4 cells or to the actions of IFN-γ or IL-4. However, in the absence of STAT6 signaling, AHR and inflammatory cell recruitment were virtually absent. Gene expression analysis indicated that this early response included activation of several transcription factors that could be involved in pulmonary remodeling. These results show that exposure to a fungus such as Pneumocystis can elicit pulmonary responses that may contribute to morbidity, even without prior sensitization, in the context of certain genetic backgrounds. PMID:21960549

  4. 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

  5. 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

  6. 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. PMID:27252684

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

    PubMed

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

    2015-12-01

    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 × 10(4) 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 × 10(4) and 3.39 × 10(3) 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

  8. Performances of Four Real-Time PCR Assays for Diagnosis of Pneumocystis jirovecii Pneumonia.

    PubMed

    Sasso, Milène; Chastang-Dumas, Elsa; Bastide, Sophie; Alonso, Sandrine; Lechiche, Catherine; Bourgeois, Nathalie; Lachaud, Laurence

    2016-03-01

    Pneumonia due to Pneumocystis jirovecii (PCP) is a frequent infection among HIV-positive or other immunocompromised patients. In the past several years, PCR on pulmonary samples has become an essential element for the laboratory diagnosis of PCP. Nevertheless, very few comparative studies of available PCR assays have been published. In this work, we evaluated the concordance between four real-time PCR assays, including three commercial kits, AmpliSens, MycAssay, and Bio-Evolution PCR, and an in-house PCR (J. Fillaux et al. 2008, J Microbiol Methods 75:258-261, doi:http://dx.doi.org/10.1016/j.mimet.2008.06.009), on 148 pulmonary samples. The results showed concordance rates ranging from 81.6% to 96.6% (kappa, 0.64 to 0.93). Concordance was excellent between three assays: the in-house assay, AmpliSens, and the MycAssay PCR (kappa, >0.8). The performances of these PCR assays were also evaluated according to the classification of the probability of PCP (proven, probable, possible, or no final diagnosis of PCP) based on clinical and radiological signs as well as on the direct examination of bronchoalveolar lavage samples. In the proven PCP category, Pneumocystis jirovecii DNA was detected with all four assays. In the probable PCP category, the in-house PCR, AmpliSens, and the MycAssay PCR were positive for all samples, while the Bio-Evolution PCR failed to detect Pneumocystis jirovecii DNA in two samples. In the possible PCP category, the percentage of positive samples according to PCR varied from 54.5% to 86.4%. Detection of colonized patients is discussed. Finally, among the four evaluated PCR assays, one was not suitable for colonization detection but showed good performance in the proven and probable PCP groups. For the three other assays, performances were excellent and allowed detection of a very low fungal burden. PMID:26719435

  9. A case of interstitial pneumonia associated with Pneumocystis carinii in a foal.

    PubMed

    Perron Lepage, M F; Gerber, V; Suter, M M

    1999-11-01

    Subacute interstitial pneumonia with diffuse alveolar damage, marked macrophage infiltration, and intracellular Pneumocystis carinii cysts is described in a 3-month-old Swiss warmblood foal. Clinically, the disease was characterized by sudden onset of respiratory distress with fatal outcome. Based on serum immunoglobulin G (IgG), IgA, and IgM values, no humoral immunosuppression was detected. Spleen, thymus, and bronchial lymph nodes did not reveal lymphoid depletion, as assessed by immunohistochemical staining of CD-3-positive cells. Immunopathogenesis of pulmonary infections with intracellular agents in foals is discussed. PMID:10568448

  10. Diamidines versus Monoamidines as Anti-Pneumocystis Agents: An in vivo Study

    PubMed Central

    Stanicki, Dimitri; Pottier, Muriel; Gantois, Nausicaa; Pinçon, Claire; Forge, Delphine; Mahieu, Isabelle; Boutry, Sébastien; Vanden Eynde, Jean Jacques; Martinez, Anna; Dei-Cas, Eduardo; Aliouat, El-Moukhtar

    2013-01-01

    Some compounds articulated around a piperazine or an ethylenediamine linker have been evaluated in vitro to determine their activity in the presence of a 3T6 fibroblast cell line and an axenic culture of Pneumocystis carinii, respectively. The most efficient antifungal derivatives, namely N,N′-bis(benzamidine-4-yl)ethane-1,2-diamine (compound 6, a diamidine) and N-(benzamidine-4-yl)-N′-phenylethane-1,2-diamine (compound 7, a monoamidine), exhibited no cytotoxicity and were evaluated in vivo in a rat model. Only the diamidine 6 emerged as a promising hit for further studies. PMID:24276317

  11. 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. PMID:14631621

  12. Quantification and assessment of viability of Pneumocystis carinii organisms by flow cytometry.

    PubMed

    Lapinsky, S E; Glencross, D; Car, N G; Kallenbach, J M; Zwi, S

    1991-05-01

    Analysis of drug efficacy in animal models of Pneumocystis carinii pneumonia requires an accurate method of quantification of organisms, as well as a means of assessing viability. Lung homogenates were prepared from a colony of athymic nude F344 rats experiencing a spontaneous outbreak of P. carinii pneumonia. With the fluorescent nucleic acid stain propidium iodide, flow cytometric analysis was able to quantify P. carinii cysts and trophozoites reproducibly. As this stain is excluded by living cells, this method was also used to assess the viability of organisms. Application of this technique to analysis of bronchoalveolar lavage specimens was demonstrated. PMID:2056058

  13. [Disseminated Pneumocystis carinii infection: clinico-pathologic findings in an AIDS patient].

    PubMed

    Valdès, E; Borzoni, F; Onnis, D; Piras, S; Vespa, A; Varsi, C

    1994-12-01

    Pneumocystis carinii pneumonia (PcP) is the most frequent cause of death in AIDS patients. Systemic diffusion of this microorganism is a rare event, mostly reported in patients receiving prophylactic aerosol therapy. The case here described is relative to a 29 years old man with AIDS, dead short by after hospital admission. Radiological and ecoscan examinations revealed structural subversion of liver and spleen, with frequent parenchymal calcification. Post mortem histological examination of lung, liver, spleen, heart, bone marrow, lymph nodes, kidney and hypophysis identified the presence of Pc, confirmed by monoclonal specified antibody immunostaining. PMID:7617399

  14. 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.

  15. Poor rectal absorption of trimethoprim/sulphamethoxazole in treating Pneumocystis carinii pneumonia.

    PubMed Central

    Dorr, R. T.; Powell, J. R.; Heick, M.; Barry, D. W.

    1981-01-01

    A 24-year-old female with Hodgkin's disease and Pneumocystis carinii pneumonia was tested with trimethoprim/sulphamethoxazole (TMP/SMX) tablets. Because treatment failure was feared owing to chronic emesis potentially resulting in incomplete drug absorption, the same TMP/SMX dose was administered by rectal suppositories after the 5th day of oral dosing. The relative fractions (rectal/oral) or the suppository dose absorbed for TMP and SMX were 3.0% and 19.5% respectively. When TMP/SMX treatment is required and the oral route is not practical, the investigational i.v. preparation should be obtained. PMID:6973756

  16. Development and Evaluation of a Direct Fluorescent Antibody Method for the Diagnosis of Pneumocystis carinii Infections in Experimental Animals

    PubMed Central

    Lim, Sook Kyung; Eveland, Warren C.; Porter, Richard J.

    1973-01-01

    Because no fully satisfactory diagnostic method has been available for use in pneumocystis infection, an attempt was made to apply the fluorescent antibody technique in the identification of Pneumocystis carinii. Hyperimmune sera were prepared in rabbits against P. carinii from human and rat sources. After proper adsorption, these antisera were conjugated with fluorescein isothiocyanate and used as reagents in a direct fluorescent antibody procedure. Each of the two reagents was found to stain trypsin-treated P. carinii organisms from either human or rat sources, indicating the presence of common antigens. Stained organisms were demonstrated in the hypopharyngeal material from rats in which pneumocystis infection had been activated by the administration of corticosteroid. From the results reported here, the procedure outlined is considered sufficiently sensitive and specific to justify tests on pneumocystis infections in man. The findings in a series of specimens from human subjects will be reported separately. The method also provides an extended approach to related research problems. The need for controls of the procedure at all points is emphasized. Images PMID:4202704

  17. 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.

  18. Mutations in the Pneumocystis jirovecii DHPS Gene Confer Cross-Resistance to Sulfa Drugs

    PubMed Central

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

    2005-01-01

    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 (T517A or P519S) 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. PMID:15673759

  19. Myeloid-Derived Suppressor Cells Impair Alveolar Macrophages through PD-1 Receptor Ligation during Pneumocystis Pneumonia

    PubMed Central

    Lei, Guang-Sheng; Zhang, Chen

    2014-01-01

    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. PMID:25404033

  20. Do inhaled corticosteroids increase the risk of Pneumocystis pneumonia in people with lung cancer?

    PubMed Central

    Msaad, Sameh; Yangui, Ilhem; Bahloul, Najla; Abid, Narjes; Koubaa, Makram; Hentati, Yosr; Ben Jemaa, Mounir; Kammoun, Samy

    2015-01-01

    Pneumocystis pneumonia (PCP) is a life-threatening infection in immunocompromised patients. It is relatively uncommon in patients with lung cancer. We report a case of PCP in a 59-year-old man with a past medical history of chronic obstructive pulmonary disease treated with formoterol and a moderate daily dose of inhaled budesonide. He had also advanced stage non-small lung cancer treated with concurrent chemo-radiation with a cisplatin-etoposide containing regimen. The diagnosis of PCP was suspected based on the context of rapidly increasing dyspnea, lymphopenia and the imaging findings. Polymerase chain reaction testing on an induced sputum specimen was positive for Pneumocystis jirovecii. The patient was treated with oral trimethoprim-sulfamethoxazole and systemic corticotherapy and had showed clinical and radiological improvement. Six months after the PCP diagnosis, he developed a malignant pleural effusion and expired on hospice care. Through this case, we remind the importance of screening for PCP in lung cancer patients under chemotherapeutic regimens and with increasing dyspnea. In addition, we alert to the fact that long-term inhaled corticosteroids may be a risk factor for PCP in patients with lung cancer. Despite intensive treatment, the mortality of PCP remains high, hence the importance of chemoprophylaxis should be considered. PMID:26380833

  1. Activity of Hoechst 33258 against Pneumocystis carinii f. sp. muris, Candida albicans, and Candida dubliniensis

    PubMed Central

    Disney, Matthew D.; Stephenson, Ruth; Wright, Terry W.; Haidaris, Constantine G.; Turner, Douglas H.; Gigliotti, Francis

    2005-01-01

    Hoechst 33258 is a compound that binds nucleic acids. We report that Hoechst 33258 exhibits antimicrobial activity against Pneumocystis carinii f. sp. muris in a mouse model for P. carinii pneumonia and against Candida albicans and Candida dubliniensis in vitro. Relative to saline treatment, a 14-day, daily treatment of mice with 37.5 mg of Hoechst 33258/kg of body weight after inoculation with P. carinii reduced by about 100-fold the number of P. carinii organisms detected by either PCR or by microscopy after silver staining. For comparison, treatment based on a dose of 15 to 20 mg of the trimethoprim component in trimethoprim-sulfamethoxazole/kg reduced the number of P. carinii by about fourfold. In vitro inhibition of P. carinii group I intron splicing was observed with a 50% inhibitory concentration (IC50)of 30 μM in 2 or 4 mM Mg2+, suggesting RNA as a possible target. However, Hoechst 33258 inhibits growth of Candida strains with and without group I introns. IC50s ranged from 1 to 9 μM for strains with group I introns and were 12 and 32 μM for two strains without group I introns. These studies demonstrate that compounds that bind fungal nucleic acids have the potential to be developed as new therapeutics for Pneumocystis and possibly other fungi, especially if they could be directed to structures that are not present in mammalian cells, such as self-splicing introns. PMID:15793106

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

    PubMed

    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

  3. 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. PMID:26724988

  4. 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

  5. Assembly and Annotation of Pneumocystis jirovecii from the Human Lung Microbiome

    PubMed Central

    Cushion, Melanie T.; Keely, Scott P.

    2013-01-01

    ABSTRACT Pneumocystis jirovecii is a fungus that causes Pneumocystis pneumonia in immunosuppressed patients and has been closely associated with AIDS since the beginning of the AIDS epidemic. Because in vitro cultivation of P. jirovecii is not possible, progress has been hindered in our understanding of its life cycle, mode of transmission, metabolic function, and genome. Limited amounts of P. jirovecii can be obtained from infected patients, but the occurrence of bacteria, other fungi, and human cells in clinical samples presents new challenges for whole-genome sequencing and downstream bioinformatic analysis. In a recent article, Cissé et al. used cell immunoprecipitation enrichment together with whole-genome amplification to generate sufficient quantities of DNA for Roche 454 and Illumina sequencing [O. H. Cissé, M. Pagni, and P. M. Hauser, mBio 4(1):e00428-12, 2012, doi:10.1128/mBio.00428-12]. In addition, a bioinformatic pipeline was devised to sort and assemble lung microbiome reads, thereby generating an 8.1-Mb P. jirovecii genome comprised of 356 contigs with an N50 (median length of all contigs) of 41.6 kb. Knowledge of this genome will open new avenues of research, including the identification of nutritional requirements for in vitro cultivation as well as the identification of new and novel drug and vaccine targets. PMID:23592264

  6. Reduction in intensity of Pneumocystis carinii pneumonia in mice by aerosol administration of gamma interferon.

    PubMed Central

    Beck, J M; Liggitt, H D; Brunette, E N; Fuchs, H J; Shellito, J E; Debs, R J

    1991-01-01

    Pneumocystis carinii pneumonia in patients with AIDS may result from impaired local release of gamma interferon from lung lymphocytes and subsequent failure of macrophage activation. We tested this hypothesis with mice rendered immunodeficient by selective depletion of CD4+ lymphocytes and inoculated intratracheally with P. carinii. After aerosol administration of recombinant murine gamma interferon, the intensity of P. carinii infection in these mice was reduced in comparison with that in mice not treated with gamma interferon. Histologic scoring of lung tissue did not reveal additional pulmonary inflammation attributable to gamma interferon. Aerosol administration of gamma interferon may reduce the intensity of P. carinii infection by augmentation of host defense, despite persistent CD4+ lymphocyte depletion. Images PMID:1682252

  7. High prevalence of Pneumocystis jirovecii colonization in Brazilian cystic fibrosis patients.

    PubMed

    Pederiva, Marco A; Wissmann, Gustavo; Friaza, Vicente; Morilla, Rubem; de La Horra, Carmen; Montes-Cano, Marco A; Goldani, Luciano Z; Calderón, Enrique J; Prolla, João C

    2012-07-01

    A high rate of Pneumocystis jirovecii colonization was observed in Brazilian cystic fibrosis (CF) patients (13 out of 34; 38.2%) who underwent bronchoscopy between March 2006 and August 2009 at the Hospital de Clinicas de Porto Alegre, Brazil. Bronchoalveolar lavage samples were collected from these patients and studied by nested PCR amplification of the mitochondrial gene coding for the large subunit ribosomal RNA (mtLSUrDNA). The observed rate of colonization was higher than that reported in European populations. Genotypic characterization of the mtLSUrDNA locus revealed a predominance of the polymorphisms 85C/248C (genotype 1) and 85T/248C (genotype 3), with all samples possessing the wild-type genotype of dihydropteroate synthase. These findings suggest that cystic fibrosis patients could be an important reservoir and source of P. jirovecii infection. Further studies are required to elucidate the role of this common fungal colonization in the evolution of CF patients. PMID:22206262

  8. Genetic variation in Pneumocystis carinii isolates from different geographic regions: implications for transmission.

    PubMed Central

    Beard, C. B.; Carter, J. L.; Keely, S. P.; Huang, L.; Pieniazek, N. J.; Moura, I. N.; Roberts, J. M.; Hightower, A. W.; Bens, M. S.; Freeman, A. R.; Lee, S.; Stringer, J. R.; Duchin, J. S.; del Rio, C.; Rimland, D.; Baughman, R. P.; Levy, D. A.; Dietz, V. J.; Simon, P.; Navin, T. R.

    2000-01-01

    To study transmission patterns of Pneumocystis carinii pneumonia (PCP) in persons with AIDS, we evaluated P. carinii isolates from patients in five U.S. cities for variation at two independent genetic loci, the mitochondrial large subunit rRNA and dihydropteroate synthase. Fourteen unique multilocus genotypes were observed in 191 isolates that were examined at both loci. Mixed infections, accounting for 17.8% of cases, were associated with primary PCP. Genotype frequency distribution patterns varied by patients' place of diagnosis but not by place of birth. Genetic variation at the two loci suggests three probable characteristics of transmission: that most cases of PCP do not result from infections acquired early in life, that infections are actively acquired from a relatively common source (humans or the environment), and that humans, while not necessarily involved in direct infection of other humans, are nevertheless important in the transmission cycle of P. carinii f. sp. hominis. PMID:10827116

  9. Pneumocystis jirovecii genotype associated with increased death rate of HIV-infected patients with pneumonia.

    PubMed

    Rabodonirina, Meja; Vaillant, Laetitia; Taffé, Patrick; Nahimana, Aimable; Gillibert, René-Pierre; Vanhems, Philippe; Hauser, Philippe M

    2013-01-01

    Pneumocystis jirovecii dihydropteroate synthase (DHPS) mutations have been associated with failure of sulfa prophylaxis; their effect on the outcome of patients with P. jirovecii pneumonia (PCP) remains controversial. P. jirovecii DHPS polymorphisms and genotypes were identified in 112 cases of PCP in 110 HIV-infected patients by using PCR single-strand conformation polymorphism. Of the 110 patients observed, 21 died; 18 of those deaths were attributed to PCP. Thirty-three percent of the PCP cases involved a P. jirovecii strain that had 1 or both DHPS mutations. The presence or absence of DHPS mutations had no effect on the PCP mortality rate within 1 month, whereas P.jirovecii type 7 and mechanical ventilation at PCP diagnosis were associated with an increased risk of death caused by PCP. Mechanical ventilation at PCP diagnosis was also associated with an increased risk of sulfa treatment failure at 5 days. PMID:23260763

  10. Common variable immune deficiency in a Pomeranian with Pneumocystis carinii pneumonia

    PubMed Central

    KANEMOTO, Hideyuki; MORIKAWA, Rei; CHAMBERS, James Kenn; KASAHARA, Koichi; HANAFUSA, Yasuko; UCHIDA, Kazuyuki; OHNO, Koichi; NAKAYAMA, Hiroyuki

    2015-01-01

    A Pomeranian dog, 1 year- and 8 month-old neutered female, was presented with persistent respiratory distress and recurrent generalized demodicosis. Physical examination revealed cyanosis, rough respiratory sounds, multifocal alopecia and dermal erosions on the dorsal side of the forelimbs, perineal area and skin around the eyes. A severe diffuse interstitial lung pattern was observed on thoracic radiographs. The blood examination revealed neutrophilia and hypoglobulinemia. Serum immunoglobulin concentrations of IgG and IgA were low. Histopathological examination revealed severe diffuse interstitial pneumonia with Pneumocystis carinii infection. Severe lymphoid depletion was observed in the spleen and other organs with lymphoid follicles consisted mainly of CD3-positive T cells and few cells of B-cell lineage. B-cell hypoplasia with subsequent antibody deficiency was suspected. PMID:25715954

  11. Lung and chest wall mechanics in patients with acquired immunodeficiency syndrome and severe Pneumocystis carinii pneumonia.

    PubMed

    D'Angelo, E; Calderini, E; Robatto, F M; Puccio, P; Milic-Emili, J

    1997-10-01

    The aim of this study was to assess the mechanical characteristics of the respiratory system in patients with acquired immune deficiency syndrome (AIDS) and acute respiratory distress syndrome (ARDS) caused by Pneumocystis carinii pneumonia (PCP). In 12 mechanically ventilated patients, total respiratory system mechanics was assessed using the technique of rapid airway occlusion during constant flow inflation, and was partitioned into lung and chest wall components using the oesophageal balloon technique. We measured interrupter resistance (Rint), which mainly reflects airway resistance, additional resistance (deltaR) due to viscoelastic behaviour and time constant inequalities, and static elastance (Est). In addition, the static inflation volume-pressure (V-P) curve was assessed. In eight patients, computed tomography scans were performed within 2 days of the assessment of respiratory mechanics. Compared to values reported in the literature for normal subjects, Est and deltaR were markedly increased in AIDS patients with PCP, whilst Rint exhibited a relatively smaller increase. These changes, which involved only the lung and airways, were mainly due to the reduction of ventilated lung units, but additional factors were involved to cause independent modifications of lung stiffness, airway calibre, and viscoelastic properties. The changes in Rint, deltaR, and Est were similar to those observed in other studies on patients with ARDS of different aetiologies. At variance with common observations in the latter patients, none of the AIDS patients with PCP exhibited an inflection point on the static inflation V-P curve, suggesting little or no alveolar recruitment during lung inflation. This finding could be related to the distinctive histopathology of Pneumocystis carinii pneumonia. Indeed, computed tomography revealed homogeneous diffuse interstitial and alveolar infiltration rather than the dense, dependent opacities observed in other studies on acute respiratory

  12. Simple detection of the 5S ribosomal RNA of Pneumocystis carinii using in situ hybridisation.

    PubMed Central

    Kobayashi, M; Urata, T; Ikezoe, T; Hakoda, E; Uemura, Y; Sonobe, H; Ohtsuki, Y; Manabe, T; Miyagi, S; Miyoshi, I

    1996-01-01

    AIMS: To investigate the effectiveness of digoxigenin incorporated double stranded DNA probes produced by the polymerase chain reaction (PCR), for the detection of Pneumocystis carinii, using in situ hybridisation (ISH). METHODS: Formalin fixed, paraffin wax embedded sections of 26 human lung samples from 11 patients with P carinii pneumonia (PCP), and 15 with various types of fungal and viral pneumonia, were obtained during necropsy or transbronchial lung biopsy. Three additional PCP induced rat lung samples were also tested. PCR probes were prepared using the digoxigenin labelling mixture, and they were amplified from the DNA of a PCP induced rat lung after administration of dexamethasone, on the basis that 5S ribosomal RNA sequences are identical in human and rat P carinii. ISH was performed using this probe, and visualised using the digoxigenin nucleic acid detection kit. An immunohistochemical study using anti-human Pneumocystis monoclonal antibody was also carried out in parallel. RESULTS: ISH positively stained eight (of eight) lung necropsy specimens from patients with PCP, three (of three) transbronchial lung biopsy specimens from patients with PCP, and none of the three PCP induced rat lung specimens. In contrast, none of the specimens from patients with pneumonia caused by Aspergillus sp (n = 5), Candida sp (n = 4), Cryptococcus sp (n = 2), mucormycosis (n = 2), or cytomegalovirus (n = 2) were positive on ISH or immunohistochemistry. CONCLUSIONS: Using a digoxigenin labelled PCR probe for the entire 5S rRNA sequence in conjunction with conventional staining, ISH is highly reactive and specific for the diagnosis of PCP. Images PMID:9038753

  13. Usefulness of FTA® cards as a Pneumocystis-DNA extraction method in bronchoalveolar lavage samples.

    PubMed

    Rodiño, Jenniffer M; Aguilar, Yudy A; Rueda, Zulma Vanessa; Vélez, Lázaro A

    2016-05-01

    Background FTA® cards (Fast Technology for Analysis of Nucleic Acids) are an alternative DNA extraction method in bronchoalveolar lavage (BAL) samples for Pneumocystis jirovecii molecular analyses. The goal was to evaluate the usefulness of FTA® cards to detect P. jirovecii-DNA by PCR in BAL samples compared to silica adsorption chromatography (SAC). Methods This study used 134 BAL samples from immunocompromised patients previously studied to establish microbiological aetiology of pneumonia, among them 15 cases of Pneumocystis pneumonia (PCP) documented by staining and 119 with other alternative diagnoses. The FTA® system and SAC were used for DNA extraction and then amplified by nested PCR to detect P. jirovecii. Performance and concordance of the two DNA extraction methods compared to P. jirovecii microscopy were calculated. The influence of the macroscopic characteristics, transportation of samples and the duration of the FTA® card storage (1, 7, 10 or 12 months) were also evaluated. Results Among 134 BAL samples, 56% were positive for P. jirovecii-DNA by SAC and 27% by FTA®. All 15 diagnosed by microscopy were detected by FTA® and SAC. Specificity of the FTA® system and SAC were 82.4% and 49.6%, respectively. Compared to SAC, positivity by FTA® decreased with the presence of blood in BAL (62% vs 13.5%). The agreement between samples at 7, 10 and 12 months was 92.5% for FTA®. Positive cases by FTA® remained the same after shipment by mail. Conclusions Results suggest that FTA® is a practical, safe and economical method to preserve P. jirovecii-DNA in BAL samples for molecular studies. PMID:26950684

  14. [Pneumocystis carinii pneumonia in AIDS: retrospective analysis of 80 documented cases (1985-1993)].

    PubMed

    Morlat, P; Bartou, C; Ragnaud, J M; Dequae, L; Lacoste, D; Buisson, M; Bernard, N; Mercié, P; Couprie, B; Beylot, J; Aubertin, J

    1996-01-01

    Eighty initial episodes of HIV-associated Pneumocystis carinii pneumonia (PCP) diagnosed at Bordeaux hospital between 1985 and 1993 are reported (57 were men and 23 women). PCP revealed HIV infection in 29 patients (36%). Others cases were patients with poor medical follow up (10%), with a CD4+ lymphocyte count above 200/mm3 at last follow-up (9%), non compliant with PCP prophylaxis (9%), or using aerolized pentamidine (AP+) (20%). The main clinical symptoms were fever (90%), dyspnea (68%), non productive (63%) and productive (17%) cough. Radiographic infiltrates were purely interstitial (59%), acinar and interstitial (25%), purely acinar (5%) and absent (11%). Thirty-eight percent of AP+ had upper lobe preferential involvement and 13% a pleural effusion. In all cases, Pneumocystis carinii was detected in bronchoalveolar lavage. Extrapulmonary localizations of pneumocystosis were noticed (eye, liver, spleen, ascitis) in two AP+. Mean CD4+ count was 54/mm3 in patients not having received aerolized pentamidine (AP-) and 22/mm3 in AP+. P24 antigenemia was positive in 53% (AP-) and 88% (AP+). PaO2 LDH and albuminemia were similar in both groups. Antimicrobial therapy (Cotrimoxazole in 91% of the cases) was combined with corticosteroids in 45% and mechanic ventilation in 19%. After 30 days of follow-up, 17 deaths were observed (21%) and 14 attributed to PCP: mortality was worse in AP+ (31%) than in AP- (19%). The main conclusions of our study are the followings: HIV related PCP is still in 1995 frequent and severe; atypical features should not rule out diagnosis; preventive measures are neither sufficient nor efficient. PCP remains in 1995 a priority in HIV related public health and therapeutical research. PMID:8677382

  15. 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. PMID:26215665

  16. Pneumocystis and Pneumocystosis: first meeting of experts from Latin-American and Portuguese-speaking countries - a mini-review.

    PubMed

    Esteves, Francisco; Medrano, Francisco J; de Armas, Yaxsier; Wissmann, Gustavo; Calderón, Enrique J; Matos, Olga

    2014-05-01

    The Pneumocystis and Pneumocystosis: first meeting of experts from Latin-American and Portuguese-speaking countries was held in Lisbon, Portugal, on 24-26 October 2013. A total of 20 speakers from Latin America, Africa and Europe participated in the meeting. The epidemiological studies presented in this meeting begin to change the misconception that since the AIDS epidemic, Pneumocystis pneumonia (PcP) has become an infrequent disease, showing that today PcP remains a major opportunistic infection in HIV-infected patients in both developed and developing countries and an emerging problem in immunocompromised patients without HIV infection worldwide. PcP management remains a challenge. Right now, the combination of caspofungin and trimethoprim-sulfamethoxazole (TMP-SMX) is a promising therapeutic approach that needs to be assessed in controlled clinical trials. PMID:24617414

  17. 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.

  18. 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

  19. [Life threatening pneumocystis carinii pneumonia in a 4-month-old boy with hyper-IgM syndrome].

    PubMed

    Heiming, R; Beuschausen, T; Liebner, T; Seidenberg, J; Roesler, J

    1993-11-01

    At the age of four months, a boy with a normal history and family history, suddenly fell ill with a life-threatening pneumocystis carinii-pneumonia. Surprisingly, this opportunistic infection was not brought about by a T-cell deficiency. However, the patient's diagnosis turned out to be the rare "Hyper-IgM-syndrome", confirmed by: serum levels of IgM always at least normal whereas IgG, IgA and IgE were markedly decreased or absent; the development of neutropenia and occasional diarrhea. Generally, infections with pneumocystis carinii are rare in isolated deficiencies of immunoglobulines, but relatively frequent in primary "Hyper-IgM-syndrome" (approx. 12% of the cases described). The boy finally recovered after receiving Cotrimoxacol (20 mg/kg bw/d) in an intensive care unit. Now, at the age of nearly two his condition is almost good under regular substitution of IgG. Cotrimoxacol (4 mg/kg bw/d) is recommended to prevent further pneumocystis carinii infections and most of the pathogenes which frequently appear in neutropenias. PMID:8283991

  20. Pneumocystis Pneumonia

    MedlinePlus

    ... Outcomes Health Professionals Statistics More Resources en Español Definición Síntomas Las Personas en Riesgo y Prevención Fuentes Diagnóstico y Exámenes Tratamiento y Resultados Profesionales de la Salud Estadísticas C. neoformans Infection Definition Symptoms People at ...

  1. Effect of a killer toxin of Pichia anomala to Pneumocystis. Perspectives in the control of pneumocystosis.

    PubMed

    Séguy, N; Polonelli, L; Dei-Cas, E; Cailliez, J C

    1998-09-01

    Despite the development of drugs in the prophylaxis of pneumocystosis, Pneumocystis carinii remains a major opportunistic microorganism in immunosuppressed individuals, especially in human immunodeficiency virus-infected patients. Since side effects were frequently observed after administration of trimethoprim-sulfamethoxazole or pentamidine, the drugs which are mainly used in treating human P. carinii pneumonia (PCP), new therapeutic strategies should be developed. Over the last years, the inhibitory effect of a Pichia anomala killer toxin (PaKT), a molecule with a wide spectrum of antimicrobial activity, was characterized on P. carinii. The susceptibility of mouse and rat-derived Pneumocystis to PaKT has been demonstrated by in vitro attachment tests and in vivo infectivity assays. Nevertheless, PaKT is strongly antigenic, toxic and could not be used directly as a therapeutic agent. Then, a new strategy using killer toxin-like anti-idiotypic antibodies (KT-antiIds) mimicking the fungal toxin activity has been developed. Different KT-antiIds were obtained by idiotypic immunization with a monoclonal antibody (mabKT4). This mabKT4 neutralized the killer properties of the PaKT. KT-antiIds were produced by immunization against the variable domain (idiotype) of mAbKT4 (internal image of the killer toxin receptor), or they were obtained directly from vaginal fluid of patients affected by recurrent vaginal candidiosis. In this last case, such natural KT-antiIds were immunopurified by affinity-chromatography with mAbKT4 and their anti-P. carinii activity was then evaluated. Our results showed that both the in vitro attachment of rat-derived parasites and their infectivity to nude rats were inhibited by the KT-antiIds. With regard to KT-antiIds obtained by immunization, the antimicrobial activity of a monoclonal KT-antiIds (mAbK10) has been evaluated by using a PCP experimental nude rat model treated by mAbK10 administered by aerosol. The pneumocystosis extension was

  2. 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. PMID:26687815

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

    PubMed

    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

  4. Detection of Pneumocystis carinii DNA in sputum and bronchoalveolar lavage samples by polymerase chain reaction.

    PubMed Central

    Olsson, M; Elvin, K; Löfdahl, S; Linder, E

    1993-01-01

    A polymerase chain reaction (PCR)-based assay was developed for the detection of Pneumocystis carinii DNA in induced sputum and bronchoscopic alveolar lavage samples. The primer pair was selected from the published sequence of the thymidylate synthase gene of P. carinii derived from infected rats. The amplified DNA fragment of 403 bp was detected by agarose gel electrophoresis and by Southern and slot blot hybridization. No positive reaction was seen with DNA from different microorganisms typically found in the respiratory tract. P. carinii DNA was demonstrated in 30 of 42 sputum samples from immunosuppressed patients, whereas 21 of 42 sputum samples were positive by indirect immunofluorescence (IFL). Among the 42 patients, 14 were receiving prophylactic chemotherapy. In that group, PCR detected P. carinii in nine sputum samples, whereas IFL detected P. carinii in only four sputum samples. A positive PCR result was also seen in 5 of 43 IFL-negative bronchoscopic alveolar lavage samples from patients with respiratory symptoms. The PCR assay detected 10 copies of the target DNA, which corresponds to 10(-18) g of the specific P. carinii sequence. The results indicate that PCR amplification in combination with DNA hybridization is specific and is a more sensitive diagnostic method than IFL for the detection of P. carinii. Images PMID:8432806

  5. 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. PMID:27550990

  6. Development and evaluation of a rapid and simple procedure for detection of Pneumocystis carinii by PCR.

    PubMed Central

    Cartwright, C P; Nelson, N A; Gill, V J

    1994-01-01

    We report the development of a simplified PCR-based assay for the detection of Pneumocystis carinii DNA in clinical specimens. The adoption of a rapid DNA extraction procedure and the introduction of a type of enzyme-linked immunosorbent assay for PCR product detection enabled this procedure to be carried out in a single working day in a clinical microbiology laboratory. The PCR assay was prospectively compared with an immunofluorescent-antibody (FA) staining method for the detection of P. carinii in induced sputum and bronchoalveolar lavage (BAL) specimens. The results of the study showed that, for induced sputum specimens, FA staining had a sensitivity of 78% (32 of 41 specimens) and a specificity of 100% (166 of 166 specimens); PCR was 100% (41 of 41 specimens) sensitive and 98% (162 of 166 specimens) specific. For BAL specimens, FA staining was 100% sensitive (21 of 21 specimens) and 100% specific (133 of 133 specimens), and PCR had a sensitivity of 100% (21 of 21 specimens) and a specificity of 99% (132 of 133 specimens). These results strongly suggest that use of our PCR-based assay could effect clinically useful improvements in the sensitivity of induced sputum specimens for the detection of P. carinii. Images PMID:7929749

  7. Clinically achievable plasma deferoxamine concentrations are therapeutic in a rat model of Pneumocystis carinii pneumonia.

    PubMed Central

    Merali, S; Chin, K; Del Angel, L; Grady, R W; Armstrong, M; Clarkson, A B

    1995-01-01

    The iron-chelating drug deferoxamine (DFO) has been shown to be active in animal models of Pneumocystis carinii pneumonia (PCP), with effective daily intraperitoneal bolus dosages being 400 and 1,000 mg of DFO mesylate kg of body weight-1 in mouse and rat models, respectively. Continuous infusion produced a moderately improved response in a rat model. The data reported here demonstrate that the response achieved by continuous infusion of 195 and 335 mg of DFO mesylate kg-1 day-1 in the rat model is associated with mean concentrations in plasma of 1.3 and 2.5 micrograms of DFO ml-1 and mean concentrations in lung tissue of 4.9 and 6.0 micrograms of DFO g of lung tissue-1, respectively. Since current clinical use of DFO mesylate for the treatment of iron overload produces higher concentrations in the plasma of patients, DFO may prove to be a useful anti-PCP treatment. The 2.4- to 3.8-fold higher DFO concentration observed in lung tissue compared with that observed in plasma may be important in the response of PCP to DFO. PMID:8540710

  8. 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

  9. 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

  10. Effects of Sulfamethoxazole-Trimethoprim on Airway Colonization with Pneumocystis jirovecii.

    PubMed

    Kushima, Hisako; Ishii, Hiroshi; Tokimatsu, Issei; Umeki, Kenji; Sato, Takako; Kadota, Jun-Ichi

    2016-05-20

    Reactivation of latent infection is considered to be the main mechanism underlying the development of Pneumocystis pneumonia in immunosuppressed patients. We retrospectively assessed the effects of prophylactic administration of sulfamethoxazole-trimethoprim on the development of P. pneumonia and airway colonization with P. jirovecii in patients undergoing examinations to diagnose or rule out P. pneumonia. Polymerase chain reaction was performed to detect P. jirovecii in bronchoalveolar lavage fluid or sputum of 60 consecutive patients between 2004 and 2012. No patients who received the prophylactic administration of sulfamethoxazole-trimethoprim (n = 10) developed P. pneumonia or demonstrated airway colonization with P. jirovecii, and none of the patients who developed P. pneumonia (n = 11) or showed colonization (n = 9) had received prophylactic treatment. Furthermore, 20 (40%) of 50 patients without prophylactic treatment showed positive results on the P. jirovecii DNA polymerase chain reaction, but all 10 patients who had prophylactic treatment showed negative results (Fisher's exact test, P = 0.02). Therefore, the prophylactic administration of sulfamethoxazole-trimethoprim has potential to be effective in preventing P. pneumonia as well as eliminating airway colonization with P. jirovecii. Further studies targeting large cohorts of patients with a variety of underlying diseases are required to develop recommendations regarding the prophylactic administration of sulfamethoxazole-trimethoprim. PMID:26255727

  11. Evaluation of an indirect fluorescent-antibody stain for detection of Pneumocystis carinii in respiratory specimens.

    PubMed Central

    Ng, V L; Yajko, D M; McPhaul, L W; Gartner, I; Byford, B; Goodman, C D; Nassos, P S; Sanders, C A; Howes, E L; Leoung, G

    1990-01-01

    Two prospective studies were undertaken to evaluate a commercial indirect fluorescent-antibody (IFA) stain for the detection of Pneumocystis carinii in respiratory specimens from individuals at risk for or with the acquired immunodeficiency syndrome. The first study compared IFA with Diff-Quik (DQ; a rapid Giemsa-like stain) for detecting P. carinii in 95 induced sputa obtained from 77 asymptomatic patients who had survived one previous episode of P. carinii pneumonia and who were being treated prophylactically with aerosolized pentamidine. Only one induced sputum specimen was found to contain P. carinii; organisms were detected by both stains. The second study compared the performance of the IFA stain versus DQ, modified toluidine blue O, and Gomori methenamine silver stains for detecting P. carinii in symptomatic individuals at risk for or with acquired immunodeficiency syndrome. Of 182 specimens examined, P. carinii was detected in 105 by one or more stains; the DQ stain detected 73 (70%), the modified toluidine blue O stain detected 75 (71%), the Gomori methenamine silver stain detected 76 (72%), and the IFA stain detected 95 (90%). The IFA stain was more sensitive (P less than 0.01) than the other traditional stains for detecting P. carinii; however, a subsequent clinical evaluation revealed that a subset of IFA-positive-only specimens were from patients whose clinical symptoms resolved without specific anti-P. carinii therapy. Images PMID:1693631

  12. 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. PMID:27550993

  13. Human immunodeficiency virus type 1 infection of human macrophages modulates the cytokine response to Pneumocystis carinii.

    PubMed Central

    Kandil, O; Fishman, J A; Koziel, H; Pinkston, P; Rose, R M; Remold, H G

    1994-01-01

    The present studies examined production of the cytokines tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and IL-6 by human monocyte-derived macrophages exposed to Pneumocystis carinii in vitro and the impact of concurrent macrophage infection with human immunodeficiency virus type 1 (HIV-1) on these cytokine responses. Macrophages were infected with the HIV-1 BaL monocytotropic strain for 10 to 14 days and then exposed to P. carinii. At various times following P. carinii treatment, culture supernatants were harvested to assess the cytokine profile. Addition of P. carinii to HIV-uninfected macrophages resulted in augmented production of IL-6, TNF-alpha, and IL-1 beta protein. By contrast, in HIV-infected macrophages exposed to P. carinii, only the release of IL-6 was increased compared with that for HIV-uninfected macrophages, while the levels of TNF-alpha and IL-1 beta decreased. This altered response was confirmed at the molecular level for TNF-alpha mRNA. Preventing physical contact between P. carinii and macrophages by a membrane filter inhibited all cytokine release. Substituting P. carinii with a preparation of P. carinii 95- to 115-kDa major membrane glycoprotein A yielded a response similar to that obtained by addition of intact P. carinii. These results suggest that HIV-1 infection of human macrophages modulates cytokine responses to P. carinii. Images PMID:8300221

  14. 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. PMID:26942578

  15. Intramuscular pentamidine for the prevention of Pneumocystis carinii pneumonia in patients infected with human immunodeficiency virus.

    PubMed

    Cheung, T W; Matta, R; Neibart, E; Hammer, G; Chusid, E; Sacks, H S; Szabo, S; Rose, D

    1993-01-01

    We retrospectively reviewed the charts of 96 patients infected with human immunodeficiency virus (HIV) who received intramuscular pentamidine for the prevention of Pneumocystis carinii pneumonia (PCP). These patients, all of whom had either a history of PCP or a CD4 lymphocyte count of < or = 0.2 x 10(9)/L, were intolerant of sulfa drugs, neutropenic, or intolerant of aerosolized treatment. Intramuscular pentamidine was given monthly by the Z-track technique at a dosage of 300 mg (4 mg/kg if the patient weighed < 50 kg). During a total of 350 months of primary prophylaxis in 47 patients and 426 months of secondary prophylaxis in 49 patients, only three cases of PCP occurred. More than 73% of the patients were receiving zidovudine concomitantly. Adverse reactions to intramuscular pentamidine included two episodes of hypotension, three of sterile abscess, two of glucose intolerance, and one of asymptomatic hypoglycemia. The administration of intramuscular pentamidine by the Z-track technique for PCP prophylaxis appears to be highly effective and minimally toxic. PMID:8448314

  16. 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. PMID:25187511

  17. Comparative Genomics Suggests that the Fungal Pathogen Pneumocystis Is an Obligate Parasite Scavenging Amino Acids from Its Host's Lungs

    PubMed Central

    Hauser, Philippe M.; Burdet, Frédéric X.; Cissé, Ousmane H.; Keller, Laurent; Taffé, Patrick; Sanglard, Dominique; Pagni, Marco

    2010-01-01

    Pneumocystis jirovecii is a fungus causing severe pneumonia in immuno-compromised patients. Progress in understanding its pathogenicity and epidemiology has been hampered by the lack of a long-term in vitro culture method. Obligate parasitism of this pathogen has been suggested on the basis of various features but remains controversial. We analysed the 7.0 Mb draft genome sequence of the closely related species Pneumocystis carinii infecting rats, which is a well established experimental model of the disease. We predicted 8’085 (redundant) peptides and 14.9% of them were mapped onto the KEGG biochemical pathways. The proteome of the closely related yeast Schizosaccharomyces pombe was used as a control for the annotation procedure (4’974 genes, 14.1% mapped). About two thirds of the mapped peptides of each organism (65.7% and 73.2%, respectively) corresponded to crucial enzymes for the basal metabolism and standard cellular processes. However, the proportion of P. carinii genes relative to those of S. pombe was significantly smaller for the “amino acid metabolism” category of pathways than for all other categories taken together (40 versus 114 against 278 versus 427, P<0.002). Importantly, we identified in P. carinii only 2 enzymes specifically dedicated to the synthesis of the 20 standard amino acids. By contrast all the 54 enzymes dedicated to this synthesis reported in the KEGG atlas for S. pombe were detected upon reannotation of S. pombe proteome (2 versus 54 against 278 versus 427, P<0.0001). This finding strongly suggests that species of the genus Pneumocystis are scavenging amino acids from their host's lung environment. Consequently, they would have no form able to live independently from another organism, and these parasites would be obligate in addition to being opportunistic. These findings have implications for the management of patients susceptible to P. jirovecii infection given that the only source of infection would be other humans. PMID

  18. 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.

  19. Unmasking Granulomatous Pneumocystis jirovecii Pneumonia with Nodular Opacity in an HIV-Infected Patient after Initiation of Antiretroviral Therapy

    PubMed Central

    Kim, Hyung-Woo; Lee, Yong-Moon; Kim, S J; Jeong, Hye Won

    2016-01-01

    Pneumocystis jirovecii pneumonia (PJP) in patients with HIV infection can, in rare cases, present with pulmonary nodules that histologically involve granulomatous inflammation. This report describes an intriguing case of granulomatous PJP with pulmonary nodules after commencing antiretroviral therapy (ART) in an HIV-infected patient without respiratory signs or symptoms. Diagnosis of granulomatous PJP was only achieved through thoracoscopic lung biopsy. This case suggests that granulomatous PJP should be considered in the differential diagnosis of pulmonary nodules in HIV-infected patients for unmasking immune reconstitution inflammatory syndrome manifestation after initiation of ART. PMID:27189304

  20. [Investigation of Pneumocystis jirovecii pneumonia and colonization in iatrogenically immunosuppressed and immunocompetent patients].

    PubMed

    Özkoç, Soykan; Bayram Delibaş, Songül

    2015-04-01

    Pneumocystis pneumonia (PCP) is a potentially life-threatening infection for the immunocompromized patients. However, Pneumocystis jirovecii colonization can also be detected in healthy individuals and in patients with various underlying lung diseases. The aim of this study was to evaluate the immunocompetent and iatrogenically immunosuppressed patients in terms of PCP and P.jirovecii colonization. A total of 92 patients (66 male, 26 female; age range: 18-93 years, median: 58.5) who underwent bronchoscopy due to various pulmonary symptoms between January 2011-April 2014, were included in the study. Of these patients, 65 were under immunosuppressive therapy (38 were treated with anti-cancer drugs, 15 with anti-rejection/immunomodulatory drugs and 12 with corticosteroids), while 27 were immunocompetent. Bronchoalveolar lavage (BAL) fluids were evaluated for the presence of P.jirovecii mitochondrial gene coding ribosomal large subunit (mtLSUrRNA) with nested PCR (nPCR) method. All of the samples were also examined by Giemsa and Gomori's methenamine silver (GMG) staining methods. P.jirovecii DNA was detected in 31 (33.7%) out of 92 BAL samples by nPCR. Although six immunosuppressed patients were positive in the first round of amplification, 26 of 65 (40%) immunosuppressed and five of 27 (18.5%) immunocompetent patients were positive with nPCR. P.jirovecii cysts and trophozoites were detected in only five (16.1%) of the 31 nPCR positive samples. The probability of being immunosuppressive among nPCR positive cases was statistically higher than nPCR negative cases (χ²= 3.940; p= 0.047). This difference was more significant in organ transplant recipients and patients under anti-rejection/immunomodulatory treatment (χ²= 6.715, p= 0.01; χ²= 5.550, p= 0.018, respectively). When clinical, laboratory and radiological findings of nPCR positive patients were considered, five patients (2 kidney transplant, 1 bone marrow transplant, 1 interstitial lung disease and 1 lung

  1. Identification of a Putative Precursor to the Major Surface Glycoprotein of Pneumocystis carinii

    PubMed Central

    Sunkin, Susan M.; Linke, Michael J.; McCormack, Francis X.; Walzer, Peter D.; Stringer, James R.

