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Sample records for pneumocystis

  1. 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 , ...

  2. 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 ...

  3. 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 ...

  4. [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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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.

  11. 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

  12. 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

  13. 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

  14. [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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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

  2. [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

  3. 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

  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. 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

  6. 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

  7. 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.

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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.

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. [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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. [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

  19. 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.

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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.

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. [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

  4. 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

  5. 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

  6. 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.

  7. 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

  8. [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

  9. 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 ...

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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.

  10. 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

  11. 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

  12. [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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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.

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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.

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. [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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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- ...

  13. 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 ...

  14. 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

  15. 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

  16. 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.

  17. 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

  18. 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

  19. 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

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

    PubMed

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

    2016-01-01

    Objective. To identify blood biomarkers to predict severity and mortality in AIDS PCP patients. Methods. Biomarkers including clinical parameters and plasma inflammatory cytokines were assessed in 32 HIV-infected patients with Pneumocystis pneumonia (PCP) at time of admission. Predictive value of the biomarkers for clinical severity and in-hospital mortality was evaluated by corresponding ROC curve. Results. Levels of CRP, WBC, LDH, HBDH, and Ferritin were significantly higher in the severe and nonsurvivor AIDS PCP patients. These important biochemical indicators have inverse correlation with oxygenation index, especially levels of LDH (P = 0.008, R (2) = 0.258), HBDH (P = 0.001, R (2) = 0.335), and Ferritin (P = 0.005, R (2) = 0.237). Plasma IL-8 and IL-6 levels were significantly higher in patients with PaO2/FiO2 ≤ 200 mmHg and nonsurvivors than in those with PaO2/FiO2 > 200 mmHg and survivors. Severe and nonsurvival groups showed higher ratio of mean IL-6/IL-10 level (1.78 ± 1.56, P < 0.001; 1.11 ± 0.72, P = 0.043), larger AUC (95% CI 0.781-1.000, P < 0.001; 95% CI 0.592-0.917, P = 0.043), and more significantly inverse correlation with the oxygenation index. Conclusion. Plasma IL-8, LDH, and HBDH levels and IL-6/IL-10 ratio could be helpful for early evaluation of the severity and predicting fatal outcomes in AIDS PCP patients. PMID:27579328

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. Pneumonia - weakened immune system

    MedlinePlus

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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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 ...

  14. 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, ...

  15. 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 ...

  16. [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

  17. 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...

  18. 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

  19. 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...

  20. Towards New Antifolates Targeting Eukaryotic Opportunistic Infections

    SciTech Connect

    Liu, J.; Bolstad, D; Bolstad, E; Wright, D; Anderson, A

    2009-01-01

    Trimethoprim, an antifolate commonly prescribed in combination with sulfamethoxazole, potently inhibits several prokaryotic species of dihydrofolate reductase (DHFR). However, several eukaryotic pathogenic organisms are resistant to trimethoprim, preventing its effective use as a therapeutic for those infections. We have been building a program to reengineer trimethoprim to more potently and selectively inhibit eukaryotic species of DHFR as a viable strategy for new drug discovery targeting several opportunistic pathogens. We have developed a series of compounds that exhibit potent and selective inhibition of DHFR from the parasitic protozoa Cryptosporidium and Toxoplasma as well as the fungus Candida glabrata. A comparison of the structures of DHFR from the fungal species Candida glabrata and Pneumocystis suggests that the compounds may also potently inhibit Pneumocystis DHFR.

  1. 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

  2. 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.

  3. Acquired immunodeficiency syndrome associated with blood-product transfusions

    SciTech Connect

    Jett, J.R.; Kuritsky, J.N.; Katzmann, J.A.; Homburger, H.A.

    1983-11-01

    A 53-year-old white man had fever, malaise, and dyspnea on exertion. His chest roentgenogram was normal, but pulmonary function tests showed impaired diffusion capacity and a gallium scan showed marked uptake in the lungs. Results of an open-lung biopsy documented Pneumocystis carinii pneumonia. Immunologic test results were consistent with the acquired immunodeficiency syndrome. The patient denied having homosexual contact or using intravenous drugs. Twenty-nine months before the diagnosis of pneumocystis pneumonia was made, the patient had had 16 transfusions of whole blood, platelets, and fresh-frozen plasma during coronary artery bypass surgery at another medical center. This patient is not a member of any currently recognized high-risk group and is believed to have contracted the acquired immunodeficiency syndrome from blood and blood-product transfusions.

  4. 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

  5. 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

  6. 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

  7. 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.

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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.

  16. [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

  17. 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

  18. 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.

  19. 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.