    1998-01-01

    The major surface glycoprotein (MSG) of Pneumocystis carinii f. sp. carinii is a family of proteins encoded by a family of heterogeneous genes. Messenger RNAs encoding different MSGs each begin with the same 365-bp sequence, called the Upstream Conserved Sequence (UCS), which is in frame with the contiguous MSG sequence. The UCS contains several potential start sites for translation. To determine if translation of MSG mRNAs begins in the UCS, polyclonal antiserum was raised against the 123-amino-acid peptide encoded by the UCS. The anti-UCS serum reacted with a P. carinii protein that migrated at 170 kDa; however, it did not react with the mature MSG protein, which migrates at 116 kDa. A 170-kDa protein was immunoprecipitated with anti-UCS serum and shown to react with a monoclonal antibody against a conserved MSG epitope. To explore the functional role of the UCS in the trafficking of MSG, the nucleotide sequence encoding the UCS peptide was ligated to the 5′ end of an MSG gene and incorporated into a recombinant baculovirus. Insect cells infected with the UCS-MSG hybrid gene expressed a 160-kDa protein which was N-glycosylated. By contrast, insect cells infected with a baculovirus carrying an MSG gene lacking the UCS expressed a nonglycosylated 130-kDa protein. These data suggest that in P. carinii, translation begins in the UCS to produce a pre-MSG protein, which is subsequently directed to the endoplasmic reticulum and processed to the mature form by proteolytic cleavage. PMID:9453635

  2. Genetic diversity of Pneumocystis jirovecii in colonized Cuban infants and toddlers.

    PubMed

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

    2014-03-01

    Pneumocystis jirovecii is a leading cause of opportunistic infections among immunocompromised patients. The aim of this study was to determine the genetic diversity of P. jirovecii from colonized Cuban infants and toddlers by analysis of four genetic loci: mitochondrial large subunit (mtLSU) rRNA, cytochrome b (CYB), superoxide dismutase (SOD) and β-tubulin (β-tub). We determined the multilocus profiles based on concatenated genotype data (multilocus genotype; MLG) and nucleotide sequences (multilocus sequence analysis; MLSA) respectively, calculated the discriminatory power of each analysis, and investigated possible associations with demographic and clinical data. Sixteen of 51 PCR-positive nasopharyngeal swab specimens (years 2010-2013) with high P. jirovecii load were selected for downstream analysis. In mixed allelic profiles all genotypes/nucleotide sequence patterns were considered separately. All samples could be genotyped based on mtLSU, CYB and β-tub locus. However, the SOD locus could be successfully amplified in only 7/16 (44%) specimens. Eight different P. jirovecii MLGs were identified among the 16 cases and eight samples presented identical MLG (MLG 1). Seventeen MLSA profiles were distinguished. No statistical association between genotypes or MLGs and demographic or clinical data could be identified. For MLSA the higher discriminatory power (S=0.976) was observed. The combination of mtLSU, CYB and β-tub loci proved to be useful for molecular epidemiology studies of P. jirovecii. A total of 17 different MLSA profiles observed in 16 specimens indicated high genetic variability of P. jirovecii circulating in colonized Cuban infants and toddlers. PMID:24412726

  3. 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. PMID:24131683

  4. Diversity of host species and strains of Pneumocystis carinii is based on rRNA sequences.

    PubMed Central

    Shah, J S; Pieciak, W; Liu, J; Buharin, A; Lane, D J

    1996-01-01

    We have amplified by PCR Pneumocystis carinii cytoplasmic small-subunit rRNA (variously referred to as 16S-like or 18S-like rRNA) genes from DNA extracted from bronchoalveolar lavage and induced sputum specimens from patients positive for P. carinii and from infected ferret lung tissue. The amplification products were cloned into pUC18, and individual clones were sequenced. Comparison of the determined sequences with each other and with published rat and partial human P.carinii small-subunit rRNA gene sequences reveals that, although all P. carinii small-subunit rRNAs are closely related (approximately 96% identity), small-subunit rRNA genes isolated from different host species (human, rat, and ferret) exhibit distinctive patterns of sequence variation. Two types of sequences were isolated from the infected ferret lung tissue, one as a predominant species and the other as a minor species. There was 96% identity between the two types. In situ hybridization of the infected ferret lung tissue with oligonucleotide probes specific for each type revealed that there were two distinct strains of P. carinii present in the ferret lung tissue. Unlike the ferret P. carinii isolates, the small-subunit rRNA gene sequences from different human P. carinii isolates have greater than 99% identity and are distinct from all rat and ferret sequences so far inspected or reported in the literature. Southern blot hybridization analysis of PCR amplification products from several additional bronchoalveolar lavage or induced sputum specimens from P. carinii-infected patients, using a 32P-labeled oligonucleotide probe specific for human P. carinii, also suggests that all of the human P. carinii isolates are identical. These findings indicate that human P. carinii isolates may represent a distinct species of P. carinii distinguishable from rat and ferret P. carinii on the basis of characterization of small-subunit rRNA gene sequences. PMID:8770515

  5. An evaluation of four methods for the detection of Pneumocystis carinii in clinical specimens.

    PubMed

    Tiley, S M; Marriott, D J; Harkness, J L

    1994-07-01

    We undertook a prospective evaluation of 4 methods for the detection of Pneumocystis carinii in clinical specimens and compared an indirect immunofluorescence assay (IFA) (Diagnostics Pasteur), and a fluorescent whitening agent (FWA) (Blankophor BA 267%, Bayer, Australia) with our standard methenamine silver (MeAg) and toluidine blue O (TB) stains. Two hundred and two specimens were received from 162 patients (133 HIV infected, 19 heart or heart-lung transplant recipients, and 10 "miscellaneous"). The specimens consisted of 132 induced sputa, 56 bronchoalveolar lavage specimens, 10 fine needle aspiration lung biopsies, and 4 pleural fluid specimens. P. carinii was detected in 44 (22%) of the specimens. The sensitivities for the detection of P. carinii pneumonia were IFA: 92% (95% CI, 83-100%), FWA: 57% (95% CI, 41-73%), MeAg: 54% (95% CI, 38-70%), and TB: 49% (95% CI, 33-65%). Discordant results were greatest in specimens from patients who were receiving specific anti-P. carinii prophylaxis, or who had received treatment for several days prior to sampling. IFA was the most sensitive test and relatively easy to perform. IFA was also the most expensive test. We found the FWA method a useful screening test as it is cheap and quick to perform. However, it is less sensitive than IFA, which should be performed on the negative specimens. With the increasing use of specific anti-P. carinii prophylaxis in HIV-infected patients, methods more specific and sensitive than MeAg and TB stains are required. We have found IFA to improve significantly the rate of detection of P. carinii in this patient group. PMID:7527514

  6. Prevalence and Genotype Distribution of Pneumocystis jirovecii in Cuban Infants and Toddlers with Whooping Cough

    PubMed Central

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

    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. PMID:24131683

  7. 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.

  8. Interleukin-23 (IL-23)-IL-17 Cytokine Axis in Murine Pneumocystis carinii Infection▿

    PubMed Central

    Rudner, Xiaowen L.; Happel, Kyle I.; Young, Erana A.; Shellito, Judd E.

    2007-01-01

    Host defense mechanisms against Pneumocystis carinii are not fully understood. Previous work in the murine model has shown that host defense against infection is critically dependent upon host CD4+ T cells. The recently described Th17 immune response is predominantly a function of effector CD4+ T cells stimulated by interleukin-23 (IL-23), but whether these cells are required for defense against P. carinii infection is unknown. We tested the hypothesis that P. carinii stimulates the early release of IL-23, leading to increases in IL-17 production and lung effector CD4+ T-cell population that mediate clearance of infection. In vitro, stimulation of alveolar macrophages with P. carinii induced IL-23, and IL-23p19 mRNA was expressed in lungs of mice infected with this pathogen. To address the role of IL-23 in resistance to P. carinii, IL-23p19−/− and wild-type control C57BL/6 mice were infected and their fungal burdens and cytokine/chemokine responses were compared. IL-23p19−/− mice displayed transient but impaired clearance of infection, which was most apparent 2 weeks after inoculation. In confirmatory studies, the administration of either anti-IL-23p19 or anti-IL-17 neutralizing antibody to wild-type mice infected with P. carinii also caused increases in fungal burdens. IL-17 and the lymphocyte chemokines IP-10, MIG, MIP-1α, MIP-1β, and RANTES were decreased in the lungs of infected IL-23p19−/− mice in comparison to their levels in the lungs of wild-type mice. In IL-23p19−/− mice infected with P. carinii, there were fewer effector CD4+ T cells in the lung tissue. Collectively, these studies indicate that the IL-23-IL-17 axis participates in host defense against P. carinii. PMID:17403873

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

    PubMed

    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

    2003-04-01

    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

  10. Multilocus microsatellite genotyping array for investigation of genetic epidemiology of Pneumocystis jirovecii.

    PubMed

    Parobek, Christian M; Jiang, Linda Y; Patel, Jaymin C; Alvarez-Martínez, Miriam J; Miro, Jose M; Worodria, William; Andama, Alfred; Fong, Serena; Huang, Laurence; Meshnick, Steven R; Taylor, Steve M; Juliano, Jonathan J

    2014-05-01

    Pneumocystis jirovecii is a symbiotic respiratory fungus that causes pneumonia (PcP) in immunosuppressed patients. Because P. jirovecii cannot be reliably cultured in vitro, it has proven difficult to study and gaps in our understanding of the organism persist. The release of a draft genome for the organism opens the door for the development of new genotyping approaches for studying its molecular epidemiology and global population structure. We identified and validated 8 putatively neutral microsatellite markers and 1 microsatellite marker linked to the dihydropteroate synthase gene (dhps), the enzymatic target of sulfa drugs used for PcP prevention and treatment. Using these tools, we analyzed P. jirovecii isolates from HIV-infected patients from three geographically distant populations: Uganda, the United States, and Spain. Among the 8 neutral markers, we observed high levels of allelic heterozygosity (average He, 0.586 to 0.842). Consistent with past reports, we observed limited global population structuring, with only the Ugandan isolates showing minor differentiation from the other two populations. In Ugandan isolates that harbored mutations in dhps, the microsatellite locus linked to dhps demonstrated a depressed He, consistent with positive directional selection for sulfa resistance mutations. Using a subset of these microsatellites, analyses of individual and paired samples from infections in San Francisco, CA, showed reliable typeability within a single infection and high discriminatory power between infections. These features suggest that this novel microsatellite typing approach will be an effective tool for molecular-epidemiological investigations into P. jirovecii population structure, transmission, and drug resistance. PMID:24523468

  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. Efficacy of DL-alpha-difluoromethylornithine in a rat model of Pneumocystis carinii pneumonia.

    PubMed

    Clarkson, A B; Williams, D E; Rosenberg, C

    1988-08-01

    Pneumocystis carinii pneumonia is often the terminal event for patients with the acquired immunodeficiency syndrome. Eflornithine (DL-alpha-difluoromethylornithine [DFMO]; Ornidyl; Merrell Dow Research Institute, Cincinnati, Ohio) has been used successfully against this protozoan disease in limited clinical trials, although not all patients respond to therapy. In contrast, results of the only reported experiments with DFMO in an animal model were negative. We retested DFMO against P. carinii in an immunosuppressed rat model by inclusion of 3% DFMO in the drinking water, a dose rate about twice that used previously. A combination of trimethoprim and sulfamethoxazole, a proven anti-P. carinii agent, was used as a positive control. After 3 weeks of anti-P. carinii pneumonia therapy, the surviving rats were sacrificed and the degree of parasitosis was judged by examination of lung sections stained with silver methenamine to reveal cysts. In three separate experiments, DFMO showed definite anti-P. carinii pneumonia activity; the parasitosis of DFMO-treated animals was significantly less than that of control animals (P less than 0.001 for all experiments). DFMO was not as active as trimethoprim-sulfamethoxazole, however. Several other experimental therapies were tested, including dapsone and two additional antiprotozoal agents: suramin and diminazene aceturate (Berenil; Farbwerke Hoechst, Frankfurt, Federal Republic of Germany). Diminazene aceturate, a veterinary drug related to the standard anti-P. carinii pneumonia agent pentamidine, was very active (P less than 10(-10]. Suramin and dapsone were weakly active. The combinations suramin-diminazene aceturate and suramin-DFMO were tested, but they were antagonistic rather than synergistic. PMID:3142346

  13. 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

  14. Contribution of T Cell Subsets to the Pathophysiology of Pneumocystis-Related Immunorestitution Disease

    PubMed Central

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

    2014-01-01

    Immune-mediated lung injury is an important component of Pneumocystis pneumonia (PcP)-related immunorestitution disease (IRD). However, the individual contribution of CD4+ and CD8+ T cells to the pathophysiology of IRD remains undetermined. Therefore, IRD was modeled in severe combined immunodeficient mice, and specific T cell depletion was used to determine how T cell subsets interact to affect the nature and severity of disease. CD4+ cells were more abundant than CD8+ cells during the acute stage of IRD that coincided with impaired pulmonary physiology and organism clearance. Conversely, CD8+ cells were more abundant during the resolution phase following P. carinii clearance. Depletion of CD4+ T cells protected mice from the acute pathophysiology of IRD. However, these mice could not clear the infection and developed severe PcP at later time points when a pathological CD8+ T cell response was observed. In contrast, mice depleted of CD8+ T cells efficiently cleared the infection, but developed more severe disease, an increased frequency of IFN-γ-producing CD4+ cells, and a prolonged CD4+ T cell response than mice with both CD4+ and CD8+ cells. These data suggest that CD4+ T cells mediate the acute respiratory disease associated with IRD. In contrast, CD8+ T cells contributed to neither lung injury nor organism clearance when CD4+ cells were present, but instead served to modulate CD4 function. In the absence of CD4+ cells, CD8+ T cells produced a non-protective, pathological immune response. These data suggest that the interplay of CD4+ and CD8+ T cells affects the ultimate outcome of PcP-related IRD. PMID:16891394

  15. Pneumocystis jirovecii pneumonia in pediatric patients: an analysis of 15 confirmed consecutive cases during 14 years

    PubMed Central

    Kim, Kyung-Ran; Kim, Jong Min; Kang, Ji-Man

    2016-01-01

    Purpose Pneumocystis jirovecii pneumonia occurs in various immunocompromised patients. Despite the prophylaxis strategies in clinical practice, certain patients develop P. jirovecii pneumonia. This study was performed to investigate pediatric cases with P. jirovecii pneumonia in a single center. Methods We identified pediatric patients younger than 19 years with microbiologically confirmed P. jirovecii pneumonia from January 2000 to February 2014. A retrospective chart review was performed. Results Fifteen episodes of P. jirovecii pneumonia in 14 patients were identified with median age of 8.3 years (range, 0.4–18.6 years). Among these patients, 11 patients had hematology-oncology diseases, 2 had primary immunodeficiency disorders (one with severe combined immunodeficiency and the other with Wiskott Aldrich syndrome), 1 had systemic lupus erythematosus and 1 received kidney transplant. Four patients were transplant recipients; 1 allogeneic and 2 autologous hematopoietic cell transplant and 1 with kidney transplant. The median absolute lymphocyte count at the diagnosis of P. jirovecii pneumonia was 5,156 cells/mm3 (range, 20–5,111 cells/mm3). In 13 episodes (13 of 15, 86.7%), patients were not receiving prophylaxis at the onset of P. jirovecii pneumonia. For treatment, trimethoprim/sulfamethoxazole was given as a main therapeutic agent in all 15 episodes. Steroid was given in 9 episodes (60%). Median treatment duration was 15 days (range, 4–33 days). Overall mortality at 60 days was 35.7% (5 of 14). Conclusion Majority of our patients developed P. jirovecii pneumonia while not on prophylaxis. Continuous efforts and more data are needed to identify high risk patients who may get benefit from P. jirovecii pneumonia prophylaxis.

  16. Respiratory failure in patients with acquired immunodeficiency syndrome and Pneumocystis carinii pneumonia.

    PubMed

    Maxfield, R A; Sorkin, I B; Fazzini, E P; Rapoport, D M; Stenson, W M; Goldring, R M

    1986-05-01

    Seven patients with acquired immunodeficiency syndrome (AIDS) and Pneumocystis carinii pneumonia were studied to define the pathophysiology of their respiratory failure. The patients had fever, cough, dyspnea, hypoxemia, and diffuse infiltrates on chest x-ray. Biopsies revealed a spectrum of alveolar filling, interstitial edema and infiltration, and fibrosis. The patients were studied on mechanical ventilation to assess the effect of positive end-expiratory pressure (PEEP) and supplemental oxygen on shunt fraction. Mean anatomic shunt (measured on 100% oxygen) was 34 +/- 8%, which increased significantly (p less than .001) to 43 +/- 9% when the FIO2 was decreased to 40% to 60% (physiologic shunt), indicating ventilation/perfusion (V/Q) imbalance or impaired diffusion. Increasing PEEP by 9 +/- 2 cm H2O reduced the anatomic shunt to 30 +/- 7% (p less than .01) and the physiologic shunt to 37 +/- 7% (p less than .02). There was a similar decrease in anatomic and physiologic shunts in five studies, a greater decrease in physiologic shunt in four, and a greater decrease in anatomic shunt in two. Evidence of alveolar recruitment with PEEP, measured by an increase in static thoracic compliance, was found in only one study. There was no correlation between the effect of PEEP on compliance and its effect on shunt. The data suggest that in patients with AIDS and P. carinii pneumonia, PEEP can decrease shunt by reducing the anatomic shunt, improving V/Q imbalance, and converting areas of anatomic shunt to areas of low V/Q. P. carinii pneumonia in patients with AIDS can produce a clinical and pathophysiologic pattern similar to that described in the adult respiratory distress syndrome. PMID:3516574

  17. Relationship Between Pneumocystis carinii Burden and the Degree of Host Immunosuppression in an Airborne Transmission Experimental Model.

    PubMed

    Khalife, Sara; Chabé, Magali; Gantois, Nausicaa; Audebert, Christophe; Pottier, Muriel; Hlais, Sani; Pinçon, Claire; Chassat, Thierry; Pierrot, Christine; Khalife, Jamal; Aliouat-Denis, Cécile-Marie; Aliouat, El Moukhtar

    2016-05-01

    To quantitatively assess the risk of contamination by Pneumocystis depending on the degree of immunosuppression (ID) of the exposed rat hosts, we developed an animal model, where rats went through different doses of dexamethasone. Then, natural and aerial transmission of Pneumocystis carinii occurred during cohousing of the rats undergoing gradual ID levels (receivers) with nude rats developing pneumocystosis (seeders). Following contact between receiver and seeder rats, the P. carinii burden of receiver rats was determined by toluidine blue ortho staining and by qPCR targeting the dhfr monocopy gene of this fungus. In this rat model, the level of circulating CD4(+) and CD8(+) T lymphocytes remained significantly stable and different for each dose of dexamethasone tested, thus reaching the goal of a new stable and gradual ID rat model. In addition, an inverse relationship between the P. carinii burden and the level of circulating CD4(+) or CD8(+) T lymphocytes was evidenced. This rat model may be used to study other opportunistic pathogens or even co-infections in a context of gradual ID. PMID:26509699

  18. Evaluation of Loop-Mediated Isothermal Amplification Assay for the Detection of Pneumocystis jirovecii in Immunocompromised Patients

    PubMed Central

    Singh, Preeti; Singh, Sundeep; Mirdha, Bijay Ranjan; Guleria, Randeep; Agarwal, Sanjay Kumar; Mohan, Anant

    2015-01-01

    Pneumocystis pneumonia (PCP) is one of the common opportunistic infection among HIV and non-HIV immunocompromised patients. The lack of a rapid and specific diagnostic test necessitates a more reliable laboratory diagnostic test for PCP. In the present study, the loop-mediated isothermal amplification (LAMP) assay was evaluated for the detection of Pneumocystis jirovecii. 185 clinical respiratory samples, including both BALF and IS, were subjected to GMS staining, nested PCR, and LAMP assay. Of 185 respiratory samples, 12/185 (6.5%), 41/185 (22.2%), and 49/185 (26.5%) samples were positive by GMS staining, nested PCR, and LAMP assay, respectively. As compared to nested PCR, additional 8 samples were positive by LAMP assay and found to be statistically significant (p < 0.05) with the detection limit of 1 pg. Thus, the LAMP assay may serve as a better diagnostic tool for the detection of P. jirovecii with high sensitivity and specificity, less turn-around time, operational simplicity, single-step amplification, and immediate visual detection. PMID:26664746

  19. 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. PMID:26231980

  20. 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

  1. Relationship between Radiological Stages and Prognoses of Pneumocystis Pneumonia in Non-AIDS Immunocompromised Patients

    PubMed Central

    Mu, Xiang-Dong; Jia, Peng; Gao, Li; Su, Li; Zhang, Cheng; Wang, Ren-Gui; Wang, Guang-Fa

    2016-01-01

    Background: Although radiological features of pneumocystis pneumonia (PCP) in non-Acquired Immune Deficiency Syndrome (AIDS) immunocompromised patients have been reported by other authors, there were no studies on the radiological stages of PCP previously. This study aimed to elucidate the radiological stages and prognoses of PCP in non-AIDS immunocompromised patients. Methods: Retrospective analysis of radiological manifestations and prognoses of 105 non-AIDS PCP immunocompromised patients from August 2009 to April 2016 was conducted. Chest radiograph was divided into three stages: early stage (normal or nearly normal chest radiograph), mid stage (bilateral pulmonary infiltrates), and late stage (bilateral pulmonary consolidations); chest high-resolution computed tomography (HRCT) was also divided into three stages: early stage (bilateral diffuse ground-glass opacity [GGO]), mid stage (bilateral diffuse GGO and patchy consolidations), and late stage (bilateral diffuse consolidations). Results: The case fatality rate (CFR) of all patients was 34.3% (36/105), all of them took routine chest X-ray (CXR), and 84 underwent chest CT examinations. According to the CXR most near the beginning of anti-PCP therapy, 18 cases were at early stage and CFR was 0 (0/18, P < 0.01), 50 cases were at mid stage and CFR was 28.0% (14/50, P > 0.05), and 37 cases were at late stage and CFR was 59.5% (22/37, P < 0.01). According to the chest HRCT most near the beginning of anti-PCP therapy, 40 cases were at early stage and CFR was 20.0% (8/40, P > 0.05), 34 cases were at mid stage and CFR was 47.1% (16/34, P > 0.05), and 10 cases were at late stage and CFR was 80.0% (8/10, P < 0.05); barotrauma, including pneumothorax, pneumomediastinum, and pneumohypoderma, was found in 18 cases and the CFR was 77.8% (14/18, P < 0.01). Conclusions: Based on the radiological manifestations, the course of PCP in non-AIDS immunocompromised patients can be divided into three stages: early stage, mid stage

  2. Simplified exercise test for the initial differential diagnosis of Pneumocystis carinii pneumonia in HIV antibody positive patients.

    PubMed Central

    Sauleda, J.; Gea, J.; Aran, X.; Aguar, M. C.; Orozco-Levi, M.; Broquetas, J. M.

    1994-01-01

    BACKGROUND--This study was designed to evaluate the usefulness of a simplified exercise test in the differential diagnosis of Pneumocystis carinii pneumonia (PCP). METHODS--Forty five subjects with antibodies against the human immunodeficiency virus (HIV) and pneumonia were included and divided into two groups: those with PCP and those with "other pneumonias" (non-PCP). The test involved pedalling for two minutes on a stretcher bed and was considered positive if SaO2 decreased by at least 3%. RESULTS--During the exercise the mean(SE) SaO2 fell in patients with PCP from 88(4)% to 84(3)%, p < 0.01, whilst it improved slightly in subjects with non-PCP from 91(1)% to 93(3)%, p < 0.05. Sensitivity was 77% and specificity 91%. CONCLUSIONS--This simple test seems potentially useful for the initial investigation of HIV antibody positive patients with pneumonia. PMID:8128398

  3. High incidence of Pneumocystis jirovecii pneumonia in patients receiving biweekly rituximab and cyclophosphamide, adriamycin, vincristine, and prednisone.

    PubMed

    Kamel, Sarah; O'Connor, Shaun; Lee, Newton; Filshie, Robin; Nandurkar, Harshal; Tam, Constantine S

    2010-05-01

    The risk of infection with Pneumocystis jirovecii pneumonia (PCP) in patients undergoing chemotherapy is closely related to the intensity of corticosteroid exposure. PCP is uncommon with classical (3-weekly) R-CHOP, but the risk may be higher with biweekly R-CHOP (R-CHOP-14) due to the increased frequency of prednisolone pulses. Among 47 consecutive patients treated with R-CHOP-14 at our institution, five (11%) developed microbiologically proven PCP, with a further two (4%) having classical clinical and radiological features of PCP, but without microbiological confirmation. None of these patients were HIV-positive or had additional risk factors for PCP. Our experience suggests that PCP prophylaxis should be considered in institutions using R-CHOP-14 for the treatment of patients with aggressive lymphomas. PMID:20367135

  4. De Novo Assembly of the Pneumocystis jirovecii Genome from a Single Bronchoalveolar Lavage Fluid Specimen from a Patient

    PubMed Central

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

    2012-01-01

    ABSTRACT Pneumocystis jirovecii is a fungus that causes severe pneumonia in immunocompromised patients. However, its study is hindered by the lack of an in vitro culture method. We report here the genome of P. jirovecii that was obtained from a single bronchoalveolar lavage fluid specimen from a patient. The major challenge was the in silico sorting of the reads from a mixture representing the different organisms of the lung microbiome. This genome lacks virulence factors and most amino acid biosynthesis enzymes and presents reduced GC content and size. Together with epidemiological observations, these features suggest that P. jirovecii is an obligate parasite specialized in the colonization of human lungs, which causes disease only in immune-deficient individuals. This genome sequence will boost research on this deadly pathogen. PMID:23269827

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

    PubMed

    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

  6. 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

  7. Short Communication: Diagnosis of Pneumocystis jirovecii Pneumonia by Detection of DNA in Blood and Oropharyngeal Wash, Compared with Sputum.

    PubMed

    van Halsema, Clare; Johnson, Leann; Baxter, Joanne; Douthwaite, Sam; Clowes, Yvonne; Guiver, Malcolm; Ustianowski, Andrew

    2016-05-01

    Molecular diagnostic methods on lower respiratory specimens for Pneumocystis pneumonia (PCP) are recommended, but specimens can be difficult to obtain. This study examined the diagnostic use of PCP polymerase chain reaction (PCR) on oropharyngeal wash (OPW) and blood versus sputum (spontaneous and induced) to find faster, simpler, and less invasive diagnostic methods. We prospectively recruited consenting adults with symptoms consistent with PCP. Real-time PCR targeted the Pneumocystis mitochondrial large subunit ribosomal RNA gene, using the aforementioned specimens. Clinical data were collected from routine records. Forty-five participants provided 45 sputa, 31 OPW, and 41 blood samples. Median age was 39 years and 41 (91%) were male, with median CD4 count being 64 cells/μL. Sputum PCR was positive in 27/45 (60%) participants. Comparative sensitivity of OPW was 9/19 (47%, 95% confidence interval [CI] 23-71) and blood 12/24 (50%, 95% CI 29-71) participants, both with specificity 100%. Including only samples obtained ≤2 days after start of treatment, sensitivity of OPW was 80% (8/10, 95% CI 51-100), that of blood was 57% (8/14, 95% CI 29-86), and that of combined tests was 88% (14/16, 95% CI 70-100). In 14/16 individuals with PCP and specimens obtained ≤2 days after start of treatment, diagnosis was possible using nonrespiratory samples. Despite moderate sensitivity of individual tests, combined PCP PCR on early blood and OPW specimens had high sensitivity and could reduce the need for invasive procedures. There were no false-positive results on nonrespiratory samples. Sampling and laboratory methods use routine technology and so require few additional resources. PMID:26739439

  8. 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

  9. SERUM AND BAL BETA-D-GLUCAN FOR THE DIAGNOSIS OF PNEUMOCYSTIS PNEUMONIA IN HIV-POSITIVE PATIENTS

    PubMed Central

    Salerno, D.; Mushatt, D.; Myers, L.; Zhuang, Y.; de la Rua, N.; Calderon, EJ.; Welsh, DA.

    2014-01-01

    The diagnosis of patients with pulmonary infiltrates and human immunodeficiency virus (HIV) infection remains a challenge. In current clinical practice the gold standard for Pneumocystis jirovecii pneumonia (PCP) diagnosis remains the identification of the organism in broncoalveolar lavage (BAL) using microscopy (e.g., silver stain). (1->3)-β -D-glucan (BG) is a polysaccharide that is present within the cell wall of Pneumocystis and other fungi. We analyzed serum and BAL lavage fluid from a cohort of 119 patients that did have HIV, a diagnosis of pneumonia and underwent bronchoscopy (FOB) for diagnosis of PCP. The discriminative power of serum BG for the diagnosis of PCP in this group of patients was very high. Using a cutoff of 300 pg/mL, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 91%, 92%, 89% and 93% respectively. A model for ROC with just serum BG (N = 108) had an AUC of 0.95. Serum procalcitonin (PCT) and BAL BG were not as accurate for the diagnosis of PCP. For BAL BG using a cutoff of 783 pg/mL, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 72%, 79%, 72% and 79% respectively. The differences between the medians for serum PCT between the group with a without PCP did not reach statistical significance (p=0.6137). The measurement of serum BG should be incorporated in the diagnostic work up of HIV positive patients with dyspnea and infiltrates on chest X ray. Our study confirms the diagnostic value of serum BG previously reported by others but we add a cutoff value that we believe is more accurate for patients with AIDS and suspicion of PCP. PMID:25448310

  10. 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

  11. Pneumocystis pneumonia associated with human immunodeficiency virus infection without elevated (1 → 3)-β-D glucan: A case report.

    PubMed

    Kamada, Takahiro; Furuta, Kenjiro; Tomioka, Hiromi

    2016-01-01

    Pneumocystis pneumonia (PCP) caused by Pneumocystis jirovecii is one of the most common opportunistic infections in immunosuppressed patients, particularly in patients with acquired immunodeficiency syndrome (AIDS). (1 → 3)-β-D-glucan is a component of the cell wall of P. jirovecii and other fungi such as Candida sp., Aspergillus sp. and Histoplasma sp. The measurement of serum (1 → 3)-β-D-glucan has been reported to be a highly sensitive test for PCP related to human immunodeficiency virus (HIV-PCP). We report a case of HIV-PCP not associated with elevated serum (1 → 3)-β-D glucan and highlight how HIV-PCP cannot be completely ruled out if (1 → 3)-β-D glucan is negative. PMID:27330956

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

    PubMed

    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

  13. 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. PMID:27550992

  14. Characterization of Major Surface Glycoprotein Genes of Human Pneumocystis carinii and High-Level Expression of a Conserved Region

    PubMed Central

    Mei, Qin; Turner, Ross E.; Sorial, Vivian; Klivington, Diane; Angus, C. William; Kovacs, Joseph A.

    1998-01-01

    To facilitate studies of Pneumocystis carinii infection in humans, we undertook to better characterize and to express the major surface glycoprotein (MSG) of human P. carinii, an important protein in host-pathogen interactions. Seven MSG genes were cloned from a single isolate by PCR or genomic library screening and were sequenced. The predicted proteins, like rat MSGs, were closely related but unique variants, with a high level of conservation among cysteine residues. A conserved immunodominant region (of approximately 100 amino acids) near the carboxy terminus was expressed at high levels in Escherichia coli and used in Western blot studies. All 49 of the serum samples, which were taken from healthy controls as well as from patients with and without P. carinii pneumonia, were reactive with this peptide by Western blotting, supporting the hypothesis that most adult humans have been infected with P. carinii at some point. This recombinant MSG fragment, which is the first human P. carinii antigen available in large quantities, may be a useful reagent for investigating the epidemiology of P. carinii infection in humans. PMID:9712777

  15. Comparative study of antipneumocystis agents in rats by using a Pneumocystis carinii-specific DNA probe to quantitate infection.

    PubMed Central

    Liberator, P A; Anderson, J W; Powles, M; Pittarelli, L A; Worley, M; Becker-Hapak, M; Graves, D C; Schmatz, D M

    1992-01-01

    A repetitive genomic DNA clone (B12-2) that specifically hybridizes to Pneumocystis carinii DNA has been identified. No cross-hybridization to genomic DNA prepared from bacteria, other fungi, protozoa, or mammals was observed. Clone B12-2 is multiply represented in the P. carinii genome. By direct hybridization to DNA prepared from the lungs of immunosuppressed rats, the probe can detect the equivalent of fewer than 1,000 P. carinii organisms. A hybridization assay employing clone B12-2 has been developed to quantitate organism load in the rat model for P. carinii. Application of the assay to track the accumulation of organisms during the immunosuppression regimen as well as to monitor the efficacy of two drug therapies used clinically for the treatment of P. carinii pneumonia is described here. The clone B12-2 hybridization assay for the determination of P. carinii organism load possesses several advantageous features and thus should serve to complement conventional staining and immunohistochemical methods. Images PMID:1452667

  16. Recovery of Pseudomonas aeruginosa in respiratory specimens from HIV positive patients being evaluated for Pneumocystis carinii pneumonia.

    PubMed Central

    Doyle, R. L.; Doherty, J. J.; Zimmerman, L. H.

    1995-01-01

    BACKGROUND--Despite the immune suppression, frequent hospital admissions, and many intercurrent illnesses associated with HIV infection, Pseudomonas aeruginosa has been cited relatively infrequently as a respiratory pathogen in HIV positive patients. METHODS--The microbiological isolates, medical records, radiographic reports, and laboratory data from 224 patients undergoing sputum induction and/or bronchoalveolar lavage for evaluation of respiratory symptoms suspicious for Pneumocystis carinii pneumonia (PCP) from 1989 to 1992 were reviewed retrospectively. RESULTS--An increasing number of respiratory isolates with Pseudomonas aeruginosa was found over this time period. Eighteen of the 224 patients were identified in whom P aeruginosa was recovered on at least one occasion. These patients were more likely to have a history of smoking and prior PCP than those in whom Pseudomonas was not recovered. Mean CD4 counts were also significantly lower in these patients. CONCLUSIONS--Pseudomonas aeruginosa may be recovered from a substantial number of respiratory isolates from HIV positive patients suspected of having PCP. The prevalence of this phenomenon may be increasing. PMID:7597670

  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. 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. PMID:25496195

  19. 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. PMID:27550991

  20. A Case of Pneumocystis jirovecii Pneumonia in a Severely Malnourished, HIV-Negative Patient: A Role for Malnutrition in Opportunistic Infections?

    PubMed

    Attalla El Halabieh, Nadia; Petrillo, Enrico; Laviano, Alessandro; Delfino, Massimo; Rossi Fanelli, Filippo

    2016-07-01

    Malnutrition increases the risk of infections in patients receiving medical and surgical procedures, but it is not clear whether it may facilitate also the development of opportunistic infections in human immunodeficiency virus (HIV)-negative patients not receiving immunosuppressive therapies. Here we report the first case of a non-HIV, severely malnourished woman who developed Pneumocystis jirovecii pneumonia. This report highlights the clinical relevance of malnutrition as a determinant of immune suppression, which in turn may also favor opportunistic infections. Therefore, routine nutrition screening and assessment, as well as timely start of nutrition therapy, should be prioritized in daily clinical practice to reduce complications and improve outcome. PMID:25172049

  1. Serum (1-3)-beta-D-glucan as a tool for diagnosis of Pneumocystis jirovecii pneumonia in patients with human immunodeficiency virus infection or hematological malignancy.

    PubMed

    Desmet, Stefanie; Van Wijngaerden, Eric; Maertens, Johan; Verhaegen, Jan; Verbeken, Eric; De Munter, Paul; Meersseman, Wouter; Van Meensel, Britt; Van Eldere, Johan; Lagrou, Katrien

    2009-12-01

    (1-3)-Beta-D-Glucan (BG) reactivity was tested in serum samples from 28 patients with human immunodeficiency virus infection or a hematological malignancy and Pneumocystis jirovecii pneumonia (PCP) and 28 control patients. The sensitivity and specificity of BG detection with the Fungitell assay for PCP were 100 and 96.4%, respectively, using a cutoff value of 100 pg/ml. Serum BG testing looks promising for the noninvasive diagnosis of PCP. Our data suggest that a higher cutoff value for the diagnosis of PCP than for the diagnosis of invasive aspergillosis or candidiasis could be used safely and will improve the specificity of the test. PMID:19846641

  2. Human herpes virus co-infection is associated with mortality in HIV-negative patients with Pneumocystis jirovecii pneumonia.

    PubMed

    Fillatre, P; Chevrier, S; Revest, M; Gacouin, A; Jouneau, S; Leroy, H; Robert-Gangneux, F; Minjolle, S; Le Tulzo, Y; Tattevin, P

    2013-02-01

    The purpose of this investigation was to characterize the management and prognosis of severe Pneumocystis jirovecii pneumonia (PJP) in human immunodeficiency virus (HIV)-negative patients. An observational cohort study of HIV-negative adults with PJP documented by bronchoalveolar lavage (BAL) through Gomori-Grocott staining or immunofluorescence, admitted to one intensive care unit (ICU) for acute respiratory failure, was undertaken. From 1990 to 2010, 70 patients (24 females, 46 males) were included, with a mean age of 58.6 ± 18.3 years. The mean Simplified Acute Physiology Score (SAPS)-II was 36.9 ± 20.4. Underlying conditions included hematologic malignancies (n = 21), vasculitis (n = 13), and solid tumors (n = 13). Most patients were receiving systemic corticosteroids (n = 63) and cytotoxic drugs (n = 51). Not a single patient received trimethoprim-sulfamethoxazole as PJP prophylaxis. Endotracheal intubation (ETI) was required in 42 patients (60.0 %), including 38 with acute respiratory distress syndrome (ARDS). In-ICU mortality was 52.9 % overall, reaching 80.9 % and 86.8 %, respectively, for patients who required ETI and for patients with ARDS. In the univariate analysis, in-ICU mortality was associated with SAPS-II (p = 0.0131), ARDS (p < 0.0001), shock (p < 0.0001), and herpes simplex virus (HSV) or cytomegalovirus (CMV) on BAL (p = 0.0031). In the multivariate analysis, only ARDS was associated with in-ICU mortality (odds ratio [OR] 23.4 [4.5-121.9], p < 0.0001). PJP in non-HIV patients remains a serious disease with high in-hospital mortality. Pulmonary co-infection with HSV or CMV may contribute to fatal outcome. PMID:22930407

  3. Investigation of Pneumocystis jirovecii colonization in patients with chronic pulmonary diseases in the People’s Republic of China

    PubMed Central

    Wang, Dong-Dong; Zheng, Ming-Quan; Zhang, Nan; An, Chun-Li

    2015-01-01

    Background The detection of Pneumocystis jirovecii DNA in respiratory specimen from individuals who do not have signs or symptoms of pneumonia has been defined as colonization. The role of P. jirovecii colonization in the development or progression of various lung diseases has been reported, but little information about P. jirovecii colonization in patients is available in the People’s Republic of China. Objective To determine the prevalence of P. jirovecii colonization in patients with various pulmonary diseases, including the acute and stable stage of COPD, interstitial lung diseases, cystic fibrosis, and chronic bronchiectasis. Materials and methods A loop-mediated isothermal amplification (LAMP) and a conventional polymerase chain reaction (PCR) method for detecting P. jirovecii were developed. Ninety-eight HIV-negative patients who were followed-up and who had undergone bronchoscopy for diagnosis of various underlying respiratory diseases were included in the study. Sputa of these patients were analyzed with LAMP amplification of P. jirovecii gene. In addition, conventional PCR, Giemsa and Gomori’s methenamine silver nitrate staining assays were applied to all specimens. Results The sensitivity and specificity test showed that there was no cross-reaction with other fungi or bacteria in detecting the specific gene of P. jirovecii by LAMP, and the minimum detection limits by LAMP was 50 copies/mL. P. jirovecii DNA was detected in 62 of 98 (63.3%) sputa specimens by LAMP assay and 22.45% (22/98) by conventional PCR. However, no P. jirovecii cysts were found by Giemsa and Gomori’s methenamine silver nitrate in all of gene-positive specimens. Conclusion The results of our study showed that prevalence of P. jirovecii colonization is particularly high in patients with chronic pulmonary diseases in the People’s Republic of China, and the LAMP method is better for evaluation of the colonization of P. jirovecii in sputum specimen than conventional PCR. PMID

  4. 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. PMID:27021425

  5. Epidemiology and Long-Term Survival in HIV-Infected Patients With Pneumocystis jirovecii Pneumonia in the HAART Era

    PubMed Central

    López-Sánchez, Cristina; Falcó, Vicenç; Burgos, Joaquin; Navarro, Jordi; Martín, María Teresa; Curran, Adrià; Miguel, Lucía; Ocaña, Inma; Ribera, Esteve; Crespo, Manel; Almirante, Benito

    2015-01-01

    Abstract As highly active antiretroviral treatment (HAART) is widely available, the incidence of Pneumocystis jirovecii pneumonia (PJP) has decreased significantly but still represents a significant cause of morbidity and mortality in developed countries. We analyzed all the cases with PJP in human immunodeficiency virus (HIV)-infected patients from 2000 to 2013 in a university hospital in Barcelona, Spain, and conducted a systematic literature review to evaluate data regarding incidence, mortality, and long-term survival after PJP in developed settings. One hundred thirty-six episodes of PJP were analyzed. During the study period, the incidence decreased significantly (from 13.4 cases/1000 patients-year to 3.3 cases/1000 patients-year, P < 0.001). Oppositely, median age of the patients increased from 34 years in 2000 to 45 in 2013 (P = 0.024). PJP preceded HIV diagnosis in nearly 50% of the cases. Fifteen (11%) patients died during the PJP episode. The main risk factor for in-hospital mortality in our cohort was age >50 years (odds ratio 4.96, 95% confidence interval [CI] 1.45–15.14). Patients who survived were followed-up during a mean time of 44 months. Overall 5-year survival of patients after hospital discharge was 73%. Survival likelihood was 54% higher (88% [95% CI 81–96]) among HAART-adherent patients. Mean age and the proportion of patients with unknown HIV infection at the time of PJP diagnosis have increased in developed countries in the HAART era. Although the incidence has decreased, in-hospital mortality remains stable in this setting. Long-term survival is very high among HAART-adherent patients. PMID:25816039

  6. Test Performance of Blood Beta-Glucan for Pneumocystis Jirovecii Pneumonia in Patients with AIDS and Respiratory Symptoms

    PubMed Central

    Wood, Brian R.; Komarow, Lauren; Zolopa, Andrew R.; Finkelman, Malcolm A.; Powderly, William G.; Sax, Paul E.

    2014-01-01

    Objective To define the test characteristics of plasma beta-glucan for diagnosis of Pneumocystis jirovecii pneumonia in AIDS patients with respiratory symptoms. Design Analysis of baseline blood samples in a randomized strategy study of patients with acute opportunistic infections, limited to participants with respiratory symptoms. Methods Participants in the 282-person ACTG A5164 trial had baseline plasma samples assayed for beta-glucan testing. As part of A5164, two study investigators independently adjudicated the diagnosis of PCP. Respiratory symptoms were identified by investigators from a list of all signs and symptoms with an onset or resolution in the 21 days prior to or 14 days following study entry. Beta-glucan was defined as positive if ≥80 pg/mL and negative if <80 pg/mL. Results Of 252 study participants with a beta-glucan result, 159 had at least one respiratory symptom, 139 of whom had a diagnosis of PCP. The sensitivity of beta-glucan for PCP in participants with respiratory symptoms was 92.8% (95% CI: 87.2%–96.5%), and specificity 75.0% (50.9%–91.3%). Among 134 individuals with positive beta-glucan and respiratory symptoms, 129 had PCP, for a positive predictive value of 96.3% (91.5%–98.8%). Fifteen of 25 patients with a normal beta-glucan did not have PCP, for a negative predictive value of 60% (38.7%–78.9%). Conclusion Elevated plasma beta-glucan has a high predictive value for diagnosis of PCP in AIDS patients with respiratory symptoms. We propose an algorithm for the use of beta-glucan as a diagnostic tool based on the pretest probability of PCP in such patients. PMID:23698062

  7. 6,7-disubstituted 2,4-diaminopteridines: novel inhibitors of Pneumocystis carinii and Toxoplasma gondii dihydrofolate reductase.

    PubMed Central

    Jackson, H C; Biggadike, K; McKilligin, E; Kinsman, O S; Queener, S F; Lane, A; Smith, J E

    1996-01-01

    Four novel, disubstituted diaminopteridines have been identified which antagonize the uptake of a folate precursor (para-aminobenzoic acid) by rat-derived Pneumocystis carinii maintained in short-term axenic culture at concentrations ranging from 4.5 to 26 microM. The compounds were at least 10 to 100 times more active than trimethoprim in this assay. None of these entities exhibited toxicity to mammalian cell lines at < 100 microM. The same structures also caused significant inhibition of Toxoplasma gondii tachyzoite replication within Madin-Darby bovine kidney cells at concentrations ranging from 0.1 to 10 microM. Three of the structures (GR92754, AH10639, and AH2504) were at least an order of magnitude more potent than the standard anti-T. gondii agent, pyrimethamine. All three entities were also significantly more potent and selective than pyrimethamine as inhibitors of T. gondii dihydrofolate reductase (DHFR), with 50% inhibitory concentrations within the range of 0.018 to 0.033 microM. One of these compounds, 6,7-dibutyl-2,4-diaminopteridine (GR92754), was also a potent and selective inhibitor of P. carinii DHFR (50% inhibitory concentration, 0.082 microM). GR92754 is the first DHFR inhibitor described that exhibits greater potency, selectivity, and intracellular activity against both organisms than any of the DHFR agents used clinically, namely, trimethoprim, pyrimethamine, and trimetrexate. This information could provide the starting point for examination of the pharmacokinetic and therapeutic potential of GR92754 and related chemical entities with animal models. PMID:8726003

  8. 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

    Desoubeaux, Guillaume; 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

    2016-05-01

    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

  9. 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. PMID:23470037

  10. Blood (1→3)-β-D-Glucan as a Diagnostic Test for HIV-Related Pneumocystis jirovecii Pneumonia

    PubMed Central

    Komarow, Lauren; Finkelman, Malcolm A.; Grant, Philip M.; Andersen, Janet; Scully, Eileen; Powderly, William G.; Zolopa, Andrew R.

    2011-01-01

    (See the editorial commentary by Morris and Masur, on pages 203–204.) Background. Improved noninvasive diagnostic tests for Pneumocystis jirovecii pneumonia (PCP) are needed. We evaluated the test characteristics of plasma (1→3)-β-D-glucan (β-glucan) for HIV-related PCP among a large group of patients presenting with diverse opportunistic infections (OIs). Methods. The study population included all 282 participants in AIDS Clinical Trials Group A5164, a study of early versus deferred antiretroviral therapy in conjunction with initial therapy of acute OIs. Baseline plasma samples were assayed for β-glucan, with standard assay reference values defining ≥80 pg/mL as positive. Before this analysis, diagnosis of PCP was independently adjudicated by 2 study investigators after reviewing reports from study sites. Results. A total of 252 persons had a β-glucan result that could be analyzed, 173 (69%) of whom had received a diagnosis of PCP. Median β-glucan with PCP was 408 pg/mL (interquartile range [IQR], 209–500 pg/mL), compared with 37 pg/mL (IQR, 31–235 pg/mL) without PCP (P < .001). The sensitivity of β-glucan dichotomized at 80 pg/mL for the diagnosis of PCP was 92% (95% confidence interval [CI], 87%–96%), and the specificity was 65% (95% CI, 53%–75%); positive and negative predictive values were 85% (95% CI, 79%–90%) and 80% (95% CI, 68%–89%) respectively, based on the study prevalence of 69% of patients with PCP. Rates of abnormal lactate dehyrogenase levels did not differ significantly between those with and without PCP. Conclusions. Blood (1→3)-β-D-glucan is strongly correlated with HIV-related PCP. In some clinical centers, this may be a more sensitive test than the induced sputum examination and could reduce the need for both bronchoscopy and empirical therapy of PCP. PMID:21690628

  11. Portable exhausters POR-004 SKID B, POR-005 SKID C, POR-006 SKID D storage plan

    SciTech Connect

    Nelson, O.D.

    1997-09-04

    This document provides a storage plan for portable exhausters POR-004 SKID B, POR-005 SKID C, AND POR-006 SKID D. The exhausters will be stored until they are needed by the TWRS (Tank Waste Remediation Systems) Saltwell Pumping Program. The storage plan provides criteria for portable exhauster storage, periodic inspections during storage, and retrieval from storage.

  12. Update on Pneumocystis carinii f. sp. hominis Typing Based on Nucleotide Sequence Variations in Internal Transcribed Spacer Regions of rRNA Genes

    PubMed Central

    Lee, Chao-Hung; Helweg-Larsen, Jannik; Tang, Xing; Jin, Shaoling; Li, Baozheng; Bartlett, Marilyn S.; Lu, Jang-Jih; Lundgren, Bettina; Lundgren, Jens D.; Olsson, Mats; Lucas, Sebastian B.; Roux, Patricia; Cargnel, Antonietta; Atzori, Chiara; Matos, Olga; Smith, James W.

    1998-01-01

    Pneumocystis carinii f. sp. hominis isolates from 207 clinical specimens from nine countries were typed based on nucleotide sequence variations in the internal transcribed spacer regions I and II (ITS1 and ITS2, respectively) of rRNA genes. The number of ITS1 nucleotides has been revised from the previously reported 157 bp to 161 bp. Likewise, the number of ITS2 nucleotides has been changed from 177 to 192 bp. The number of ITS1 sequence types has increased from 2 to 15, and that of ITS2 has increased from 3 to 14. The 15 ITS1 sequence types are designated types A through O, and the 14 ITS2 types are named types a through n. A total of 59 types of P. carinii f. sp. hominis were found in this study. PMID:9508304

  13. [Neutrophilia in the bronchoalveolar lavage of patients with AIDS and Pneumocystis carinii pneumonia. Reflections on its prognostic value in the Spanish setting].

    PubMed

    Sauleda, J; Gea, J; Aran, X; Gimferrer, E; Conangla, M; Broquetas, J M

    1994-04-01

    The prognostic value of neutrophilia (> 5%) in bronchoalveolar lavage (BAL) in our context is studied in 21 patients with AIDS and Pneumocystis carinii pneumonia. Neutrophilia does not seem to be a good prognostic indicator in our context. We have found this condition, with a mean of 6 +/- 4%, in only 33% of our sample. The sensitivity of this parameter with respect to risk of death was very low (25%), while specificity was moderate (65%). In contrast with what has been reported in studies done with Anglo-Saxon populations, neutrophilia in BAL is probably of little prognostic use in our context. This may be due to various factors, among them the type of population (most being intravenous drug users) and the therapeutic protocol (early empirical treatment). PMID:8025785

  14. A Case of Pneumonia Caused by Pneumocystis Jirovecii and Cryptococcus Neoformans in a Patient with HTLV-1 Associated Adult T- Cell Leukemia/Lymphoma: Occam's Razor Blunted.

    PubMed

    Desai, Anish; Fe, Alexander; Desai, Amishi; Ilowite, Jonathan; Cunha, Burke A; Mathew, Joseph P

    2016-02-01

    Adult T-cell leukemia/lymphoma (ATLL) is usually preceded by infection with human T-cell lymphotropic virus I (HTLV-I). Patients with ATLL frequently get opportunistic infections of the lungs, intestines, and central nervous system. Pneumocystis pneumonia is commonly known as an AIDS defining illness. Grocott's methenamine silver stain of bronchoalveolar lavage (BAL) samples obtained via bronchoscopy remain the gold standard for diagnosis. Pulmonary cryptococcosis is seen in patients with T-cell deficiencies and a diagnosis is made by culture of sputum, BAL, or occasionally of pleural fluid. We present the second case of coinfection with these two organisms in a patient with ATLL who was successfully treated with trimethoprim-sulfamethoxazole, corticosteroids, and fluconazole. We illustrate the need for high clinical vigilance for seeking out an additional diagnosis, especially in immunocompromised patients if they are not improving despite receiving appropriate treatment. PMID:27024978

  15. Pneumocystis jirovecii infection and the associated dihydropteroate synthase (DHPS) and dihydrofolate reductase (DHFR) mutations in HIV-positive individuals from Pune, India.

    PubMed

    Mane, Arati; Gujar, Pankaj; Chandra, Jipsi; Lokhande, Rahul; Dhamgaye, Tilak; Ghorpade, Shivhari; Risbud, Arun

    2015-02-01

    The present study was undertaken to detect Pneumocystis jirovecii infection among HIV-positive patients presenting with symptoms of lower respiratory tract infection and analyze the associated dihydropteroate synthase (DHPS) and dihydrofolate reductase (DHFR) mutations. P. jirovecii infection was detected in 12.6% cases. We did not find DHPS gene mutations at the commonest positions of codon 55 and 57; however, mutation at codon 171 was detected in two cases. No mutations in DHFR gene were detected. The results indicate low prevalence of DHPS and DHFR mutations in Indian P. jirovecii isolates, suggesting that the selective pressure of sulfa drugs on the local strains has probably not reached the levels found in developed nations. PMID:25266324

  16. Analysis of a Population-Based Pneumocystis carinii Pneumonia Index as an Outcome Measure of Access and Quality of Care for the Treatment of HIV Disease

    PubMed Central

    Arno, Peter S.; Gourevitch, Marc N.; Drucker, Ernest; Fang, Jing; Goldberg, Clara; Memmott, Margaret; Bonuck, Karen; Deb, Nandini; Schoenbaum, Ellie

    2002-01-01

    Objectives. A population-based Pneumocystis carinii pneumonia (PCP) Index was developed in New York City to identify geographic areas and subpopulations at increased risk for PCP. Methods. A zip code–level PCP Index was created from AIDS surveillance and hospital discharge records and defined as (number of PCP-related hospitalizations)/(number of persons living with AIDS). Results. In 1997, there were 2262 hospitalizations for PCP among 39 740 persons living with AIDS in New York City (PCP Index = .05691). PCP Index values varied widely across neighborhoods with high AIDS prevalence (West Village = .02532 vs Central Harlem = .08696). Some neighborhoods with moderate AIDS prevalence had strikingly high rates (Staten Island = .14035; northern Manhattan = .08756). Conclusions. The PCP Index highlights communities in particular need of public health interventions to improve HIV-related service delivery. (Am J Public Health. 2002;92:395–398) PMID:11867318

  17. Development and Evaluation of a Real-Time PCR Assay for Detection of Pneumocystis jirovecii on the Fully Automated BD MAX Platform

    PubMed Central

    Hofko, Marjeta; Zimmermann, Stefan

    2013-01-01

    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 (R2 = 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. PMID:23678059

  18. Detection of Pneumocystis jirovecii by Quantitative PCR To Differentiate Colonization and Pneumonia in Immunocompromised HIV-Positive and HIV-Negative Patients.

    PubMed

    Fauchier, T; Hasseine, L; Gari-Toussaint, M; Casanova, V; Marty, P M; Pomares, C

    2016-06-01

    Pneumocystis jirovecii pneumonia (PCP) is an acute and life-threatening lung disease caused by the fungus Pneumocystis jirovecii The presentation of PCP in HIV-positive patients is well-known and consists of a triad of dyspnea, fever, and cough, whereas the presentation of PCP in HIV-negative patients is atypical and consists of a sudden outbreak, O2 desaturation, and a rapid lethal outcome without therapy. Despite the availability of direct and indirect identification methods, the diagnosis of PCP remains difficult. The cycle threshold (CT) values obtained by quantitative PCR (qPCR) allow estimation of the fungal burden. The more elevated that the fungal burden is, the higher the probability that the diagnosis is pneumonia. The purposes of the present study were to evaluate the CT values to differentiate colonization and pneumonia in a population of immunocompromised patients overall and patients stratified on the basis of their HIV infection status. Testing of bronchoalveolar lavage (BAL) fluid samples from the whole population of qPCR-positive patients showed a mean CT value for patients with PCP of 28 (95% confidence interval [CI], 26 to 30) and a mean CT value for colonized patients of 35 (95% CI, 34 to 36) (P < 10(-3)). For the subgroup of HIV-positive patients, we demonstrated that a CT value below 27 excluded colonization and a CT value above 30 excluded PCP with a specificity of 100% and a sensitivity of 80%, respectively. In the subgroup of HIV-negative patients, we demonstrated that a CT value below 31 excluded colonization and a CT value above 35 excluded PCP with a specificity of 80% and a sensitivity of 80%, respectively. Thus, qPCR of BAL fluid samples is an important tool for the differentiation of colonization and pneumonia in P. jirovecii-infected immunocompromised patients and patients stratified on the basis of HIV infection status with different CT values. PMID:27008872

  19. Clinically HIV but negative serology: Think of idiopathic CD4+ lymphocytopenia

    PubMed Central

    Nagar, Vidya Sanjay; Kadu, Rahul; Chauhan, Shamshersingh Gajendra; Chatterjee, Rudrarpan; Kaushik, Aniruddha; Patel, Deniskumar Vashrambhai; Sood, Ankita

    2016-01-01

    idiopathic CD4+ lymphocytopenia (ICL) is a rare disorder characterized by the presence of depleted CD4 cell line without the presence of HIV infection. Slight male preponderance is noticed and is usually seen in the middle age group. Opportunistic infections are the reason for their discovery and here we describe a case where a man was diagnosed as having Pneumocystis jiroveci pneumonia and oral candidiasis. PMID:27390465

  20. Pneumocystis Pneumonia (PCP)

    MedlinePlus

    ... a drug that is usually inhaled in an aerosol form to prevent PCP. Pentamidine is also used ... between $120 and $250 per month. Patients using aerosol pentamidine get PCP more often than people taking ...

  1. 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.

  2. 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. PMID:25631478

  3. 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 Central

    Gago, Sara; Esteban, Cristina; Valero, Clara; Zaragoza, Óscar; Puig de la Bellacasa, Jorge

    2014-01-01

    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 (r2 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. PMID:24478409

  4. 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

  5. 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. PMID:27579328

  6. Pneumocystis carinii (jirovecii) pneumonia (PCP): the most common opportunistic infection observed in HIV/AIDS cases at the University Malaya Medical Centre, Kuala Lumpur, Malaysia.

    PubMed

    Jamaiah, I; Rohela, M; Tok, E L; Tan, C L; Tan, W H; Teo, W S; Leow, H F

    2012-07-01

    This retrospective study was conducted among 59 HIV/AIDS patients with opportunistic infections admitted to the University Malaya Medical Centre between 2000 and 2009. Fifty-five point nine percent of cases were Chinese, 25.4% were Malays, 11.9% were Indians and 6.8% were of unknown ethnic origin. The male:female ratio was 2.9:1 (44 males and 15 females). The highest prevalence (38.9%) occurred in the 30-39 year old age group. Men comprised 47.7% and women 53.3%; the majority of both were married. The majority of cases were Malaysians (89.8%) and the rest (10.2%) were immigrants. Most of the patients (18.6%) were non-laborers, followed by laborers (11.9%), the unemployed (5.1%) and housewives (3.4%). The most common risk factor was unprotected sexual activity (20.3%). The two most common HIV/AIDS related opportunistic infections were Pneumocystis carinii (jirovecii) pneumonia (PCP) (62.7%) and toxoplasmosis (28.8%). Seventy-two point nine percent of patients had a CD4 count <200 cells/microl and 5.1% had a CD4 count >500 cells/microl. Eleven point nine percent of cases died during study period. A low CD4 count had a greater association with opportunistic infections. Most of the patients presented with fever (44.1%), cough (42.4%) and shortness of breath (28.8%). Detection of the etiologic pathogens aids clinicians in choosing appropriate management strategies. PMID:23077803

  7. Post-diagnostic Kinetics of the (1→3)-β-D-Glucan Assay in Invasive Aspergillosis, Invasive Candidiasis, and Pneumocystis jirovecii Pneumonia

    PubMed Central

    Koo, Sophia; Baden, Lindsey R.; Marty, Francisco M.

    2012-01-01

    The kinetics of serum (1→3)-β-D-glucan (BG) following the diagnosis of invasive fungal disease and administration of antifungal therapy are poorly characterized. It is unknown whether early BG changes have prognostic implications. We assessed the post-diagnostic kinetics of BG in patients with an initial serum BG ≥80 pg/mL and at least one additional post-diagnostic BG value in the setting of invasive aspergillosis (IA, n=69), invasive candidiasis (IC, n=40), or Pneumocystis jirovecii pneumonia (PCP, n=18), treated with antifungal therapy. Clinical failure of antifungal therapy and mortality were assessed at 6 and 12 weeks, and Cox modeling was used to assess the hazard of initial BG and change in BG at 1 or 2 weeks for these outcomes. In patients with ≥2 BG values, median initial BG was >500 pg/mL (IQR (interquartile range) 168, >500; range 80, >500) in IA, 136 pg/mL (IQR 88, >500; range 31, >500) in IC, and >500 pg/mL (IQR 235, >500; range 86, >500) in PCP. In patients with ≥2 BG values through one week after diagnosis, overall one-week decline in BG was 0 pg/mL (IQR 0, 53) in IA, 0 (IQR −65, 12) in IC, and 17 (IQR 0, 82) in PCP. Most patients with BG values through 6 and 12 weeks had persistent levels >80 pg/mL. Initial BG and the early trajectory of BG were not predictive of 6 or 12-week clinical failure or mortality. While BG eventually declines in patients with IA, IC, and PCP, it lacks prognostic value within a clinically meaningful time frame. PMID:22404638

  8. 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

  9. Multicenter Study of Trimethoprim/Sulfamethoxazole-Related Hepatotoxicity: Incidence and Associated Factors among HIV-Infected Patients Treated for Pneumocystis jirovecii Pneumonia

    PubMed Central

    Yang, Jen-Jia; Huang, Chung-Hao; Liu, Chun-Eng; Tang, Hung-Jen; Yang, Chia-Jui; Lee, Yi-Chien; Lee, Kuan-Yeh; Tsai, Mao-Song; Lin, Shu-Wen; Chen, Yen-Hsu; Lu, Po-Liang; Hung, Chien-Ching

    2014-01-01

    The incidence of hepatotoxicity related to trimethoprim/sulfamethoxazole (TMP/SMX) administered at a therapeutic dose may vary among study populations of different ethnicities and hepatotoxic metabolites of TMP/SMX may be decreased by drug-drug interaction with fluconazole. We aimed to investigate the incidence of hepatotoxicity and the role of concomitant use of fluconazole in HIV-infected patients receiving TMP/SMX for Pneumocystis jirovecii pneumonia. We reviewed medical records to collect clinical characteristics and laboratory data of HIV-infected patients who received TMP/SMX for treatment of P. jirovecii pneumonia at 6 hospitals around Taiwan between September 2009 and February 2013. Hepatotoxicity was defined as 2-fold or greater increase of aminotransferase or total bilirubin level from baselines. Roussel UCLAF Causality Assessment Method (RUCAM) was used to analyze the causality of drug-induced liver injuries. NAT1 and NAT2 acetylator types were determined with the use of polymerase-chain-reaction (PCR) restriction fragment length polymorphism to differentiate common single-nucleotide polymorphisms (SNPs) predictive of the acetylator phenotypes in a subgroup of patients. During the study period, 286 courses of TMP/SMX treatment administered to 284 patients were analyzed. One hundred and fifty-two patients (53.1%) developed hepatotoxicity, and TMP/SMX was considered causative in 47 (16.4%) who had a RUCAM score of 6 or greater. In multivariate analysis, concomitant use of fluconazole for candidiasis was the only factor associated with reduced risk for hepatotoxicity (adjusted odds ratio, 0.372; 95% confidence interval, 0.145–0.957), while serostatus of hepatitis B or C virus, NAT1 and NAT2 acetylator types, or receipt of combination antiretroviral therapy was not. The incidence of hepatotoxicity decreased with an increasing daily dose of fluconazole up to 4.0 mg/kg. We conclude that the incidence of TMP/SMX-related hepatotoxicity was 16.4% in HIV

  10. Multicenter study of trimethoprim/sulfamethoxazole-related hepatotoxicity: incidence and associated factors among HIV-infected patients treated for Pneumocystis jirovecii pneumonia.

    PubMed

    Yang, Jen-Jia; Huang, Chung-Hao; Liu, Chun-Eng; Tang, Hung-Jen; Yang, Chia-Jui; Lee, Yi-Chien; Lee, Kuan-Yeh; Tsai, Mao-Song; Lin, Shu-Wen; Chen, Yen-Hsu; Lu, Po-Liang; Hung, Chien-Ching

    2014-01-01

    The incidence of hepatotoxicity related to trimethoprim/sulfamethoxazole (TMP/SMX) administered at a therapeutic dose may vary among study populations of different ethnicities and hepatotoxic metabolites of TMP/SMX may be decreased by drug-drug interaction with fluconazole. We aimed to investigate the incidence of hepatotoxicity and the role of concomitant use of fluconazole in HIV-infected patients receiving TMP/SMX for Pneumocystis jirovecii pneumonia. We reviewed medical records to collect clinical characteristics and laboratory data of HIV-infected patients who received TMP/SMX for treatment of P. jirovecii pneumonia at 6 hospitals around Taiwan between September 2009 and February 2013. Hepatotoxicity was defined as 2-fold or greater increase of aminotransferase or total bilirubin level from baselines. Roussel UCLAF Causality Assessment Method (RUCAM) was used to analyze the causality of drug-induced liver injuries. NAT1 and NAT2 acetylator types were determined with the use of polymerase-chain-reaction (PCR) restriction fragment length polymorphism to differentiate common single-nucleotide polymorphisms (SNPs) predictive of the acetylator phenotypes in a subgroup of patients. During the study period, 286 courses of TMP/SMX treatment administered to 284 patients were analyzed. One hundred and fifty-two patients (53.1%) developed hepatotoxicity, and TMP/SMX was considered causative in 47 (16.4%) who had a RUCAM score of 6 or greater. In multivariate analysis, concomitant use of fluconazole for candidiasis was the only factor associated with reduced risk for hepatotoxicity (adjusted odds ratio, 0.372; 95% confidence interval, 0.145-0.957), while serostatus of hepatitis B or C virus, NAT1 and NAT2 acetylator types, or receipt of combination antiretroviral therapy was not. The incidence of hepatotoxicity decreased with an increasing daily dose of fluconazole up to 4.0 mg/kg. We conclude that the incidence of TMP/SMX-related hepatotoxicity was 16.4% in HIV

  11. Evolution of NADPH-cytochrome P450 oxidoreductases (POR) in Apiales - POR 1 is missing.

    PubMed

    Andersen, Trine Bundgaard; Hansen, Niels Bjørn; Laursen, Tomas; Weitzel, Corinna; Simonsen, Henrik Toft

    2016-05-01

    The NADPH-dependent cytochrome P450 oxidoreductase (POR) is the obligate electron donor to eukaryotic microsomal cytochromes P450 enzymes. The number of PORs within plant species is limited to one to four isoforms, with the most common being two PORs per plant. These enzymes provide electrons to a huge number of different cytochromes P450s (from 50 to several hundred within one plant). Within the eudicotyledons, PORs can be divided into two major clades, POR 1 and POR 2. Based on our own sequencing analysis and publicly available data, we have identified 45 PORs from the angiosperm order Apiales. These were subjected to a phylogenetic analysis along with 237 other publicly available (NCBI and oneKP) POR sequences found within the clade Asterids. Here, we show that the order Apiales only harbor members of the POR 2 clade, which are further divided into two distinct subclades. This is in contrast to most other eudicotyledon orders that have both POR 1 and POR 2. This suggests that through gene duplications and one gene deletion, Apiales only contain members of the POR 2 clade. Three POR 2 isoforms from Thapsia garganica L., Apiaceae, were all full-length in an Illumina root transcriptome dataset (available from the SRA at NCBI). All three genes were shown to be functional upon reconstitution into nanodiscs, confirming that none of the isoforms are pseudogenes. PMID:26854662

  12. Portable exhauster POR-007/Skid E and POR-008/Skid F storage plan

    SciTech Connect

    Nelson, O.D.

    1998-07-25

    This document provides storage requirements for 1,000 CFM portable exhausters POR-O07/Skid E and POR-008/Skid F. These requirements are presented in three parts: preparation for storage, storage maintenance and testing, and retrieval from storage. The exhauster component identification numbers listed in this document contain the prefix POR-007 or POR-008 depending on which exhauster is being used.

  13. Imaging infection.

    PubMed

    Ketai, Loren; Jordan, Kirk; Busby, Katrina H

    2015-06-01

    Thoracic imaging is widely used to detect lower respiratory tract infections, identify their complications, and aid in differentiating infectious from noninfectious thoracic disease. Less commonly, the combination of imaging findings and a clinical setting can favor infection with a specific organism. This confluence can occur in cases of bronchiectatic nontuberculous mycobacterial infections in immune-competent hosts, invasive fungal disease among neutropenic patients, Pneumocystis jiroveci pneumonia in patients with AIDS, and in cytomegalovirus infections in patients with recent hematopoietic cell transplantation. These specific diagnoses often depend on computed tomography scanning rather than chest radiography alone. PMID:26024600

  14. Value of anti-infective chemoprophylaxis in primary systemic vasculitis: what is the evidence?

    PubMed Central

    2009-01-01

    Although infections are a major concern in patients with primary systemic vasculitis, actual knowledge about risk factors and evidence concerning the use of anti-infective prophylaxis from clinical trials are scarce. The use of high dose glucocorticoids and cyclophosphamide pose a definite risk for infections. Bacterial infections are among the most frequent causes of death, with Staphylococcus aureus being the most common isolate. Concerning viral infections, cytomegalovirus and varicella-zoster virus reactivation represent the most frequent complications. The only prophylactic measure that is widely accepted is trimethoprim/sulfamethoxazole to avoid Pneumocystis jiroveci pneumonia in small vessel vasculitis patients with generalised disease receiving therapy for induction of remission. PMID:19886977

  15. Consequences of POR mutations and polymorphisms.

    PubMed

    Miller, Walter L; Agrawal, Vishal; Sandee, Duanpen; Tee, Meng Kian; Huang, Ningwu; Choi, Ji Ha; Morrissey, Kari; Giacomini, Kathleen M

    2011-04-10

    P450 oxidoreductase (POR) transports electrons from NADPH to all microsomal cytochrome P450 enzymes, including steroidogenic P450c17, P450c21 and P450aro. Severe POR mutations A287P (in Europeans) and R457H (in Japanese) cause the Antley-Bixler skeletal malformation syndrome (ABS) plus impaired steroidogenesis (causing genital anomalies), but the basis of ABS is unclear. We have characterized the activities of ∼40 POR variants, showing that assays based on P450c17 activities, but not cytochrome c assays, correlate with the clinical phenotype. The human POR gene is highly polymorphic: the A503V sequence variant, which decreases P450c17 activities to ∼60%, is found on ∼28% of human alleles. A promoter polymorphism (∼8% of Asians and ∼13% of Caucasians) at -152 reduces transcriptional activity by half. Screening of 35 POR variants showed that most mutants lacking activity with P450c17 or cytochrome c also lacked activity to support CYP1A2 and CYP2C19 metabolism of EOMCC (a fluorogenic non-drug substrate), although there were some remarkable differences: Q153R causes ABS and has ∼30% of wild-type activity with P450c17 but had 144% of WT activity with CYP1A2 and 284% with CYP2C19. The effects of POR variants on CYP3A4, which metabolizes nearly 50% of clinically used drugs, was examined with multiple, clinically relevant drug substrates, showing that A287P and R457H dramatically reduce drug metabolism, and that A503V variably impairs drug metabolism. The degree of activity can vary with the drug substrate assayed, as the drugs can influence the conformation of the P450. POR is probably an important contributor to genetic variation in both steroidogenesis and drug metabolism. PMID:21070833

  16. Consequences of POR mutations and polymorphisms

    PubMed Central

    Miller, Walter L.; Agrawal, Vishal; Sandee, Duanpen; Tee, Meng Kian; Huang, Ningwu; Choi, Ji Ha; Morrissey, Kari; Giacomini, Kathleen M.

    2015-01-01

    P450 oxidoreductase (POR) transports electrons from NADPH to all microsomal cytochrome P450 enzymes, including steroidogenic P450c17, P450c21 and P450aro. Severe POR mutations A287P (in Europeans) and R457H (in Japanese) cause the Antley-Bixler skeletal malformation syndrome (ABS) plus impaired steroidogenesis (causing genital anomalies), but the basis of ABS is unclear. We have characterized the activities of ~40 POR variants, showing that assays based on P450c17 activities, but not cytochrome c assays, correlate with the clinical phenotype. The human POR gene is highly polymorphic: the A503V sequence variant, which decreases P450c17 activities to ~60%, is found on ~28% of human alleles. A promoter polymorphism (~8% of Asians and ~13% of Caucasians) at −152 reduces transcriptional activity by half. Screening of 35 POR variants showed that most mutants lacking activity with P450c17 or cytochrome c also lacked activity to support CYP1A2 and CYP2C19 metabolism of EOMCC (a fluorogenic non-drug substrate), although there were some remarkable differences: Q153R causes ABS and has ~30% of wild-type activity with P450c17 but had 144% of WT activity with CYP1A2 and 284% with CYP2C19. The effects of POR variants on CYP3A4, which metabolizes nearly 50% of clinically used drugs, was examined with multiple, clinically-relevant drug substrates, showing that A287P and R457H dramatically reduce drug metabolism, and that A503V variably impairs drug metabolism. The degree of activity can vary with the drug substrate assayed, as the drugs can influence the conformation of the P450. POR is probably an important contributor to genetic variation in both steroidogenesis and drug metabolism. PMID:21070833

  17. Desigualdades por cáncer

    Cancer.gov

    Información básica de las desigualdades en salud por cáncer en EE. UU., factores que contribuyen a la carga desproporcionada del cáncer en algunos grupos y ejemplos de desigualdades en incidencia y mortalidad entre ciertos grupos de la población.

  18. Structural Insights into the PorK and PorN Components of the Porphyromonas gingivalis Type IX Secretion System

    PubMed Central

    Gorasia, Dhana G.; Veith, Paul D.; Hanssen, Eric G.; Glew, Michelle D.; Sato, Keiko; Yukitake, Hideharu; Nakayama, Koji; Reynolds, Eric C.

    2016-01-01

    The type IX secretion system (T9SS) has been recently discovered and is specific to Bacteroidetes species. Porphyromonas gingivalis, a keystone pathogen for periodontitis, utilizes the T9SS to transport many proteins including the gingipain virulence factors across the outer membrane and attach them to the cell surface via a sortase-like mechanism. At least 11 proteins have been identified as components of the T9SS including PorK, PorL, PorM, PorN and PorP, however the precise roles of most of these proteins have not been elucidated and the structural organization of these components is unknown. In this study, we purified PorK and PorN complexes from P. gingivalis and using electron microscopy we have shown that PorN and the PorK lipoprotein interact to form a 50 nm diameter ring-shaped structure containing approximately 32–36 subunits of each protein. The formation of these rings was dependent on both PorK and PorN, but was independent of PorL, PorM and PorP. PorL and PorM were found to form a separate stable complex. PorK and PorN were protected from proteinase K cleavage when present in undisrupted cells, but were rapidly degraded when the cells were lysed, which together with bioinformatic analyses suggests that these proteins are exposed in the periplasm and anchored to the outer membrane via the PorK lipid. Chemical cross-linking and mass spectrometry analyses confirmed the interaction between PorK and PorN and further revealed that they interact with the PG0189 outer membrane protein. Furthermore, we established that PorN was required for the stable expression of PorK, PorL and PorM. Collectively, these results suggest that the ring-shaped PorK/N complex may form part of the secretion channel of the T9SS. This is the first report showing the structural organization of any T9SS component. PMID:27509186

  19. Structural Insights into the PorK and PorN Components of the Porphyromonas gingivalis Type IX Secretion System.

    PubMed

    Gorasia, Dhana G; Veith, Paul D; Hanssen, Eric G; Glew, Michelle D; Sato, Keiko; Yukitake, Hideharu; Nakayama, Koji; Reynolds, Eric C

    2016-08-01

    The type IX secretion system (T9SS) has been recently discovered and is specific to Bacteroidetes species. Porphyromonas gingivalis, a keystone pathogen for periodontitis, utilizes the T9SS to transport many proteins including the gingipain virulence factors across the outer membrane and attach them to the cell surface via a sortase-like mechanism. At least 11 proteins have been identified as components of the T9SS including PorK, PorL, PorM, PorN and PorP, however the precise roles of most of these proteins have not been elucidated and the structural organization of these components is unknown. In this study, we purified PorK and PorN complexes from P. gingivalis and using electron microscopy we have shown that PorN and the PorK lipoprotein interact to form a 50 nm diameter ring-shaped structure containing approximately 32-36 subunits of each protein. The formation of these rings was dependent on both PorK and PorN, but was independent of PorL, PorM and PorP. PorL and PorM were found to form a separate stable complex. PorK and PorN were protected from proteinase K cleavage when present in undisrupted cells, but were rapidly degraded when the cells were lysed, which together with bioinformatic analyses suggests that these proteins are exposed in the periplasm and anchored to the outer membrane via the PorK lipid. Chemical cross-linking and mass spectrometry analyses confirmed the interaction between PorK and PorN and further revealed that they interact with the PG0189 outer membrane protein. Furthermore, we established that PorN was required for the stable expression of PorK, PorL and PorM. Collectively, these results suggest that the ring-shaped PorK/N complex may form part of the secretion channel of the T9SS. This is the first report showing the structural organization of any T9SS component. PMID:27509186

  20. The PorX Response Regulator of the Porphyromonas gingivalis PorXY Two-Component System Does Not Directly Regulate the Type IX Secretion Genes but Binds the PorL Subunit

    PubMed Central

    Vincent, Maxence S.; Durand, Eric; Cascales, Eric

    2016-01-01

    The Type IX secretion system (T9SS) is a versatile multi-protein complex restricted to bacteria of the Bacteriodetes phylum and responsible for the secretion or cell surface exposition of diverse proteins that participate to S-layer formation, gliding motility or pathogenesis. The T9SS is poorly characterized but a number of proteins involved in the assembly of the secretion apparatus in the oral pathogen Porphyromonas gingivalis have been identified based on genome substractive analyses. Among these proteins, PorY, and PorX encode typical two-component system (TCS) sensor and CheY-like response regulator respectively. Although the porX and porY genes do not localize at the same genetic locus, it has been proposed that PorXY form a bona fide TCS. Deletion of porX in P. gingivalis causes a slight decrease of the expression of a number of other T9SS genes, including sov, porT, porP, porK, porL, porM, porN, and porY. Here, we show that PorX and the soluble cytoplasmic domain of PorY interact. Using electrophoretic mobility shift, DNA-protein co-purification and heterologous host expression assays, we demonstrate that PorX does not bind T9SS gene promoters and does not directly regulate expression of the T9SS genes. Finally, we show that PorX interacts with the cytoplasmic domain of PorL, a component of the T9SS membrane core complex and propose that the CheY-like PorX protein might be involved in the dynamics of the T9SS.

  1. Identification of Porphyromonas gingivalis proteins secreted by the Por secretion system.

    PubMed

    Sato, Keiko; Yukitake, Hideharu; Narita, Yuka; Shoji, Mikio; Naito, Mariko; Nakayama, Koji

    2013-01-01

    The Gram-negative bacterium Porphyromonas gingivalis possesses a number of potential virulence factors for periodontopathogenicity. In particular, cysteine proteinases named gingipains are of interest given their abilities to degrade host proteins and process other virulence factors such as fimbriae. Gingipains are translocated on the cell surface or into the extracellular milieu by the Por secretion system (PorSS), which consists of a number of membrane or periplasmic proteins including PorK, PorL, PorM, PorN, PorO, PorP, PorQ, PorT, PorU, PorV (PG27, LptO), PorW and Sov. To identify proteins other than gingipains secreted by the PorSS, we compared the proteomes of P. gingivalis strains kgp rgpA rgpB (PorSS-proficient strain) and kgp rgpA rgpB porK (PorSS-deficient strain) using two-dimensional gel electrophoresis and peptide-mass fingerprinting. Sixteen spots representing 10 different proteins were present in the particle-free culture supernatant of the PorSS-proficient strain but were absent or faint in that of the PorSS-deficient strain. These identified proteins possessed the C-terminal domains (CTDs), which had been suggested to form the CTD protein family. These results indicate that the PorSS is used for secretion of a number of proteins other than gingipains and that the CTDs of the proteins are associated with the PorSS-dependent secretion. PMID:23075153

  2. System design description for portable 1,000 CFM exhauster Skids POR-007/Skid E and POR-008/Skid F

    SciTech Connect

    Nelson, O.D.

    1998-07-25

    The primary purpose of the two 1,000 CFM Exhauster Skids, POR-007-SKID E and POR-008-SKID F, is to provide backup to the waste tank primary ventilation systems for tanks 241-C-106 and 241-AY-102, and the AY-102 annulus in the event of a failure during the sluicing of tank 241-C-106 and subsequent transfer of sluiced waste to 241-AY-102. This redundancy is required since both of the tank ventilation systems have been declared as Safety Class systems.

  3. Disminuyen en los Estados Unidos las infecciones por VPH.

    Cancer.gov

    La infección por los tipos del virus del papiloma humano (VPH) en el blanco de la vacuna cuadrivalente se redujo en casi dos tercios en las adolescentes desde que se recomendó la vacunación en los Estados Unidos.

  4. Centros oncológicos designados por el NCI

    Cancer.gov

    El programa de centros oncológicos designados por el Instituto Nacional del Cáncer (NCI) reconoce a los centros de todo el país que cumplen con rigurosos criterios para participar en proyectos avanzados de primer nivel para la investigación multidisciplinaria del cáncer.

  5. Disseminated mycobacterium avium complex as protein-losing enteropathy in a non-HIV patient.

    PubMed

    Konjeti, Venkata Rajesh; Paluri, Sravanthi

    2014-01-01

    Disseminated mycobacterium avium complex (MAC) causing protein-losing enteropathy (PLE) due to intestinal lymphangiectasia (IL) in a non-HIV immunocompromised state is extremely rare. We present a case of 56-year-old male who was evaluated for worsening dyspnea and found to have right-sided chylous pleural effusion as well as worsening abdominal and retroperitoneal lymphadenopathy. He had a history of psoriasis for which hewas on etanercept and alefacept which were stopped two years prior to the presentation. The evaluation revealed a MAC infection in his lymph nodes--a low CD4 count but negative for HIV. He was started on MAC therapy. He subsequently developed noninfectious diarrhea, Hypoalbuminemia, recurrentpleural effusions, ascites, and Pneumocystis jiroveci pneumonia (PJP). Despite appropriate antibiotics and management--including total parental nutrition (TPN) with a medium-chain triglyceride enriched low fat diet--the patient's clinical condition deteriorated rapidly resulting in death. PMID:25672059

  6. [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. PMID:17728918

  7. Aspergillosis in a Patient Receiving Temozolomide for the Treatment of Glioblastoma

    PubMed Central

    Munhoz, Rodrigo Ramella; Pereira Picarelli, Andrea Arvai; Troques Mitteldorf, Cristina Aparecida; Feher, Olavo

    2013-01-01

    Leukopenia and selective CD4+ lymphopenia represent major adverse events associated with the use of temozolomide (TMZ), an oral alkylating agent incorporated in the treatment of glioblastoma (GBM). The increased risk of opportunistic infections, including those caused by Pneumocystis jiroveci and cytomegalovirus, has been previously described in the literature. Here we report the case, the first to our knowledge, of a patient with pulmonary invasive aspergillosis immediately after the completion of chemoradiation with TMZ for GBM. Diagnosis was confirmed through a CT-guided lung biopsy, and the patient had excellent response to systemic voriconazole. This case illustrates that TMZ can be associated with severe opportunistic infections, presumably associated with T lymphocyte immune dysfunction, and patients exposed to this agent should be carefully monitored. PMID:24019780

  8. Se evitaron casi 800 000 muertes por descenso del tabaquismo

    Cancer.gov

    Programas y estrategias de control del tabaco del siglo XX fueron responsables de la prevención de más de 795 000 muertes por cáncer de pulmón en Estados Unidos de 1975 al 2000. Si todo el tabaquismo en este país hubiera cesado después de la publicación d

  9. Neisseria meningitidis Lacking the Major Porins PorA and PorB Is Viable and Modulates Apoptosis and the Oxidative Burst of Neutrophils.

    PubMed

    Peak, Ian R; Chen, Adrienne; Jen, Freda E-C; Jennings, Courtney; Schulz, Benjamin L; Saunders, Nigel J; Khan, Arshad; Seifert, H Steven; Jennings, Michael P

    2016-08-01

    The bacterial pathogen Neisseria meningitidis expresses two major outer-membrane porins. PorA expression is subject to phase-variation (high frequency, random, on-off switching), and both PorA and PorB are antigenically variable between strains. PorA expression is variable and not correlated with meningococcal colonisation or invasive disease, whereas all naturally-occurring strains express PorB suggesting strong selection for expression. We have generated N. meningitidis strains lacking expression of both major porins, demonstrating that they are dispensable for bacterial growth in vitro. The porAB mutant strain has an exponential growth rate similar to the parental strain, as do the single porA or porB mutants, but the porAB mutant strain does not reach the same cell density in stationary phase. Proteomic analysis suggests that the double mutant strain exhibits compensatory expression changes in proteins associated with cellular redox state, energy/nutrient metabolism, and membrane stability. On solid media, there is obvious growth impairment that is rescued by addition of blood or serum from mammalian species, particularly heme. These porin mutants are not impaired in their capacity to inhibit both staurosporine-induced apoptosis and a phorbol 12-myristate 13-acetate-induced oxidative burst in human neutrophils suggesting that the porins are not the only bacterial factors that can modulate these processes in host cells. PMID:26562068

  10. Compton imaging with the PorGamRays spectrometer

    NASA Astrophysics Data System (ADS)

    Judson, D. S.; Boston, A. J.; Coleman-Smith, P. J.; Cullen, D. M.; Hardie, A.; Harkness, L. J.; Jones, L. L.; Jones, M.; Lazarus, I.; Nolan, P. J.; Pucknell, V.; Rigby, S. V.; Seller, P.; Scraggs, D. P.; Simpson, J.; Slee, M.; Sweeney, A.; PorGamRays Collaboration

    2011-10-01

    The PorGamRays project aims to develop a portable gamma-ray detection system with both spectroscopic and imaging capabilities. The system is designed around a stack of thin Cadmium Zinc Telluride (CZT) detectors. The imaging capability utilises the Compton camera principle. Each detector is segmented into 100 pixels which are read out through custom designed Application Specific Integrated Circuits (ASICs). This device has potential applications in the security, decommissioning and medical fields. This work focuses on the near-field imaging performance of a lab-based demonstrator consisting of two pixelated CZT detectors, each of which is bonded to a NUCAM II ASIC. Measurements have been made with point 133Ba and 57Co sources located ˜35 mm from the surface of the scattering detector. Position resolution of ˜20 mm FWHM in the x and y planes is demonstrated.

  11. Acceptance test report for portable exhauster POR-007/Skid E

    SciTech Connect

    Kriskovich, J.R.

    1998-07-24

    This document describes Acceptance Testing performed on Portable Exhauster POR-007/Skid E. It includes measurements of bearing vibration levels, pressure decay testing, programmable logic controller interlocks, high vacuum, flow and pressure control functional testing. The purpose of Acceptance testing documented by this report was to demonstrate compliance of the exhausters with the performance criteria established within HNF-0490, Rev. 1 following a repair and upgrade effort at Hanford. In addition, data obtained during this testing is required for the resolution of outstanding Non-conformance Reports (NCR), and finally, to demonstrate the functionality of the associated software for the pressure control and high vacuum exhauster operating modes provided for by W-320. Additional testing not required by the ATP was also performed to assist in the disposition and close out of receiving inspection report and for application design information (system curve). Results of this testing are also captured within this document.

  12. Typing and surface charges of the variable loop regions of PorB from Neisseria meningitidis.

    PubMed

    Stefanelli, Paola; Neri, Arianna; Tanabe, Mikio; Fazio, Cecilia; Massari, Paola

    2016-06-01

    PorB is a pan-Neisserial major outer membrane protein with a trimeric β-barrel structure. Each monomer presents eight periplasmic turns and eight surface exposed loop regions with sequence variability. PorB induces activation of host cell responses via a TLR2-dependent mechanism likely mediated by electrostatic interactions between TLR2 and PorB surface exposed loops. Variability in the loop amino acid sequence is known to influence cell responses to PorB in vitro, particularly for the residues in L5 and L7. In this work, the sequence of the porB gene and the electrostatic surface charges of PorB from 35 invasive meningococcal isolates belonging to the main clonal complexes identified in Italy and from five carriage genomes available on the website http://pubmlst.org/neisseria/ were examined. Analysis of the porB encoding regions from the invasive meningococci has identified four new alleles and a potential association between porB alleles, serogroup, and clonal complexes. Through computer-based modeling and analysis of the electrostatic surface charges of PorB from these strains, loop charge segregation between PorB from invasive serogroups B and C was observed. Specifically, loops 1, 4, and 7 were negatively charged and L2 and L8 were mostly neutral in serogroup B isolates, while an overall homogeneous positive surface charge was present in PorB from invasive serogroup C strains. A higher PorB sequence variability was observed among carriage genomes, and a general prevalence of negative loop surface charges. The surface charge differences in PorB from serogroups B and C invasive and carriage strains may, in part, influence the outcomes of Neisseriae interactions with host cells. © 2016 IUBMB Life, 68(6):488-495, 2016. PMID:27156582

  13. Acceptance test report for portable exhauster POR-008/Skid F

    SciTech Connect

    Kriskovich, J.R.

    1998-07-24

    Portable Exhauster POR-008 was procured via HNF-0490, Specification for a Portable Exhausted System for Waste Tank Ventilation. Prior to taking ownership, acceptance testing was performed at the vendors. However at the conclusion of testing a number of issues remained that required resolution before the exhausters could be used by Project W-320. The purpose of acceptance testing documented by this report was to demonstrate compliance of the exhausters with the performance criteria established within HNF-O49O, Rev. 1 following a repair and upgrade effort at Hanford. In addition, data obtained during this testing is required for the resolution of outstanding Non-conformance Reports (NCR), and finally, to demonstrate the functionality of the associated software for the pressure control and high vacuum exhauster operating modes provided for by W-320. Additional testing not required by the ATP was also performed to assist in the disposition and close out of receiving inspection report and for application design information (system curve). Results of this testing are also captured within this document.

  14. VDAC and the bacterial porin PorB of Neisseria gonorrhoeae share mitochondrial import pathways.

    PubMed

    Müller, Anne; Rassow, Joachim; Grimm, Jan; Machuy, Nikolaus; Meyer, Thomas F; Rudel, Thomas

    2002-04-15

    The human pathogen Neisseria gonorrhoeae induces host cell apoptosis during infection by delivering the outer membrane protein PorB to the host cell's mitochondria. PorB is a pore-forming beta-barrel protein sharing several features with the mitochondrial voltage-dependent anion channel (VDAC), which is involved in the regulation of apoptosis. Here we show that PorB of pathogenic Neisseria species produced by host cells is efficiently targeted to mitochondria. Imported PorB resides in the mitochondrial outer membrane and forms multimers with similar sizes as in the outer bacterial membrane. The mitochondria completely lose their membrane potential, a characteristic previously observed in cells infected with gonococci or treated with purified PorB. Closely related bacterial porins of non-pathogenic Neisseria mucosa or Escherichia coli remain in the cytosol. Import of PorB into mitochondria in vivo is independent of a linear signal sequence. Insertion of PorB into the mitochondrial outer membrane in vitro depends on the activity of Tom5, Tom20 and Tom40, but is independent of Tom70. Our data show that human VDAC and bacterial PorB are imported into mitochondria by a similar mechanism. PMID:11953311

  15. Successful Mnemonics for "por"/"para" and Affirmative Commands with Pronouns.

    ERIC Educational Resources Information Center

    Mason, Keith

    1992-01-01

    Two mnemonic devices, "4A Rule" and "PERFECT," are described to simplify the learning of two grammar points: the placement of object pronouns with respect to commands and the distinction between "por" and "para." (five references) (LB)

  16. Genome Sequences of Pseudomonas oryzihabitans Phage POR1 and Pseudomonas aeruginosa Phage PAE1.

    PubMed

    Dyson, Zoe A; Seviour, Robert J; Tucci, Joseph; Petrovski, Steve

    2016-01-01

    We report the genome sequences of two double-stranded DNA siphoviruses, POR1 infective for Pseudomonas oryzihabitans and PAE1 infective for Pseudomonas aeruginosa The phage POR1 genome showed no nucleotide sequence homology to any other DNA phage sequence in the GenBank database, while phage PAE1 displayed synteny to P. aeruginosa phages M6, MP1412, and YuA. PMID:27313312

  17. Genome Sequences of Pseudomonas oryzihabitans Phage POR1 and Pseudomonas aeruginosa Phage PAE1

    PubMed Central

    Dyson, Zoe A.; Seviour, Robert J.; Tucci, Joseph

    2016-01-01

    We report the genome sequences of two double-stranded DNA siphoviruses, POR1 infective for Pseudomonas oryzihabitans and PAE1 infective for Pseudomonas aeruginosa. The phage POR1 genome showed no nucleotide sequence homology to any other DNA phage sequence in the GenBank database, while phage PAE1 displayed synteny to P. aeruginosa phages M6, MP1412, and YuA. PMID:27313312

  18. [Pneumocystosis in non-HIV-infected immunocompromised patients].