  20. Dapsone-induced pure red cell aplasia and cholestatic jaundice: A new experience for diagnosis and management

    PubMed Central

    Sawlani, Kamal Kumar; Chaudhary, Shyam Chand; Singh, Jitendra; Raja, Deep Chandh; Mishra, Sanjay; Goel, Madhu Mati

    2016-01-01

    Dapsone (4,4’- diaminodiphenylsulfone) is the parent compound of the sulfones, and it has potent antiparasitic, anti-inflammatory, and immunomodulatory effects. It is used in the treatment of leprosy, dermatitis herpetiformis, and prophylactically to prevent Pneumocystis pneumonia and toxoplasmosis in patients unable to tolerate trimethoprim with sulfamethoxazole. We hereby report a case of dapsone toxicity who developed pure red cell aplasia and cholestatic jaundice in a suspected case of dermatitis herpetiformis. Patient had an excellent response to corticosteroids after withdrawal of dapsone. PMID:27512715

  1. 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

  2. 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

  3. 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.

  4. 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

  5. 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

  6. 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

  7. [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

  8. 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

  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. 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

  17. 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

  18. 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.

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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.

  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. 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

  8. 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

  9. [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

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. 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

  16. 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

  17. [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

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. Spectrum of Opportunistic Infections and Risk Factors for In-Hospital Mortality of Admitted AIDS Patients in Shanghai

    PubMed Central

    Luo, Bin; Sun, Jianjun; Cai, Rentian; Shen, Yinzhong; Liu, Li; Wang, Jiangrong; Zhang, Renfang; Shen, Jiayin; Lu, Hongzhou

    2016-01-01

    Abstract To investigate the frequency and the spectrum of major opportunistic infections (OIs), evaluate the major clinical factors associated with each specific OI, and identify the risk factors for in-hospital death among HIV patients in East China. A retrospective cohort study was made including all the HIV-infected patients who were admitted for the first time to the Shanghai Public Health Clinical Center during June 1, 2013 to June 1, 2015. The demographic and clinical data were collected. Comparison of continuous variables was analyzed by one-way ANOVA and rank sum test. Person χ2 test and Fisher exact test were applied to analyze the categorical variables. A Cox proportional hazards regression model was used to determine the risk for the occurrence of in-hospital death. In total, 920 patients were enrolled with age of 41.59 ± 13.36 years and 91% male. Median CD4 was 34 (IQR, 13–94) cells/μL. Among these patients, 94.7% acquired OIs while the rest developed malignancies. Pneumocystis pneumonia and bacterial coinfection (42.1%) was found to be the most common OIs, followed by tuberculosis (31.4%), CMV (20.9%), Cryptococcosis (9.0%), and MAC infection (5.2%). Of the above 5 major OIs, CMV-infected patients had the lowest median CD4 cell count 22.50 (IQR, 7.50–82.00) while the patients with tuberculosis infection had the highest count 61.00 (IQR, 27.00–176.00). In-hospital death rate was 4.2 per 100 person-years among these patients. Of note, admitted patients with 2 types of OIs (2.20, 95% CI 1.39–3.48) and those patients who were 40-year old or older (1.75, 95% CI 1.10–2.78) had a higher risk of such death. Pneumocystis pneumonia and tuberculosis were still the leading causes for the admission of HIV-infected patients in East China, and these patients tended to have very low CD4 cell counts. It is believed that expanding the HIV screening test and pushing the infected ones get ART earlier is required for generating a more successful HIV management

  10. Spectrum of Opportunistic Infections and Risk Factors for In-Hospital Mortality of Admitted AIDS Patients in Shanghai.

    PubMed

    Luo, Bin; Sun, Jianjun; Cai, Rentian; Shen, Yinzhong; Liu, Li; Wang, Jiangrong; Zhang, Renfang; Shen, Jiayin; Lu, Hongzhou