    PubMed

    Fillâtre, P; Revest, M; Belaz, S; Robert-Gangneux, F; Zahar, J-R; Roblot, F; Tattevin, P

    2016-05-01

    Pneumocystis jiroveci (formerly P. carinii) is an opportunistic fungus responsible for pneumonia in immunocompromised patients. Pneumocystosis in non-HIV-infected patients differs from AIDS-associated pneumocystosis in mostly two aspects: diagnosis is more difficult, and prognosis is worse. Hence, efforts should be made to target immunocompromised patients at higher risk of pneumocystosis, so that they are prescribed long-term, low-dose, trimethoprime-sulfamethoxazole, highly effective for pneumocystosis prophylaxis. Patients at highest risk include those with medium and small vessels vasculitis, lymphoproliferative B disorders (chronic or acute lymphocytic leukaemia, non-Hodgkin lymphoma), and solid cancer on long-term corticosteroids. Conversely, widespread use of prophylaxis in all patients carrier of inflammatory diseases on long-term corticosteroids is not warranted. The management of pneumocystosis in non-AIDS immunocompromised patients follows the rules established for AIDS patients. The diagnosis relies on the detection of P. jiroveci cyst on respiratory samples, while PCR does not reliably discriminate infection from colonization, in 2015. High-doses trimethoprim-sulfamethoxazole is, by far, the treatment of choice. The benefit of adjuvant corticosteroid therapy for hypoxic patients, well documented in AIDS patients, has a much lower level of evidence in non-HIV-infected patients, most of them being already on corticosteroid by the time of pneumocystosis diagnosis anyway. However, based on its striking impact on morbi-mortality in AIDS patients, adjuvant corticosteroid is recommended in hypoxic, non-HIV-infected patients with pneumocystosis by many experts and scientific societies. PMID:26644039

  19. Contribution of the (1-->3)-beta-D-glucan assay for diagnosis of invasive fungal infections.

    PubMed

    Persat, Florence; Ranque, Stéphane; Derouin, Francis; Michel-Nguyen, Annie; Picot, Stéphane; Sulahian, Annie

    2008-03-01

    Diagnosis of invasive fungal infection (IFI) remains a challenge. A retrospective study was performed on 279 patients at three French university hospitals to evaluate the performance of the (1-->3)-beta-D-glucan assay (BG assay; Fungitell; Associates of Cape Cod, Inc.) for the diagnosis of IFI. The results of one serum per subject were analyzed for 117 patients who had probable or proven IFI according to the European Organization for Research and Treatment of Cancer criteria (70 invasive pulmonary aspergilloses [IPA], 27 fungal bloodstream infections, and 20 Pneumocystis jiroveci pneumonias), 40 blood donors, and 122 patients who were hospitalized in hematology wards or intensive care units and were at risk for IFI but in whom IFI had not been diagnosed. For the overall IFI diagnosis, the BG assay had 77.8% sensitivity and specificities of 92.5 and 70.5% for blood donors and patients at risk, respectively. The assay was positive in 48 patients with IPA (68%), in 23 with bloodstream infections (85.2%), and in all who had P. jiroveci pneumonias (100%), and the false-positive rate varied depending on the controls used. It allowed a higher rate of detection among IPA patients compared to the galactomannan enzyme-linked immunosorbent assay (ELISA) (48 versus 39 patients, respectively) and among candidemia patients compared to the mannan ELISA (20 versus 11 patients, respectively). This assay therefore appears to be useful in the diagnosis of IFI, particularly for serum analysis of pneumocystosis pneumonia patients, but further studies are needed to evaluate false-positive rates and its future role in IFI diagnosis. PMID:18160456

  20. 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. PMID:25982207

  1. Structural basis for solute transport, nucleotide regulation, and immunological recognition of Neisseria meningitidis PorB

    PubMed Central

    Tanabe, Mikio; Nimigean, Crina M.; Iverson, T. M.

    2010-01-01

    PorB is the second most prevalent outer membrane protein in Neisseria meningitidis. PorB is required for neisserial pathogenesis and can elicit a Toll-like receptor mediated host immune response. Here, the x-ray crystal structure of PorB has been determined to 2.3 Å resolution. Structural analysis and cocrystallization studies identify three putative solute translocation pathways through the channel pore: One pathway transports anions nonselectively, one transports cations nonselectively, and one facilitates the specific uptake of sugars. During infection, PorB likely binds host mitochondrial ATP, and cocrystallization with the ATP analog AMP–PNP suggests that binding of nucleotides regulates these translocation pathways both by partial occlusion of the pore and by restricting the motion of a putative voltage gating loop. PorB is located on the surface of N. meningitidis and can be recognized by receptors of the host innate immune system. Features of PorB suggest that Toll-like receptor mediated recognition outer membrane proteins may be initiated with a nonspecific electrostatic attraction. PMID:20351243

  2. An investigation of exploitation versus exploration in GBEA optimization of PORS 15 and 16 Problems

    SciTech Connect

    Koch, Kaelynn

    2012-01-01

    It was hypothesized that the variations in time to solution are driven by the competing mechanisms of exploration and exploitation.This thesis explores this hypothesis by examining two contrasting problems that embody the hypothesized tradeoff between exploration and exploitation. Plus one recall store (PORS) is an optimization problem based on the idea of a simple calculator with four buttons: plus, one, store, and recall. Integer addition and store are classified as operations, and one and memory recall are classified as terminals. The goal is to arrange a fixed number of keystrokes in a way that maximizes the numerical result. PORS 15 (15 keystrokes) represents the subset of difficult PORS problems and PORS 16 (16 keystrokes) represents the subset of PORS problems that are easiest to optimize. The goal of this work is to examine the tradeoff between exploitation and exploration in graph based evolutionary algorithm (GBEA) optimization. To do this, computational experiments are used to examine how solutions evolve in PORS 15 and 16 problems when solved using GBEAs. The experiment is comprised of three components; the graphs and the population, the evolutionary algorithm rule set, and the example problems. The complete, hypercube, and cycle graphs were used for this experiment. A fixed population size was used.

  3. Crystallographic analysis of Neisseria meningitidis PorB extracellular loops potentially implicated in TLR2 recognition.

    PubMed

    Kattner, Christof; Toussi, Deana N; Zaucha, Jan; Wetzler, Lee M; Rüppel, Nadine; Zachariae, Ulrich; Massari, Paola; Tanabe, Mikio

    2014-03-01

    Among all Neisseriae species, Neisseria meningitidis and Neisseria gonorrhoeae are the only human pathogens, causative agents of bacterial meningitis and gonorrhoea, respectively. PorB, a pan-Neisseriae trimeric porin that mediates diffusive transport of essential molecules across the bacterial outer membrane, is also known to activate host innate immunity via Toll-like receptor 2 (TLR2)-mediated signaling. The molecular mechanism of PorB binding to TLR2 is not known, but it has been hypothesized that electrostatic interactions contribute to ligand/receptor binding. Strain-specific sequence variability in the surface-exposed loops of PorB which are potentially implicated in TLR2 binding, may explain the difference in TLR2-mediated cell activation in vitro by PorB homologs from the commensal Neisseriae lactamica and the pathogen N. meningitidis. Here, we report a comparative structural analysis of PorB from N. meningitidis serogroup B strain 8765 (63% sequence homology with PorB from N. meningitidis serogroup W135) and a mutant in which amino acid substitutions in the extracellular loop 7 lead to significantly reduced TLR2-dependent activity in vitro. We observe that this mutation both alters the loop conformation and causes dramatic changes of electrostatic surface charge, both of which may affect TLR2 recognition and signaling. PMID:24361688

  4. Structural basis for solute transport, nucleotide regulation, and immunological recognition of Neisseria meningitidis PorB

    SciTech Connect

    Tanabe, Mikio; Nimigean, Crina M.; Iverson, T.M.

    2010-06-25

    PorB is the second most prevalent outer membrane protein in Neisseria meningitidis. PorB is required for neisserial pathogenesis and can elicit a Toll-like receptor mediated host immune response. Here, the x-ray crystal structure of PorB has been determined to 2.3 {angstrom} resolution. Structural analysis and cocrystallization studies identify three putative solute translocation pathways through the channel pore: One pathway transports anions nonselectively, one transports cations nonselectively, and one facilitates the specific uptake of sugars. During infection, PorB likely binds host mitochondrial ATP, and cocrystallization with the ATP analog AMP-PNP suggests that binding of nucleotides regulates these translocation pathways both by partial occlusion of the pore and by restricting the motion of a putative voltage gating loop. PorB is located on the surface of N. meningitidis and can be recognized by receptors of the host innate immune system. Features of PorB suggest that Toll-like receptor mediated recognition outer membrane proteins may be initiated with a nonspecific electrostatic attraction.

  5. Molecular characterisation of Porcine rubulavirus (PorPV) isolates from different outbreaks in Mexico.

    PubMed

    Cuevas-Romero, S; Rivera-Benítez, J F; Blomström, A-L; Ramliden, M; Hernández-Baumgarten, E; Hernández-Jáuregui, P; Ramírez-Mendoza, H; Berg, M

    2016-02-01

    Since the report of the initial outbreak of Porcine rubulavirus (PorPV) infection in pigs, only one full-length genome from 1984 (PorPV-LPMV/1984) has been characterised. To investigate the overall genetic variation, full-length gene nucleotide sequences of current PorPV isolates were obtained from different clinical cases of infected swine. Genome organisation and sequence analysis of the encoded proteins (NP, P, F, M, HN and L) revealed high sequence conservation of the NP protein and the expression of the P and V proteins in all PorPV isolates. The V protein of one isolate displayed a mutation that has been implicated to antagonise the antiviral immune responses of the host. The M protein indicated a variation in a short region that could affect the electrostatic charge and the interaction with the membrane. One PorPV isolate recovered from the lungs showed a mutation at the cleavage site (HRKKR) of the F protein that could represent an important factor to determine the tissue tropism and pathogenicity of this virus. The HN protein showed high sequence identity through the years (up to 2013). Additionally, a number of sequence motifs of very high amino acid conservation among the PorPV isolates important for polymerase activity of the L protein have been identified. In summary, genetic comparisons and phylogenetic analyses indicated that three different genetic variants of PorPV are currently spreading within the swine population, and a new generation of circulating virus with different characteristics has begun to emerge. PMID:26728078

  6. Por Secretion System-Dependent Secretion and Glycosylation of Porphyromonas gingivalis Hemin-Binding Protein 35

    PubMed Central

    Shoji, Mikio; Sato, Keiko; Yukitake, Hideharu; Kondo, Yoshio; Narita, Yuka; Kadowaki, Tomoko; Naito, Mariko; Nakayama, Koji

    2011-01-01

    The anaerobic Gram-negative bacterium Porphyromonas gingivalis is a major pathogen in severe forms of periodontal disease and refractory periapical perodontitis. We have recently found that P. gingivalis has a novel secretion system named the Por secretion system (PorSS), which is responsible for secretion of major extracellular proteinases, Arg-gingipains (Rgps) and Lys-gingipain. These proteinases contain conserved C-terminal domains (CTDs) in their C-termini. Hemin-binding protein 35 (HBP35), which is one of the outer membrane proteins of P. gingivalis and contributes to its haem utilization, also contains a CTD, suggesting that HBP35 is translocated to the cell surface via the PorSS. In this study, immunoblot analysis of P. gingivalis mutants deficient in the PorSS or in the biosynthesis of anionic polysaccharide-lipopolysaccharide (A-LPS) revealed that HBP35 is translocated to the cell surface via the PorSS and is glycosylated with A-LPS. From deletion analysis with a GFP-CTD[HBP35] green fluorescent protein fusion, the C-terminal 22 amino acid residues of CTD[HBP35] were found to be required for cell surface translocation and glycosylation. The GFP-CTD fusion study also revealed that the CTDs of CPG70, peptidylarginine deiminase, P27 and RgpB play roles in PorSS-dependent translocation and glycosylation. However, CTD-region peptides were not found in samples of glycosylated HBP35 protein by peptide map fingerprinting analysis, and antibodies against CTD-regions peptides did not react with glycosylated HBP35 protein. These results suggest both that the CTD region functions as a recognition signal for the PorSS and that glycosylation of CTD proteins occurs after removal of the CTD region. Rabbits were used for making antisera against bacterial proteins in this study. PMID:21731719

  7. Gliding Motility and Por Secretion System Genes Are Widespread among Members of the Phylum Bacteroidetes

    PubMed Central

    Zhu, Yongtao

    2013-01-01

    The phylum Bacteroidetes is large and diverse, with rapid gliding motility and the ability to digest macromolecules associated with many genera and species. Recently, a novel protein secretion system, the Por secretion system (PorSS), was identified in two members of the phylum, the gliding bacterium Flavobacterium johnsoniae and the nonmotile oral pathogen Porphyromonas gingivalis. The components of the PorSS are not similar in sequence to those of other well-studied bacterial secretion systems. The F. johnsoniae PorSS genes are a subset of the gliding motility genes, suggesting a role for the secretion system in motility. The F. johnsoniae PorSS is needed for assembly of the gliding motility apparatus and for secretion of a chitinase, and the P. gingivalis PorSS is involved in secretion of gingipain protease virulence factors. Comparative analysis of 37 genomes of members of the phylum Bacteroidetes revealed the widespread occurrence of gliding motility genes and PorSS genes. Genes associated with other bacterial protein secretion systems were less common. The results suggest that gliding motility is more common than previously reported. Microscopic observations confirmed that organisms previously described as nonmotile, including Croceibacter atlanticus, “Gramella forsetii,” Paludibacter propionicigenes, Riemerella anatipestifer, and Robiginitalea biformata, exhibit gliding motility. Three genes (gldA, gldF, and gldG) that encode an apparent ATP-binding cassette transporter required for F. johnsoniae gliding were absent from two related gliding bacteria, suggesting that the transporter may not be central to gliding motility. PMID:23123910

  8. Oral administration of recombinant Neisseria meningitidis PorA genetically fused to H. pylori HpaA antigen increases antibody levels in mouse serum, suggesting that PorA behaves as a putative adjuvant.

    PubMed

    Vasquez, Abel E; Manzo, Ricardo A; Soto, Daniel A; Barrientos, Magaly J; Maldonado, Aurora E; Mosqueira, Macarena; Avila, Anastasia; Touma, Jorge; Bruce, Elsa; Harris, Paul R; Venegas, Alejandro

    2015-01-01

    The Neisseria meningitidis outer membrane protein PorA from a Chilean strain was purified as a recombinant protein. PorA mixed with AbISCO induced bactericidal antibodies against N. meningitidis in mice. When PorA was fused to the Helicobacter pylori HpaA antigen gene, the specific response against H. pylori protein increased. Splenocytes from PorA-immunized mice were stimulated with PorA, and an increase in the secretion of IL-4 was observed compared with that of IFN-γ. Moreover, in an immunoglobulin sub-typing analysis, a substantially higher IgG1 level was found compared with IgG2a levels, suggesting a Th2-type immune response. This study revealed a peculiar behavior of the purified recombinant PorA protein per se in the absence of AbISCO as an adjuvant. Therefore, the resistance of PorA to proteolytic enzymes, such as those in the gastrointestinal tract, was analyzed, because this is an important feature for an oral protein adjuvant. Finally, we found that PorA fused to the H. pylori HpaA antigen, when expressed in Lactococcus lactis and administered orally, could enhance the antibody response against the HpaA antigen approximately 3 fold. These observations strongly suggest that PorA behaves as an effective oral adjuvant. PMID:25750999

  9. Oral administration of recombinant Neisseria meningitidis PorA genetically fused to H. pylori HpaA antigen increases antibody levels in mouse serum, suggesting that PorA behaves as a putative adjuvant

    PubMed Central

    Vasquez, Abel E; Manzo, Ricardo A; Soto, Daniel A; Barrientos, Magaly J; Maldonado, Aurora E; Mosqueira, Macarena; Avila, Anastasia; Touma, Jorge; Bruce, Elsa; Harris, Paul R; Venegas, Alejandro

    2015-01-01

    The Neisseria meningitidis outer membrane protein PorA from a Chilean strain was purified as a recombinant protein. PorA mixed with AbISCO induced bactericidal antibodies against N. meningitidis in mice. When PorA was fused to the Helicobacter pylori HpaA antigen gene, the specific response against H. pylori protein increased. Splenocytes from PorA-immunized mice were stimulated with PorA, and an increase in the secretion of IL-4 was observed compared with that of IFN-γ. Moreover, in an immunoglobulin sub-typing analysis, a substantially higher IgG1 level was found compared with IgG2a levels, suggesting a Th2-type immune response. This study revealed a peculiar behavior of the purified recombinant PorA protein per se in the absence of AbISCO as an adjuvant. Therefore, the resistance of PorA to proteolytic enzymes, such as those in the gastrointestinal tract, was analyzed, because this is an important feature for an oral protein adjuvant. Finally, we found that PorA fused to the H. pylori HpaA antigen, when expressed in Lactococcus lactis and administered orally, could enhance the antibody response against the HpaA antigen approximately 3 fold. These observations strongly suggest that PorA behaves as an effective oral adjuvant. PMID:25750999

  10. An Analysis of Interlanguage Development Over Time: Part 1, "por" and "para".

    ERIC Educational Resources Information Center

    Guntermann, Gail

    1992-01-01

    The first part of a larger planned investigation, this study examines the use of "por" and "para" by nine Peace Corps volunteers in oral interviews at the end of training and roughly one year later, to trace their acquisition over time, in two learning contexts. (24 references) (LB)

  11. The Acquisition of Lexical Meaning in a Study Abroad Context: The Spanish Prepositions "por" and "para."

    ERIC Educational Resources Information Center

    Lafford, Barbara A.; Ryan, John M.

    1995-01-01

    Examination of the development of form/function relations of the prepositions "por" and "para" at different levels of proficiency in the interlanguage of study-abroad students in Granada, Spain, revealed "noncanonical" as well as "canonical" uses of these prepositions. The most common noncanonical uses were as substitutions for other prepositions…

  12. The porA gene in serogroup A meningococci: evolutionary stability and mechanism of genetic variation.

    PubMed

    Suker, J; Feavers, I M; Achtman, M; Morelli, G; Wang, J F; Maiden, M C

    1994-04-01

    Molecular analyses were applied to the genes encoding variants of the serosubtyping antigen, the class 1 outer membrane protein (PorA), from 55 serogroup A Neisseria meningitidis strains. These genes were evolutionarily stable and exhibited a limited range of genetic variation, primarily generated by recombination. Translation of the gene sequences revealed a total of 19 distinct amino acid sequences in the variable regions of the protein, 6 of which were not recognized by currently available serosubtyping monoclonal antibodies. Knowledge of these amino acid sequences permitted a rational re-assignment of serosubtype names. Comparison of the complete genes with porA gene sequences from serogroup B and C meningococci showed that serogroup A possessed a limited number of the possible porA genes from a globally distributed gene pool. Each serogroup A subgroup was characterized by one of four porA gene types, probably acquired upon subgroup divergence, which was stable over periods of decades and during epidemiological spread. Comparison with other variable genes (pil and iga) indicated that the three alleles were independently assorted within the subgroup, suggesting that their gene types were older than the subgroups in which they occurred. PMID:8057850

  13. Informe a la Nación de mortalidad por cáncer sigue bajando

    Cancer.gov

    El Informe Anual a la Nación sobre el Estado del Cáncer, de 1975 a 2009, indica que los índices generales de mortalidad por cáncer siguen bajando en los Estados Unidos en hombres y mujeres, entre todos los grupos raciales y étnicos principales y para todo

  14. Detección y estudio mediante Fluorescencia Inducida por Láser de radicales libres formados por Disociación Multifotónica Infrarroja

    NASA Astrophysics Data System (ADS)

    Santos, M.; Díaz, L.; Torresano, J. A.; Rubio, L.; Samoudi, B.

    Una de las principales aplicaciones actuales de los procesos de disociación multifotónica inducidos por radiación láser infrarroja (DMI) es la producción de radiales libres, con el fin de estudiar sus propiedades cinéticas y espectroscópicas. La disociación de moléculas poliatómicas en el IR con láseres de CO2 tiene lugar desde la superficie de energía molecular mas baja y conduce generalmente a la formación de fragmentos en el estado electrónico fundamental, con diversos grados de excitación vibracional. En el Grupo de Procesos Multifotónicos del Instituto de Estructura de la Materia del C.S.I.C. hemos puesto a punto la técnica de Fluorescencia Inducida por Láser (LIF) para la detección y análisis en tiempo real de los fragmentos producidos en la DMI inducida mediante uno o dos campos láseres de diferentes longitudes de onda. Objetivos de nuestro trabajo han sido el estudio de los canales de disociación mayoritarios y de las especies transitoria producidas, así como de la distribución de energía interna con que éstas son generadas. En particular hemos detectado mediante LIF las especies: C2, CF, CH, SiH2, CF2, CH2, SiHCl, y CF3 a partir de la disociación de, entre otras, las siguientes moléculas: C2H3Br, C3F6, C4H8Si, C2H5ClSi y CH5ClSi. En este trabajo presentamos algunos de los resultados obtenidos mediante el estudio por LIF de estos radicales: estudio temporal de la señal LIF obtenida con determinación de tiempos de vida, espectros de excitación y fluorescencia, temperaturas vibracionales de formación, variación de la intensidad LIF con el tiempo de retraso entre los láseres de disociación y prueba, etc.

  15. ATP for the portable 500 CFM exhauster POR-005 skid C

    SciTech Connect

    Keller, C.M.

    1997-06-27

    This Acceptance Test Plan is for a 500 CFM Portable Exhauster POR-005 to be used for saltwell pumping. The Portable Exhauster System will be utilized to eliminate potential flammable gases that may exist within the dome space of the tank. This Acceptance Plan will test and verify that the exhauster meets the specified design criteria, safety requirements, operations requirements, and will provide a record of the functional test results.

  16. ATP for the portable 500 CFM exhauster POR-006 skid D

    SciTech Connect

    Keller, C.M.

    1997-07-29

    This Acceptance Test Plan is for a 500 CFM Portable Exhauster POR-006 to be used for saltwell pumping. The Portable Exhauster System will be utilized to eliminate potential flammable gases that may exist within the dome space of the tank. This Acceptance Plan will test and verify that the exhauster meets the specified design criteria, safety requirements, operations requirements, and will provide a record of the functional test results.

  17. ATP for the portable 500 CFM exhauster POR-004 skid B

    SciTech Connect

    Keller, C.M.

    1997-05-06

    This Acceptance Test Plan is for a 500 CFM Portable Exhauster POR-004 to be used for saltwell pumping. The Portable Exhauster System will be utilized to eliminate potential flammable gases that may exist within the dome space of the tank. This Acceptance Plan will test and verify that the exhauster meets the specified design criteria, safety requirements, operations requirements, and will provide a record of the functional test results.

  18. Correlation between Serological and Sequencing Analyses of the PorB Outer Membrane Protein in the Neisseria meningitidis Serotyping System

    PubMed Central

    Sacchi, Claudio T.; Lemos, Ana P. S.; Whitney, Anne M.; Solari, Claude A.; Brandt, Mary E.; Melles, Carmo E. A.; Frasch, Carl E.; Mayer, Leonard W.

    1998-01-01

    The current serological typing scheme for Neisseria meningitidis is not comprehensive; a proportion of isolates are not serotypeable. DNA sequence analysis and predicted amino acid sequences were used to characterize the structures of variable-region (VR) epitopes on N. meningitidis PorB proteins (PorB VR typing). Twenty-six porB gene sequences were obtained from GenBank and aligned with 41 new sequences. Primary amino acid structures predicted from those genes were grouped into 30 VR families of related variants that displayed at least 60% similarity. We correlated VR families with monoclonal antibody (MAb) reactivities, establishing a relationship between VR families and epitope locations for 15 serotype-defining MAbs. The current panel of serotype-defining MAbs underestimates by at least 50% the PorB VR variability because reagents for several major VR families are lacking or because a number of VR variants within some families are not recognized by serotype-defining MAbs. These difficulties, also reported for serosubtyping based on the PorA protein, are shown as inconsistent results between serological and sequence analyses, leading to inaccurate strain identification and incomplete epidemiological data. The information from this study enabled the expansion of the panel of MAbs currently available for serotyping, by including MAbs of previously undetermined specificities. Use of the expanded serotype panel enabled us to improve the sensitivity of serotyping by resolving a number of formerly nonserotypeable strains. In most cases, this information can be used to predict the VR family placement of unknown PorB proteins without sequencing the entire porB gene. PorB VR typing complements serotyping, and a combination of both techniques may be used for full characterization of meningococcal strains. The present work represents the most complete and integrated data set of PorB VR sequences and MAb reactivities of serogroup B and C meningococci produced to date. PMID

  19. [Pulmonary fungal infection in patients with AIDS].

    PubMed

    Denis, B; Lortholary, O

    2013-10-01

    Fungal infections are the most common opportunistic infections (OI) occurring during the course of HIV infection, though their incidence has decreased dramatically with the introduction of highly active antiretroviral therapy (cART). Most cases occur in untreated patients, noncompliant patients or patients whose multiple antiretroviral regimens have failed and they are a good marker of the severity of cellular immunodepression. Pneumocystis jiroveci pneumonia is the second most frequent OI in France and cryptococcosis remains a major problem in the Southern Hemisphere. With the increase in travel, imported endemic fungal infection can occur and may mimic other infections, notably tuberculosis. Fungal infections often have a pulmonary presentation but an exhaustive search for dissemination should be made in patients infected with HIV, at least those at an advanced stage of immune deficiency. Introduction of cART in combination with anti-fungal treatment depends on the risk of AIDS progression and on the risk of cumulative toxicity and the immune reconstitution inflammatory syndrome (IRIS) if introduced too early. Fungal infections in HIV infected patients remain a problem in the cART era. IRIS can complicate the management and requires an optimised treatment regime. PMID:24182654

  20. Infectious cause of death determination using minimally invasive autopsies in developing countries.

    PubMed

    Martínez, Miguel J; Massora, Sergio; Mandomando, Inácio; Ussene, Esperança; Jordao, Dercio; Lovane, Lucilia; Muñoz-Almagro, Carmen; Castillo, Paola; Mayor, Alfredo; Rodriguez, Cristina; Lopez-Villanueva, Miriam; Ismail, Mamudo R; Carrilho, Carla; Lorenzoni, Cesaltina; Lacerda, Marcus V G; Bassat, Quique; Menéndez, Clara; Ordi, Jaume; Vila, Jordi

    2016-01-01

    In developing countries, the knowledge of the microorganisms causing fatal infections is critical and could help designing and implementing more effective preventive interventions and treatment guidelines. We aimed to develop and validate protocols for microbiological analysis in post-mortem samples obtained during minimally invasive autopsy (MIA) procedures and to assess their performance. Thirty MIAs performed in adults at Maputo Central Hospital in Southern Mozambique were included in the analysis. Microbiological tests included a universal screening for HIV, hepatitis B and C viruses, Plasmodium falciparum, and bacterial/fungal culture. In addition, a variety of molecular microbiology assays guided by the histological results were performed in blood, cerebrospinal fluid and a variety of tissue samples including liver, lung and central nervous system. The combination of culture-based methods together with molecular microbiological assays led to the identification of 17 out of 19 (89.5%) of the infectious deaths. Microorganisms identified included Mycobacterium tuberculosis, Toxoplasma gondii, Pneumocystis jiroveci, Cryptococcus neoformans, hepatitis B virus, human herpesvirus 8, cytomegalovirus, Streptococcus pneumoniae, Streptococcus dysgalactiae, Ryzopus oryzae, and Acinetobacter baumannii. The combination of classical cultures, serological tests and molecular assays performed in samples obtained through MIA allows the identification of most infectious agents causing death. PMID:26508103

  1. [Glucocorticoids and... infections, doping, surgery, sexuality].

    PubMed

    Grossi, O; Généreau, T

    2013-05-01

    The risk of infection is increased in patients treated with glucocorticoids, especially in those taking long-term and high dosage treatment. However, there is little valid practice for the prevention of infections in this patient population. The risk of reactivation or worsening of a latent infection (e.g., hepatitis B, tuberculosis, strongyloidiasis) is proved and individual reflection should be conducted in at-risk patients. Preventions of Pneumocystis jiroveci or upper urinary tract infections are considered differently according to practitioners' habits and their specialties. Adequate prevention should be prescribed in glucocorticoid-treated patients who have been in contact with varicella zoster or measles virus. Many vaccines could be prescribed in those people but live vaccines should be avoided. A consultation of travel medicine should be systematically proposed before a travel in intertropical zone. Anti-inflammatory and stimulant properties of glucocorticoids are frequently misused in order to improve sport performances. All glucocorticoids are considered as performance-enhancing drugs. Their prescription should therefore be adapted to the laws in force in the sport. By reducing vomiting and pain, glucocorticoids may be beneficial in patients undergoing surgery. However, in people prescribed long-term glucocorticoid therapy, the risk of postoperative adrenal insufficiency has to be considered, even though very few data are available on this topic. Oral contraceptives or intra-uterine devices are effective contraceptives methods in patients treated with systemic glucocorticoids. PMID:23415059

  2. Tuberculosis in a patient on temozolomide: a case report.

    PubMed

    de Paiva, Tadeu Ferreira; de Barros e Silva, Milton José; Rinck, José Augusto; Fanelli, Marcello Ferreti; Gimenes, Daniel Luiz

    2009-03-01

    Temozolomide (TMZ) is a cytotoxic agent of the imidazotetrazine class, chemically related to dacarbazine. Its use poses higher risks of lymphopenia and opportunistic infections. Prophylaxis for Pneumocystis jiroveci must be considered up to 12 months after treatment discontinuation. The due literature (MEDLINE) makes no mention of a possible connection between the use of TMZ and tuberculosis (TB). A female patient, aged 59, featuring glioblastoma multiforme and having undergone solely a brain biopsy, was submitted to TMZ along with radiotherapy. After the first TMZ maintenance cycle, the referred patient was admitted displaying a background of a 40-day afternoon fever and productive coughing. She was thus submitted to a bronchoscopy and LBA, which resulted BAAR 1+/4+. TMZ was then suspended, and rifampicin, isoniazid, and pyrazinamide introduced. Considerations on prophylaxis with isoniazide in cancer patients are long-lived and scarce. Some subgroups are likely to benefit from the prophylactic administration of isoniazide during TMZ treatment, such as those patients under high doses of corticoids, patients with past medical history of TB, the malnourished, patients from endemic regions, and patients with highly reactive tuberculinic tests. That, nevertheless, must not restrict the administration of TMZ, but, rather, stand for a warning about its possible toxicity, and thus mitigate complications. PMID:18974931

  3. Zinc Finger Nuclease Knock-out of NADPH:Cytochrome P450 Oxidoreductase (POR) in Human Tumor Cell Lines Demonstrates That Hypoxia-activated Prodrugs Differ in POR Dependence*

    PubMed Central

    Su, Jiechuang; Gu, Yongchuan; Pruijn, Frederik B.; Smaill, Jeff B.; Patterson, Adam V.; Guise, Christopher P.; Wilson, William R.

    2013-01-01

    Hypoxia, a ubiquitous feature of tumors, can be exploited by hypoxia-activated prodrugs (HAP) that are substrates for one-electron reduction in the absence of oxygen. NADPH:cytochrome P450 oxidoreductase (POR) is considered one of the major enzymes responsible, based on studies using purified enzyme or forced overexpression in cell lines. To examine the role of POR in HAP activation at endogenous levels of expression, POR knock-outs were generated in HCT116 and SiHa cells by targeted mutation of exon 8 using zinc finger nucleases. Absolute quantitation by proteotypic peptide mass spectrometry of DNA sequence-confirmed multiallelic mutants demonstrated expression of proteins with residual one-electron reductase activity in some clones and identified two (Hko2 from HCT116 and S2ko1 from SiHa) that were functionally null by multiple criteria. Sensitivities of the clones to 11 HAP (six nitroaromatics, three benzotriazine N-oxides, and two quinones) were compared with wild-type and POR-overexpressing cells. All except the quinones were potentiated by POR overexpression. Knocking out POR had a marked effect on antiproliferative activity of the 5-nitroquinoline SN24349 in both genetic backgrounds after anoxic exposure but little or no effect on activity of most other HAP, including the clinical stage 2-nitroimidazole mustard TH-302, dinitrobenzamide mustard PR-104A, and benzotriazine N-oxide SN30000. Clonogenic cell killing and reductive metabolism of PR-104A and SN30000 under anoxia also showed little change in the POR knock-outs. Thus, although POR expression is a potential biomarker of sensitivity to some HAP, identification of other one-electron reductases responsible for HAP activation is needed for their rational clinical development. PMID:24196959

  4. Characterization of Plasmid pOR1 from Ornithobacterium rhinotracheale and Construction of a Shuttle Plasmid

    PubMed Central

    Jansen, Ruud; Chansiripornchai, Niwat; Gaastra, Wim; van Putten, Jos P. M.

    2004-01-01

    The bacterium Ornithobacterium rhinotracheale has been recognized as an emerging pathogen in poultry since about 10 years ago. Knowledge of this bacterium and its mechanisms of virulence is still very limited. Here we report the development of a transformation system that enables genetic modification of O. rhinotracheale. The system is based on a cryptic plasmid, pOR1, that was derived from an O. rhinotracheale strain of serotype K. Sequencing indicated that the plasmid consisted of 14,787 nucleotides. Sequence analysis revealed one replication origin and several rep genes that control plasmid replication and copy number, respectively. In addition, pOR1 contains genes with similarity to a heavy-metal-transporting ATPase, a TonB-linked siderophore receptor, and a laccase. Reverse transcription-PCR demonstrated that these genes were transcribed. Other putative open reading frames exhibited similarities with a virulence-associated protein in Actinobacillus actinomycetemcomitans and a number of genes coding for proteins with unknown function. An Escherichia coli-O. rhinotracheale shuttle plasmid (pOREC1) was constructed by cloning the replication origin and rep genes from pOR1 and the cfxA gene from Bacteroides vulgatus, which codes for resistance to the antibiotic cefoxitin, into plasmid pGEM7 by using E. coli as a host. pOREC1 was electroporated into O. rhinotracheale and yielded cefoxitin-resistant transformants. The pOREC1 isolated from these transformants was reintroduced into E. coli, demonstrating that pOREC1 acts as an independent replicon in both E. coli and O. rhinotracheale, fulfilling the criteria for a shuttle plasmid that can be used for transformation, targeted mutagenesis, and the construction of defined attenuated vaccine strains. PMID:15466524

  5. Expression, purification and preliminary X-ray analysis of the Neisseria meningitidis outer membrane protein PorB

    SciTech Connect

    Tanabe, Mikio; Iverson, Tina M.

    2010-01-28

    The Neisseria meningitidis outer membrane protein PorB was expressed in Escherichia coli and purified from inclusion bodies by denaturation in urea followed by refolding in buffered LDAO on a size-exclusion column. PorB has been crystallized in three different crystal forms: C222, R32 and P6{sub 3}. The C222 crystal form may contain either one or two PorB monomers in the asymmetric unit, while both the R32 and P6{sub 3} crystal forms contained one PorB monomer in the asymmetric unit. Of the three, the P6{sub 3} crystal form had the best diffraction quality, yielding data extending to 2.3 {angstrom} resolution.

  6. Application of POR-Tveks to the radiochemical recovery of yttrium-90

    SciTech Connect

    Maksimova, A.M.; Kvasnitskii, I.B.

    1988-01-01

    The authors describe a method for the radiochemical analysis of fish bones for the accumulation of strontium 90 and yttrium 90 from power plant contamination of surface waters which involves labelling the sample with isotopes and subsequent adsorption of the yttrium component with the use of POR-Tveks, an adsorbent based on a copolymer of styrene and divinylbenzene with heteroradical phosphine oxide. The yield of yttrium is determined from the mass of the oxide and from the half-life of the yttrium isotope.

  7. Antigenic topology of chlamydial PorB protein and identification of targets for immune neutralization of infectivity.

    PubMed

    Kawa, Diane E; Stephens, Richard S

    2002-05-15

    The outer membrane protein PorB is a conserved chlamydial protein that functions as a porin and is capable of eliciting neutralizing Abs. A topological antigenic map was developed using overlapping synthetic peptides representing the Chlamydia trachomatis PorB sequence and polyclonal immune sera. To identify which antigenic determinants were surface accessible, monospecific antisera were raised to the PorB peptides and were used in dot-blot and ELISA-based absorption studies with viable chlamydial elementary bodies (EBs). The ability of the surface-accessible antigenic determinants to direct neutralizing Ab responses was investigated using standardized in vitro neutralization assays. Four major antigenic clusters corresponding to Phe(34)-Leu(59) (B1-2 and B1-3), Asp(112) -Glu(145) (B2-3 and B2-4), Gly(179)-Ala(225) (B3-2 to B3-4), and Val(261)-Asn(305) (B4-4 to B5-2) were identified. Collectively, the EB absorption and dot-blot assays established that the immunoreactive PorB Ags were exposed on the surface of chlamydial EBs. Peptide-specific antisera raised to the surface-accessible Ags neutralized chlamydial infectivity and demonstrated cross-reactivity to synthetic peptides representing analogous C. pneumoniae PorB sequences. Furthermore, neutralization of chlamydial infectivity by C. trachomatis PorB antisera was inhibited by synthetic peptides representing the surface-exposed PorB antigenic determinants. These findings demonstrate that PorB Ags may be useful for development of chlamydial vaccines. PMID:11994474

  8. Multiple active site residues are important for photochemical efficiency in the light-activated enzyme protochlorophyllide oxidoreductase (POR).

    PubMed

    Menon, Binuraj R K; Hardman, Samantha J O; Scrutton, Nigel S; Heyes, Derren J

    2016-08-01

    Protochlorophyllide oxidoreductase (POR) catalyzes the light-driven reduction of protochlorophyllide (Pchlide), an essential, regulatory step in chlorophyll biosynthesis. The unique requirement of the enzyme for light has provided the opportunity to investigate how light energy can be harnessed to power biological catalysis and enzyme dynamics. Excited state interactions between the Pchlide molecule and the protein are known to drive the subsequent reaction chemistry. However, the structural features of POR and active site residues that are important for photochemistry and catalysis are currently unknown, because there is no crystal structure for POR. Here, we have used static and time-resolved spectroscopic measurements of a number of active site variants to study the role of a number of residues, which are located in the proposed NADPH/Pchlide binding site based on previous homology models, in the reaction mechanism of POR. Our findings, which are interpreted in the context of a new improved structural model, have identified several residues that are predicted to interact with the coenzyme or substrate. Several of the POR variants have a profound effect on the photochemistry, suggesting that multiple residues are important in stabilizing the excited state required for catalysis. Our work offers insight into how the POR active site geometry is finely tuned by multiple active site residues to support enzyme-mediated photochemistry and reduction of Pchlide, both of which are crucial to the existence of life on Earth. PMID:27285815

  9. Diagnóstico diferencial en la encefalitis por anticuerpos contra el receptor NMDA

    PubMed Central

    González-Valcárcel, J.; Rosenfeld, M.R.; Dalmau, J.

    2011-01-01

    Resumen Introducción La encefalitis por anticuerpos contra el receptor de NMDA (NMDAR) suele desarrollarse como un síndrome característico de evolución multifásica y diagnóstico diferencial amplio. Pacientes Presentamos a 2 pacientes diagnosticadas de encefalitis por anticuerpos NMDAR con un cuadro clínico típico, pero que inicialmente señaló otras etiologías. Discusión La afectación frecuente de pacientes jóvenes con manifestaciones psiquiátricas prominentes indica frecuentemente otras consideraciones diagnósticas; las más frecuentes son las encefalitis virales, los procesos psiquiátricos y el síndrome neuroléptico maligno. Varios síndromes previamente definidos de manera parcial o descriptiva en adultos y pacientes pediátricos probablemente eran casos de encefalitis anti-NMDAR. Conclusiones La encefalitis anti-NMDAR debe considerarse en pacientes jóvenes con manifestaciones psiquiátricas subagudas, movimientos anormales y alteraciones autonómicas. La caracterización clínica e inmunológica de esta enfermedad ha llevado a la identificación de nuevos anticuerpos que afectan a procesos de memoria, aprendizaje, conducta y psicosis. PMID:20964986

  10. Effect of SPM-based cleaning POR on EUV mask performance

    NASA Astrophysics Data System (ADS)

    Choi, Jaehyuck; Lee, Han-shin; Yoon, Jinsang; Shimomura, Takeya; Friz, Alex; Montgomery, Cecilia; Ma, Andy; Goodwin, Frank; Kang, Daehyuk; Chung, Paul; Shin, Inkyun; Cho, H.

    2011-11-01

    EUV masks include many different layers of various materials rarely used in optical masks, and each layer of material has a particular role in enhancing the performance of EUV lithography. Therefore, it is crucial to understand how the mask quality and patterning performance can change during mask fabrication, EUV exposure, maintenance cleaning, shipping, or storage. The fact that a pellicle is not used to protect the mask surface in EUV lithography suggests that EUV masks may have to undergo more cleaning cycles during their lifetime. More frequent cleaning, combined with the adoption of new materials for EUV masks, necessitates that mask manufacturers closely examine the performance change of EUV masks during cleaning process. We have investigated EUV mask quality and patterning performance during 30 cycles of Samsung's EUV mask SPM-based cleaning and 20 cycles of SEMATECH ADT exposure. We have observed that the quality and patterning performance of EUV masks does not significantly change during these processes except mask pattern CD change. To resolve this issue, we have developed an acid-free cleaning POR and substantially improved EUV mask film loss compared to the SPM-based cleaning POR.

  11. Methodology for obtaining stakeholder assessments of obesity policy options in the PorGrow project.

    PubMed

    Stirling, A; Lobstein, T; Millstone, E

    2007-05-01

    The Policy Options for Responding to the Growing Challenge of Obesity Research Project (PorGrow) study provided a unique opportunity to develop a large-scale application of a semi-quantitative technique for exploring interviewees' views on options to tackle obesity, using multi-criteria mapping. This 'heuristic' approach utilizes the advantages of a structured interviews framework by predefining a set of options for appraisal, while leaving interviewees free to select their own criteria for making their judgements. Additional information can be gleaned from the interview transcripts and related materials to set the appraisals in their policy context, and allowing interviewees to express their views on the options presented and their own appraisals. The PorGrow study team agreed a predefined set of 20 options for appraisal, and interviewed sets of stakeholders representing more than 20 aspects of policy development in each of the nine participating countries. The details of the methodology adopted are set out in this paper. PMID:17371304

  12. Effects of heme precursors on CYP1A2 and POR expression in the baculovirus/Spodoptera frugiperda system☆

    PubMed Central

    Lu, Huiyuan; Ma, Jun; Liu, Nian; Wang, Shoulin

    2010-01-01

    Objective CYP1A2 and NADPH-CYP450 oxidoreductase (POR) were expressed in the baculovirus/Spodoptera frugiperda (sf9) system. The aim of this study was to investigate the effects of heme precursors on the expression of CYP1A2 and POR. Methods The heme precursors [δ-Aminolaevulinic Acid (5-ALA), Fe3+ and hemin] were introduced into the system to evaluate their effects on the expression of CYP1A2, POR and their co-expression. All the proteins were identified using immunoblotting, CO-difference spectroscopy, or cytochrome c assay. Results In the present study, functional CYP1A2 and POR were successfully expressed in the baculovirus/sf9 system, and both of them showed high activities. Co-addition of 5-ALA and Fe3+ significantly improved expression of CYP1A2 by about 50% compared with the addition of 5-ALA, Fe3+ or hemin alone. Either co-addition of 5-ALA and Fe3+ or addition of 5-ALA or Fe3+ alone improved the POR expression level 2 fold and its activity 7-10 fold compared with control (no addition). However, unlike CYP1A2, there was no difference between the co-addition and addition of these heme precursors alone. Different ratios of BvCYP1A2 to BvPOR also affected the co-expression of CYP1A2 and POR, with a 3:1 ratio of BvCYP1A2 / BvPOR significantly increasing their co-expression. Surprisingly, the addition of 0.1 mM 5-ALA or Fe3+ alone, but not their co-addition, could significantly improve the CYP1A2 and POR co-expression (P < 0.05). Conclusion 5-ALA and Fe3+ increased the expression of CYP1A2 and POR in a baculovirus/sf9 system, but the pattern of their expression was different between their expression alone and co-expression. PMID:23554636

  13. Pneumonia - weakened immune system

    MedlinePlus

    ... immunocompromised host." Related conditions include: Hospital-acquired pneumonia Pneumocystis jirovecii (previously called Pneumocystis carinii) pneumonia Pneumonia - cytomegalovirus Pneumonia ...

  14. Geometry sensing through POR1 regulates Rac1 activity controlling early osteoblast differentiation in response to nanofiber diameter.

    PubMed

    Higgins, A M; Banik, B L; Brown, J L

    2015-02-01

    Bone grafting procedures in the United States rely heavily upon autografts and allografts, which are donor-dependent, cause donor site pain, and can transmit disease. Synthetic bone grafts can reduce these risks; however, synthetics lack the bone differentiating (osteoinductive) abilities of auto- and allografts. Achieving innate osteoinductive properties of synthetics through surface modifications is currently under investigation. This study focuses on nanofibers, with emphasis on how fiber diameter and the potential curvature sensor POR1 affect the activation of the signaling molecules Rac1 and Arf1, and leading to expression of alkaline phosphatase (ALP), an osteoinductive marker. Diameters of 0.1, 0.3, and 1.0 μm were compared against a flat control. The highest level of Rac1 activation was achieved on the smallest fibers (0.1 μm), a trend that was lost in POR1 knockdowns. This supports the hypothesis that on small nanofibers, POR1 favorably binds to highly curved cell membranes, which allows Rac1 to subsequently dissociate and activate. When the curvature is insufficient to bind POR1, POR1 binds to inactive Rac1 and competitively inhibits its activation. Arf1 activation followed an opposite trend, with the largest nanofibers exhibiting the highest activity. This trend reinforces the known interaction between Rac1 and Arf1 through the GIT-PIX complex, an Arf1 GAP and Rac1 GEF, respectively. Large, (1.0 μm), nanofibers demonstrated the highest ALP activity, indicating that ALP expression is inversely dependent on Rac1 activation. Knockdown of POR1 resulted in increased ALP activity across the substrates but without regard to the curvature sensing trend seen previously. Thus, POR1 senses curvature and increases Rac1 activity, which negatively regulates bone differentiation. PMID:25539497

  15. Substrate-specific modulation of CYP3A4 activity by genetic variants of cytochrome P450 oxidoreductase (POR)

    PubMed Central

    Agrawal, Vishal; Choi, Ji Ha; Giacomini, Kathleen M.; Miller, Walter L.

    2010-01-01

    Objectives CYP3A4 receives electrons from P450 oxidoreductase (POR) to metabolize about 50% of clinically used drugs. There is substantial inter-individual variation in CYP3A4 catalytic activity that is not explained by CYP3A4 genetic variants. CYP3A4 is flexible and distensible, permitting it to accommodate substrates varying in shape and size. To elucidate mechanisms of variability in CYP3A4 catalysis, we examined the effects of genetic variants of POR, and explored the possibility that substrate-induced conformational changes in CYP3A4 differentially affect the ability of POR variants to support catalysis. Methods We expressed human CYP3A4 and four POR variants (Q153R, A287P, R457H, A503V) in bacteria, reconstituted them in vitro and measured the Michaelis constant and maximum velocity with testosterone, midazolam, quinidine and erythromycin as substrates. Results POR A287P and R457H had low activity with all substrates; Q153R had 76–94% of wild type (WT) activity with midazolam and erythromycin, but 129–150% activity with testosterone and quinidine. The A503V polymorphism reduced CYP3A4 activity to 61–77% of wild type with testosterone and midazolam, but had nearly wild type activity with quinidine and erythromycin. Conclusion POR variants affect CYP3A4 activities. The impact of a POR variant on catalysis by CYP3A4 is substrate-specific, probably due to substrate-induced conformational changes in CYP3A4. PMID:20697309

  16. Intermitência alfvênica gerada por caos na atmosfera solar e no vento solar

    NASA Astrophysics Data System (ADS)

    Rempel, E. L.; Chian, A. C.-L.; Macau, E. E. N.; Rosa, R. R.

    2003-08-01

    Dados medidos no vento solar rápido proveniente dos buracos coronais revelam que os plasmas no meio interplanetário são dominados por flutuações Alfvênicas, caracterizadas por uma alta correlação entre as variações do campo magnético e da velocidade do plasma. As flutuações exibem muitas características esperadas em turbulência magneto-hidrodinâmica totalmente desenvolvida, tais como intermitência e espectros contínuos. Contudo, os mecanismos responsáveis pela evolução de turbulência Alfvênica intermitente não são completamente compreendidos. Neste trabalho a teoria de caos é usada para explicar como sistemas Alfvênicos, modelados pela equação Schrödinger não-linear derivativa e pela equação Kuramoto-Sivashinsky, podem se tornar fortemente caóticos à medida em que parâmetros do plasma são variados. Pequenas perturbações no parâmetro de dissipação podem fazer com que o sistema mude bruscamente de um regime periódico, ou fracamente caótico, para um regime fortemente caótico. As séries temporais das flutuações do campo magnético nos regimes fortemente caóticos exibem comportamento intermitente, em que fases laminares ou fracamente caóticas são interrompidas por fortes estouros caóticos. É mostrado que o regime fortemente caótico é atingido quando as soluções periódicas ou fracamente caóticas globalmente estáveis interagem com soluções do sistema que são fortemente caóticas, mas globalmente instáveis. Estas soluções globalmente instáveis são conjuntos caóticos não-atrativos conhecidos como selas caóticas, e são responsáveis pelos fortes estouros nos regimes intermitentes. Selas caóticas têm sido detectadas experimentalmente em uma grande variedade de sistemas, sendo provável que elas desempenhem um papel importante na turbulência intermitente observada em plasmas espaciais.

  17. Fabrication of por-Si/SnO{sub x} nanocomposite layers for gas microsensors and nanosensors

    SciTech Connect

    Bolotov, V. V. Korusenko, P. M.; Nesov, S. N.; Povoroznyuk, S. N.; Roslikov, V. E.; Kurdyukova, E. A.; Sten'kin, Yu. A.; Shelyagin, R. V.; Knyazev, E. V.; Kan, V. E.; Ponomareva, I. V.

    2011-05-15

    Two-phase nanocomposite layers based on porous silicon and nonstoichiometric tin oxide were fabricated by various methods. The structure, as well as elemental and phase composition, of the obtained nanocomposites were studied using transmission and scanning electron microscopy, Raman spectroscopy, Auger electron spectroscopy, and X-ray photoelectron spectroscopy. The results obtained confirm the formation of nanocomposite layers with a thickness as large as 2 {mu}m thick and SnO{sub x} stoichiometry coefficients x = 1.0-2.0. Significant tin diffusion into the porous silicon matrix with D{sub eff} Almost-Equal-To 10{sup -14} cm{sup 2} s{sup -1} was observed upon annealing at 770 K. Test sensor structures based on por-Si/SnO{sub x} nanocomposite layers grown by magnetron deposition showed fairly high stability of properties and sensitivity to NO{sub 2}.

  18. Recovery of naphthalene during evaporative concentration. [Tenax; XAD-2; POR-Q, XE-340

    SciTech Connect

    Higgins, C.E.; Guerin, M.R.

    1980-10-01

    The analysis of trace organics usually requires concentrating organic extracts to small volumes prior to instrumental analysis. The use of a concentration apparatus employing a nitrogen blanket and reduced pressure is desirable because the inert atmosphere and low temperature help to ensure stable composition. Unfortunately, diaromatic compounds such as the naphthalenes and biphenyls are frequently almost completely lost during the concentration step. Even under carefully controlled conditions only 26 +- 11% of the naphthalene is recovered. By placing a sorbent either in or downstream of the evaporation concentration flask, recovery of diaromatic compounds can be improved significantly. In this investigation, the following sorbents, Tenax, XAD-2, POR-Q, and XE-340 were tested. Recoveries with and without the use of sorbents, effects of solute concentration, purge time after solvent removal, and type of solvent used are reported here.

  19. Using the PORS Problems to Examine Evolutionary Optimization of Multiscale Systems

    SciTech Connect

    Reinhart, Zachary; Molian, Vaelan; Bryden, Kenneth

    2013-01-01

    Nearly all systems of practical interest are composed of parts assembled across multiple scales. For example, an agrodynamic system is composed of flora and fauna on one scale; soil types, slope, and water runoff on another scale; and management practice and yield on another scale. Or consider an advanced coal-fired power plant: combustion and pollutant formation occurs on one scale, the plant components on another scale, and the overall performance of the power system is measured on another. In spite of this, there are few practical tools for the optimization of multiscale systems. This paper examines multiscale optimization of systems composed of discrete elements using the plus-one-recall-store (PORS) problem as a test case or study problem for multiscale systems. From this study, it is found that by recognizing the constraints and patterns present in discrete multiscale systems, the solution time can be significantly reduced and much more complex problems can be optimized.

  20. Display of a PorA peptide from Neisseria meningitidis on the bacteriophage T4 capsid surface.

    PubMed Central

    Jiang, J; Abu-Shilbayeh, L; Rao, V B

    1997-01-01

    The exterior of bacteriophage T4 capsid is coated with two outer capsid proteins, Hoc (highly antigenic outer capsid protein; molecular mass, 40 kDa) and Soc (small outer capsid protein; molecular mass, 9 kDa), at symmetrical positions on the icosahedron (160 copies of Hoc and 960 copies of Soc per capsid particle). Both these proteins are nonessential for phage infectivity and viability and assemble onto the capsid surface after completion of capsid assembly. We developed a phage display system which allowed in-frame fusions of foreign DNA at a unique cloning site in the 5' end of hoc or soc. A DNA fragment corresponding to the 36-amino-acid PorA peptide from Neisseria meningitidis was cloned into the display vectors to generate fusions at the N terminus of Hoc or Soc. The PorA-Hoc and PorA-Soc fusion proteins retained the ability to bind to the capsid surface, and the bound peptide was displayed in an accessible form as shown by its reactivity with specific monoclonal antibodies in an enzyme-linked immunosorbent assay. By employing T4 genetic strategies, we show that more than one subtype-specific PorA peptide can be displayed on the capsid surface and that the peptide can also be displayed on a DNA-free empty capsid. Both the PorA-Hoc and PorA-Soc recombinant phages are highly immunogenic in mice and elicit strong antipeptide antibody titers even with a weak adjuvant such as Alhydrogel or no adjuvant at all. The data suggest that the phage T4 hoc-soc system is an attractive system for display of peptides on an icosahedral capsid surface and may emerge as a powerful system for construction of the next generation multicomponent vaccines. PMID:9353063

  1. Rescue of cytochrome P450 oxidoreductase (Por) mouse mutants reveals functions in vasculogenesis, brain and limb patterning linked to retinoic acid homeostasis.

    PubMed

    Ribes, Vanessa; Otto, Diana M E; Dickmann, Leslie; Schmidt, Katy; Schuhbaur, Brigitte; Henderson, Colin; Blomhoff, Rune; Wolf, C Roland; Tickle, Cheryll; Dollé, Pascal

    2007-03-01

    Cytochrome P450 oxidoreductase (POR) acts as an electron donor for all cytochrome P450 enzymes. Knockout mouse Por(-/-) mutants, which are early embryonic (E9.5) lethal, have been found to have overall elevated retinoic acid (RA) levels, leading to the idea that POR early developmental function is mainly linked to the activity of the CYP26 RA-metabolizing enzymes (Otto et al., Mol. Cell. Biol. 23, 6103-6116). By crossing Por mutants with a RA-reporter lacZ transgene, we show that Por(-/-) embryos exhibit both elevated and ectopic RA signaling activity e.g. in cephalic and caudal tissues. Two strategies were used to functionally demonstrate that decreasing retinoid levels can reverse Por(-/-) phenotypic defects, (i) by culturing Por(-/-) embryos in defined serum-free medium, and (ii) by generating compound mutants defective in RA synthesis due to haploinsufficiency of the retinaldehyde dehydrogenase 2 (Raldh2) gene. Both approaches clearly improved the Por(-/-) early phenotype, the latter allowing mutants to be recovered up until E13.5. Abnormal brain patterning, with posteriorization of hindbrain cell fates and defective mid- and forebrain development and vascular defects were rescued in E9.5 Por(-/-) embryos. E13.5 Por(-/-); Raldh2(+/-) embryos exhibited abdominal/caudal and limb defects that strikingly phenocopy those of Cyp26a1(-/-) and Cyp26b1(-/-) mutants, respectively. Por(-/-); Raldh2(+/-) limb buds were truncated and proximalized and the anterior-posterior patterning system was not established. Thus, POR function is indispensable for the proper regulation of RA levels and tissue distribution not only during early embryonic development but also in later morphogenesis and molecular patterning of the brain, abdominal/caudal region and limbs. PMID:17126317

  2. Functional POR A503V is associated with the risk of bladder cancer in a Chinese population

    PubMed Central

    Xiao, Xue; Ma, Gaoxiang; Li, Shushu; Wang, Meilin; Liu, Nian; Ma, Lan; Zhang, Zhan; Chu, Haiyan; Zhang, Zhengdong; Wang, Shou-Lin

    2015-01-01

    Human cytochrome P450 oxidoreductase (POR) plays important roles in the metabolism of exogenous carcinogens and endogenous sterol hormones. However, few studies have explored the association between POR variants and the risk of bladder cancer. In this study, we first sequenced all 16 POR exons among 50 randomly selected controls, and found three variants, rs1135612, rs1057868 (A503V) and rs2228104, which were then assessed the relation to risk of bladder cancer in a case-control study of 1,050 bladder cancer cases and 1,404 cancer-free controls in a Chinese population. People with A503V TT genotype have a decreased risk of bladder cancer in a recessive model (TT vs. CC/CT, OR = 0.73, 95% CI = 0.57–0.93), which was more pronounced among elderly male, non-smoking, subjects. Especially, A503V TT genotype showed a protective effect in the invasive tumor stage. Functional analysis revealed that A503V activity decreased in cytochrome c reduction (50.5 units/mg vs. 135.4 units/mg), mitomycin C clearance (38.3% vs. 96.8%), and mitomycin C-induced colony formation (78.0 vs 34.3 colonies per dish). The results suggested that POR A503V might decrease the risk of bladder cancer by reducing its metabolic activity, and should be a potential biomarker for predicting the susceptibility to human bladder cancer. PMID:26123203

  3. Global Microlending in Education Reform: Enseñá Por Argentina and the Neoliberalization of the Grassroots

    ERIC Educational Resources Information Center

    Friedrich, Daniel S.

    2010-01-01

    This article examines the workings and underlying assumptions behind Enseñá por Argentina (Teach for Argentina), one specific program that takes part in the larger and expanding network of Teach for All, by thinking about the ways in which a global push for redefining teaching and teacher education encounters local characteristics and histories,…

  4. [Professor Frantisek Por MD and Professor Robert Klopstock MD, students at Budapest and Prague Faculties of Medicine].

    PubMed

    Mydlík, M; Derzsiová, K

    2010-11-01

    Professor Frantisek Por MD and Professor Robert Klopstock MD were contemporaries, both born in 1899, one in Zvolen, the other in Dombovar, at the time of Austro-Hungarian Monarchy. Prof. Por attended the Faculty of Medicine in Budapest from 1918 to 1920, and Prof. Klopstock studied at the same place between 1917 and 1919. From 1920 until graduation on 6th February 1926, Prof. Por continued his studies at the German Faculty of Medicine, Charles University in Prague. Prof. Klopstock had to interrupt his studies in Budapest due to pulmonary tuberculosis; he received treatment at Tatranske Matliare where he befriended Franz Kafka. Later, upon Kafka's encouragement, he changed institutions and continued his studies at the German Faculty of Medicine, Charles University in Prague, where he graduated the first great go. It is very likely that, during their studies in Budapest and Prague, both professors met repeatedly, even though their life paths later separated. Following his graduation, Prof. Por practiced as an internist in Prague, later in Slovakia, and from 1945 in Kosice. In 1961, he was awarded the title of university professor of internal medicine at the Faculty of Medicine, Pavol Jozef Safarik University in Kosice, where he practiced until his death in 1980. Prof. Klopstock continued his studies in Kiel and Berlin. After his graduation in 1933, he practiced in Berlin as a surgeon and in 1938 left for USA. In 1962, he was awarded the title of university professor of pulmonary surgery in NewYork, where he died in 1972. PMID:21250499

  5. Inversor Resonante de Tres Elementos L-LC con Caracteristica Cortocircuitable para Aplicaciones de Calentamiento por Induccion

    NASA Astrophysics Data System (ADS)

    Espi Huerta, Jose Miguel

    Los generadores de calentamiento por induccion son puentes inversores con carga resonante, cuya mision es basicamente crear una corriente sinusoidal de gran amplitud sobre la "bobina de caldeo", que forma parte del tanque resonante. En el interior de esta bobina se introduce la pieza que se desea calentar. EI campo magnetico creado induce corrientes superficiales (corrientes de Foucault) sobre la pieza, que producen su calentamiento. Los tanques resonantes (tambien llamados osciladores) utilizados en la actualidad son el resonante serie y el resonante paralelo. Aunque ya desde hace algun tiempo se vienen construyendo generadores de alta potencia basados en estos dos osciladores, el exito nunca ha. sido completo en ninguno de los dos casos. Tal y como se explica en la introduccion de esta memoria, los puentes inversores utilizados deben operar sobre una carga inductiva (corriente retrasada) para evitar el fenomeno de la recuperacion inversa de sus diodos y la consiguiente ruptura de los transistores. De la restriccion topologica anterior se deduce que el generador paralelo debe conmutar a frecuencias inferiores a la resonancia, y el serie a frecuencias superiores. A esta restriccion topologica hay que unir otra que es exclusiva del calentamiento por induccion: La corriente por la bobina de caldeo debe ser sinusoidal. De no ser asi, resultaria imposible disponer toda la potencia de calentamiento sobre la pieza en el espesor requerido por la aplicacion. Como consecuencia, los inversores no pueden operar por debajo de la frecuencia de resonancia del oscilador, pues en ese caso se amplifican los armonicos de orden superior de la tension/corriente de entrada situados sobre la resonancia, con la consiguiente distorsion de la corriente de salida. La conjuncion de las dos restricciones anteriores obligan al inversor paralelo a funcionar a la frecuencia de resonancia del oscilador. Esto imposibilita un control por variacion de frecuencia, regulandose la potencia desde la

  6. Encefalitis por anticuerpos contra el receptor de NMDA: experiencia con seis pacientes pediátricos. Potencial eficacia del metotrexato

    PubMed Central

    Bravo-Oro, Antonio; Abud-Mendoza, Carlos; Quezada-Corona, Arturo; Dalmau, Josep; Campos-Guevara, Verónica

    2016-01-01

    Introducción La encefalitis por anticuerpos contra el receptor de N-metil-D-aspartato (NMDA) es una entidad cada vez más diagnosticada en edad pediátrica. A diferencia de los adultos, en muchos casos no se asocia a tumores y las manifestaciones iniciales en niños más frecuentes son crisis convulsivas y trastornos del movimiento, mientras que en los adultos predominan las alteraciones psiquiátricas. Casos clínicos Presentamos seis casos pediátricos confirmados con anticuerpos contra la subunidad NR1 del receptor de NMDA en suero y líquido cefalorraquídeo. Cinco de los casos comenzaron con crisis convulsivas como manifestación clínica inicial antes de desarrollar el cuadro clásico de esta entidad. En todos los casos se utilizaron esteroides como primera línea de tratamiento, con los que sólo se observó control de las manifestaciones en uno, por lo que el resto de los pacientes requirió inmunomoduladores de segunda línea. Todos los pacientes recibieron metotrexato como tratamiento inmunomodulador para evitar recaídas y la evolución fue a la mejoría en todos ellos. Conclusiones En nuestra serie de pacientes con encefalitis por anticuerpos contra el receptor de NMDA, ninguno se asoció a tumores. Todos los casos recibieron metotrexato por lo menos durante un año, no observamos eventos adversos clínicos ni por laboratorio, ni hubo secuelas neurológicas ni recaídas durante el tratamiento. Aunque es una serie pequeña y es deseable incrementar el número y tiempo de evolución, consideramos el metotrexato una excelente alternativa como tratamiento inmunomodulador para esta patología. PMID:24150952

  7. Prevalencia y tamizaje del Trastorno por Déficit de Atención con Hiperactividad en Costa Rica

    PubMed Central

    Weiss, Nicholas T.; Schuler, Jovita; Monge, Silvia; McGough, James J.; Chavira, Denise; Bagnarello, Monica; Herrera, Luis Diego; Mathews, Carol A.

    2015-01-01

    Resumen La investigación tuvo como propósito estimar la prevalencia del Trastorno por Déficit de Atención con Hiperactividad (TDAH) en Costa Rica y determinar si la versión en español del cuestionario Swanson Nolan and Pelham Scale IV (SNAP-IV) es un instrumento de tamizaje útil en una población de niños y niñas escolares costarricenses. El instrumento fue entregado a padres y maestros de 425 niños entre 5 y 13 años de edad (promedio = 8.8). Todos fueron evaluados con el instrumento Swanson, Kotkin, Agler, M-Flynn and Pelham Scale (SKAMP). Su diagnóstico fue confirmado con una entrevista clínica. La sensibilidad y la especificidad del SNAP-IV fueron evaluadas como predictores de criterios de diagnóstico según el DSM-IV. La prevalencia puntual en la muestra del TDAH fue del 5%. El tamizaje más preciso lo hizo el SNAP-IV completado por el maestro en un corte de 20%, con una sensibilidad de 96% y una especificidad de un 82%. La sensibilidad de los instrumentos completados por los padres fue más baja que aquella de los maestros. El SNAP-IV completado por las maestras con un corte aislando el 20% de los mayores puntajes categorizó correctamente a un 87% de los sujetos. PMID:22432094

  8. Epitope specificity of murine and human bactericidal antibodies against PorA P1.7,16 induced with experimental meningococcal group B vaccines.

    PubMed

    Rouppe van der Voort, E M; Kuipers, B; Brugghe, H F; van Unen, L M; Timmermans, H A; Hoogerhout, P; Poolman, J T

    1997-03-01

    Synthetic peptides derived from the predicted loops 1 and 4 of meningococcal PorA, sero-subtype P1.7,16, were used to study the epitope specificity of murine and human PorA P1.7,16 bactericidal antibodies. The predicted loops 1 and 4 are surface exposed and carry in their apices the sero-subtype epitopes P1.7 (loop 1) or P1.16 (loop 4), respectively. Peptides were synthesized as mono- and multimeric peptides. Murine monoclonal and polyclonal antibodies were induced with meningococcal whole cell preparations. Polyclonal antibodies were evoked in volunteers after one immunization with 50 micrograms or 100 micrograms protein of a hexavalent meningococcal PorA vesicle vaccine. The induction of PorA antibodies was determined in ELISA using purified PorA P1.7,16. The epitope specificity of anti-PorA antibodies for both murine and human antibodies could be demonstrated by direct peptide ELISA using overlapping multimeric peptides almost spanning the entire loops 1 or 4 of the protein. The capacity of peptides to inhibit the bactericidal activity of murine and human antibodies was investigated using meningococcal strain H44/76 (B:15:P1.7,16) as a target strain. Bactericidal activities could be inhibited with both monomeric and multimeric peptides derived from epitopes P1.7 and P1.16. PMID:9093834

  9. Targeting of Neisserial PorB to the mitochondrial outer membrane: an insight on the evolution of β-barrel protein assembly machines.

    PubMed

    Jiang, Jhih-Hang; Davies, John K; Lithgow, Trevor; Strugnell, Richard A; Gabriel, Kipros

    2011-11-01

    Mitochondria originated from Gram-negative bacteria through endosymbiosis. In modern day mitochondria, the Sorting and Assembly Machinery (SAM) is responsible for eukaryotic β-barrel protein assembly in the mitochondrial outer membrane. The SAM is the functional equivalent of the β-barrel assembly machinery found in the outer membrane of Gram-negative bacteria. In this study we examined the import pathway of a pathogenic bacterial protein, PorB, which is targeted from pathogenic Neisseria to the host mitochondria. We have developed a new method for measurement of PorB assembly into mitochondria that relies on the mobility shift exhibited by bacterial β-barrel proteins once folded and separated under semi-native electrophoretic conditions. We show that PorB is targeted to the outer mitochondrial membrane with a dependence on the intermembrane space shuttling chaperones and the core component of the SAM, Sam50, which is a functional homologue of BamA that is required for PorB assembly in bacteria. The peripheral subunits of the SAM, Sam35 and Sam37, which are essential for eukaryotic β-barrel protein assembly but do not have distinguishable functional homologues in bacteria, are not required for PorB assembly in eukaryotes. This shows that PorB uses an evolutionary conserved 'bacterial like' mechanism to infiltrate the host mitochondrial outer membrane. PMID:22032638

  10. A novel intronic splice site deletion of the IL-2 receptor common gamma chain results in expression of a dysfunctional protein and T-cell-positive X-linked Severe combined immunodeficiency.

    PubMed

    Gray, P E A; Logan, G J; Alexander, I E; Poulton, S; Roscioli, T; Ziegler, J

    2015-02-01

    X-linked severe combined immunodeficiency is caused by mutations in the IL-2 receptor common gamma chain and classically presents in the first 6 months of life with predisposition to bacterial, viral and fungal infections. In most instances, affected individuals are lymphopenic with near complete absence of T cells and NK cells. We report a boy who presented at 12 months of age with Pneumocystis jiroveci pneumonia and a family history consistent with X-linked recessive inheritance. He had a normal lymphocyte count including the presence of T cells and a broad T-cell-receptor diversity, as well as normal surface expression of the common gamma chain (CD132) protein. He however had profound hypogammaglobulinaemia, and IL-2-induced STAT5 phosphorylation was absent. Sequencing of IL-2RG demonstrated a 12-base pair intronic deletion close to the canonical splice site of exon 5, which resulted in a variety of truncated IL2RG mRNA species. A review of the literature identified 4 other patients with T-cell-positive X-SCID, with the current patient being the first associated with an mRNA splicing defect. This case raises the question of how a dysfunctional protein incapable of mediating STAT5 phosphorylation might nonetheless support T-cell development. Possible explanations are that STAT5-mediated signal transduction may be less relevant to IL7-receptor-mediated T-cell development than are other IL7R-induced intracellular transduction pathways or that a low level of STAT5 phosphorylation, undetectable in the laboratory, may be sufficient to support some T-cell development. PMID:25443657

  11. Antimicrobial therapy for the treatment of opportunistic infections in HIV/AIDS patients: a critical appraisal

    PubMed Central

    Seddon, Jo; Bhagani, Sanjay

    2011-01-01

    The widespread use of antiretroviral therapy (ART) has entirely changed the management of human immunodeficiency virus (HIV) infection and dramatically reduced the rates of opportunistic infections (OI). However, OI continue to cause significant morbidity and mortality in both developed countries, where presentation with advanced HIV infection is common, and also in developing countries where ART is less widely available. Evidence to direct OI guidelines is partly limited by the fact that many large-scale studies date from the pre-ART era and more recent studies are sometimes poorly powered due to the falling rates of OI. Treatment of OI is now known to be as much about antimicrobials as about immune reconstitution with ART, and recent studies help guide the timing of initiation of ART in different infections. OI have also become complicated by the immune reconstitution inflammatory syndrome phenomenon which may occur once successful immune recovery begins. Trimethoprim-sulfamethoxazole has long been one of the most important antibiotics in the treatment and prevention of OI and remains paramount. It has a broad spectrum of activity against Pneumocystis jiroveci, toxoplasmosis, and bacterial infections and has an important role to play in preventing life-threatening OI. New advances in treating OI are coming from a variety of quarters: in cytomegalovirus eye disease, the use of oral rather than intravenous drugs is changing the face of therapy; in cryptococcal meningitis, improved drug formulations and combination therapy is improving clearance rates and reducing drug toxicities; and in gut disease, the possibility of rapid immune restitution with ART is replacing the need for antimicrobials against cryptosporidia and microsporidia. PMID:22096404

  12. Prophylactic Trimethoprim-Sulfamethoxazole Does Not Affect Pharmacokinetics or Pharmacodynamics of Methotrexate.

    PubMed

    Watts, Courtney S; Sciasci, Joseph N; Pauley, Jennifer L; Panetta, John C; Pei, Deqing; Cheng, Cheng; Christensen, Caroline M; Mikkelsen, Torben S; Pui, Ching-Hon; Jeha, Sima; Relling, Mary V

    2016-08-01

    Trimethoprim-sulfamethoxazole (TMP/SMX) is used as prophylaxis against Pneumocystis jiroveci during chemotherapy. Many groups recommend withholding TMP/SMX during high-dose methotrexate (HDMTX) for concerns that it will delay methotrexate clearance. We compared methotrexate exposure following HDMTX (NCT00549848) in 424 patients including 783 courses that were given concurrently and 602 courses that were not given concurrently with TMP/SMX. Among 176 patients (555 courses) on the low-risk arm (HDMTX=2.5 g/m/24 h), there was no difference in clearance (110.7 [1.8%] vs. 108.2 [0.9%] mL/min/m, P=0.3) nor in 42 hour methotrexate concentration (0.37 [5.1%] vs. 0.40 (5.0%) μM, P=0.23). Among 248 patients (830 courses) on the standard/high-risk arm (HDMTX ~5 g/m/24 h), there was slightly higher clearance (95.5 [1.4%] vs. 91.2 [0.8%] mL/min/m, P=0.005) in those receiving TMP/SMX, with no difference in the 42 hour methotrexate concentration (0.59 [4.1%] vs. 0.66 [4.2%] μM, P=0.06). There was no difference in neutrophil counts based on TMP/SMX during HDMTX (P=0.83). TMP/SMX also did not have a significant impact on myelosuppression of low-dose methotrexate (40 mg/m) given during continuation therapy among 230 patients enrolled on a prior study (NCT00137111). Thus, we found no evidence for an interaction between methotrexate and TMP/SMX given prophylactically. PMID:27322715

  13. Adverse events and infectious burden, microbes and temporal outline from immunosuppressive therapy in antineutrophil cytoplasmic antibody-associated vasculitis with native renal function

    PubMed Central

    McGregor, JulieAnne G.; Negrete-Lopez, Roberto; Poulton, Caroline J.; Kidd, Jason M.; Katsanos, Suzanne L.; Goetz, Lindsey; Hu, Yichun; Nachman, Patrick H.; Falk, Ronald J.; Hogan, Susan L.

    2015-01-01

    Background Disease control in anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) with immunosuppression is effective but burdened by adverse events, especially infections. The study goal was to evaluate risks and types of infections in patients with AAV. Methods Biopsy-proven AAV patients (diagnosed 1/1991–6/2011) followed in an inception cohort were evaluated for adverse events. Severe infections (requiring intravenous antibiotics, intensive care unit, or causing death) were recorded. Infection number was grouped as none, 1–2 or ≥3. Cox regression was used to estimate hazard ratios with 95% confidence intervals. Results A total of 489 patients (median age 59; 47% female, 55% myeloperoxidase-ANCA) were followed for 2.8 years (median). At 1, 2 and 5 years cumulative incidence of infection was 51, 58 and 65% and severe infection was 22, 23 and 26%. Pulmonary and upper respiratory infections were most common (42 and 30% ever experienced each, respectively), highest in the first 3 months. Staphylococcus aureus was most frequently seen among positive cultures (41%, 78 S. aureus/192 total positive cultures), and only one Pneumocystis jiroveci pneumonia (6 weeks into treatment). All-cause death in 12 months was associated with infections (% deaths: 0 infections 3%; 1–2 infections 10%, ≥3 infections 13%, P = 0.002). Controlling for age, sex and kidney function, patients with severe infections were 4.2 times more likely to die within 12 months (95% CI 2.0–8.7; P = 0.001). Conclusions More infections increase the risk of a severe infection which increases risk of all-cause mortality. Respiratory and S. aureus infections are dominant. Targeted prophylactic therapy could decrease morbidity. PMID:25805747

  14. Systematic review and meta-analysis: influence of smoking cessation on incidence of pneumonia in HIV

    PubMed Central

    2013-01-01

    Background Smoking is common in people infected with HIV but cessation support is not a routine part of clinical care. The aim was to assess whether smoking is a risk factor for pneumonia in people with HIV and whether smoking cessation ameliorates excess risk. Methods We performed MEDLINE and Embase database searches and included cohort or case-control studies conducted in adult patients infected with HIV extracting a hazard ratio (HR) or odds ratio (OR) that compared the incidence of bacterial pneumonia or pneumonia caused by Pneumocystis jiroveci (PCP) between two smoking categories. Studies were appraised for quality and combined using inverse variance meta-analysis. Results Fourteen cohort and case-control studies were included. Assessment of outcome was good, but assessment of exposure status was poor. Current smokers were at higher risk of bacterial pneumonia than former smokers: HR 1.37 (95% confidence interval (CI): 1.06, 1.78). There was no evidence that former smokers were at higher risk than never smokers: HR 1.24 (95%CI: 0.96, 1.60). Current smokers were at higher risk of bacterial pneumonia than current non-smokers: HR of 1.73 (95%CI: 1.44, 2.06). There was no evidence that smoking increased the incidence of PCP. The HR for current versus non-smokers was 0.94 (95%CI: 0.79, 1.12), but from case-control studies the OR was 1.76 (95%CI: 1.25, 2.48) with heterogeneity. Confined to higher quality studies, the OR was 0.97 (95%CI: 0.81, 1.16). Residual confounding is possible, but available data suggest this is not an adequate explanation. Conclusions Smoking is a risk factor for bacterial pneumonia but not PCP and smoking cessation reduces this risk. See related article: http://www.biomedcentral.com/1741-7015/11/16 PMID:23339513

  15. Dapsone-Induced Methemoglobinemia: A Dose Related Occurrence?

    PubMed Central

    Esbenshade, Adam J; Ho, Richard H.; Shintani, Ayumi; Zhao, Zhiguo; Smith, Lesley-Ann; Friedman, Debra L.

    2011-01-01

    Objectives Dapsone, used for Pneumocystis jiroveci (PCP) prophylaxis, is associated with increased risk of methemoglobinemia. Absence of cytochrome b5 reductase enzyme activity (CYB5RA) causes congenital methemoglobinemia, but its role in dapsone-associated methemoglobinemia is unknown. We sought to elucidate drug-related risk factors for dapsone-associated methemoglobinemia in pediatric oncology patients, including contribution of CYB5RA. Patients and Methods Among 167 pediatric patients treated for hematologic malignancies or aplastic anemia who received dapsone for PCP prophylaxis, demographic and dapsone treatment data were retrospectively collected. Drug-related risk factors were evaluated by Cox proportional hazards, and in a cross-sectional subgroup of 40 patients, CYB5RA was assessed. Results Methemoglobinemia (median methemoglobin level = 9.0% [3.5–22.4]) was documented in 32 patients (19.8%). There was a 73% risk reduction in methemoglobinemia with dosing ≥20% below the target dose 2mg/kg/day (HR = 0.27; 95% confidence interval (CI) 0.09, 0.78; p=0.016), while methemoglobinemia risk was increased with dosing ≥20% above the target dose (HR = 6.25; 95% CI 2.45, 15.93; p<0.001). Sex, body mass index, and age were not associated with increased risk. CYB5RA did not differ by methemoglobinemia status (median 8.6 IU/g Hb; [5.5 – 12.1] vs. 9.1 IU/g Hb; [6.7 – 12.7]). No patient developed PCP on dapsone. Conclusions Methemoglobinemia occurred in almost 20% of pediatric oncology patients receiving dapsone for PCP prophylaxis. Higher dapsone dosing is associated with increased risk. A cross-sectionally acquired CYB5RA level was not associated with methemoglobinemia risk. Studies are needed to define biologic correlates of methemoglobinemia and evaluate lower dapsone doses for PCP prophylaxis. PMID:21246536

  16. Positive Family History, Infection, Low Absolute Lymphocyte Count (ALC) and Absent Thymic Shadow: Diagnostic Clues for all Molecular Forms of Severe Combined Immunodeficiency (SCID)

    PubMed Central

    McWilliams, Laurie M; Railey, Mary Dell; Buckley, Rebecca H

    2015-01-01

    Background Severe Combined Immunodeficiency (SCID) is a syndrome uniformly fatal during infancy unless recognized and treated successfully by bone marrow transplantation or gene therapy. Because SCID infants have no abnormal physical appearance, diagnosis is usually delayed unless newborn screening is performed. Objective In this study, we sought to evaluate the presenting features of all 172 SCID patients transplanted at this institution over the past 31 years. Methods We reviewed original charts from 172 consecutive classic SCID patients who received either T cell-depleted HLA-haploidentical (N=154) or HLA-identical (N=18) non-ablative related marrow transplants at Duke University Medical Center from 1982–2013. Results The mean age at presentation was 4.87 months. When there was a family history of early infant death or known SCID (63/172 or 37%), the mean presentation age was much earlier, 2.0 months compared to 6.6 months. Failure to thrive was common, with 84 patients (50%) having a weight less than the 5th percentile. The leading infections included oral moniliasis (43%), viral infections (61/172 35.5%) and Pneumocystis jiroveci (26%) pneumonia. The group mean ALC was 1454/cmm; 88% of the infants had an ALC less than 3000/cmm. Absent thymic shadow was seen in 92% of infants with electronic radiographic data available. An absence of T cell function was found in all patients. Conclusions SCID infants appear normal at birth but later present with failure to thrive and/or recurrent fungal, viral and bacterial infections. Low ALCs and absent thymic shadow on chest x-ray are key diagnostic clues. The absence of T cell function confirms the diagnosis. PMID:25824440

  17. HIV-related Pneumocystis carinii Pneumonia in Older Patients Hospitalized in the Early HAART Era

    PubMed Central

    Kim, Benjamin; Lyons, Thomas M; Parada, Jorge P; Uphold, Constance R; Yarnold, Paul R; Hounshell, Jennie B; Sipler, Alison M; Goetz, Matthew B; DeHovitz, Jack A; Weinstein, Robert A; Campo, Rafael E; Bennett, Charles L

    2001-01-01

    OBJECTIVE To determine whether older age continues to influence patterns of care and in-hospital mortality for hospitalized persons with HIV-related Pneumocustis carinii pneumonia (PCP), as determined in our prior study from the 1980s. DESIGN Retrospective chart review. PATIENTS/SETTING Patients (1,861) with HIV-related PCP at 78 hospitals in 8 cities from 1995 to 1997. MEASUREMENTS Medical record notation of possible HIV infection; alveolar-arterial oxygen gradient; CD4 lymphocyte count; presence or absence of wasting; timely use of anti-PCP medications; in-hospital mortality. MAIN RESULTS Compared to younger patients, patients ≥50 years of age were less likely to have HIV mentioned in their progress notes (70% vs 82%, P < .001), have mild or moderately severe PCP cases at admission (89% vs 96%, P < .002), receive anti-PCP medications within the first 2 days of hospitalization (86% vs 93%, P <.002), and survive hospitalization (82% vs 90%, P < .003). However, age was not a significant predicator of mortality after adjustment for severity of PCP and timeliness of therapy. CONCLUSIONS While inpatient PCP mortality has improved by 50% in the past decade, 2-fold age-related mortality differences persist. As in the 1980s, these differences are associated with lower rates of recognition of HIV, increased severity of illenss at admission, and delays in initiation of PCP-specific treatments among older individuals—factors suggestive of delayed recognition of HIV infection, pneumonia, and PCP, respectively. Continued vigilance for the possibility of HIV and HIV-related PCP among persons ≥50 years of age who present with new pulmonary symptoms should be encouraged. PMID:11556938

  18. Unsuspected Pneumocystis carinii pneumonia and vertically acquired HIV infection in infants requiring intensive care.

    PubMed Central

    Tasker, R. C.; Wilkinson, K.; Slater, T. J.; Novelli, V.

    1994-01-01

    When an infant develops acute respiratory failure of sufficient severity to necessitate supportive mechanical ventilation a cause should always be sought. A chest radiograph showing predominantly interstitial lung disease and an infant's failure to respond to standard antibiotic treatment are indications for non-bronchoscopic bronchoalveolar lavage. If P carinii pneumonia is diagnosed a congenital immunodeficiency should be sought and the parents counselled about HIV infection. Earlier investigation may be indicated by features of immunodeficiency when taking a history, performing a general examination, or analysing the results of basic haematological testing. Images p462-a PMID:8124183

  19. Análise dos Conceitos Astronômicos Apresentados por Professores de Algumas Escolas Estaduais Brasileiras

    NASA Astrophysics Data System (ADS)

    Voelzke, Marcos Rincon; Gonzaga, Edson Pereira

    2011-12-01

    A razão para o desenvolvimento deste trabalho baseia-se no fato de que muitos professores da Educação Básica (EB) não lidam com conceitos relacionados à astronomia, e quando o fazem eles simplesmente seguem livros didáticos que podem conter erros conceituais. Como é de conhecimento geral a astronomia é um dos conteúdos a serem ensinados na EB fazendo parte dos Parâmetros Curriculares Nacionais e das Propostas Curriculares do Estado de São Paulo, mas é um fato, que vários pesquisadores apontam, a existência de muitos problemas no ensino da astronomia. Com o propósito de minimizar algumas dessas deficiências foi realizado um trabalho de pesquisa com a utilização de questionários pré e pós pesquisa, para tanto foi desenvolvido um Curso de Extensão Universitária para professores da Diretoria de Ensino Regional (DE) que abrange Mauá, Ribeirão Pires e Rio Grande da Serra (no Estado de São Paulo) com os seguintes objetivos: levantar concepções alternativas; subsidiar os professores por meio de palestras, debates e workshops, e verificar o sucesso da aprendizagem após o curso, adotando-se como referência, para a análise dos resultados, os dicionários de Língua Portuguesa (FERREIRA, 2004) e Enciclopédico de Astronomia e Astronáutica (MOURĀO, 1995). Portanto, dezesseis questões foram aplicadas antes e após o curso, assim pode-se verificar após a pesquisa que 100,0% dos professores sabiam os nomes das fases da Lua, 97,0% entenderam que o Sistema Solar é composto por oito planetas, 78,1% foram capazes de explicar como ocorre um eclipse lunar, um eclipse solar e um solstício, 72,7% sabiam como explicar a ocorrência das estações do ano; 64,5% explicaram corretamente a ocorrência do equinócio, 89,7% foram capazes de definir adequadamente o termo cometa; 63,6% definiram asteróide, 54,5% meteoro, 58,1% galáxia, e 42,4% planeta. Os resultados obtidos indicam uma aprendizagem significativa por parte dos participantes.

  20. Immunogenicity and reactogenicity in UK infants of a novel meningococcal vesicle vaccine containing multiple class 1 (PorA) outer membrane proteins.

    PubMed

    Cartwright, K; Morris, R; Rümke, H; Fox, A; Borrow, R; Begg, N; Richmond, P; Poolman, J

    1999-06-01

    The development of effective vaccines against serogroup B meningococci is of great public health importance. We assessed a novel genetically engineered vaccine containing six meningococcal class 1 (PorA) outer membrane proteins representing 80% of prevalent strains in the UK. 103 infants were given the meningococcal vaccine at ages 2, 3 and 4 months with routine infant immunisations, with a fourth dose at 12-18 months. The vaccine was well tolerated. Three doses evoked good immune responses to two of six meningococcal strains expressing PorA proteins contained in the vaccine. Following a fourth dose, larger bactericidal responses to all six strains were observed, suggesting that the initial course had primed memory lymphocytes and revaccination stimulated a booster response. This hexavalent PorA meningococcal vaccine was safe and evoked encouraging immune responses in infants. Vaccines of this type warrant further development and evaluation. PMID:10418910

  1. Crystallization and preliminary X-ray analysis of the C-terminal fragment of PorM, a subunit of the Porphyromonas gingivalis type IX secretion system.

    PubMed

    Stathopulos, Julien; Cambillau, Christian; Cascales, Eric; Roussel, Alain; Leone, Philippe

    2015-01-01

    PorM is a membrane protein involved in the assembly of the type IX secretion system (T9SS) from Porphyromonas gingivalis, a major bacterial pathogen responsible for periodontal disease in humans. The periplasmic domain of PorM was overexpressed in Escherichia coli and purified. A fragment of the purified protein was obtained by limited proteolysis. Crystals of this fragment belonged to the tetragonal space group P4(3)2(1)2. Native and MAD data sets were recorded to 2.85 and 3.1 Å resolution, respectively, using synchrotron radiation. PMID:25615973

  2. "Estudio tribologico de aceros para moldes. Aplicacion al moldeo por inyeccion de polibutilentereftalato reforzado con fibra de vidrio"

    NASA Astrophysics Data System (ADS)

    Martinez Mateo, Isidoro Jose

    Mould materials for injection moulding of polymers and polymer-matrix composites represent a relevant industrial economic sector due to the large quantity of pieces and components processed. The material selection for mould manufacturing, its composition and heat treatment, the hardening procedures and machining and finishing processes determine the service performance and life of the mould. In the first part of the present study, the relationship between the hardness and microstructure and the wear resistance of mould steels from large blocks has been studied by pin-on-disc tests, studying the main wear mechanisms. In order to determine the surface damage on mould steels under real injection conditions, different commercial steels have been studied by measuring the variation of surface roughness with the number of injected pieces with different reinforcement percentages and different mould geometries, by using optical profilometry and scanning electron microscopy techniques. It was important to determine the variation of surface roughness of the moulded pieces with the number of injection operations. The materials used were polybutyleneterephthalate pure and reinforced with either 20% or 50% glass fibre. For the different mould designs, the evolution of the glass fibre orientation with injection flow has been determined by image analysis and related to roughness changes and surface damage, both of the composite parts and of the mould steel surface. Finally, the abrasion resistance of the composite parts has been studied by scratch tests as a function of the number of injected parts and of the scratch direction with respect to injection flow and glass fibre orientation. Los materiales para moldes de inyeccion de polimeros y materiales compuestos representan un sector economicamente muy relevante debido al gran aumento del numero de componentes fabricados a partir de materiales polimericos obtenidos mediante moldeo por inyeccion. La seleccion del material para la

  3. Adult Student Retention and Achievement with Language-Based Modular Materials. POR FIN: Program Organizing Related Family Instruction in the Neighborhood.

    ERIC Educational Resources Information Center

    Bexar County School Board, San Antonio, TX.

    The goal of the POR FIN research design was to develop a language-based curriculum emphasizing the audiolingual approach and integrating academic and social-functioning subject matter. The modular curriculum is designed so that each lesson is independent and complete in itself, and provides a high degree of motivation, retention, and achievement…

  4. P(O)R2-directed Pd-catalyzed C–H functionalization of biaryl derivatives to synthesize chiral phosphorous ligands

    PubMed Central

    Hu, Rong-Bin; Wang, Hong-Li; Zhang, Hong-Yu; Zhang, Heng; Ma, Yan-Na

    2014-01-01

    Summary Chiral phosphorus ligands have been widely used in transition metal-catalyzed asymmetric reactions. Herein, we report a new synthesis approach of chiral biaryls containing a phosphorus moiety using P(O)R2-directed Pd-catalyzed C–H activation; the functionalized products are produced with good enantioselectivity. PMID:25246966

  5. El proceso hacia la integracion de la equidad por genero al curriculo.(The Process of the Integration of Gender Equity in the Curriculum.)

    ERIC Educational Resources Information Center

    Rivera-Bermudez, Carmen D.

    "El Proyecto Colaborativo de Equidad por Genero en la Educacion," or the Collaborative Project for Gender Equity in Education, was undertaken in Puerto Rico between 1990 and 1992 to study how to facilitate the integration of gender equity themes in the curriculum through the direct action of participating teachers. A study examined the attitudes…

  6. Informe a la nación indica que los índices de muertes por cáncer siguen bajando

    Cancer.gov

    Los índices de mortalidad por todos los cánceres combinados para hombres, mujeres y niños siguieron bajando en Estados Unidos entre 2004 y 2008, según el Informe Anual a la Nación sobre el Estado del Cáncer de 1975 a 2008. El índice general de diagnóstico

  7. Community-based education in nutrition and cancer: the Por La Vida Cuidándome curriculum.

    PubMed

    Navarro, A M; Rock, C L; McNicholas, L J; Senn, K L; Moreno, C

    2000-01-01

    The Por La Vida (PLV) intervention model relies on community lay health advisors trained to conduct education sessions among members of their existing social networks. PLV Cuidándome was funded by the NCI to develop, implement, and evaluate the PLV model with respect to nutrition and cancer prevention, as well as early detection of breast and cervical cancers. The target population is the Latino community, for which substantial barriers to health care access exist. This article presents the curriculum that guides the sessions and describes its development, which was based on semi-structured interviews with Latina lay-health community workers to explore relevant attitudes and behaviors. Also key to the process was the work of the educational materials committee, whose members offered community representation as well as expertise in nutritional sciences, educational technologies, and community-based health promotion interventions and research. The 12-session curriculum's goal was to increase both the variety and the quality of fruits and/or vegetables consumed. It included information about consumption of fiber and fat in the importance of balance between energy intake and physical activity. The program has been well received. An ongoing study examines how it enhances nutrition and cancer prevention. PMID:11019766

  8. Estimaciones de Prevalencia del VIH por Género y Grupo de Riesgo en Tijuana, México: 2006

    PubMed Central

    Iñiguez-Stevens, Esmeralda; Brouwer, Kimberly C.; Hogg, Robert S.; Patterson, Thomas L.; Lozada, Remedios; Magis-Rodriguez, Carlos; Elder, John P.; Viani, Rolando M.; Strathdee, Steffanie A.

    2010-01-01

    OBJETIVO Estimar la prevalencia del VIH en adultos de 15-49 años de edad en Tijuana, México - en la población general y en subgrupos de riesgo en el 2006. METODOS Se obtuvieron datos demográficos del censo Mexicano del 2005, y la prevalencia del VIH se obtuvo de la literatura. Se construyó un modelo de prevalencia del VIH para la población general y de acuerdo al género. El análisis de sensibilidad consistió en estimar errores estándar del promedio-ponderado de la prevalencia del VIH y tomar derivados parciales con respecto a cada parámetro. RESULTADOS La prevalencia del VIH es 0.54%(N = 4,347) (Rango: 0.22%–0.86%, (N = 1,750–6,944)). Esto sugiere que 0.85%(Rango: 0.39%–1.31%) de los hombres y 0.22%(Rango: 0.04%–0.40%) de las mujeres podrían ser VIH-positivos. Los hombres que tienen sexo con hombres (HSH), las trabajadoras sexuales usuarias de drogas inyectables (MTS-UDI), MTS-noUDI, mujeres UDI, y los hombres UDI contribuyeron las proporciones más elevadas de personas infectadas por el VIH. CONCLUSIONES El número de adultos VIH-positivos entre subgrupos de riesgo en la población de Tijuana es considerable, marcando la necesidad de enforcar las intervenciones de prevención en sus necesidades específicas. El presente modelo estima que hasta 1 en cada 116 adultos podrían ser VIH-positivos. PMID:19685824

  9. Study of the interaction mechanisms between absorbed NO{sub 2} and por-Si/SnO{sub x} nanocomposite layers

    SciTech Connect

    Bolotov, V. V.; Kan, V. E. Makushenko, R. K.; Biryukov, M. Yu.; Ivlev, K. E.; Roslikov, V. E.

    2013-10-15

    The interaction mechanisms between NO{sub 2} molecules and the surface of por-Si/SnO{sub x} nanocomposites obtained by magnetron deposition and chemical vapor deposition (CVD) are studied by infrared absorption spectroscopy and electron paramagnetic resonance methods. The observed increase in the free carrier concentration in the por-Si/SnO{sub x} nanocomposite layers is explained by a change in the charge state of P{sub b} centers due to the formation of neutral 'surface defect-adsorbed NO{sub 2} molecule' complexes with free carrier generation in the crystallite bulk. In the nanocomposite layers grown by the CVD method, the increase in the free hole concentration during NO{sub 2} adsorption is much less pronounced in comparison with the composite grown by magnetron deposition, which is caused by the competing interaction channel of NO{sub 2} molecules with electrically neutral P{sub b} centers.

  10. Binding of Complement Factor H to PorB3 and NspA Enhances Resistance of Neisseria meningitidis to Anti-Factor H Binding Protein Bactericidal Activity

    PubMed Central

    Giuntini, Serena; Pajon, Rolando; Ram, Sanjay

    2015-01-01

    Among 25 serogroup B Neisseria meningitidis clinical isolates, we identified four (16%) with high factor H binding protein (FHbp) expression that were resistant to complement-mediated bactericidal activity of sera from mice immunized with recombinant FHbp vaccines. Two of the four isolates had evidence of human FH-dependent complement downregulation independent of FHbp. Since alternative complement pathway recruitment is critical for anti-FHbp bactericidal activity, we hypothesized that in these two isolates binding of FH to ligands other than FHbp contributes to anti-FHbp bactericidal resistance. Knocking out NspA, a known meningococcal FH ligand, converted both resistant isolates to anti-FHbp susceptible isolates. The addition of a nonbactericidal anti-NspA monoclonal antibody to the bactericidal reaction also increased anti-FHbp bactericidal activity. To identify a role for FH ligands other than NspA or FHbp in resistance, we created double NspA/FHbp knockout mutants. Mutants from both resistant isolates bound 10-fold more recombinant human FH domains 6 and 7 fused to Fc than double knockout mutants prepared from two sensitive meningococcal isolates. In light of recent studies showing functional FH-PorB2 interactions, we hypothesized that PorB3 from the resistant isolates recruited FH. Allelic exchange of porB3 from a resistant isolate to a sensitive isolate increased resistance of the sensitive isolate to anti-FHbp bactericidal activity (and vice versa). Thus, some PorB3 variants functionally bind human FH, which in the presence of NspA enhances anti-FHbp resistance. Combining anti-NspA antibodies with anti-FHbp antibodies can overcome resistance. Meningococcal vaccines that target both NspA and FHbp are likely to confer greater protection than either antigen alone. PMID:25644002

  11. Los índices de mortalidad por cáncer de pulmón siguen en descenso y contribuyen a la continua reducc

    Cancer.gov

    El Informe Anual a la Nación sobre el Estado del Cáncer (1975 a 2010), mostró un descenso más acelerado que en años anteriores de los índices de mortalidad por cáncer de pulmón. También contiene una sección especial que destaca los efectos significativos

  12. La doctora Amelie Ramírez y la investigación de desigualdades de salud por cáncer en la comunidad la

    Cancer.gov

    La doctora Ramírez es la investigadora principal de Redes en Acción, un centro del programa de redes comunitarias subvencionado por el NCI que se propone reducir la incidencia del cáncer en la comunidad latina a través de una red nacional de grupos comunitarios, investigadores, agencias de salud gubernamentales y la población en general.

  13. Adjuvant Effects Elicited by Novel Oligosaccharide Variants of Detoxified Meningococcal Lipopolysaccharides on Neisseria meningitidis Recombinant PorA Protein: A Comparison in Mice

    PubMed Central

    Mehta, Ojas H.; Norheim, Gunnstein; Hoe, J . Claire; Rollier, Christine S.; Nagaputra, Jerry C.; Makepeace, Katherine; Saleem, Muhammad; Chan, Hannah; Ferguson, David J. P.; Jones, Claire; Sadarangani, Manish; Hood, Derek W.; Feavers, Ian; Derrick, Jeremy P.; Pollard, Andrew J.; Moxon, E . Richard

    2014-01-01

    Neisseria meningitidis lipopolysaccharide (LPS) has adjuvant properties that can be exploited to assist vaccine immunogenicity. The modified penta-acylated LPS retains the adjuvant properties of hexa-acylated LPS but has a reduced toxicity profile. In this study we investigated whether two modified glycoform structures (LgtE and IcsB) of detoxified penta-acylated LPS exhibited differential adjuvant properties when formulated as native outer membrane vesicles (nOMVs) as compared to the previously described LgtB variant. Detoxified penta-acylated LPS was obtained by disruption of the lpxL1 gene (LpxL1 LPS), and three different glycoforms were obtained by disruption of the lgtB, lgtE or icsB genes respectively. Mice (mus musculus) were immunized with a recombinant PorA P1.7-2,4 (rPorA) protein co-administered with different nOMVs (containing a different PorA serosubtype P1.7,16), each of which expressed one of the three penta-acylated LPS glycoforms. All nOMVs induced IgG responses against the rPorA, but the nOMVs containing the penta-acylated LgtB-LpxL1 LPS glycoform induced significantly greater bactericidal activity compared to the other nOMVs or when the adjuvant was Alhydrogel. Compared to LgtE or IcsB LPS glycoforms, these data support the use of nOMVs containing detoxified, modified LgtB-LpxL1 LPS as a potential adjuvant for future meningococcal protein vaccines. PMID:25545241

  14. Binding of complement factor H to PorB3 and NspA enhances resistance of Neisseria meningitidis to anti-factor H binding protein bactericidal activity.

    PubMed

    Giuntini, Serena; Pajon, Rolando; Ram, Sanjay; Granoff, Dan M

    2015-04-01

    Among 25 serogroup B Neisseria meningitidis clinical isolates, we identified four (16%) with high factor H binding protein (FHbp) expression that were resistant to complement-mediated bactericidal activity of sera from mice immunized with recombinant FHbp vaccines. Two of the four isolates had evidence of human FH-dependent complement downregulation independent of FHbp. Since alternative complement pathway recruitment is critical for anti-FHbp bactericidal activity, we hypothesized that in these two isolates binding of FH to ligands other than FHbp contributes to anti-FHbp bactericidal resistance. Knocking out NspA, a known meningococcal FH ligand, converted both resistant isolates to anti-FHbp susceptible isolates. The addition of a nonbactericidal anti-NspA monoclonal antibody to the bactericidal reaction also increased anti-FHbp bactericidal activity. To identify a role for FH ligands other than NspA or FHbp in resistance, we created double NspA/FHbp knockout mutants. Mutants from both resistant isolates bound 10-fold more recombinant human FH domains 6 and 7 fused to Fc than double knockout mutants prepared from two sensitive meningococcal isolates. In light of recent studies showing functional FH-PorB2 interactions, we hypothesized that PorB3 from the resistant isolates recruited FH. Allelic exchange of porB3 from a resistant isolate to a sensitive isolate increased resistance of the sensitive isolate to anti-FHbp bactericidal activity (and vice versa). Thus, some PorB3 variants functionally bind human FH, which in the presence of NspA enhances anti-FHbp resistance. Combining anti-NspA antibodies with anti-FHbp antibodies can overcome resistance. Meningococcal vaccines that target both NspA and FHbp are likely to confer greater protection than either antigen alone. PMID:25644002

  15. Corynebacterium jeikeium jk0268 Constitutes for the 40 Amino Acid Long PorACj, Which Forms a Homooligomeric and Anion-Selective Cell Wall Channel

    PubMed Central

    Norouzy, Amir; Schulz, Robert; Nau, Werner M.; Kleinekathöfer, Ulrich; Tauch, Andreas; Benz, Roland

    2013-01-01

    Corynebacterium jeikeium, a resident of human skin, is often associated with multidrug resistant nosocomial infections in immunodepressed patients. C. jeikeium K411 belongs to mycolic acid-containing actinomycetes, the mycolata and contains a channel-forming protein as judged from reconstitution experiments with artificial lipid bilayer experiments. The channel-forming protein was present in detergent treated cell walls and in extracts of whole cells using organic solvents. A gene coding for a 40 amino acid long polypeptide possibly responsible for the pore-forming activity was identified in the known genome of C. jeikeium by its similar chromosomal localization to known porH and porA genes of other Corynebacterium strains. The gene jk0268 was expressed in a porin deficient Corynebacterium glutamicum strain. For purification temporarily histidine-tailed or with a GST-tag at the N-terminus, the homogeneous protein caused channel-forming activity with an average conductance of 1.25 nS in 1M KCl identical to the channels formed by the detergent extracts. Zero-current membrane potential measurements of the voltage dependent channel implied selectivity for anions. This preference is according to single-channel analysis caused by some excess of cationic charges located in the channel lumen formed by oligomeric alpha-helical wheels. The channel has a suggested diameter of 1.4 nm as judged from the permeability of different sized hydrated anions using the Renkin correction factor. Surprisingly, the genome of C. jeikeium contained only one gene coding for a cell wall channel of the PorA/PorH type found in other Corynebacterium species. The possible evolutionary relationship between the heterooligomeric channels formed by certain Corynebacterium strains and the homooligomeric pore of C. jeikeium is discussed. PMID:24116064

  16. Obtención de la curva de luz en la ocultación de 35 Sgr por Júpiter el 6 de marzo de 1996

    NASA Astrophysics Data System (ADS)

    Paolantonio, S.; Duffard, R.; Carranza, G.

    La ocultación de la estrella de quinta magnitud 35 Sgr por Júpiter, se produjo el 6 de Marzo de 1996 a las 13 hs. TU. El objetivo era medir el cambio del flujo de la estrella en el ingreso y egreso por el limbo del planeta. Con estos datos se pueden determinar parámetros físicos del planeta (radio, eccentricidad) y de su atmósfera (escala de altura, temperatura, densidad, presión) Para lograr ésto se programó la cámara CCD TH 7896 1024 x 1025 instalada en el telescopio de 1.54 m de Bosque Alegre con el objetivo de lograr 2 imágenes por segundo. De esta forma se obtuvieron 2100 imágenes de la inmersión y otras tantas de la emersión. Hubo que tener grandes precauciones para evitar la saturación del CCD ya que la observación se realizó de día. En este momento las imágenes se encuentran en el Department of Planetary Sciences, Lunar and Planetary Laboratory, University of Arizona, para su reducción.

  17. Immunogenicity studies with a genetically engineered hexavalent PorA and a wild-type meningococcal group B outer membrane vesicle vaccine in infant cynomolgus monkeys.

    PubMed

    Rouppe van der Voort, E; Schuller, M; Holst, J; de Vries, P; van der Ley, P; van den Dobbelsteen, G; Poolman, J

    2000-01-31

    The immunogenicity of two meningococcal outer membrane vesicle (OMV) vaccines, namely the Norwegian wild-type OMV vaccine and the Dutch hexavalent PorA OMV vaccine, were examined in infant cynomolgus monkeys. For the first time, a wild-type- and a recombinant OMV vaccine were compared. Furthermore, the induction of memory and the persistence of circulating antibodies were measured. The Norwegian vaccine contained all four classes of major outer membrane proteins (OMP) and wild-type L3/L8 lipopolysaccharide (LPS). The Dutch vaccine consisted for 90% of class 1 OMPs, had low expression of class 4 and 5 OMP, and GalE LPS. Three infant monkeys were immunised with a human dose at the age of 1.5, 2.5 and 4.5 months. Two monkeys of each group received a fourth dose at the age of 11 months. In ELISA, both OMV vaccines were immunogenic and induced booster responses, particularly after the fourth immunisation. The Norwegian vaccine mostly induced sero-subtype P1.7,16 specific serum bactericidal antibodies (SBA), although some other SBA were induced as well. The antibody responses against P1.7,16, induced by the Norwegian vaccine, were generally higher than for the Dutch vaccine. However, the Dutch vaccine induced PorA specific SBA against all six sero-subtypes included in the vaccine showing differences in the magnitude of SBA responses to the various PorAs. PMID:10618530

  18. Astronomy in the Classroom: Why? (Spanish Title: Astronomía en la Clase: ¿Por Qué?) Astronomia na Sala de Aula: Por Quê?

    NASA Astrophysics Data System (ADS)

    Daros Gama, Leandro; Bagdonas Henrique, Alexandre

    2010-07-01

    There are many discussions about the relevance of the topics covered in classes. One subject in particular is the focus of this essay: astronomy. In what sense and to what extent it would be worth to teach it in science or other kind of classes? In this paper we discuss some aspects of the advantages of dealing with this area of knowledge in schools, taking into account the epistemological and axiological dimensions of astronomy, in light of the vision of science as an intelligent dialogue with the world (Bachelard), in addition to the "problematization" knowledge of Paulo Freire. We propose that in fact the Astronomy does not need to be seen as just a new set of contents to be taught, but appears as a set of motivational contents for historical-philosophical discussions, and permit the discussion of concepts of other disciplines. Numerosas discusiones se están llevando a cabo acerca de la pertinencia de los temas tradicionalmente tratados en las clases. Uno de los temas, en particular, es el foco de este ensayo: la astronomía. ¿En qué sentido y en qué medida sería conveniente tratarla en clase, ya sea en clases de ciencias naturales, específicamente en las de astronomía o asignaturas afines? Elaboramos en este artículo algunos aspectos de las ventajas de tratar esta área del conocimiento en las escuelas, teniendo en cuenta las dimensiones epistemológica y axiológica de la astronomía, a la luz de la visión de la ciencia como un diálogo inteligente con el mundo (Bachelard), además de la propuesta del conocimiento "problematizador" de Paulo Freire. Proponemos que en realidad la astronomía no tiene por qué ser vista sólo como un nuevo conjunto de contenidos que se enseñan, sino que aparece como un conjunto de temas de motivación para el debate histórico-filosófico y para permitir la discusión de los conceptos típicos de otras disciplinas. Muitas discussões vêm acontecendo sobre a relevância dos temas abordados em sala de aula. Um tema, em

  19. Pincharse sin infectarse: estrategias para prevenir la infección por el VIH y el VHC entre usuarios de drogas inyectables

    PubMed Central

    MATEU-GELABERT, P.; FRIEDMAN, S.; SANDOVAL, M.

    2011-01-01

    Resumen Objetivo Desde principios de los noventa, en la ciudad de Nueva York se han implementado con éxito programas para reducir la incidencia del virus de la inmunodeficiencia humana (VIH) y, en menor medida, del virus de la hepatitis C (VHC). A pesar de ello, aproximadamente el 70% de los usuario de drogas inyectables (UDI) están infectados por el VHC. Queremos investigar cómo el 30% restante se las ha arreglado para no infectarse. El Staying safe (nombre original del estudio) explora los comportamientos y mecanismos que ayudan a evitar la infección por el VHC y el VIH a largo plazo. Material y métodos Hemos utilizado el concepto de «desviación positiva» aplicado en otros campos de salud pública. Estudiamos las estrategias, prácticas y tácticas de prevención de aquellos UDI que, viviendo en contextos de alta prevalencia, se mantienen sin infectar por VIH y el VHC, a pesar de haberse inyectado heroína durante años. Los resultados preliminares presentados en este artículo incluyen el análisis de las entrevistas realizadas a 25 UDI (17 doble negativos, 3 doble positivos y 5 con infección por el VHC y sin infección por el VIH). Se usaron entrevistas semiestructuradas que exploraban con detalle la historia de vida de los sujetos, incluyendo su consumo de drogas, redes sociales, contacto con instituciones, relaciones sexuales y estrategias de protección y vigilancia. Resultados La intencionalidad es importante para no infectarse, especialmente durante períodos de involución (períodos donde hay un deterioro económico y/o social que llevan al que se inyecta a situaciones de mayor riesgo). Presentamos tres dimensiones independientes de intencionalidad que conllevan comportamientos que pueden ayudar a prevenir la infección: a) evitar «el mono» (síntomas de abstención) asegurando el acceso a la droga; b) «llevarlo bien» para no convertirse en un junkie y así evitar la «muerte social» y la falta de acceso a los recursos, y c) seguir sin

  20. [Ag20 {S2 P(OR)2 }12 ]: A Superatom Complex with a Chiral Metallic Core and High Potential for Isomerism.

    PubMed

    Dhayal, Rajendra S; Lin, Yan-Ru; Liao, Jian-Hong; Chen, Yuan-Jang; Liu, Yu-Chiao; Chiang, Ming-Hsi; Kahlal, Samia; Saillard, Jean-Yves; Liu, C W

    2016-07-11

    The synthesis and structural determination of a silver nanocluster [Ag20 {S2 P(OiPr)2 }12 ] (2), which contains an intrinsic chiral metallic core, is produced by reduction of one silver ion from the eight-electron superatom complex [Ag21 {S2 P(OiPr)2 }12 ](PF6 ) (1) by borohydrides. Single-crystal X-ray analysis displays an Ag20 core of pseudo C3 symmetry comprising a silver-centered Ag13 icosahedron capped by seven silver atoms. Its n-propyl derivative, [Ag20 {S2 P(OnPr)2 }12 ] (3), can also be prepared by the treatment of silver(I) salts and dithiophosphates in a stoichiometric ratio in the presence of excess amount of [BH4 ](-) . Crystal structure analyses reveal that the capping silver-atom positions relative to their icosahedral core are distinctly different in 2 and 3 and generate isomeric, chiral Ag20 cores. Both Ag20 clusters display an emission maximum in the near IR region. DFT calculations are consistent with a description within the superatom model of an 8-electron [Ag13 ](5+) core protected by a [Ag7 {S2 P(OR)2 }12 ](5-) external shell. Two additional structural variations are predicted by DFT, showing the potential for isomerism in such [Ag20 {S2 P(OR)2 }12 ] species. PMID:27189869

  1. A survey of homopteran species (Auchenorrhyncha) from coffee shrubs and poró and laurel trees in shaded coffee plantations, in Turrialba, Costa Rica.

    PubMed

    Rojas, L; Godoy, C; Hanson, P; Hilje, L

    2001-01-01

    A survey of homopteran species (Auchenorryncha) was conducted in coffee plantations with no shade (C), and in those with shade of either poró (Erythrina poeppigiana) (CP) or poró plus laurel (Cordia alliodora) (CPL), in Turrialba, Costa Rica. A total of 130 species in ten families were collected, dominated by Cicadellidae (82 species). Species richness was highest in the CP system (88), followed by CPL (74) and C systems (60). Five most common species for all systems were Fusigonalia lativittata, Hebralebra nicaraguensis, Neocoelidia sp., Oliarus sp. and Clastoptera sp. Diversification of the coffee agroecosystem favors some species while limiting others, and have no effect on the majority of species. Thus, only F. lativittata, Neocoelidia sp. and Scaphytopius ca. latidens were well represented in all systems, but were more abundant in coffee shrubs. Additionally, the following were the dominant species in each system: Graphocephala sp. 1 (C), F. lativittata (CP) and H. nicaraguensis (CPL). Four species abundant on laurel trees, including H. nicaraguensis, appeared almost exclusively on these tree species. Species similarity was highest on the CP and CPL systems (51% of the species in common), followed by the C and CP (39%) and the C and CPL systems (38%). These findings show that even disturbed systems can harbor many insect species, so that they deserve attention from conservation advocates and biologists. PMID:12189787

  2. Opportunistic Infections among People Living with HIV (PLHIV) with Diabetes Mellitus (DM) Attending a Tertiary Care Hospital in Coastal City of South India

    PubMed Central

    Shalini, Shenoy; Vaman, Kulkarni

    2015-01-01

    Background HIV/AIDS and Diabetes Mellitus are the diseases’ known to supress cell mediated immunity and predispose patients for opportunistic infections. Hence, we conducted a study to compare the common opportunistic infections (OIs) between People Living with HIV with DM (PLHIV-DM) and PLHIV without DM (PLHIV). Methodology PLHIV with DM and without DM (1:1) were prospectively included in the study from January 2011 to January 2012 at a tertiary care hospital in Mangalore city. Patients were classified as Diabetic if their fasting plasma glucose was ≥ 7.0mmol/l (126mg/dl) or 2–h plasma glucose was ≥11.1mmol/l (200mg/dl). Standard procedures and techniques were followed for diagnosis of OIs as per WHO guidelines. The data was entered and analyzed using Statistical Package for Social Sciences (SPSS) version 11.5. Findings The study included 37 PLHIV with DM and 37 PLHIV without DM and both groups were treated with Anti-Retroviral Therapy (ART). The median age was 47 years (IQR: 41-55years) for PLHIV-DM as compared to 40 years (IQR: 35–45.5 years) for PLHIV (p<0.0001). PLHIV-DM had median CD4 counts of 245 (IQR: 148–348) cells/μl compared to 150(IQR: 70–278) cells/μl for PLHIV (p = 0.02). Common OIs included oral candidiasis (49% of PLHIV-DM and 35% of PLHIV); Cryptococcal meningitis (19% of PLHIV-DM and 16% of PLHIV); Pneumocystis jiroveci pneumonia (5% of PLHIV-DM and 18% of PLHIV); extra pulmonary tuberculosis (22% of PLHIV-DM and 34.5% of PLHIV); and Cerebral toxoplasmosis (11% of PLHIV–DM and 13.5% of PLHIV). Microbiological testing of samples from PLHIV- DM, C krusei was the most common Candida species isolated from 9 out of 18 samples. Out of six pulmonary TB samples cultured, four grew Non-tuberculosis mycobacteria (NTM) and two Mycobacterium tuberculosis complexes. Conclusions Study did not identify any significant difference in profile of opportunistic infections (OIs) between PLHIV with and without Diabetes. PMID:26287949

  3. Risk of Kaposi sarcoma during the first months on combination antiretroviral therapy

    PubMed Central

    Lacombe, Jean-Marc; Boue, François; Grabar, Sophie; Viget, Nathalie; Gazaignes, Sandrine; Lascaux-Cametz, Anne-Sophie; Pacanowski, Jérome; Partisani, Marialuisa; Launay, Odile; Matheron, Sophie; Rosenthal, Eric; Rouveix, Elisabeth; Tattevin, Pierre; de Truchis, Pierre; Costagliola, Dominique; Goedert, James J

    2013-01-01

    Objective Determine if incident AIDS-defining Kaposi sarcoma (KS) or Pneumocystis jiroveci pneumonia (PJP) is associated with combination antiretroviral therapy (cART) initiation. Design Compare risk for KS and PJP by time on cART and CD4 reconstitution. Methods In the FHDH-ANRS CO4 cohort (N=66,369), KS (N=1811) and PJP (N=1718) incidence rates were computed by demographic and HIV strata. Crude and adjusted relative risk (RR) with 95% confidence intervals (CI) following cART initiation were calculated by Poisson regression with untreated patients during 1996–2009 as reference. CD4 counts were compared by Wilcoxon rank sum tests. Results KS risk was very high during months 1–3 on cART (N=160, RRCrude 3.94, CI 3.26–4.76), which was incompletely attenuated by adjustment for demographics and contemporaneous CD4 count (RRAdj 1.25, CI 1.02–1.53). Corresponding PJP risk was minimally elevated (N=84, RRCrude 1.80, CI 1.42–2.30) and markedly reduced with adjustment on the same variables and PJP prophylaxis (RRAdj 0.52, CI 0.41–0.67). HIV load had no added effect. Median CD4 cell count at cART initiation was much lower in patients with incident KS (82/mm3) or PJP (61/mm3) within 3 months compared with those without (>250/mm3). Notably, median CD4 change was +44 cells/month with incident KS within 3 months of cART initiation versus 0 cells/month with incident PJP (P=0.0003). Conclusions Failure of CD4 reconstitution during months 1–3 on cART fully accounted for incident PJP. In contrast, there were 1.6 additional KS cases per 1000 person-years during months 1–3 on cART, suggesting that immune reconstitution may contribute to the risk for AIDS-defining KS. PMID:23196937

  4. Variable Impact on Mortality of AIDS-Defining Events Diagnosed during Combination Antiretroviral Therapy: Not All AIDS-Defining Conditions Are Created Equal

    PubMed Central

    2011-01-01

    Background The extent to which mortality differs following individual acquired immunodeficiency syndrome (AIDS)–defining events (ADEs) has not been assessed among patients initiating combination antiretroviral therapy. Methods We analyzed data from 31,620 patients with no prior ADEs who started combination antiretroviral therapy. Cox proportional hazards models were used to estimate mortality hazard ratios for each ADE that occurred in >50 patients, after stratification by cohort and adjustment for sex, HIV transmission group, number of anti-retroviral drugs initiated, regimen, age, date of starting combination antiretroviral therapy, and CD4+ cell count and HIV RNA load at initiation of combination antiretroviral therapy. ADEs that occurred in <50 patients were grouped together to form a “rare ADEs” category. Results During a median follow-up period of 43 months (interquartile range, 19–70 months), 2880 ADEs were diagnosed in 2262 patients; 1146 patients died. The most common ADEs were esophageal candidiasis (in 360 patients), Pneumocystis jiroveci pneumonia (320 patients), and Kaposi sarcoma (308 patients). The greatest mortality hazard ratio was associated with non-Hodgkin’s lymphoma (hazard ratio, 17.59; 95% confidence interval, 13.84–22.35) and progressive multifocal leukoencephalopathy (hazard ratio, 10.0; 95% confidence interval, 6.70–14.92). Three groups of ADEs were identified on the basis of the ranked hazard ratios with bootstrapped confidence intervals: severe (non-Hodgkin’s lymphoma and progressive multifocal leukoencephalopathy [hazard ratio, 7.26; 95% confidence interval, 5.55–9.48]), moderate (cryptococcosis, cerebral toxoplasmosis, AIDS dementia complex, disseminated Mycobacterium avium complex, and rare ADEs [hazard ratio, 2.35; 95% confidence interval, 1.76–3.13]), and mild (all other ADEs [hazard ratio, 1.47; 95% confidence interval, 1.08–2.00]). Conclusions In the combination antiretroviral therapy era, mortality rates

  5. Phase I study of hypofractionated intensity modulated radiation therapy with concurrent and adjuvant temozolomide in patients with glioblastoma multiforme

    PubMed Central

    2013-01-01

    identified in our cohort of patients. Three patients tolerated dose level I with no dose limiting toxicity and hence the remainder of the patients were treated with dose level II according to the dose escalation protocol. Grade 3–4 hematological toxicity was limited to two patients and one patient developed Grade 4 Pneumocystis jiroveci pneumonia. Conclusion Hypo-IMRT using HT given with concurrent TMZ is feasible and safe. The median OS and PFS are comparable to those observed with conventional fractionation. Hypofractionated radiation therapy offers the advantage of a shorter treatment period which is imperative in this group of patients with limited life expectancy. PMID:23425509

  6. Fuentes de variabilidad en el diagnóstico de gastritis atrófica multifocal asociada con la infección por Helicobacter pylori1

    PubMed Central

    Bravo, Luis Eduardo; Bravo, Juan Carlos; Realpe, José Luis; Zarama, Guillermo; Piazuelo, MarÍa Blanca; Correa, Pelayo

    2014-01-01

    RESUMEN Introducción El mapeo de las diferentes regiones del estómago y el número de fragmentos de mucosa gástrica disponibles para evaluación histopatológica son fuentes importantes de variación en el momento de clasificar y hacer la gradación de la gastritis crónica. Objetivos Estimar la sensibilidad del número de fragmentos de mucosa gástrica necesarios para establecer los diagnósticos de gastritis atrófica con metaplasia intestinal (MI), displasia y estado de infección por Helicobacter pylori. Además evaluar la variabilidad intra-observador en la clasificación de estas lesiones precursoras del cáncer gástrico. Materiales y métodos En una cohorte de 6 años de seguimiento se evaluaron 1,958 procedimientos de endoscopia realizados por dos gastroenterólogos. En cada procedimiento y de cada participante se obtuvieron 5 biopsias de mucosa gástrica que representaban antro, incisura angularis y cuerpo. Un único patólogo hizo la interpretación histológica de las 5 biopsias y proporcionó un diagnóstico definitivo global que se utilizó como patrón de referencia. Cada fragmento de mucosa gástrica examinado condujo a un diagnóstico individual para cada biopsia que se comparó con el patrón de referencia. La variabilidad intra-observador se evaluó en 127 personas que corresponden a una muestra aleatoria de 20% del total de endoscopias hechas a los 72 meses de seguimiento. Resultados La sensibilidad del diagnóstico de MI y displasia gástrica aumentó de manera significativa con el número de fragmentos de mucosa gástrica evaluados El sitio anatómico de mayor sensibilidad para el diagnóstico de MI y displasia fue la incisura angularis. Para descubrir H. pylori se logró alta sensibilidad con el estudio de un solo fragmento de mucosa gástrica (95.9%) y fue independiente del sitio de obtención de la biopsia. El acuerdo intra-observador para el diagnóstico de gastritis crónica fue 86.1% con valor kappa de 0.79 IC 95% (0.76-0.85). Las

  7. A UV-vis study of the effects of alcohols on formation and stability of Mn(por)(O)(OAc) complexes

    NASA Astrophysics Data System (ADS)

    Mohajer, Daryoush; Jahanbani, Maryam

    2012-06-01

    Interactions of three different (acetato) (tetraarylporphyrinato) manganese (III) MnIII(por) with tetra-n-butylammonium hydrogen monopersulfate (n-Bu4NHSO5), in the presence of excess tetra-n-butylammonium acetate (n-Bu4NOAc) and in the absence or presence of various alcohols (alcohols = CH3OH, C2H5OH, i-C3H7OH, t-C4H9OH) in CH2Cl2, were monitored by their UV-vis spectral changes, under identical conditions, at room temperature. (Acetato) (tetrakispentafluorophenylporphyrinato) manganese (III) MnIII(tpfpp)(OAc) and (acetato) (tetramesitylporphyrinato) manganese (III) MnIII(tmp)(OAc) produced their corresponding high valent Mn(tpfpp)(O)(OAc) and Mn(tmp)(O)(OAc) both in the absence or presence of alcohols. Whereas, (acetato) (tetraphenylporphyrinato) manganese (III) MnIII(tpp)(OAc) only generated Mn(tpp)(O)(OAc) in the presence of less bulky alcohols. In the absence of alcohols or in the presence of t-C4H9OH, the UV-vis spectra displayed a very weak sign of formation of Mn(tpp)(O)(OAc) complex. It was observed that alcohols generally increased the rate of formation of Mn-oxo species in accordance with their acidity or hydrogen bonding strength, and enhanced the stability of Mn-oxo complexes, as their size increases. Attempts are made to explain these effects. A mechanistic scheme is also suggested for the decomposition of HSO5- to O2 and HSO4-, through the formation and dimerization of Mn-oxo species.

  8. Estudio teórico de la desorción de Na y K de SiO2 estimulada por la acción de fotones o electrones

    NASA Astrophysics Data System (ADS)

    Domínguez Ariza, D.; López, N.; Illas, F.; Pacchioni, G.; Madey, T. E.

    Se ha estudiado el mecanismo de generación de sodio y potasio atómico a partir de muestras de SiO2 utilizando cálculos basados tanto en la teoría del funcional de la densidad como en métodos post-Hartree Fock, así como en el método de cluster para modelar el sólido. Como consecuencia del estudio se han propuesto distintos caminos posibles para la desorción, estimulada por la acción de fotones o electrones, de sodio y potasio desde el óxido de silicio, proporcionando por lo tanto una explicación a la atmósfera tenue de sodio y potasio de La Luna.

  9. La inserción en el mercado laboral de los inmigrantes latinos en España y en los Estados Unidos: Diferencias por país de origen y estatus legal

    PubMed Central

    Connor, Phillip; Massey, Douglas

    2013-01-01

    Resumen Este artículo compara los resultados económicos entre los inmigrantes latinoamericanos en España y Estados Unidos. Detectamos un efecto de selección por el que la mayoría de los inmigrantes latinoamericanos en España proceden de Sudamérica de un entorno de clases medias, mientras la mayoría de los inmigrantes que van a los Estados Unidos son centroamericanos de clase baja. Este efecto de selección explica las diferencias transnacionales en la probabilidad de empleo, logro ocupacional y salarios obtenidos. A pesar de las diferencias en los orígenes y las características de los latinoamericanos en ambos países, los factores demográficos, humanos y de capital social parecen operar de forma similar en ambos países; y cuando los modelos se estiman separadamente por estatus legal, descubrimos que los efectos se acentúan más entre los inmigrantes irregulares cuando se los compara con los regulares, especialmente en Estados Unidos. PMID:24532857

  10. Aquisição fonológica do português brasileiro por crianças ouvintes bilíngues bimodais e surdas usuárias de implante coclear

    PubMed Central

    Cruz, Carina Rebello; Finger, Ingrid

    2014-01-01

    Resumo O presente estudo investiga a aquisição fonológica do Português Brasileiro (PB) por 24 crianças ouvintes bilíngues bimodais, com acesso irrestrito à Língua Brasileira de Sinais (Libras), e por 6 crianças surdas que utilizam implante coclear (IC), com acesso restrito ou irrestrito à Libras. Para a avaliação do sistema fonológico das crianças em PB, foi utilizada a Parte A, Prova de Nomeação, do ABFW – Teste de Linguagem Infantil (ANDRADE et al. 2004). Os resultados revelaram que as crianças ouvintes bilíngues bimodais e a criança surda usuária de IC com acesso irrestrito à Libras apresentaram processo de aquisição fonológica esperada (normal) para a sua faixa etária. Considera-se que a aquisição precoce e o acesso irrestrito à Libras podem ter sido determinantes para o desempenho dessas crianças no teste oral utilizado. PMID:25506105

  11. The Understanding of Astronomy Concepts by Students from Basic Education of a Public School. (Spanish Title: El Entendimiento de Conceptos de Aastronmía Por Los Alumnos de Educación Básica en Una Escuela Pública.) O Entendimento de Conceitos de Astronomia Por Alunos da Educação Básica: O Caso de Uma Escola Pública Brasileira

    NASA Astrophysics Data System (ADS)

    Iria Machado, Daniel; dos Santos, Carlos

    2011-07-01

    We present the results obtained in a research on the comprehension of basic astronomical concepts, in which 561 students from fifth grade middle school to third grade high school of a public school of the city of Foz do Iguaçu (Brazil) took part. A test with 20 multiple-choice questions was applied to indentify the most common conceptions expressed by the students. This test was elaborated based on the literature about misconceptions and covered the following topics: the day-night cycle; the time zones; the seasons of the year; the phases of the Moon; the movement of the Moon; the apparent movement of the Sun in the celestial sphere; the eclipses; the dimensions and distances in the Universe; the brightness of the stars and its observation from Earth. Though a small progress was verified in the proportion of scientifically acceptable answers when comparing the eighth grade of middle school to the fifth, and the third grade of high school to the first, there was an overall predominance of alternative conceptions regarding most of the explored subjects, which persisted up to the last year of secondary school. The comparison to data found in this research made in other socio-cultural contexts revealed, in many aspects, similar notions and difficulties revealed by the students. Se presentan los resultados de una investigación sobre la comprensión de conceptos astronómicos básicos, en la cual participaron 561 estudiantes que cursaban entre el quinto grado de la enseñanza primaria y el tercer año de la enseñanza secundaria de una escuela pública de la ciudad de Foz do Iguaçu (Brasil). Se utilizó un test de 20 preguntas de opción múltiple para identificar las concepciones más comunes expresadas por los estudiantes. Este instrumento de recolección de datos se desarrolló en base a la literatura sobre las concepciones alternativas y trató los siguientes temas: el ciclo día-noche, los husos horarios, las estaciones del año, las fases de la Luna, el

  12. The Understanding of Astronomy Concepts by Students from Basic Education of a Public School. (Spanish Title: El Entendimiento de Conceptos de Aastronmía Por Los Alumnos de Educación Básica en Una Escuela Pública.) O Entendimento de Conceitos de Astronomia Por Alunos da Educação Básica: O Caso de Uma Escola Pública Brasileira

    NASA Astrophysics Data System (ADS)

    Iria Machado, Daniel; dos Santos, Carlos

    2011-07-01

    We present the results obtained in a research on the comprehension of basic astronomical concepts, in which 561 students from fifth grade middle school to third grade high school of a public school of the city of Foz do Iguaçu (Brazil) took part. A test with 20 multiple-choice questions was applied to indentify the most common conceptions expressed by the students. This test was elaborated based on the literature about misconceptions and covered the following topics: the day-night cycle; the time zones; the seasons of the year; the phases of the Moon; the movement of the Moon; the apparent movement of the Sun in the celestial sphere; the eclipses; the dimensions and distances in the Universe; the brightness of the stars and its observation from Earth. Though a small progress was verified in the proportion of scientifically acceptable answers when comparing the eighth grade of middle school to the fifth, and the third grade of high school to the first, there was an overall predominance of alternative conceptions regarding most of the explored subjects, which persisted up to the last year of secondary school. The comparison to data found in this research made in other socio-cultural contexts revealed, in many aspects, similar notions and difficulties revealed by the students. Se presentan los resultados de una investigación sobre la comprensión de conceptos astronómicos básicos, en la cual participaron 561 estudiantes que cursaban entre el quinto grado de la enseñanza primaria y el tercer año de la enseñanza secundaria de una escuela pública de la ciudad de Foz do Iguaçu (Brasil). Se utilizó un test de 20 preguntas de opción múltiple para identificar las concepciones más comunes expresadas por los estudiantes. Este instrumento de recolección de datos se desarrolló en base a la literatura sobre las concepciones alternativas y trató los siguientes temas: el ciclo día-noche, los husos horarios, las estaciones del año, las fases de la Luna, el

  13. Evaluation of PCR in Bronchoalveolar Lavage Fluid for Diagnosis of Pneumocystis jirovecii Pneumonia: A Bivariate Meta-Analysis and Systematic Review

    PubMed Central

    Fan, Li-Chao; Lu, Hai-Wen; Cheng, Ke-Bin; Li, Hui-Ping; Xu, Jin-Fu

    2013-01-01

    Background As a promising tool, PCR in bronchoalveolar lavage fluid (BALF) has not been accepted as a diagnostic criterion for PJP. Objective We undertook a systematic review of published studies to evaluate the diagnostic accuracy of PCR assays in BALF for PJP. Methods Eligible studies from PubMed, Embase and Web of Science reporting PCR assays in BALF for diagnosing PJP were identified. A bivariate meta-analysis of the method’s sensitivity, specificity, and positive and negative likelihood ratios with a 95% confidence interval (CI) were analyzed. The post-test probability was performed to evaluate clinical usefulness. A summary receiver operating characteristics (SROC) curve was used to evaluate overall performance. Subgroup analyses were carried out to analysis the potential heterogeneity. Results Sixteen studies published between 1994 and 2012 were included. The summary sensitivity and specificity values (95% CI) of PCR in BALF for diagnosis of PJP were 98.3% (91.3%–99.7%) and 91.0% (82.7%–95.5%), respectively. The positive and negative likelihood ratios were 10.894 (5.569–21.309) and 0.018 (0.003–0.099), respectively. In a setting of 20% prevalence of PJP, the probability of PJP would be over 3-fold if the BALF-PCR test was positive, and the probability of PJP would be less than 0.5% if it was negative. The area under the SROC curve was 0.98 (0.97–0.99). Conclusions The method of PCR in BALF shows high sensitivity and good specificity for the diagnosis of PJP. However, clinical practice for the diagnosis of PJP should consider the consistent respiratory symptoms, radiographic changes and laboratory findings of the suspected patients. PMID:24023814

  14. Characterization of fHbp, nhba (gna2132), nadA, porA, Sequence Type (ST), and Genomic Presence of IS1301 in Group B Meningococcal ST269 Clonal Complex Isolates from England and Wales▿

    PubMed Central

    Lucidarme, Jay; Comanducci, Maurizio; Findlow, Jamie; Gray, Stephen J.; Kaczmarski, Edward B.; Guiver, Malcolm; Kugelberg, Elisabeth; Vallely, Pamela J.; Oster, Philipp; Pizza, Mariagrazia; Bambini, Stefania; Muzzi, Alessandro; Tang, Christoph M.; Borrow, Ray

    2009-01-01

    Highly effective glycoconjugate vaccines exist against four of the five major pathogenic groups of meningococci: A, C, W-135, and Y. An equivalent vaccine against group B meningococci (menB) has remained elusive due to the poorly immunogenic capsular polysaccharide. A promising alternative, the investigational recombinant menB (rMenB)- outer membrane vesicle (OMV) vaccine, contains fHBP, NHBA (previously GNA2132), NadA, and outer membrane vesicles (OMVs) from the New Zealand MeNZB vaccine. MenB currently accounts for 90% of meningococcal disease in England and Wales, where the multilocus sequence type (ST) 269 (ST269) clonal complex (cc269) has recently expanded to account for a third of menB cases. To assess the potential cc269 coverage of the rMenB-OMV vaccine, English and Welsh cc269 isolates from the past decade were genetically characterized with respect to fHBP, NHBA, and NadA. All of the isolates harbored fHbp and nhba alleles, while 98% of the cc269 isolates were devoid of nadA. Subvariant profiling of fHbp, nhba, and porA against STs revealed the presence of two broadly distinct and well-defined clusters of isolates, centered around ST269 and ST275, respectively. An additional molecular marker, insertion sequence IS1301, was found to be present in 100% and <2% of isolates of the respective clusters. On the basis of the genetic data, the potential rMenB-OMV coverage of cc269 in England and Wales is high (up to 100%) within both clusters. Expression studies and serum bactericidal antibody assays will serve to enhance predictions of coverage and will augment ongoing studies regarding the significance of IS1301 within the ST269 cluster. PMID:19759227

  15. Characterization of invasive Neisseria meningitidis from Atlantic Canada, 2009 to 2013: With special reference to the nonpolysaccharide vaccine targets (PorA, factor H binding protein, Neisseria heparin-binding antigen and Neisseria adhesin A)

    PubMed Central

    Tsang, Raymond SW; Law, Dennis KS; Gad, Rita R; Mailman, Tim; German, Gregory; Needle, Robert

    2015-01-01

    BACKGROUND: Serogroup B Neisseria meningitidis (MenB) has always been a major cause of invasive meningococcal disease (IMD) in Canada. With the successful implementation of a meningitis C conjugate vaccine, the majority of IMD in Canada is now caused by MenB. OBJECTIVE: To investigate IMD case isolates in Atlantic Canada from 2009 to 2013. Data were analyzed to determine the potential coverage of the newly licensed MenB vaccine. METHODS: Serogroup, serotype and serosubtype antigens were determined from IMD case isolates. Clonal analysis was performed using multilocus sequence typing. The protein-based vaccine antigen genes were sequenced and the predicted peptides were investigated. RESULTS: The majority of the IMD isolates were MenB (82.5%, 33 of 40) and, in particular, sequence type (ST)-154 B:4:P1.4 was responsible for 47.5% (19 of 40) of all IMD case isolates in Atlantic Canada. Isolates of this clone expressed the PorA antigen P1.4 and possessed the nhba genes encoding for Neisseria heparin-binding antigen peptide 2, which together matched exactly with two of the four components of the new four-component meningococcal B vaccine. Nineteen MenB isolates had two antigenic matches, another five MenB and one meningitis Y isolate had one antigenic match. This provided 75.8% (25 of 33) potential coverage for MenB, or a 62.5% (25 of 40) overall potential coverage for IMD. CONCLUSION: From 2009 to 2013, IMD in Atlantic Canada was mainly caused by MenB and, in particular, the B:4:P1.4 ST-154 clone, which accounted for 47.5% of all IMD case isolates. The new four-component meningococcal B vaccine appeared to offer adequate coverage against MenB in Atlantic Canada. PMID:26744586

  16. Characterization of fHbp, nhba (gna2132), nadA, porA, and Sequence Type in Group B Meningococcal Case Isolates Collected in England and Wales during January 2008 and Potential Coverage of an Investigational Group B Meningococcal Vaccine▿

    PubMed Central

    Lucidarme, Jay; Comanducci, Maurizio; Findlow, Jamie; Gray, Stephen J.; Kaczmarski, Edward B.; Guiver, Malcolm; Vallely, Pamela J.; Oster, Philipp; Pizza, Mariagrazia; Bambini, Stefania; Muzzi, Alessandro; Borrow, Ray

    2010-01-01

    Invasive disease caused by meningococcal capsular groups A, C, W-135, and Y is now preventable by means of glycoconjugate vaccines that target their respective polysaccharide capsules. The capsule of group B meningococci (MenB) is poorly immunogenic and may induce autoimmunity. Vaccines based on the major immunodominant surface porin, PorA, are effective against clonal epidemics but, thus far, have a limited scope of coverage against the wider MenB population at large. In an alternative approach, the first-generation, investigational, recombinant MenB (rMenB) plus outer membrane vesicle (OMV) (rMenB-OMV) vaccine contains a number of relatively conserved surface proteins, fHBP, NHBA (previously GNA2132), and NadA, alongside PorA P1.4-containing OMVs from the New Zealand MeNZB vaccine. MenB currently accounts for approximately 90% of cases of meningococcal disease in England and Wales. To assess potential rMenB-OMV vaccine coverage of pathogenic MenB isolates within this region, all English and Welsh MenB case isolates from January 2008 (n = 87) were genetically characterized with respect to fHBP, NHBA, NadA, and PorA. Alleles for fHbp, nhba, and porA were identified in all of the isolates, of which 22% were also found to harbor nadA alleles. On the basis of genotypic data and predicted immunological cross-reactivity, the potential level of rMenB-OMV vaccine coverage in England and Wales ranges from 66% to 100%. PMID:20375242

  17. Neisseria gonorrhoeae antimicrobial susceptibility in Barcelona: penA, ponA, mtrR, and porB mutations and NG-MAST sequence types associated with decreased susceptibility to cephalosporins.

    PubMed

    Serra-Pladevall, J; Barberá, M J; Rodriguez, S; Bartolomé-Comas, R; Roig, G; Juvé, R; Andreu, A

    2016-09-01

    The aims of this study were to determine the antimicrobial susceptibility of Neisseria gonorrhoeae (NG) in our area, to analyze the molecular mechanisms involved in cephalosporins resistance, and to undertake molecular typing of our NG strains. Antimicrobial susceptibility was determined using the Etest. The genes penA, mtrR, penB, and ponA were studied. Molecular typing was performed by N. gonorrhoeae multiantigen sequence typing. Of 329 strains analyzed in 2013, none showed high-level cephalosporin resistance, but 8.2 % had resistance to cefixime [minimum inhibitory concentration (MIC) > 0.125 μg/mL] and 0.6 % to ceftriaxone (MIC > 0.125 μg/mL). Azithromycin resistance was documented in 4.3 % and ciprofloxacin resistance in 49.2 %. Among 48 strains with an MIC ≥ 0.125 μg/mL to cefixime, 58.3 % showed the penA mosaic pattern XXXIV, 98 % a Leu → Pro substitution at position 421 of the ponA gene, 100 % amino acid changes at positions 101 and 102 of the PorB1b porin, and 87.5 % of strains an adenine deletion in the promoter region of the MtrC-D-E efflux pump. A significant difference between strains with and without decreased cephalosporin susceptibility (MIC ≥ 0.125 μg/mL) was observed for these four genes. Of the 48 strains with an MIC ≥ 0.125 μg/mL to cefixime, 43.8 % belonged to the genogroup G1407 and 27.1 % belonged to the genogroup G2400. A significant association of G1407 with decreased susceptibility (MIC ≥ 0.125 μg/mL) and G2992 with susceptibility was found, and also between G1407 and mosaic pattern XXXIV and between G2400 and A501T substitution in penA. The NG resistance rate in our area is higher than the median of Europe. We have detected the emergence of G2400, which may be a source of antimicrobial resistance. PMID:27255221

  18. Eficacia de la detección sistemática de la gripe en las fronteras en los viajeros que llegan por vía aérea*

    PubMed Central

    Priest, Patricia C.; Jennings, Lance C.; Duncan, Alasdair R.; Brunton, Cheryl R.; Baker, Michael G.

    2015-01-01

    Objetivos. Se midieron los síntomas y la prevalencia de la gripe (también llamada influenza), así como la eficacia del mecanismo de detección sistemática basado en los síntomas y la temperatura para diagnosticar la gripe en viajeros internacionales que llegaban por vía aérea. Métodos. El presente estudio transversal recopiló datos de viajeros que llegaron al aeropuerto internacional de Christchurch (Nueva Zelandia) en el invierno del 2008 mediante un cuestionario de salud, medición de la temperatura y toma de muestras de las vías respiratorias. Resultados. De los viajeros, 15 976 (68%) entregaron los formularios completos. De ellos, 17% notificaron al menos un síntoma de gripe; los síntomas más comunes fueron rinorrea o congestión nasal (10%) y tos (8%). Se tomaron muestras de las vías respiratorias de 3 769 viajeros. La prevalencia estimada de la gripe fue de 1,1% (4% en las personas sintomáticas, 0,2% en las asintomáticas). La sensibilidad de los criterios de detección varió de 84% para “cualquier síntoma” a 3% para la fiebre de 37,8 °C o mayor. El valor predictivo positivo fue bajo para todos los criterios. Conclusiones. El método de detección sistemática en las fronteras mediante la autonotificación de síntomas y la toma de la temperatura presenta limitaciones para impedir que una gripe pandémica entre en un país. Basarse en criterios como “cualquier síntoma” o la tos haría que se investigara a varias personas no infectadas, mientras que algunas personas infectadas pasarían inadvertidas. Si se usaran criterios más específicos como la fiebre, la mayoría de las personas infectadas entrarían en el país a pesar del mecanismo de detección.

  19. 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

  20. New halide-centered discrete Ag(I)(8) cubic clusters containing diselenophosphate ligands, [Ag(8)(X)[Se(2)P(OR)(2)](6)](PF(6)) (X = Cl, Br; R = Et, Pr, (i)Pr): syntheses, structures, and DFT calculations.

    PubMed

    Liu, C W; Haia, Hsien-Chung; Hung, Chiu-Mine; Santra, Bidyut Kumar; Liaw, Ben-Jie; Lin, Zhenyang; Wang, Ju-Chun

    2004-07-12

    Six clusters Ag(8)(micro(8)-X)[Se(2)P(OR)(2)](6)(PF(6)) (R = Et, X = Cl, 1a, X = Br, 1b; R = Pr, X = Cl, 2a, X = Br, 2b; R = (i)Pr, X = Cl, 3a, X = Br, 3b) were isolated from the reaction of [Ag(CH(3)CN)(4)](PF(6)), NH(4)[Se(2)P(OR)(2)], and Bu(4)NX in a molar ratio of 4:3:1 in CH(2)X(2). Positive FAB mass spectra show m/z peaks at 2573.2 for 1a, 2617.3 for 1b, 2740.9 for 2a, 2786.9 for 2b, 2742.3 for 3a, and 2787.0 for 3b due to respective molecular cation, (M - PF(6))(+). (31)P NMR spectra of 1a-3b display a singlet at delta 82.3, 81.5, 82.9, 81.7, 76.3, and 75.8 ppm with a set of satellites (J(PSe) = 661, 664, 652, 652, 656, and 656 Hz, respectively). The X-ray structure (1a-2b) consists of a discrete cationic cluster in which eight silver ions are linked by six diselenophosphate ligands and a central micro(8)-Cl or micro(8)-Br ion with a noncoordinating PF(6)(-) anion. The shape of the molecule is a halide-centered distorted Ag(8) cubic cluster. The dsep ligand exhibits a tetrametallic tetraconnective (micro(2), micro(2)) coordination pattern, and each caps on a square face of the cube. Each silver atom of the cube is coordinated by three selenium atoms and the central chloride or bromide ion. Additionally, molecular orbital calculations at the B3LYP level of the density functional theory have been carried out to study the Ag-micro(8)-X (X = Cl, Br) interactions for cluster cations [Ag(8)(micro(8)-X)[Se(2)P(OR)(2)](6)](+). Calculations show very weak bonding interactions exist between micro(8)-X and Ag atoms of the cube. PMID:15236560

  1. Novel chloride-centered discrete CuI8 cubic clusters containing diselenophosphate ligands. Syntheses and structures of [Cu8(mu8-Cl)[Se2P(OR)2](6)](PF6) (R = Et, Pr, iPr)1.

    PubMed

    Liu, C W; Hung, Chiu-Mine; Santra, Bidyut Kumar; Chen, Hsiu-Chih; Hsueh, Hsin-Hsueh; Wang, Ju-Chung

    2003-05-19

    Three clusters 1-3, Cu(8)(mu8-Cl)[Se(2)P(OR)(2)](6)(PF(6)) (R= Et, Pr, (i)Pr), were synthesized in high yield from the reaction of [Cu(CH(3)CN)(4)](PF(6)), NH(4)[Se(2)P(OR)(2)], and Bu(4)NCl in a molar ratio of 4:3:1 in diethyl ether. FAB mass spectra show m/z peaks at 2218.10 for 1, 2386.10 for 2, and 2387.34 for 3 which are due to molecular cations, [1-PF(6)]+, [2-PF(6)]+, and [3-PF(6)]+, respectively. (31)P NMR spectra of 1-3 display a singlet at delta 76.48, 76.73, and 69.32 ppm with satellites (J(PSe) = 652, 653, and 648 Hz), respectively. The (77)Se NMR spectra of 1-3 exhibit a doublet peak at -21.7, -16.42, and 2.3 ppm, respectively (J(SeP) = 652 Hz for 1, 653 Hz for 2, and 648 Hz for 3). The X-ray structure (1-3) consists of a discrete cationic cluster in which eight copper ions are linked by six diselenophosphate ligands and a central mu8-Cl ion with a noncoordinating PF(6)(-) anion. The shape of the molecule is a chloride-centered distorted Cu(8) cube in clusters 1 and 2 and a near perfect Cu(8) cube for cluster 3. The dsep ligand exhibits a tetrametallic tetraconnective (mu2, mu2)) coordination pattern, and each occupies a square face of the cube. Each copper atom of the cube is coordinated by three selenium atoms with a strong interaction with the central chloride ion. The observed Cu-Cl distances lie in the range 2.649-2.878 A. PMID:12739962

  2. On the Use of "Por" Plus Agent with "Se" Construction

    ERIC Educational Resources Information Center

    De Mello, George

    1978-01-01

    Two explanations for the role of "se" in such constructions as "Se construyen casas" are given by grammarians; one states that it is a passive interpretation ("Houses are built"), the other advocates an impersonal interpretation ("One builds houses"). Different views are presented and analyzed. (Author/NCR)

  3. Por los Ninos (For the Children): Education of Undocumented Children.

    ERIC Educational Resources Information Center

    Gonzalez, Elena R.; Team, Linda B.

    Published as a special project of Texas IMPACT and the Texas Conference of Churches, this booklet outlines legal aspects of the education of undocumented children, lists moral and practical reasons for educating them, provides reasons for changing the Texas law which prohibits use of state funds for education of children who are not legally…

  4. POR FIN (Program Organizing Related Family Instruction in the Neighborhood).

    ERIC Educational Resources Information Center

    1971

    A project was undertaken in San Antonio, Texas, to develop a recruitment approach which would be more effective than the traditional mass media approach in recruiting hard-core undereducated individuals into adult education classes. An experiment was designed to test a recruiting method which would employ a personal, face-to-face interview…

  5. [The right to avoid pregnancy] [POR, ENG translation included].

    PubMed

    1981-01-21

    Signs are finally appearing in Brazil that despite the government's hesitations and the hostility of the Catholic Church the decade of the 1980s shall bring effective changes intended to restrain population growth. Now, 4 years after its inclusion in the social program of the Geisel administration in 1977, family planning will become a reality. It is certainly about time, for at the present rate of growth the Brazilian population increases by about 6 persons per minute--about 3 million a year. At this pace, only a large scale State intervention that provides the population with information, assistance and free access to contraception may decisively reverse the trend. Figueiredo's government has decided that family planning should be introduced slowly, gradually and subtly, thus avoiding specific programs and publicity campaigns through the mass communication vehicles. In an effort to get around sharper criticism from the Church and the opposition, the government intends to mobilize catholic laypersons, priests, and nuns and, if possible, bishops in a national attempt to disseminate information on natural methods of birth control. As a 1st step, the Ministry of Health will widely distribute information on human reproduction and fecundity along with explanations of artificial contraceptive methods. Subject to the couple's decision and under medical indications, the free supply of contraceptive means to low income families shall be ensured by the government. The government will also allow sterilization. Despite its cautious approach, in actuality the government's program will in many places and circumstances be a massive inducement to contraceptive use. PMID:12337558

  6. La busqueda textual por computadora (Textual Search by Computer)

    ERIC Educational Resources Information Center

    Davison, Ned J.

    1977-01-01

    Describes the use of the computer program EDIT for textual searches to locate a certain programmed word or word root. In the examples explained here, the vocabulary search is performed on poetry and allows examination of the metaphorical and conceptual poetic atmosphere achieved through word use. (Text is in Spanish.) (CHK)

  7. Síndrome del Outlet Torácico: ¿Una Patología Siempre Quirúrgica? Análisis de una Serie de 31 Cirugías Realizadas por Vía Supraclavicular Serie clínica

    PubMed Central

    Socolovsky, Mariano; Di Masi, Gilda; Binaghi, Daniela; Campero, Álvaro; Páez, Miguel Domínguez; Dubrovsky, Alberto

    2014-01-01

    Introducción: El síndrome de outlet torácico es una compresión del plexo braquial que suscita polémica. Se clasifica en Outlet Torácico Verdadero o neurogénico (OTV) y Outlet Torácico Disputado o no neurogénico (OTD). El primero presenta síntomas motores en la mano, mientras que el segundo sólo síntomas sensitivos en el miembro superior. El objetivo de este trabajo es analizar los resultados obtenidos en una serie de 31 cirugías. Métodos: Se analizaron las cirugías de nervios efectuadas entre 2003-2012, tomando los diagnósticos de outlet torácico cuyo período de seguimiento post-operatorio mínimo fuera de 6 meses. Se buscaron los siguientes datos: edad, sexo, presencia de síntomas sensitivos y/o motores, clasificación, resultado de los estudios neurofisiológicos y de imágenes, resultado de la cirugía, complicaciones post-operatorias y recidivas. Resultados: Se incluyeron 31 cirugías realizadas en 30 pacientes, 9 OTV (8 mujeres) de 24.3 años, y 21 con OTD (18 mujeres) de 37.4 años de edad en promedio. Un 90% presentaron alteraciones neurofisiológicas preoperatorias, y 66,6% imagenológicas. En el intraoperatorio, el 100% de los OTV presentó una alteración anatómica relacionada con la sintomatología, hecho observado sólo en el 36.7% de los OTD operados. El 87,5% de los OTV mejoraron sensitivamente, mientras que 77,7% mejoraron la atrofia. Por el contrario, 45.4% de los OTD mejoraron permanentemente, 36.3% no tuvieron cambios, 13.6% mejoraron transitoriamente y 4.5% (un caso) empeoró. Las complicaciones post-operatorias fueron más frecuentes aunque transitorias en el grupo de OTV (3 casos sobre 9 operados, 33.3%) que en los OTD (3 casos sobre 22, un 13.6%). Conclusión: El OTV suele mayormente mejorar luego de la cirugía, igual que el OTD aunque en una proporción mucho menor. Estos hallazgos coinciden con otros reportes recientes de esta patología. PMID:25165614

  8. A Comparison Between PSRK and GERG-2004 Equation of State for Simulation of Non-Isothermal Compressible Natural Gases Mixed with Hydrogen in Pipelines / Porównanie równań stanu opracowanych według metody PSRK oraz GERG-2004 wykorzystanych do symulacji zachowania ściśliwych mieszanin gazu ziemnego i wodoru w rurociągach, w warunkach przepływów nie-izotermicznych

    NASA Astrophysics Data System (ADS)

    Uilhoorn, Frits E.

    2013-06-01

    In this work, the GERG-2004 equation of state based on a multi-fluid approximation explicit in the reduced Helmholtz energy is compared with the predictive Soave-Redlich-Kwong group contribution method. In the analysis, both equations of state are compared by simulating a non-isothermal transient flow of natural gas and mixed hydrogen-natural gas in pipelines. Besides the flow conditions also linepack-energy and energy consumption of the compressor station are computed. The gas flow is described by a set of partial differential equations resulting from the conservation of mass, momentum and energy. A pipeline section of the Yamal-Europe gas pipeline on Polish territory has been selected for the case study. W artykule dokonano porównania wyników uzyskanych przy wykorzystaniu równania stanu GERG- 2004 opartego na jawnym przybliżeniu wyników dla wielu cieczy w oparciu o zredukowaną energię Helmhotza oraz wyników uzyskanych w oparciu o metodę Soave-Redlich Kwonga. Obydwa równania stanu porównano poprzez przeprowadzenie symulacji stanów przejściowych przepływów gazu ziemnego oraz mieszanin gazu ziemnego i wodoru w rurociągach w warunkach przepływów nie-izotermicznych. Oprócz warunków przepływu, określono energię w napełnionym układzie oraz zużycie energii przez stację kompresora. Przepływ gazu opisano zbiorem równań różniczkowych cząstkowych, wyprowadzonych w oparciu o prawa zachowania masy, pędu i energii. Jako studium przypadku wybrano fragment rurociągu jamalskiego (Yamal- Europa) przebiegającego przez terytorium Polski.

  9. Lung gallium scan

    MedlinePlus

    ... inflammation in the lungs, most often due to sarcoidosis or a certain type of pneumonia. Normal Results ... up very little gallium. What Abnormal Results Mean Sarcoidosis Other respiratory infections, most often pneumocystis jirovecii pneumonia ...

  10. 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, ...

  11. See the World on the Internet: Tips for Parents of Young Readers--and "Surfers" = Vea el mundo por Internet: Ideas por padres de jovenes lectores y exploradores.

    ERIC Educational Resources Information Center

    Moss, Jeanette

    Regardless of whether a parent has Internet access at home, it is essential that parents learn with their children and be aware of where their travels on the Internet are taking them. Many libraries have Internet workshops for parents or children or both. In the excitement of looking at sites, children may not even realize they are reading. Many…

  12. Verification and validation interim report for portable 1,000 CFM exhauster skids POR-007/Skid E and POR-008/Skid F

    SciTech Connect

    Nelson, O.D.

    1998-07-25

    This Verification and Validation (V/V) interim report summarizes to date the results of the V/V tasks performed in each of the following life cycle phases: concept, requirements, design, implementation, test, installation and checkout, and operation and maintenance. At the end of the installation and checkout phase, the V/V final report will be issued. This interim report contains or references the following for each phase: Description of V/V tasks performed; Summary of task results; Summary of anomalies and resolution; Assessment of system quality; Recommendations.

  13. The Escuela Moderna Movement of Francisco Ferrer: "Por la Verdad y la Justicia."

    ERIC Educational Resources Information Center

    Fidler, Geoffrey C.

    1985-01-01

    The educational theory and practice of the Escuela Modern (Modern School) movement of the Spanish educator Francisco Ferrer, born in 1850, are discussed. Two fundamental tendencies of the movement are child-centered education and education in didactic terms. (RM)

  14. Phantom of RAMSES (POR): A new Milgromian dynamicsN-body code

    NASA Astrophysics Data System (ADS)

    Lüghausen, Fabian; Famaey, Benoit; Kroupa, Pavel

    2015-02-01

    Since its first formulation in 1983, Milgromian dynamics (MOND) has been very successful in predicting the gravitational potential of galaxies from the distribution of baryons alone, including general scaling relations and detailed rotation curves of large statistical samples of individual galaxies covering a large range of masses and sizes. Most predictions however rely on static models, and only a handful of N-body codes have been developed over the years to investigate the consequences of the Milgromian framework for the dynamics of complex evolving dynamical systems. In this work, we present a new Milgromian N-body code, which is a customized version of the RAMSES code (Teyssier 2002) and thus comes with all its features: it includes particles and gas dynamics, and importantly allows for high spatial resolution of complex systems due to the adaptive mesh refinement (AMR) technique. It further allows the direct comparison between Milgromian simulations and standard Newtonian simulations with dark matter particles. We provide basic tests of this customized code and demonstrate its performance by presenting N-body computations of dark-matter-free spherical equilibrium models as well as dark-matter-free disk galaxies in Milgromian dynamics.

  15. Abuso sexual por parte de los empleados del colegio (Sexual Misconduct by School Employees). ERIC Digest.

    ERIC Educational Resources Information Center

    Goorian, Brad

    This digest in Spanish defines sexual misconduct and offers guidelines that school boards and administrators can initiate to protect students from unwanted sexual behavior. The law recognizes two types of sexual misconduct: quid pro quo, when a school employee grants a student a favor in exchange for sexual gratification, and hostile environment,…

  16. Looking for a Job: Step by Step = Buscando Trabajo: Paso por Paso.

    ERIC Educational Resources Information Center

    Edwards, Patricia

    This bilingual document provides guidelines and learning activities to assist migrant workers in looking for a job. The document covers the following areas: (1) a checklist providing an overview of job search skills; (2) developing a fact sheet of personal information; (3) listing good work qualities; (4) identifying references and securing…

  17. Applying Cognitive Linguistics to Teaching the Spanish Prepositions "Por" and "Para"

    ERIC Educational Resources Information Center

    Lam, Yvonne

    2009-01-01

    L2 prepositions are traditionally taught in a non-explanatory manner by having students learn each use individually. This study examines the effectiveness of an alternative explanatory approach based on cognitive linguistics, which considers the multiple uses of a preposition as related. Consequently, learners can be shown a general schema that…

  18. Home before You Know It = De regres en casa en un dos por tres.

    ERIC Educational Resources Information Center

    Vida Health Communications, Inc., Cambridge, MA.

    The arrival of a newborn requires a great deal of adjustment. Intended for new and expectant parents, this booklet and companion video provide practical advice and hands-on demonstrations of the essentials of mother and baby care, from birth to the first visit to the pediatrician. The first part of the booklet, which comes in both English- and…

  19. Teaching Probability for Conceptual Change (La Ensenanza de la Probabilidad por Cambio Conceptual).

    ERIC Educational Resources Information Center

    Castro, Cesar Saenz

    1998-01-01

    Presents a theoretical proposal of a methodology for the teaching of probability theory. Discusses the importance of the epistemological approach of Lakatos and the perspective of the conceptual change. Discusses research using a proposed didactic method with Spanish high school students (N=6). Concludes that significant differences on all…

  20. Neuropatía periférica inducida por quimioterapia

    Cancer.gov

    Artículo sobre un efecto secundario de la quimioterapia que causa dolor y malestar en las manos y los pies. También incluye información sobre los esfuerzos para mejorar las opciones de detección, tratamiento y prevención.

  1. Ensenando El Espanol por Medio de Accion (Teaching Spanish through Action).

    ERIC Educational Resources Information Center

    Segal, Bertha

    A teaching guide containing 102 elementary to intermediate level Spanish lessons is presented. The lessons are based on the Total Physical Response technique of second language teaching. They follow the stages of first language acquisition: listening, speaking, and reading. Each of the ten units contains a list of new vocabulary words, individual…

  2. El Libro de la Escritura por Pinguino Tinto (The Writing Book, by Inky Penguin).

    ERIC Educational Resources Information Center

    Padgett, Ron

    Presented completely in Spanish and intended for elementary level students, this book offers 12 writing ideas and several suggestions on how students can make a book using their writing. Each writing idea is presented with a brief description (addressed to the student), several examples of student writing, and a blank page on which to write.…

  3. Producao d Dijatos por Dupla Troca de Pomeron Exclusiva no Experimento D0

    SciTech Connect

    Murilo Santana Rangel

    2008-01-01

    The first search for exclusive diffractive dijet production with invariant mass ≳ 100 GeV in Run II of the Fermilab Tevatron Collider is performed. The set of data used is the Run IIa, corresponding to an integrated luminosity of 30 pb-1 of p$\\bar{p}$ collisions at √s = 1.96 TeV taken with the D0 detector. At 95% CL, an upper limit for the ratio between the number of diffractive exclusive events and the number of non diffractive events is set to be 7.5 x 10-6, excluding two of the three models proposed to explain this production.

  4. The PorGrow project: overall cross-national results, comparisons and implications.

    PubMed

    Millstone, E; Lobstein, T

    2007-05-01

    European policymakers need more information on policy responses to obesity that stakeholders judge effective and acceptable. The Policy Options for Responding to the Growing Challenge of Obesity Research Project gathered such intelligence by interviewing key stakeholder groups in nine countries. Interviews used an innovative multi-criteria mapping (MCM) methodology that gathers quantitative and qualitative information on the stakeholders' perceptions and judgements. Aggregating across all participants, a comprehensive portfolio of policy measures, integrated into a coherent programme, would be well-supported by broad coalitions of stakeholders. Those portfolios should include measures (i) to provide improved educations in schools and to the general adult population; (ii) measures to improve access to and incentives for physical activity; (iii) measures to improve information about both foods and physical activity and (iv) changes to the supply of and demand for foodstuffs. There was little support for fiscal measures and technological 'fixes'; they were judged ineffective and unacceptable. Significant differences were found across European regions, and across different stakeholder perspectives, but not across genders. There is a strong case for improved monitoring of body mass index levels, dietary habits and physical activity. An MCM study can effectively cover several countries, rather than being confined to just one, and generate both national and cross-national policy analyses and proposals. PMID:17371305

  5. Luchando por una educacion: A Qualitative Understanding of Undocumented Latina/o College Student Motivation

    ERIC Educational Resources Information Center

    Navarro, Elvia Lorena

    2013-01-01

    The current qualitative study explored the factors and resources that motivate undocumented Latino/a college students to persist in higher education. Through the data obtained from the four qualitative open-ended survey questions, a content analysis revealed specific codes, themes, and subthemes addressing the factors and resources that motivate…

  6. "Por Los Ojos De Madres": Latina Mothers' Understandings of College Readiness

    ERIC Educational Resources Information Center

    Cortez, Laura Jean; Martinez, Melissa Ann; Sáenz, Victor B.

    2014-01-01

    In this study, data from six focus groups with 30 Latina mothers in South Texas were analyzed utilizing a "funds of knowledge" approach to uncover their understandings of college readiness and their role in ensuring their children are college ready. Findings indicate that Latina mothers perceived college readiness in a holistic fashion,…

  7. Master equipment list 500 CFM portable exhauster POR-005 skid C

    SciTech Connect

    KRISKOVICH, J.R.

    1999-07-08

    The Master Equipment List (MEL) lists all the major components of the 500 cfm exhauster PORO5. The purpose of this Master Equipment List is to provide basic information and references to other documents for the listed components.

  8. PREJUICIO Y DISTANCIA SOCIAL HACIA PERSONAS HOMOSEXUALES POR PARTE DE JÓVENES UNIVERSITARIOS

    PubMed Central

    Fernández Rodríguez, María del C.; Squiabro, José Calderón

    2014-01-01

    Se realizó un estudio descriptivo transversal con el propósito de explorar actitudes de rechazo y distancia social hacia las personas gays y lesbianas (GL) en 565 universitarios. Se utilizó una escala para medir Prejuicio y otra escala para medir Distancia Social. Los participantes reflejaron niveles moderados de prejuicio y distancia social (DS) hacia las personas gays y lesbianas. Los varones (M=104.5, DT= 27.47) mostraron significativamente más prejuicio que las mujeres (M=98.8, DT= 23.41). Los hombres (M=22.7, DT= 7.00) mostraron significativamente mayor DS que las mujeres (M=21.1, DT= 5.41). Las personas que asisten con regularidad a la iglesia mostraron más prejuicio y DS que los que no asisten. Se analiza importancia de incluir el tema de la diversidad sexual a través del currículo para desmontar prejuicios hacia la comunidad homosexual. PMID:25606066

  9. Renovando la Esperanza por una Educacion sin Exclusiones (Rekindling the Hope for an Education without Exclusion).

    ERIC Educational Resources Information Center

    Revista Interamericana de Educacion de Adultos, 2001

    2001-01-01

    Articles in this issue, written in Spanish, focus on the following: current status and outlook of youth and adult education; opening statement of the 50th anniversary commemoration; regional framework for the education of youth and adults in Latin America and the Caribbean; interculturalism and the education of youth and adults; participation of…

  10. El Titulo IX y La Discriminacion por Sexo (Title IX and Sex Discrimination).

    ERIC Educational Resources Information Center

    Office for Civil Rights (ED), Washington, DC.

    Title IX of the Education Amendments of 1972 protects people from discrimination based on sex in education programs or activities that receive Federal financial assistance. This brochure outlines the responsibilities of education programs and activities covered by Title IX, the responsibilities of the Office for Civil Rights (OCR) in enforcing…

  11. Enfermedad diarreica aguda por Escherichia coli patógenas en Colombia

    PubMed Central

    Gómez-Duarte, Oscar G.

    2014-01-01

    Resumen Las cepas de E. coli patógenas intestinales son causas importantes de la enfermedad diarreica aguda (EDA) en niños menores de 5 años en América Latina, África y Asia y están asociadas a alta mortalidad en niños en las comunidades más pobres de África y el Sudeste Asiático. Estudios sobre el papel de las E. coli patógenas intestinales en la EDA infantil en Colombia y otros países de América Latina son limitados debido a la carencia de ensayos para detección de estos patógenos en los laboratorios clínicos de centros de salud. Estudios recientes han reportado la detección de E. coli patógenas intestinales en Colombia, siendo la E. coli enterotoxigénica la cepa más frecuentemente asociada a diarrea en niños menores de 5 años. Otros patógenos detectados en estos pacientes incluyen las E. coli enteroagregativa, enteropatógena, productora de toxina Shiga, y de adherencia difusa. Con base en estudios que reportan la presencia de E. coli productora de toxina Shiga y E. coli enteroagregativa en carnes y vegetales en supermercados, se cree que productos alimentarios contaminados contribuyen a la transmisión de estos patógenos y a la infección del huésped susceptible. Más estudios son necesarios para evaluar los mecanismos de transmisión, el impacto en la epidemiologia de la EDA, y las pautas de manejo y prevención de estos patógenos que afectan la población pediátrica en Colombia. PMID:25491457

  12. Synergy of CAY-1, a Fungicidal Saponin, With Amphotericin B and Itreconazole Against Aspergillus spp and Candida albicans

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: CAY-1 (mol.wt. 1243), a fungicidal saponin in cayenne (Capsicum fruitescens) is highly lethal for Aspergillus species, Candida albicans, and Pneumocystis carinii below 24.8 ug/ml. To further characterize CAY-1, synergy studies with amphotericin B (AMB) and itraconazole (IT) were perform...

  13. Fatal case due to methicillin-resistant Staphylococcus aureus small colony variants in an AIDS patient.

    PubMed Central

    Seifert, H.; von Eiff, C.; Fätkenheuer, G.

    1999-01-01

    We describe the first known case of a fatal infection with small colony variants of methicillin-resistant Staphylococcus aureus in a patient with AIDS. Recovered from three blood cultures as well as from a deep hip abscess, these variants may have resulted from long-term antimicrobial therapy with trimethoprim/sulfamethoxazole for prophylaxis of Pneumocystis carinii pneumonia. PMID:10341185

  14. EFFECT OF PENTAMIDINE ON CYTOKINE (IL-1B, TNFA, IL-6) PRODUCTION BY HUMAN ALVEOLAR MACROPHAGES IN VITRO

    EPA Science Inventory

    Pentamidine (Pe) is an aromatic diamidine drug used clinically to treat Pneumocystis carinii pneumonia by aerosol inhalation. othing has been reported about the effects of this drug on human alveolar macrophage (AM) properties. n this study AM were exposed in vitro to various con...

  15. Que hay de nuevo acerca de la inmersion? Un Breve Recorrido por sus Fundamentos y por las Investigaciones Actuales (What's New in Immersion? A Brief Overview of Its Bases and Present-Day Research).

    ERIC Educational Resources Information Center

    Sierra, Josu

    This discussion briefly surveys the development of the immersion method of second language teaching, outlining the central program strategies and characteristics using Curtain's and Pesola's descriptions. An overview of recent research focuses on error correction and feedback studies as an example of pedagogical-methodological evolution in this…

  16. Haciendo que los colegios se hagan responsables por el logro (Holding Schools Accountable for Achievement). ERIC Digest.

    ERIC Educational Resources Information Center

    Lashway, Larry

    This digest in Spanish describes the key features of current accountability systems and explores their implications for administrators. It discusses various aspects of accountability systems, such as rigorous content standards and the alignment of professional development with standards and test results, and how these elements work together to…

  17. Medida da razao de ramificacao do Decaimento D+ {right arrow}K- K+ K+ duplamente suprimido por cabibbo

    SciTech Connect

    da Silva Carvalho, H.

    1997-11-01

    In this thesis, we performed a study for the decay D{sup +}{yields}K{sup -}K{sup +}K{sup +} and D{sub s}{sup +}{yields}K{sup -}K{sup +}K{sup +}, using the data collected by the E791, a hadroproduction of charm experiment at Fermilab. The D{sup +}{yields}K{sup -}K{sup +}K{sup +} decay is doubly Cabibbo suppressed while the D{sub s}{sup +}{yields}K{sup -}K{sup +}K{sup +} decay is singly Cabibbo suppressed. We found 11.6{+-}3.9 events in the D{sup +} mass region and 8.9{+-}3.3 in the D{sub s}{sup +} mass region. The D{sup +}{yields}K{sup -}K{sup +}K{sup +} branching ratio is measured to be (3.7{+-}1.3{+-}0.6)x10{sup -4} while the D{sub s}{sup +}{yields}K{sup -}K{sup +}K{sup +} branching ratio relative to D{sub s}{sup +}{yields}{phi}{pi}{sup +} is measured to be (4.2{+-}1.5{+-}0.6)x10{sup -2}.

  18. Reconnaissance evaluation of Honduran geothermal sites. Una evaluacion por medio de reconocimiento de seis areas geotermicas en Honduras

    SciTech Connect

    Eppler, D.; Fakundiny, R.; Ritchie, A.

    1986-12-01

    Six geothermal spring sites were selected on the basis of preliminary investigations conducted in Honduras over the last decade and were evaluated in terms of their development potential. Of the six, the Platanares and San Ignacio sites have high base temperatures and high surface fluid discharge rates and appear to have the best potential for further development as sources of electrical power. A third site, Azacualpa, has a high enough base temperature and discharge rate to be considered as a back-up, but the logistical problems involved in geophysical surveys make it less attractive than the two primary sites. Of the remaining three sites, Pavana may be a source of direct-use heat for local agricultural processing. Sambo Creek and El Olivar have either severe logistical problems that would impede further investigation and development or base temperatures and flow rates that are too low to warrant detailed investigation at this time.

  19. En otras palabras: Perfeccionamiento del espanol por medio de la traduccion (In Other Words: Perfecting Spanish Language Skills through Translation).

    ERIC Educational Resources Information Center

    Lunn, Patricia V.; Lunsford, Ernest J.

    This publication, written primarily in Spanish, is an activity book designed to teach Spanish through translation based on the theory that, in order to produce an acceptable translation, students must focus their attention on lexical and grammatical detail. The book combines incisive grammar explanations, relevant lexical information, and a wide…

  20. Evaluacion de que consister y por que se lleva acabo? (Evaluation: What Does it Consist of, and for What Purpose?).

    ERIC Educational Resources Information Center

    Austin Independent School District, TX. Office of Research and Evaluation.

    A guide is presented for the evaluation of the bilingual programs in the Austin, Texas, Independent School District. The reasons for an evaluation and a definition of program objectives and evaluation instruments are given. The program components, objectives and evaluation instruments for each grade level (K-4) are listed. The components involved…

  1. Como ayudar a los padres a prevenir el envenenamiento por plomo (Helping Parents Prevent Lead Poisoning). ERIC Digest.

    ERIC Educational Resources Information Center

    Binns, Helen J.; Ricks, Omar Benton

    Children are at greater risk than adults for lead poisoning because children absorb lead more readily than adults, and a small amount of lead in children's bodies can do a great deal of harm. This Spanish-language Digest summarizes some of the causes and effects of childhood lead poisoning and suggests some lead poisoning prevention strategies…

  2. Monitoreo óptico de eta-Carina durante el pasaje por el periastro en 2014.6

    NASA Astrophysics Data System (ADS)

    Fernández-Lajús, E.; Salerno, N. E.; Scalia, M. C.; Ramos, X. S.; Giudici, F. N.; Gamen, R. C.

    2015-08-01

    We present the H light curves resulting from the 2013 and 2014 observing seasons of Car as well as its spectral evolution, including the latest ``event'' occurred in mid-2014. The direct CCD observations were made with the telescope ``VS Niemela'' the Observatory of La Plata, and spectroscopic observations were made with the telescope ``J. Sahade'' of Casleo, Argentina.

  3. Disponibilidade de nutrientes na fitomassa produzida por cultivares de milho (Zea mays L.) de diferentes niveis tecnologicos

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Macronutrient uptake, accumulation, and exportation can be affected by corn genetic selection. The objectives of this study were to quantify macronutrient extraction and to evaluate C/P and C/N ratio. The experiment was established at Rolândia County, Paraná State. Ten corn varieties divided into pa...

  4. Distribución superficial de impactos en Iapetus originada por el remanente de una colisión

    NASA Astrophysics Data System (ADS)

    Zoppetti, F. A.; Leiva, A. M.; Briozzo, C. B.

    2015-08-01

    By means of Circular Restricted Three Body Problem Saturn--Iapetus, we analize potential impact distributions on the surface of Iapetus, originated from considering a low-energy population generated as remnants of a collisional event occurred in the past on the surface of this satellite. The results are analized in order to offer a new approach to explain the origin of the albedo dichotomy observed on Iapetus.

  5. 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.

  6. Antimicrobial activity of polycationic peptides.

    PubMed

    Giacometti, A; Cirioni, O; Barchiesi, F; Del Prete, M S; Scalise, G

    1999-11-01

    The in vitro activity of six polycationic peptides, buforin II, cecropin P1, indolicidin, magainin II, nisin, and ranalexin, were evaluated against several clinical isolates of gram-positive and gram-negative aerobic bacteria, yeasts, Pneumocystis carinii and Cryptosporidium parvum, by using microbroth dilution methods. The peptides exhibited different antibacterial activities and rapid time-dependent killing. The gram-negative organisms were more susceptible to buforin II and cecropin P1, whereas buforin II and ranalexin were the most active compounds against the gram-positive strains. Similarly, ranalexin showed the highest activity against Candida spp., whereas magainin II exerted the highest anticryptococcal activity. Finally, the peptides showed high anti-Pneumocystis activity, whereas no compound had strong inhibitory effect on C. parvum. PMID:10612440

  7. 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.

  8. 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.

  9. 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. PMID:23280633

  10. Antifungal and cytotoxic activity of withanolides from Acnistus arborescens.

    PubMed

    Roumy, Vincent; Biabiany, Murielle; Hennebelle, Thierry; Aliouat, El Moukhtar; Pottier, Muriel; Joseph, Henry; Joha, Sami; Quesnel, Bruno; Alkhatib, Racha; Sahpaz, Sevser; Bailleul, François

    2010-07-23

    Three compounds were isolated from Acnistus arborescens, a tree commonly used in South and Central America in traditional medicine against several infectious diseases, some of which are caused by fungi. Bioassay-guided fractionation of a MeOH extract of leaves, based on its anti-Pneumocystis carinii activity, led to the isolation of compounds 1-3. Mono- and bidimensional NMR analyses enabled identification of two new withanolides, (20R,22R)-5beta,6beta-epoxy-4beta,12beta,20-trihydroxy-1-oxowith-2-en-24-enolide (1) and (20R,22R)-16beta-acetoxy-3beta,4beta;5beta,6beta-diepoxy-12beta,20-dihydroxy-1-oxowith-24-enolide (2), and withanolide D (3). Antifungal activity on 13 fungi responsible for human infections (five dermatophytes, one nondermatophyte mold, six yeasts, and Pneumocystis carinii) was examined. Cytotoxicity of these compounds was also evaluated in vitro. PMID:20590148

  11. 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.

  12. Immune reconstitution syndrome in a human immunodeficiency virus infected child due to giardiasis leading to shock.

    PubMed

    Nandy, Sneha; Shah, Ira

    2015-01-01

    Human immunodeficiency virus (HIV)-associated immune reconstitution inflammatory syndrome has been reported in association with tuberculosis, herpes zoster (shingles), Cryptococcus neoformans, Kaposi's sarcoma, Pneumocystis pneumonia, hepatitis B virus, hepatitis C virus, herpes simplex virus, Histoplasma capsulatum, human papillomavirus, and Cytomegalovirus. However, it has never been documented with giardiasis. We present a 7-year-old HIV infected girl who developed diarrhea and shock following the initiation of antiretroviral therapy, and her stool showed the presence of giardiasis. PMID:26985424

  13. Substantial variation in post-engraftment infection prophylaxis and revaccination practice in autologous stem cell transplant patients.

    PubMed

    Lim, H Y; Grigg, A

    2016-03-01

    There is a paucity of evidence supporting the necessity or duration of Pneumocystis jirovecii and antiviral prophylaxis as well as revaccination following autologous stem cell transplant (ASCT). A survey aimed at evaluating these policies was distributed to 34 ASCT centres across Australasia. The 26 survey respondents demonstrated significant heterogeneity in their infection prophylaxis and revaccination strategy post-transplant despite the availability of consensual guidelines. PMID:26968596

  14. Immune reconstitution syndrome in a human immunodeficiency virus infected child due to giardiasis leading to shock

    PubMed Central

    Nandy, Sneha; Shah, Ira

    2015-01-01

    Human immunodeficiency virus (HIV)-associated immune reconstitution inflammatory syndrome has been reported in association with tuberculosis, herpes zoster (shingles), Cryptococcus neoformans, Kaposi's sarcoma, Pneumocystis pneumonia, hepatitis B virus, hepatitis C virus, herpes simplex virus, Histoplasma capsulatum, human papillomavirus, and Cytomegalovirus. However, it has never been documented with giardiasis. We present a 7-year-old HIV infected girl who developed diarrhea and shock following the initiation of antiretroviral therapy, and her stool showed the presence of giardiasis. PMID:26985424

  15. 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). PMID:24209377

  16. Efectos de Campos Magnéticos en las Tasas de Consumo de Madera por Coptotermes formosanus, la Termita Subterránea de Formosa.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sixty groups of 500 workers and 50 soldiers of Coptotermes formosanus were maintained in costume designed containers and fed with a piece of red oak wood (Quercus rubra). Twenty of these groups were exposed to permanent magnets with a flux of 800 G. Another 20 groups were exposed to a permanent mag...

  17. Realidades Suburbanas: Latinos en el Condado de Dakota. Una Investigacion Dirigida por HACER = Suburban Realities: Latinos in Dakota County. A Study Conducted by HACER.

    ERIC Educational Resources Information Center

    HACER: Hispanic Advocacy and Community Empowerment through Research, Minneapolis, MN.

    A research project was conducted between April and December of 1998 to learn about the experiences of the sizable numbers of Latinos who live in Dakota County (Minnesota). This diverse group was studied through examining existing demographic information, conducting interviews with 45 Latino and Anglo individuals, and conducting several focus…

  18. Effect of por-SiC buffer layer on the parameters of thin Er2O3 layers on silicon carbide substrates

    NASA Astrophysics Data System (ADS)

    Bacherikov, Yu Yu; Konakova, R. V.; Okhrimenko, O. B.; Berezovska, N. I.; Kapitanchuk, L. M.; Svetlichnyi, A. M.; Svetlichnaya, L. A.

    2015-04-01

    Using optical absorption and Auger spectrometry techniques, we studied the effect of rapid thermal annealing (RTA) on the properties of erbium oxide films deposited onto a porous silicon carbide buffer layer formed on 4H-SiC substrates. An analysis of atomic composition of the films under investigation as a function of RTA duration was performed. It is shown that phase composition of erbium oxide films on silicon carbide substrates with a porous SiC layer can be changed by varying RTA duration.

  19. Escucheme Por Favor/Please Listen to Me: An Analysis of the Perceptions of Latino Students and Teachers in a High School Multilingual Teacher Academy

    ERIC Educational Resources Information Center

    Palacio, Peter Vincent

    2010-01-01

    This case study used photo elicitation interviewing (PEI) to analyze perceptions of Latino students and their teachers in a multilanguage high school academy. It examined student involvement in school, dropout rate, and pursuit of a college education. Ten academy teachers and 10 Latino senior students were interviewed. Observations obtained…

  20. Library Safari: Tips for Parents of Young Readers and Explorers = De safari por la biblioteca: Consejos para padres de lectores y exploradores jovenes.

    ERIC Educational Resources Information Center

    Clements, Aedin

    Visiting the library is a great way for parents to encourage their child's imagination and learning. It gives parents the opportunity to model good reading behavior and to show their child that they value books and reading. No matter how young the child is, a trip to the library can be an enjoyable outing for parents and their children. Most…

  1. The HoMBReS and HoMBReS Por un Cambio Interventions to Reduce HIV Disparities Among Immigrant Hispanic/Latino Men.

    PubMed

    Rhodes, Scott D; Leichliter, Jami S; Sun, Christina J; Bloom, Fred R

    2016-02-12

    Hispanics/Latinos in the United States are affected disproportionately by human immunodeficiency virus (HIV) infection, acquired immunodeficiency syndrome (AIDS), and other sexually transmitted diseases (STDs); however, few effective evidence-based prevention interventions for this population exist. This report describes the Hombres Manteniendo Bienestar y Relaciones Saludables (Men Maintaining Wellbeing and Healthy Relationships) (HoMBReS) intervention, which was developed by a community-based, participatory research partnership in North Carolina and initially implemented during 2005-2009. HoMBReS is an example of an effective intervention that uses lay health advisors (known as Navegantes [navigators]) in the context of existing social networks (i.e., recreational soccer teams) to promote consistent condom use and HIV and STD testing among Hispanic/Latino men. In 2012, HoMBReS was classified as a best-evidence community-level HIV prevention intervention (CDC. Compendium of evidence-based behavioral interventions and best practices for HIV prevention. Atlanta, GA: US Department of Health and Human Services, CDC; 2015). The intervention has been implemented elsewhere, enhanced, and further evaluated in longitudinal intervention and implementation studies. HoMBReS has been adapted for other populations, including men who have sex with men and transgender persons. Additional evaluation has found that Navegantes continue in their roles as health advisors, opinion leaders, and community advocates after study support ends. Hispanic/Latino men's social networks can be leveraged to promote sexual health within the community by decreasing HIV risk behaviors among Hispanics/Latinos in the United States. PMID:26916740

  2. "Pig in a poke (gato por liebre)": the "mota" (Calophysus macropterus) fishery, molecular evidence of commercialization in Colombia and toxicological analyses.

    PubMed

    Salinas, Cristian; Cubillos, Juan Camilo; Gómez, Rigoberto; Trujillo, Fernando; Caballero, Susana

    2014-06-01

    Overfishing has affected the population abundance trends of many commercial fish species. In the Amazon, the fishery of a catfish commonly known as "mota" or "piracatinga" (Calophysus macropterus) has become an important economic activity in the region as this species has replaced a number of other overexploited great catfish species in the markets. Due to this high exploitation, ways in which to increase captures have been identified. One strategy is to use decomposing animal carcasses as bait. Such strategy has increased the hunting pressure on endangered species such as caimans and river dolphins. We investigated which catfish species are currently commercialized in Colombian fish markets using DNA barcoding, and measured mercury concentration in the tissues of fish molecularly identified as C. macropterus. We collected 86 fish samples in markets of four Colombian cities. Sixty-eight of these were identified molecularly as C.macropterus. The mercury concentration of 29 such samples was analyzed. Samples presented total Hg concentrations higher than the limit for human consumption established by the WHO (0.5 μg/g). These results are worrisome and suggest that (1) C. macropterus is a widely used fish species for human consumption in Colombia and (2) C. macropterus has high concentrations of total Hg, making its consumption a public health risk. Results presented here suggest that C. macropterus has replaced capaz in most Colombian markets. This fishery threatens wild species of river dolphins and caimans, and is also a public health risk given the high mercury levels we found in a subsample of these fishes. PMID:24419666

  3. Communicating with Mexican Americans: Por Su Buena Salud = Communicando Con Mexico Americanos: For Their Good Health. Proceedings of the Conference (Houston, TX, September 13-14, 1979).

    ERIC Educational Resources Information Center

    Moore, Thomas J., Ed.; And Others

    The conference focused on the role of the Mexican American's cultural language, tradition, life style, health practices, and media utilization in the design of effective health education and information programs. Representing various local, state, and national health, education, and media organizations, the 108 participants attended sessions on…

  4. Comienza la construcción de instalación patrocinada por el NCI en Puerto Rico para realizar estudios

    Cancer.gov

    El gobierno de Puerto Rico ha destinado $196 millones de dólares para construir un hospital oncológico de 287 000 pies cuadrados en San Juan, que contará con 96 camas. El nuevo hospital es el primero en su clase en la región caribeña y en él se llevarán a

  5. Adolescentes que no habrían fumado pueden ser atraídos por los cigarrillos electrónicos

    Cancer.gov

    Artículo del blog Temas y relatos sobre un estudio reciente que sugiere que los adolescentes están usando cigarrillos electrónicos no solo como sustituto de cigarrillos convencionales sino cigarrillos electrónicos están atrayendo nuevos usuarios de tabaco

  6. Comparacion de Modelos de Educacion Sexual en El Conocimiento y Cambio de Actitudes en Practicas Sexuales por Alumnos de Nivel Superior en La Region De Caguas, Puerto Rico

    ERIC Educational Resources Information Center

    Juan, Vallejo Ramos L.

    2012-01-01

    In opposition to the Sexual Education Traditional Model (SETM) that is used in the state schools of Puerto Rico, the Health Beliefs Model (HBM) appears. It facilitates a curricular design that improves the ability of the students to respond to the group pressure by means of attitudes that stimulate sexual conducts of smaller risk of propagation of…

  7. Stakeholder views on policy options for responding to the growing challenge from obesity in France: findings from the PorGrow project.

    PubMed

    Holdsworth, M; Kameli, Y; Delpeuch, F

    2007-05-01

    To explore the perspectives of key stakeholders towards a range of policy options to prevent obesity in France, a multi-criteria mapping method was used to gather quantitative and qualitative data from 21 types of stakeholder groups. During structured interviews, stakeholders appraised a set of pre-defined options by reference to criteria of their own choosing and provided relative weights to their criteria, and overall rankings of the policy options. Efficacy, feasibility and societal benefits were the groups of criteria given most importance by stakeholders. There was most consensus and preference for options related to health education, particularly in schools, compared with options that aimed at changing the environment to prevent obesity, i.e. options around physical activity; options that modified food supply and demand; and information-related options. There was little support for technological solutions or institutional reforms. While there was broad interest in a range of different options, those related to behaviour change through education were the most valued by stakeholders. Raising awareness among policymakers about the convincing scientific evidence for the effectiveness of environmental level policy options will be a crucial first step. PMID:17371308

  8. Ameiridae Boeck and Argestidae Por revisited, with establishment of Parameiropsidae, a new family of Harpacticoida (Crustacea, Copepoda) from deep-sea sediments

    NASA Astrophysics Data System (ADS)

    Corgosinho, P. H. C.; Martínez Arbizu, P.

    2010-09-01

    Four new species of Parameiropsis are described from Angola and Guinea Basins and the Arctic Laptev Sea. The male of Parameiropsis poseidonicus sp. n. differs from that of P. neptuni sp. n. and P. senckenbergi sp. n. in antennule segmentation, length of the proximal aesthetasc, length of the outermost seta of the antennary endopod, degree of reduction of the mouthparts, relative length of the inner spine of the basis of thoracopod 1, shape of the furca and body length. The female of P. amphitriteae sp. n. differs from previously described females of other species in the smaller exopod and endpod of thoracopod 1, reduced armature of thoracopods 1-6, length of the outer setae of exopods and endopods of thoracopods 2-4, and mandible exopod weakly developed and fused to the basis. Parameiropsis is redefined by the following autapomorphies: presence of aesthetasc on 3rd segment of female antennule; antenna strong, with endopod curved upwardly, and shape of the outermost (strongly ornamented) spine; triangular labrum; elongated corpus mandibularis, gnathobasis very long; basis of mandibular palp unarmed; elongated maxillule, with long and flexible setae on praecoxal arthrite; basis of the maxilla with strongly modified claw. To discuss the phylogenetic position of Parameiropsis, we revaluated the subfamilies of Ameiridae (viz. Ameirinae and Stenocopiinae) and the family Argestidae. Anoplosomella and Malacopsyllus revealed to be not closely related to Ameiridae and are transferred to Argestidae, sharing with other members of this family the morphology of the mandible gnathobasis, armature of maxilla and armature and length of the first segment of the antennule. Argestoides prehensilis does not show any of the characters that we consider autapomorphic for Argestidae. Instead, it shows many characters in common with several Ameiridae species. Parameiropsis does not have any character that could justify its inclusion within Ameiridae or even within Podogennonta. It also cannot be included satisfactorily within Argestidae nor Exanechentera. Therefore, we here propose a new family for Parameiropsis, with unclear relationships within Harpacticoida. After these taxonomic rearrangements, Ameiridae and Argestidae are considered monophyletic based on certain maxilla characters that we consider autapomorphic for each group. A key to the identification of the known species of Parameiropsis is added at the end.

  9. Comparacion de modelos de Educacion Sexual en el conocimiento y cambio de actitudes en practicas sexuales por alumnos de nivel superior en la region de Caguas, Puerto Rico

    NASA Astrophysics Data System (ADS)

    Juan, Vallejo Ramos L.

    In opposition to the Sexual Education Traditional Model (SETM) that is used in the state schools of Puerto Rico, the Health Beliefs Model (HBM) appears. It facilitates a curricular design that improves the ability of the students to respond to the group pressure by means of attitudes that stimulate sexual conducts of smaller risk of propagation of the Sexually Transmitted Diseases (STD). In addition, it provides activities to increase the self-esteem, the communication and the decision making. This investigation had the intention to compare the SETM and the HBM in the increase of knowledge and change of attitudes of high risk of propagation of the STD using a validated questionnaire (Agency of the United States for the International-USAID Development), named "Endesa 2007" and, adapted to Puerto Rico by the Dra.Marta Collazo to a sample of students between the 17 and 19 years of 2 state schools of San Lorenzo, as a pretest, and, selected by convenience. Then, a 10 hours training was administered to half of the students using the SETM to STD and condom use lessons. The other half of the students received additional lessons using the HBM. Finally, both groups took the questionnaire again as a posttest. The sample of students, in average, did not reach the knowledge and basic levels of attitudes towards the STD in the pretest. This reflected 2 possible implications on the SETM. In first place, that the way in which the STD is implemented as part of the Sexual Education curriculum is inefficient. Secondly, the possibility that the acquired information or attitudes does not have permanence. Culminated the questionnaire, the HBM increase the knowledge of the STD in 0.41 points (average) over the SETM. There was not a significant difference between both models, in attitudes, implying that both models are equally effective. The findings suggests that the HBM is more effective increasing the knowledge on the STD, but equally effective than the SETM in attitude change for the Puerto Rican youth.

  10. The effects of the porous buffer layer and doping with dysprosium on internal stresses in the GaInP:Dy/por-GaAs/GaAs(100) heterostructures

    SciTech Connect

    Seredin, P. V.; Gordienko, N. N.; Glotov, A. V.; Zhurbina, I. A.; Domashevskaya, E. P.; Arsent'ev, I. N. Shishkov, M. V.

    2009-08-15

    In structures with a porous buffer layer, residual internal stresses caused by a mismatch between the crystal-lattice parameters of the epitaxial GaInP alloy and the GaAs substrate are redistributed to the porous layer that acts as a buffer and is conducive to disappearance of internal stresses. Doping of the epitaxial layer with dysprosium exerts a similar effect on the internal stresses in the film-substrate structure.

  11. Unanswered Questions in Colombia's Foreign Language Education Policy (Preguntas por responder en la política educativa de lenguas extranjeras en Colombia)

    ERIC Educational Resources Information Center

    Bonilla Carvajal, Camilo Andrés; Tejada-Sánchez, Isabel

    2016-01-01

    Following the trend of much of the Western, non-English speaking world, Colombia has tirelessly strived for spreading English education in an effort to augment economic benefits. This paper aims at providing a critical account of foreign language education policy in Colombia, with special attention to English. It outlines the impact of its…

  12. "¿Por qué leemos esto en la clase de español?": The Politics of Teaching Literature in Spanglish

    ERIC Educational Resources Information Center

    Postma, Regan L.

    2013-01-01

    This article discusses what is at stake in teaching works written in "Spanglish" in Spanish departments and what teaching such works might mean for students and the scholarly community at large. This article primarily comes out of the author's experiences teaching "Spanglish" works in Spanish courses at a major research…

  13. Beneficios y riesgos de la terapia estrogénica en la menopausia varían por edad, de acuerdo con el e

    Cancer.gov

    Los datos de seguimiento a largo plazo del estudio Iniciativa para la Salud de la Mujer (WHI) proporcionan información nueva e importante sobre los posibles riesgos y beneficios de la terapia hormonal para tratar síntomas relacionadas con la menopausia.

  14. Lower Respiratory Tract Infection in a Renal Transplant Recipient: Do not Forget Metapneumovirus

    PubMed Central

    Noel, N.; Rammaert, B.; Zuber, J.; Sayre, N.; Mamzer-Bruneel, M. F.; Leruez-Ville, M.; Mascard, L.; Lecuit, M.; Lortholary, O.

    2012-01-01

    Human metapneumovirus (hMPV) is emerging as a cause of a severe respiratory tract infection in immunocompromised patients. hMPV pneumonia has only been seldom reported in nonpulmonary solid organ transplanted patients, such as renal transplant recipients. We report here a case of a 39-year-old patient presenting with fever, cough, and interstitial opacities on CT scan diagnosed as a nonsevere hMPV pneumonia 11 years after a renal transplantation. Infection resolved spontaneously. Differential diagnosis with Pneumocystis pneumonia was discussed. We review the medical literature and discuss clinical presentation and detection methods that can be proposed in solid organ transplant recipients. PMID:23213611

  15. HIV Associated Opportunistic Pneumonias.

    PubMed

    Ismail, T; Lee, C

    2011-03-01

    Opportunistic pneumonias are major causes of morbidity and mortality in HIV infected individuals. The majority of new HIV infections in Malaysia are adults aged 20 to 39 years old and many are unaware of their HIV status until they present with an opportunistic infection. HIV associated opportunistic pneumonias can progress rapidly without appropriate therapy. Therefore a proper diagnostic evaluation is vital and prompt empiric treatment of the suspected diagnosis should be commenced while waiting for the results of the diagnostic studies. Tuberculosis, Pneumocystis pneumonia (PCP) and recurrent bacterial pneumonias are common causes of AIDS-defining diseases and are discussed in this article. PMID:23765154

  16. Eye signs that alert the clinician to a diagnosis of AIDS.

    PubMed

    Meyer, D

    2005-10-01

    One of the hallmarks of progressive immune deficiency is a steady decline in the absolute number of CD4+ T-lymphocytes. As the immune response thus becomes suppressed, opportunistic systemic infections such as protozoal (Pneumocystis carinii pneumonia, disseminated toxoplasmosis), viral (Cytomegalovirus pneumonitis and colitis and persistent invasive herpes simplex lesions), fungal (cryptococcossis and esophageal candidiasis) and bacterial infections (atypical mycobacterial and extrapulmonary tuberculosis) set in to claim their toll. Ocular complications occur in about 75% of AIDS patients and may be divided into four categories: Retinal microangiopathy, Opportunistic infections, Tumours, Neuro-ophthalmological lesions. Only the most frequently occurring manifestations will be highlighted. PMID:16320530

  17. 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.

  18. [Corticosteroids in the treatment of infectious diseases].

    PubMed

    Kronig, I; Schibler, M; Rougemont, M; Emonet, S

    2013-04-24

    The addition of a corticosteroid has become a common practice for the treatment of some infectious diseases, such as meningitis, septic shock, moderate to severe Pneumocystis jirovecii pneumonia. The belief that steroids may have a beneficial effect in the early stage of pro-inflammatory infections explains the renewed interest for these treatments. This review of recent literature helps determine the use of steroids in the treatment of infectious diseases as formal guidance, questionable or rather contraindicated. When there is a clear scientific indication for the use of corticosteroids regardless of the current infection, the latter is never a formal contraindication. PMID:23697079

  19. 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.

  20. 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.

  1. 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

  2. Dapsone-induced pure red cell aplasia and cholestatic jaundice: A new experience for diagnosis and management.

    PubMed

    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

  3. I hear you knockin' (but you can't come in): potent new HIV therapies are shutting out opportunistic infections.

    PubMed

    Fichtenbaum, C J

    1998-07-01

    Highly active antiretroviral therapy (HAART) has positively impacted the epidemiology of opportunistic infections in HIV- infected patients. The following opportunistic infections and their responses to HAART and prophylaxis recommendations are examined: pneumocystis carinii pneumonia (PCP), cytomegalovirus (CMV) disease, mycobacterium avium complex (MAC) disease, and fungal diseases. The question of whether opportunistic infection prophylaxis should be continued in persons who respond to HAART is discussed. A table provides recommendations for opportunistic illness prophylaxis, listing the primary choice of therapy for each illness followed by alternative choices of therapy for each illness. PMID:11365645

  4. 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.

  5. Rhodococcus equi Sepsis in a Renal Transplant Recipient: A Case Study

    PubMed Central

    Macken, Eline; de Jonge, Hylke; Van Caesbroeck, Daniël; Verhaegen, Jan; Van Kerkhoven, Dana; Van Wijngaerden, Eric; Kuypers, Dirk

    2015-01-01

    Abstract Rhodococcus equi is an unusual cause of infection in humans, but has emerged as an opportunistic pathogen among immunocompromised patients. Primary pulmonary involvement is the most common clinical presentation, although the spectrum of disease is broad. Diagnosing R. equi infections remains challenging, both from clinical and microbiological view, and no standard treatment has been established. In this report, we present a detailed case of a 57-year-old male renal transplant recipient who developed R. equi bacteremia with a concomitant Pneumocystis jirovecii pneumonia. We describe the clinical features of R. equi infections, highlight the importance of an early diagnosis, and briefly review treatment options for this rare infection. PMID:27500216

  6. Acute hemolysis in a patient with a newly diagnosed glioblastoma.

    PubMed

    Murphy, Adrian G; Grossman, Stuart A

    2016-07-01

    We describe a 62-year-old of Egyptian origin who presented with sudden, severe and symptomatic anemia requiring hospitalization shortly after beginning concurrent radiation and temozolomide for his newly diagnosed glioblastoma. He had also recently been started on steroids, anticonvulsants and Pneumocystis jirovecii prophylaxis. He was ultimately diagnosed with G6PD deficiency with an acute hemolytic anemia precipitated by dapsone. Screening for G6PD deficiency should be considered in high-risk patient populations where P. jirovecii prophylaxis is planned. PMID:27230975

  7. 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

  8. [Extrapulmonary and disseminated pneumocystosis in AIDS. A review of the literature].

    PubMed

    Grasland, A; Pouchot, J; Michon, C; Hertig, A; Simonpoli, A M; Vinceneux, P

    1997-01-01

    We present a literature review about extrapulmonary and disseminated pneumocystosis in AIDS. The prevalence of such infections seems low but is probably under-estimated. Disseminated pneumocystosis occurs in patients with profound immunosuppression, who do not receive prophylaxis against Pneumocystis carinii pneumonia or are treated with aerolized pentamidine. The lack of specificity of symptoms may delay the diagnosis. Most organs may be involved. Three different presentations may be individualized: disseminated pneumocystosis, intra-thoracic only disseminated pneumocystosis, in an intra-thoracic localization alone, and localized extrapulmonary pneumocystosis. The mortality from disseminated disease is high, especially in the presence of low serum albumin level. PMID:9238445

  9. T cell immunodeficiency in dyskeratosis congenita.

    PubMed Central

    Lee, B W; Yap, H K; Quah, T C; Chong, A; Seah, C C

    1992-01-01

    Dyskeratosis congenita has been found to be associated with abnormal immune function. In this study we report a patient with this association. He developed Pneumocystis carinii interstitial pneumonia, and impaired cell mediated immunity was confirmed by the presence of depressed lymphoproliferative responses to in vitro stimulation with mitogen. Enumeration of T cell subsets showed a severely depressed CD4:CD8 ratio (0.38), which is the likely cause for impaired cell mediated immunity. The T cell activation pathway appeared intact, as his T lymphocytes were able to express activation markers (CD25 and HLA-DR) after mitogen stimulation. PMID:1580685

  10. 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

  11. [Pneumocystosis during HIV infection].

    PubMed

    El Fane, M; Sodqi, M; Oulad Lahsen, A; Chakib, A; Marih, L; Marhoum El Filali, K

    2016-08-01

    Pneumocystosis is an opportunistic disease caused by invasion of unicellular fungus Pneumocystic jirovecii which is responsible for febrile pneumonia among patients with cellular immunodeficiency especially those HIV infected. Despite the decreasing of its incidence due to the introduction of antiretroviral therapy, as well as anti-Pneumocystis prophylaxis among these patients, Pneumocystis pneumonia remains the first AIDS-defining event and a leading cause of mortality among HIV-infected patients. The usual radiological presentation is that of diffuse interstitial pneumonia. The diagnosis is confirmed by the detection of trophozoides and/or cysts P. jirovecii in bronchoalveolar lavage (BAL) samples using several staining techniques. The use of polymerase chain reaction in the BAL samples in conjunction with standard immunofluorescent or colorimetric tests have allowed for more has allowed for more rapid and accurate diagnosis. The standard regimen of treatment is the association of trimethoprim-sulfamethoxazole which has been utilized as an effective treatment with a favourable recovery. Early HIV diagnosis and antiretroviral therapy should reduce the incidence of this dreaded disease. PMID:27349824

  12. Pathology Image of the Month:Cough and Shortness of Breath in a Noncompliant Patient with HIV/AIDS.

    PubMed

    Thomasson, Reggie; Dewenter, Tracy; McGoey, Robin R

    2015-01-01

    A 37- year-old man with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) was admitted to the intensive care unit following a four month history of progressive shortness of breath, productive cough, and flu-like symptoms. His HIV/AIDS was diagnosed at the age of 19 (CD4 count =15; viral load = 294,436 copies/ mL) and was complicated by hemodialysis-dependent, HIV-associated nephropathy, prior Pneumocystis pneumonia and known noncompliance with prescribed antiretroviral therapy. Chest film at admission was interpreted as diffuse bilateral interstitial and airspace opacities with a right sided layering density representative of laminar pleural effusion. Bacterial blood cultures were subsequently negative. A bronchoalveolar lavage was performed and an image from the cytologic cell block is seen above in Figure 1. The patient's respiratory status continued to deteriorate and he was converted to comfort care. Following death, an unlimited autopsy examination was requested by the family and authorized by the coroner. At autopsy, additional gross pathologic findings included 350ml of chylous appearing pleural fluid and serous ascites (700ml). Histopathology revealed intra-alveolar acute fibrinopurulent exudate, chronic pericarditis and end-stage nephropathy. Similar cells to those shown above in Figure 1 were identified in lung epithelium and in pancreatic acinar cells. Special stain for Pneumocystis was negative. PMID:27159517

  13. 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.

  14. Population-Based Analysis of Invasive Fungal Infections, France, 2001–2010

    PubMed Central

    Bitar, Dounia; Lortholary, Olivier; Le Strat, Yann; Nicolau, Javier; Coignard, Bruno; Tattevin, Pierre; Dromer, Françoise

    2014-01-01

    To determine the epidemiology and trends of invasive fungal infections (IFIs) in France, we analyzed incidence, risk factors, and in-hospital death rates related to the most frequent IFIs registered in the national hospital discharge database during 2001–2010. The identified 35,876 IFI cases included candidemia (43.4%), Pneumocystis jirovecii pneumonia (26.1%), invasive aspergillosis (IA, 23.9%), cryptococcosis (5.2%), and mucormycosis (1.5%). The overall incidence was 5.9/100,000 cases/year and the mortality rate was 27.6%; both increased over the period (+1.5%, +2.9%/year, respectively). Incidences substantially increased for candidemia, IA, and mucormycosis. Pneumocystis jirovecii pneumonia incidence decreased among AIDS patients (−14.3%/year) but increased in non-HIV–infected patients (+13.3%/year). Candidemia and IA incidence was increased among patients with hematologic malignancies (>+4%/year) and those with chronic renal failure (>+10%/year). In-hospital deaths substantially increased in some groups, e.g., in those with hematologic malignancies. IFIs occur among a broad spectrum of non–HIV-infected patients and should be a major public health priority. PMID:24960557

  15. 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

  16. TECNOLOGÍAS DE INFORMACIÓN Y COMUNICACIÓN PARA LA PREVENCIÓN Y CONTROL DE LA INFECCIÓN POR EL VIH Y OTRAS ITS*

    PubMed Central

    Curioso, Walter H.; Blas, Magaly M.; Kurth, Ann E.; Klausner, Jeffrey D.

    2010-01-01

    Avances tecnológicos innovadores como Internet, computadoras personales de bolsillo, teléfonos celulares y otros equipos son un arsenal en crecimiento en el esfuerzo de impedir y controlar el VIH y otras infecciones de transmisión sexual (ITS). A pesar que existe una diversidad de tecnologías de información y comunicación en diferentes etapas de desarrollo para la prevención del VIH e ITS, la investigación en esta área se encuentra aún en crecimiento, y el impacto en la incidencia de enfermedad, las evaluaciones con diseños rigurosos y los estudios económicos todavía son muy limitados. Sin embargo, algunas de estas evidencias son prometedoras y poseen un gran potencial para su uso en nuestro medio. En este artículo hemos realizado una revisión sistemática de la literatura relacionada con el uso de la tecnología aplicada a la prevención y control del VIH e ITS. De ser usada apropiadamente, esta tecnología podría mejorar la vigilancia del VIH y otras ITS, diagnóstico, notificación de parejas, prevención, manejo clínico, y capacitación de profesionales de la salud. PMID:26339254

  17. Encouraging Students to Enhance Their Listening Performance (Cómo animar a los estudiantes para que mejoren su desempeño en comprensión oral por sí mismos)

    ERIC Educational Resources Information Center

    Hernández-Ocampo, Sonia Patricia; Vargas, Sonia Patricia

    2013-01-01

    Spanish-speaking students constantly complain about the difficulty they have comprehending spoken English. It seems teachers do not often provide them with strategies to alleviate that. This article reports on a pedagogical experience carried out at a Colombian university to help pre-service teachers at an intermediate level of English to improve…

  18. About to Graduate from High School? Consider Career Education Opportunities. EdSource Student/Parent Guide = Estas por graduarte de la escuela preparatoria? Considera oportunidades para seguir tu educacion de carrera. EdSource guia de estudiantes y padres

    ERIC Educational Resources Information Center

    EdSource, 2006

    2006-01-01

    Getting a sound education is important to a student's ability to make a good living in a field they will enjoy. For many students graduating from high school, that includes high quality career technical (or vocational) education tailored to a specific job. In California, such programs are available in a wide range of fields, from healthcare to the…

  19. Fields without Borders: An Anthology of Documentary Writing and Photography by Student Action with Farmworkers' Interns = Campos sin Fronteras: Una Antologia de Obras Escritas y Fotografia por Estudiantes Internos de Accion Estudiantil con Trabajadores Agricolas.

    ERIC Educational Resources Information Center

    Manly, Libby, Ed.; Okie, Alejandra, Ed.; Wiggins, Melinda, Ed.

    In this booklet, essays and poems, presented both in English and in Spanish, portray the feelings, conditions, and economic plight of migrant and seasonal farmworkers in North and South Carolina, often in their own words. A preface describes Student Action with Farmworkers summer internships in which college students spend 10 weeks working with…

  20. The Latinas' Guide to the Information Superhighway: A Bilingual Guide for Latinas by Latinas = Guia para Mujeres Latinas sobre la Supercarretera de la Informacion: Una Guia Bilingue para Latinas por medio de Latinas.

    ERIC Educational Resources Information Center

    MANA, A National Latina Organization, Washington, DC.

    This guide to the Internet is designed to give Latinas basic information on computers and the information superhighway. Written in both Spanish and English, the guide begins by defining the Internet and making some suggestions about acquiring access to a computer. Among the topics discussed are how to choose an Internet service provider, how to…

  1. Por Que Rosa No Es Valiente? Cuarto Modulo de una Serie para Maestros de Escuela Elemental (Why Isn't Rosie Brave? Fourth Module of a Series for Elementary School Teachers).

    ERIC Educational Resources Information Center

    Molina, Carmen Eneida, Ed.; And Others

    This guide in English and Spanish provides teachers with methods for identifying textbook bias and stereotyping. A pre-test and post-test designed to measure awareness of textbook stereotypes are included. Four object lessons discuss the function of repetition, cumulative effect, omission, and distortion in reinforcing stereotypes, especially…

  2. Por Que Mami No Puede Cambiar una Goma? Tercer Modulo de una Serie para Maestros de Escuela Elemental. (Why Can't Mommy Change a Flat Tire? Third Module of a Series for Elementary School Teachers).

    ERIC Educational Resources Information Center

    Molina, Carmen Eneida, Ed.; And Others

    This guide for teachers, in English and Spanish, examines the role parents play in the socialization of sex roles. A pre-test and post test are included to measure the user's awareness of sexual stereotyping. Five object lessons cover the following topics: (1) stereotypes which exist prior to a baby's birth; (2) behavioral standards on which…

  3. Viajando por la Carretera de la Educacion Especial: Una Guia para los Padres para Tener un Viaje Feliz y Seguro (Traveling the Special Education Highway: A Parent's Guide to a Safe and Happy Journey).

    ERIC Educational Resources Information Center

    Santa Maria, Karen

    Designed for Spanish-speaking parents, this brochure, written in Spanish, uses a car-trip analogy to describe special education services for students with disabilities. It addresses: (1) child find; (2) initial evaluation and eligibility determination; (3) categories of students who receive special education services and related services; (4)…

  4. Guiandose por la Intrincada Senda de la Educacion Especial: Una Guia para Padres y Maestros. Tercera Edicion. (Negotiating the Special Education Maze: A Guide for Parents & Teachers. Third Edition).

    ERIC Educational Resources Information Center

    Anderson, Winifred; Chitwood, Stephen; Hayden, Deidre

    Designed to assist Spanish-speaking parents and teachers in understanding special education procedures, this book describes the process for obtaining school services for children with disabilities. An introduction reviews six major provisions of the Individuals with Disabilities Education Act (IDEA) that relate to children's rights to a free,…

  5. Less and Less for More and More. Economic Organization Booklet 1. Teacher's Edition=Menos y menos por mas y mas. Organizacion economica libro 1. Manual para El Maestro.

    ERIC Educational Resources Information Center

    California State Univ., Los Angeles. National Dissemination and Assessment Center.

    The booklet is part of a grade 10-12 social studies series produced for bilingual education. The series consists of six major thematic modules, with four to five booklets in each. The interdisciplinary modules are based on major ideas and are designed to help students understand some major human problems and make sound, responsive decisions to…

  6. VISIÓN GENERAL DE LA EVALUACIÓN DEL RIESGO EN SALUD INFANTIL EMPLEANDO UN ENFOQUE POR ETAPAS DE DESARROLLO (American translation is: Overview of a Life Stage Approach to Children's Health Risk Assessment)

    EPA Science Inventory

    Discussing the challenges associated with estimating and interpreting toxicant exposures and health risks from biomonitoring data. This extended abstract was translated in Spanish and published in Acta Toxicologica Argentina.

  7. Ingestion Reiterada de Cuerpos Extranos. Forma Inusual de Presentacion del Sindrome de Munchausen por Poderes (Reiterated Ingestion of Foreign Bodies. Unusual Form of Presentation of Munchausen Syndrome by Proxy).

    ERIC Educational Resources Information Center

    Terreros, I. Gomez de; And Others

    1996-01-01

    An unusual case of Munchausen syndrome by proxy is reported. A mother with a psychiatric record of behavior disorders and family dysfunction perpetrated the ingestion of foreign bodies (for example, earrings, a screw, sewing needles) on a 10-month-old infant with a history of prematurity, repeated visits to emergency rooms, and nonjustified…

  8. John Tracy Clinic: Programa de Ensenanza por Correspondencia para Los Padres de Ninos Sordo-Ciegos de Edad Preescolar (John Tracy Clinic Correspondence Learning Program for Parents of Preschool Deaf-Blind Children).

    ERIC Educational Resources Information Center

    Thielman, Virginia B.; And Others

    Written in Spanish, the document contains a correspondence learning program for parents of deaf blind preschoolers. An introductory section gives preliminary instructions, an introduction to sign language, and a list of resources for deaf blind children. Twelve lessons follow with information on: the parent's role in teaching the child, visual…

  9. The comparison of algorithms for key points extraction in simplification of hybrid digital terrain models. (Polish Title: Porównanie algorytmów ekstrakcji punktów istotnych w upraszczaniu numerycznych modeli terenu o strukturze hybrydowej)

    NASA Astrophysics Data System (ADS)

    Bakuła, K.

    2014-12-01

    The presented research concerns methods related to reduction of elevation data contained in digital terrain model (DTM) from airborne laser scanning (ALS) in hydraulic modelling. The reduction is necessary in the preparation of large datasets of geospatial data describing terrain re lief. Its course should not be associated with regular data filtering, which o ften occurs in practice. Such a method leads to a number of important forms important for hydraulic modeling being missed. One of the proposed solutions for the reduction of elevation data contained in DTM is to change the regular grid into the hybrid structure with regularly distributed points and irregularly located critical points. The purpose of this paper is to compare algorithms for extracting these key points from DTM. They are used in hybrid mod el generation as a part of elevation data reduction process that retains DTM accuracy and reduces the size of output files. In experiments, the following algorithms were tested: Topographic Position Index (TPI), Very Important Points (VIP) and Z - tolerance. Their effectiveness in reduction (maintaining the accuracy and reducing datasets) was evaluated in respect to input DTM from ALS. The best results were obtained for the Z - tolerance algorithm, but they do not diminish the capabilities of the other two algorithms: VIP and TPI which can generalize DTM quite well. The results confirm the possibility of obtaining a high degree of reduction reaching only a few percent of the input data with a relatively low decrease of vertical DTM accuracy to a few centimetres.

  10. Engaging Foreign Language Learners in a Web 2.0-Mediated Collaborative Learning Process (Inclusión de estudiantes de lenguas extranjeras en procesos colaborativos de aprendizaje mediados por la web 2.0)

    ERIC Educational Resources Information Center

    Cote Parra, Gabriel Eduardo

    2015-01-01

    The purpose of this action research was to explore the types of interactions that foreign language learners experience while using a wiki as a supporting tool for a face-to-face research course. This design allowed me to play a dual role: first, I studied my own classroom setting and students. Second, I implemented a pedagogical intervention based…

  11. Acquired immunodeficiency syndrome: neuroradiologic findings.

    PubMed

    Kelly, W M; Brant-Zawadzki, M

    1983-11-01

    Central nervous system complications depicted by CT in ten patients with acquired immunodeficiency syndrome are described. Three patients had multifocal intra-axial enhancing lesions representing atypical brain abscesses (two with toxoplasmosis, one with candidiasis). A fourth patient with multifocal "ring" lesions whose biopsy was interpreted as suggestive of toxoplasmosis responded poorly to treatment. Following his death three months later of Pneumocystis carinii pneumonia, autopsy revealed primary intracerebral immunoblastic lymphoma. One patient had Kaposi sarcoma involving the right frontal lobe (seen as an enhancing mass on the CT scan). CT findings in the remaining five patients revealed mild to moderate enlargement of cerebrospinal fluid spaces (including ventricles and basal cisternae) as a result of cryptococcal meningitis in three patients and "aseptic" meningitis in two. The two patients in whom early biopsy confirmed toxoplasmosis responded well to anti-infective therapy, resulting in dramatic clinical recoveries. PMID:6622693

  12. 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.

  13. Human Immunodeficiency Virus and Allergic Bronchopulmonary Aspergillosis: Case Report and Review of Literature

    PubMed Central

    Galiatsatos, Panagis; Melia, Michael T.; Silhan, Leann L.

    2016-01-01

    Allergic bronchopulmonary aspergillosis (ABPA) results from a hypersensitivity response to airways colonization with Aspergillus fumigatus, and it occurs most often in individuals with asthma or cystic fibrosis. Allergic bronchopulmonary aspergillosis is an indolent, but potentially progressive, disease in patients. In patients infected with human immunodeficiency virus (HIV), ABPA is rare, and its description in the literature is limited to case reports. We describe the occurrence of ABPA in a 37-year-old woman with well controlled HIV infection. This represents the first documented case of ABPA in an HIV-infected patient whose only pulmonary comorbidity included the ramifications of prior acute respiratory distress syndrome due to Pneumocystis jirovecii pneumonia. We also review prior case reports of ABPA in HIV-infected patients and consider risk factors for its development. PMID:27419184

  14. Imaging of community-acquired pneumonia: Roles of imaging examinations, imaging diagnosis of specific pathogens and discrimination from noninfectious diseases

    PubMed Central

    Nambu, Atsushi; Ozawa, Katsura; Kobayashi, Noriko; Tago, Masao

    2014-01-01

    This article reviews roles of imaging examinations in the management of community-acquired pneumonia (CAP), imaging diagnosis of specific CAP and discrimination between CAP and noninfectious diseases. Chest radiography is usually enough to confirm the diagnosis of CAP, whereas computed tomography is required to suggest specific pathogens and to discriminate from noninfectious diseases. Mycoplasma pneumoniae pneumonia, tuberculosis, Pneumocystis jirovecii pneumonia and some cases of viral pneumonia sometimes show specific imaging findings. Peribronchial nodules, especially tree-in-bud appearance, are fairly specific for infection. Evidences of organization, such as concavity of the opacities, traction bronchiectasis, visualization of air bronchograms over the entire length of the bronchi, or mild parenchymal distortion are suggestive of organizing pneumonia. We will introduce tips to effectively make use of imaging examinations in the management of CAP. PMID:25349662

  15. Fungal Infections and New Biologic Therapies.

    PubMed

    Vallabhaneni, Snigdha; Chiller, Tom M

    2016-05-01

    The development of biologic therapies targeting proinflammatory mediators has led to significant advances in the treatment of immune-mediated inflammatory diseases (IMIDs). Blocking undesired inflammatory effects also has the potential to disrupt the body's immune response and increase the risk for infections, including fungal infections. This review summarizes the published data on the frequency and risk for fungal infections among patients treated with biologics, with a focus on the newer therapies approved for use with IMIDs in the last 10 years. The use of biologics is associated with a small but important risk of fungal infections. Pneumocystis jirovecii pneumonia, histoplasmosis, and candidiasis are some of the most common fungal infections associated with biologics. Providers should be vigilant for fungal infection among patients taking biologics, be aware that biologic agents may alter the typical presentation of fungal infections, and take timely steps to diagnose and treat fungal infection to reduce resultant morbidity and mortality. PMID:27032792

  16. 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. PMID:305493

  17. A case of fatal idiopathic enteritis and multiple opportunistic infections associated with dendritic cell deficiencies.

    PubMed

    Lord, James D; Chen, Janice; Kozarek, Richard A

    2013-03-01

    We present a case of an adult patient with new-onset severe, idiopathic, protein-wasting enteropathy, in whom an extensive immunological workup was performed. We found a lack of dendritic cell (DC) subsets in the blood and bowel, as well as elevated circulating TGF-beta levels and decreased numbers of circulating FOXP3+ regulatory T cells with diminished CTLA4 expression. She failed to respond to glucocorticoids and infliximab, and instead developed a constellation of opportunistic infections, including CMV ileitis, Mucormycosis, and Pneumocystis carinii pneumonia, and ultimately passed away. While the cause of her lack of DCs is unknown, this data suggests a key role for these cells in both regulating mucosal immunity and promoting effective cell-mediated immunity against pathogens in humans. PMID:23539396

  18. The AIDS epidemic.

    PubMed

    Conant, M A

    1994-09-01

    The nature of the clinical presentation of HIV infection continues to evolve over time. New cutaneous (e.g., seborrheic dermatitis, onychomycosis, and tinea pedis) and systemic (e.g., Aspergillus fumigatus and Penicillium marneffei) opportunistic fungal infections can now be added to the classic clinical markers for progressive HIV infection, such as Kaposi's sarcoma, Pneumocystis carinii pneumonia, Mycobacterium avium intercellulare infections, and cryptococcal meningitis. The fact that the appearance of many of these fungal diseases is directly correlated with the patient's CD4 cell count is a valuable tool for ongoing clinical evaluation. Although systemic manifestations characterize a progression from asymptomatic HIV infection to AIDS, many of the signs of disease progression are cutaneous. Prophylaxis against many of the potentially life-threatening systemic opportunistic infections associated with HIV positivity has had a positive impact on the life expectancy of patients with AIDS. PMID:7915731

  19. Pneumocystosis in wild small mammals from California

    USGS Publications Warehouse

    Laakkonen, J.; Fisher, R.N.; Case, T.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 and Notiosorex crawfordi, Chrysosporium sp. (Emmonsia) from M. californicus, and a nematode from S. ornatus.

  20. Care of Patients With HIV Infection: Medical Complications and Comorbidities.

    PubMed

    Bolduc, Philip; Roder, Navid; Colgate, Emily; Cheeseman, Sarah H

    2016-04-01

    Care of patients with HIV infection starts with diagnosis as soon as possible, preferably at or near the time of acute infection. Opportunistic infections, malignancies, and other conditions develop progressively over time, particularly in untreated patients. The AIDS-defining opportunistic infections most common in the United States include Pneumocystis jirovecii pneumonia, Candida esophagitis, toxoplasmic encephalitis, tuberculosis, disseminated Mycobacterium avium complex, cryptococcal meningitis, and cytomegalovirus retinitis. Specific prophylaxis regimens exist for several opportunistic infections, and effective antiretroviral therapy reduces the risk of most others. Other AIDS-defining conditions include wasting syndrome and HIV encephalopathy. AIDS-defining malignancies include Kaposi sarcoma, systemic non-Hodgkin lymphoma, primary central nervous system lymphoma, and invasive cervical cancer. Although not an AIDS-defining condition, anal cancer is common in patients with HIV infection. Other HIV-related conditions include thrombocytopenia, recurrent bacterial respiratory infections, HIV-associated nephropathy, and HIV-associated neurocognitive disorder. PMID:27092563

  1. [HIV in the lung from 1982 to 2013].

    PubMed

    Mayaud, C; Cadranel, J

    2014-02-01

    During the last 30 years pulmonary involvement has played a major role in the history of HIV infection. Initially, the unexplained occurrence of pneumocystis revealed the emergence of AIDS and the suspicion of its African origin. Before the era of triple therapy the natural history of AIDS was dominated by the occurrence of repeated lung infections and respiratory physicians were at the forefront of their diagnosis, treatment and prophylaxis. With the provision of antiretroviral therapy (ART), the natural history of AIDS has been transformed in those patients who benefit from it. In addition to paradoxical reactions observed following the introduction of ART, the pulmonologist is also facing a chronic stage of controlled HIV infection, and unexpected events, the incidence of which increases with time: pulmonary arterial hypertension and lung cancer certainly, COPD and fibrosis perhaps… but this story remains to be written. PMID:24602679

  2. 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. PMID:24691418

  3. 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

  4. 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.

  5. 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.

  6. 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. PMID:26449508

  7. Primary structure of dihydrofolate reductase and mitochondrial ribosomal protein L36 genes from the basidiomycete Coprinus cinereus.

    PubMed

    Aimi, Tadanori; Fukuhara, Shoji; Ishiguro, Maki; Kitamoto, Yutaka; Morinaga, Tsutomu

    2004-08-01

    We amplified and sequenced the dihydrofolate reductase (DHFR) gene of the basidiomycete Coprinus cinereus. Downstream of the DHFR coding region, a mitochondrial (mt) ribosomal protein L36 (RPL36) gene was discovered in the opposite orientation to DHFR gene. Putative polyadenylation signals of the two genes overlapped, both containing the 8-bp palindrome 5'-aatatatt-3'. The finding that C. cinereus DHFR gene is closely clustered with a mt protein gene strongly suggests that C. cinereus DHFR is closely related to mt function and evolution. The amino acid sequence of C. cinereus DHFR is most homologous to eukaryotic proteins such as Cryptococcus neoformans and Pneumocystis carinii DHFRs. However, the sequence of C. cinereus mt RPL36 closely resembles RPL36 of bacteria and cyanobacteria such as Synechocystis sp. and Escherichia coli. This result strongly supports the serial endosymbiotic theory of the development of ancestral eukaryotes, and suggests that C. cinereus mt RPL36 gene originated from the ancestral eubacterial genome. PMID:15620217

  8. Critical Care in Human Immunodeficiency Virus-Infected Patients.

    PubMed

    Akgün, Kathleen M; Miller, Robert F

    2016-04-01

    Intensive care unit (ICU) survival has been improved significantly for HIV-infected patients since the advent of antiretroviral therapy (ART). Non-AIDS conditions account for the majority of ICU admission diagnoses in areas with access to ART. However, opportunistic infections such as Pneumocystis jirovecii pneumonia still account for a significant proportion of ICU admissions, particularly in newly diagnosed HIV-infected patients, and are associated with increased ICU mortality. We discuss risk factors and outcomes for HIV-infected admitted to the ICU in the current ART era. We review the changing patterns in ICU admission diagnoses over time and how common ICU conditions are managed in HIV-infected compared with uninfected patients. We next address issues specific to the care for HIV-infected patients in the ICU, focusing on immune reconstitution inflammatory syndrome, ART continuation or initiation, and some common and potentially life-threatening ART-associated toxicities. PMID:26974306

  9. [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. PMID:26979032

  10. 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. PMID:19657988

  11. Human Immunodeficiency Virus and Allergic Bronchopulmonary Aspergillosis: Case Report and Review of Literature.

    PubMed

    Galiatsatos, Panagis; Melia, Michael T; Silhan, Leann L

    2016-04-01

    Allergic bronchopulmonary aspergillosis (ABPA) results from a hypersensitivity response to airways colonization with Aspergillus fumigatus, and it occurs most often in individuals with asthma or cystic fibrosis. Allergic bronchopulmonary aspergillosis is an indolent, but potentially progressive, disease in patients. In patients infected with human immunodeficiency virus (HIV), ABPA is rare, and its description in the literature is limited to case reports. We describe the occurrence of ABPA in a 37-year-old woman with well controlled HIV infection. This represents the first documented case of ABPA in an HIV-infected patient whose only pulmonary comorbidity included the ramifications of prior acute respiratory distress syndrome due to Pneumocystis jirovecii pneumonia. We also review prior case reports of ABPA in HIV-infected patients and consider risk factors for its development. PMID:27419184

  12. 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. PMID:23704574

  13. Psychosocial considerations in the therapy of epidemic Kaposi's sarcoma.

    PubMed

    Holland, J C; Tross, S

    1987-06-01

    Since the acquired immune deficiency syndrome (AIDS) burst into prominence in 1981, it has claimed victims at an exponential rate and taxed the resources of physicians, health workers, and social support agencies. A sizeable minority of AIDS patients, mainly male homosexuals, have been presented with epidemic Kaposi's sarcoma (EKS). Although life expectancy with this presentation may be greater than with Pneumocystis carinii pneumonia or other opportunistic infection, the underlying immunodeficiency still foreshadows an untimely death, usually from infection. Those remaining months or years are frequently marked by a poor quality of life attended by pain, functional impairment, cosmetic stigmata, central nervous system (CNS) complications, loss of employment, poverty, ostracism, guilt, and anger. Psychologic burdens may disrupt the patient's efforts to deal with the disease. Health care workers must often overcome their own prejudices and fears about AIDS to provide effective management. PMID:3603057

  14. Polyarteritis nodosa. Diagnostic challenges in a patient with cutaneous vasculitis, psoriasis, psoriatic arthritis and pancytopenia: fatal progression after treatment with G-CSF

    PubMed Central

    Jobanputra, Paresh

    2016-01-01

    A 60-year-old man presented with cutaneous vasculitis, leucopenia and psoriasis. He was treated initially with ciclosporin A. On withdrawal of ciclosporin, due to inadequate improvement of cutaneous vasculitis, he developed psoriatic arthritis. Worsening neutropenia and pancytopenia, believed to be immune mediated, developed. He was treated with prednisolone, methotrexate and adalimumab but developed pneumocystis pneumonia. Leucocyte levels improved markedly with granulocyte colony-stimulating factor (G-CSF). However, whilst being treated with G-CSF his condition deteriorated. He developed gastrointestinal and neurological symptoms and progressive weight loss. Diagnosis was delayed, but eventually polyarteritis nodosa was diagnosed and he was treated with cyclophosphamide. The patient improved initially but died from small bowel perforation due to vasculitis. Evidence showing a temporal association of his deterioration with use of G-CSF is shown. The use of G-CSF in patients with autoimmune conditions including vasculitis should be undertaken with great caution. PMID:27123310

  15. A Woman in Her 30s With a Past History of HIV Disease Presented With Recurrent Fever, Night Sweats, and Small Bilateral Pulmonary Nodules.

    PubMed

    Hashmi, Hafiz Rizwan Talib; Niazi, Masooma; Adrish, Muhammad

    2016-06-01

    A woman in her 30s presented with recurrent low-grade fever and cough (onset, 1 week). She reported occasional night sweats and weight loss of approximately 20 pounds over the past 4 months. She denied nausea, vomiting, diarrhea, or any urinary complaints. Her past medical history was significant for chronic hepatitis C and HIV infection, the latter diagnosed in 2001. She was noncompliant with highly active antiretroviral therapy for more than 4 years and had pneumocystis pneumonia 2 years prior to this presentation. She had a 10-pack per year smoking history and reported active use of cocaine and heroin. The patient denied any occupational exposures. PMID:27287594

  16. Trimethoprim-sulfamethoxazole-induced aseptic meningitis.

    PubMed Central

    Wambulwa, Charles; Bwayo, Salome; Laiyemo, Adeyinka O.; Lombardo, Fredric

    2005-01-01

    We present a 46-year-old African-American man with AIDS who was admitted on two different occasions within three weeks for signs and symptoms of meningitis after using trimethoprim/sulfamethoxazole (TMP/SMX). TMP/SMX is primarily used for the treatment of pneumocystis carinii pneumonia prophylaxis in AIDS patients. Drug-induced aseptic meningitis (DIAM) is commonly seen with nonsteroidal anti-inflammatory drugs (NSAIDS), antibiotics (with TMP/SMX being the most frequently implicated), intravenous immunoglobulins and OKT3 antibodies. However, the implication of TMP/SMX inducing aseptic meningitis has been underreported to FDA/MEDWATCH program. This might be due to the fact that it has also been used to treat bacterial meningitis from organisms like Listeria monocytogenes, which is a common pathogen in the elderly and in infants. We reviewed the literature in an attempt to characterize the pattern and predictors of TMP/SMX-induced aseptic meningitis. PMID:16396068

  17. Pneumocystosis in wild small mammals from California.

    PubMed

    Laakkonen, J; Fisher, R N; Case, T J

    2001-04-01

    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 and Notiosorex crawfordi, Chrysosporium sp. (Emmonsia) from M. californicus, and a nematode from S. ornatus. PMID:11310900

  18. 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

  19. How to manage lung infiltrates in adults suffering from haematological malignancies outside allogeneic haematopoietic stem cell transplantation.

    PubMed

    Maschmeyer, Georg; Donnelly, J Peter

    2016-04-01

    Pulmonary complications affect up to 40% of patients with severe neutropenia lasting for more than 10 d. As they are frequently associated with fever and elevation of C-reactive protein or other signs of inflammation, they are mostly handled as pneumonia. However, the differential diagnosis is broad, and a causative microbial agent remains undetected in the majority of cases. Pulmonary side effects from cytotoxic treatment or pulmonary involvement by the underlying malignancy must always be taken into account and may provide grounds for invasive diagnostic procedures in selected patients. Pneumocystis jirovecii (in patients not receiving co-trimoxazole as prophylaxis), multi-resistant gram-negative bacilli, mycobacteria or respiratory viruses may be involved. High-risk patients may be infected by filamentous fungi, such as Aspergillus spp., but these infections are seldom proven when treatment is initiated. Microorganisms isolated from cultures of blood, bronchoalveolar lavage or respiratory secretions need careful interpretation as they may be irrelevant for determining the aetiology of pulmonary infiltrates, particularly when cultures yield coagulase-negative staphylococci, enterococci or Candida species. Non-culture based diagnostics for detecting Aspergillus galactomannan, beta-D-glucan or DNA from blood, bronchoalveolar lavage or tissue samples can facilitate the diagnosis, but must always be interpreted in the context of clinical and imaging findings. Systemic antifungal treatment with mould-active agents, given in combination with broad-spectrum antibiotics, improves clinical outcome when given pre-emptively. Co-trimoxazole remains the first-line treatment for Pneumocystis pneumonia, while cytomegalovirus pneumonia will respond to ganciclovir or foscarnet in most cases. The clinical outcome of acute respiratory failure can also be successful with proper intensive care, when indicated. PMID:26729577

  20. Detection of (1, 3)-β-D-glucan in bronchoalveolar lavage and serum samples collected from immunocompromised hosts.

    PubMed

    Theel, Elitza S; Jespersen, Deborah J; Iqbal, Seher; Bestrom, Jean E; Rollins, Leonard O; Misner, Lori J; Markley, Barbara J; Mandrekar, Jayawant; Baddour, Larry M; Limper, Andrew H; Wengenack, Nancy L; Binnicker, Matthew J

    2013-02-01

    The incidence of invasive fungal infections (IFI) has increased in recent years, especially among immunocompromised hosts (ICH). In 2003, the Fungitell(®) assay received FDA clearance for the presumptive diagnosis of IFI using serum and detects (1-3)-β-D-glucan, which is a major cell wall component of certain fungi (e.g., Candida, Aspergillus, and Pneumocystis). The goal of the current study was to assess the performance of the assay on bronchoalveolar lavage (BAL) fluid and serum to identify IFI in ICH. Patients were classified as having proven, probable, possible, or no IFI according to the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) guidelines. Among 109 patients for whom the results of Fungitell were compared to the EORTC/MSG criteria, Fungitell showed a low positive predictive value for the identification of IFI from both BAL (20.0%) and serum (26.7%). However, the negative predictive value of Fungitell was significantly higher for both sample types (BAL, 83.0%; serum, 84.8%). Interestingly, the results of Fungitell were positive in BAL and serum in 7/8 (87.5%) patients diagnosed with Pneumocystis pneumonia (PcP) by real-time, non-nested PCR. These data indicate that the Fungitell assay has a low positive predictive value for the diagnosis of IFI in ICH, regardless of the specimen type that is tested. However, testing of serum samples by Fungitell may permit a rapid and noninvasive initial screening approach in patients with presumed PcP. PMID:22945270