    2016-05-01

    To investigate the frequency and the spectrum of major opportunistic infections (OIs), evaluate the major clinical factors associated with each specific OI, and identify the risk factors for in-hospital death among HIV patients in East China.A retrospective cohort study was made including all the HIV-infected patients who were admitted for the first time to the Shanghai Public Health Clinical Center during June 1, 2013 to June 1, 2015. The demographic and clinical data were collected. Comparison of continuous variables was analyzed by one-way ANOVA and rank sum test. Person χ test and Fisher exact test were applied to analyze the categorical variables. A Cox proportional hazards regression model was used to determine the risk for the occurrence of in-hospital death.In total, 920 patients were enrolled with age of 41.59 ± 13.36 years and 91% male. Median CD4 was 34 (IQR, 13-94) cells/μL. Among these patients, 94.7% acquired OIs while the rest developed malignancies. Pneumocystis pneumonia and bacterial coinfection (42.1%) was found to be the most common OIs, followed by tuberculosis (31.4%), CMV (20.9%), Cryptococcosis (9.0%), and MAC infection (5.2%). Of the above 5 major OIs, CMV-infected patients had the lowest median CD4 cell count 22.50 (IQR, 7.50-82.00) while the patients with tuberculosis infection had the highest count 61.00 (IQR, 27.00-176.00). In-hospital death rate was 4.2 per 100 person-years among these patients. Of note, admitted patients with 2 types of OIs (2.20, 95% CI 1.39-3.48) and those patients who were 40-year old or older (1.75, 95% CI 1.10-2.78) had a higher risk of such death.Pneumocystis pneumonia and tuberculosis were still the leading causes for the admission of HIV-infected patients in East China, and these patients tended to have very low CD4 cell counts. It is believed that expanding the HIV screening test and pushing the infected ones get ART earlier is required for generating a more successful HIV management strategy. PMID

  11. [Rituximab therapy in the treatment of anti-neutrophil cytoplasmic antibody (ANCA) -positive interstitial pneumonia: case report].

    PubMed

    Miyaoka, Tokiko; Itabashi, Mitsuyo; Kumon, Saeko; Akiyama, Kenichi; Iwabuchi, Yuko; Kataoka, Hiroshi; Moriyama, Takahito; Takei, Takashi; Nitta, Kosaku

    2016-01-01

    pneumocystis pneumonia. In this case, rituximab was effective for IP due to MPA, but pneumocystis pneumonia could not be prevented in spite of prophylactic antibiotics. This case suggests that deliberative dose adjustments, careful patient observation, and prophylactic measures for infection are critical in rituximab treatment. PMID:26950980

  12. Structural analysis of a holoenzyme complex of mouse dihydrofolate reductase with NADPH and a ternary complex with the potent and selective inhibitor 2, 4-diamino-6-(2′-hydroxydibenz[b, f]azepin-5-yl)methylpteridine

    SciTech Connect

    Cody, Vivian; Pace, Jim; Rosowsky, Andre

    2008-09-01

    The structures of mouse DHFR holo enzyme and a ternary complex with NADPH and a potent inhibitor are described. It has been shown that 2, 4-diamino-6-arylmethylpteridines and 2, 4-diamino-5-arylmethylpyrimidines containing an O-carboxylalkyloxy group in the aryl moiety are potent and selective inhibitors of the dihydrofolate reductase (DHFR) from opportunistic pathogens such as Pneumocystis carinii, the causative agent of Pneumocystis pneumonia in HIV/AIDS patients. In order to understand the structure–activity profile observed for a series of substituted dibenz[b, f]azepine antifolates, the crystal structures of mouse DHFR (mDHFR; a mammalian homologue) holo and ternary complexes with NADPH and the inhibitor 2, 4-diamino-6-(2′-hydroxydibenz[b, f]azepin-5-yl)methylpteridine were determined to 1.9 and 1.4 Å resolution, respectively. Structural data for the ternary complex with the potent O-(3-carboxypropyl) inhibitor PT684 revealed no electron density for the O-carboxylalkyloxy side chain. The side chain was either cleaved or completely disordered. The electron density fitted the less potent hydroxyl compound PT684a. Additionally, cocrystallization of mDHFR with NADPH and the less potent 2′-(4-carboxybenzyl) inhibitor PT682 showed no electron density for the inhibitor and resulted in the first report of a holoenzyme complex despite several attempts at crystallization of a ternary complex. Modeling data of PT682 in the active site of mDHFR and P. carinii DHFR (pcDHFR) indicate that binding would require ligand-induced conformational changes to the enzyme for the inhibitor to fit into the active site or that the inhibitor side chain would have to adopt an alternative binding mode to that observed for other carboxyalkyloxy inhibitors. These data also show that the mDHFR complexes have a decreased active-site volume as reflected in the relative shift of helix C (residues 59–64) by 0.6 Å compared with pcDHFR ternary complexes. These data are consistent with the

  13. Structural Analysis of a Holoenzyme Complex of Mouse Dihydrofolate Reductase With NADPH And a Ternary Complex With the Potent And Selective Inhibitor 2,4-Diamino-6-(2'-Hydroxydibenz[b,F]azepin-5-YI)

    SciTech Connect

    Cody, V.; Pace, J.; Rosowsky, A.

    2009-05-12

    It has been shown that 2,4-diamino-6-arylmethylpteridines and 2,4-diamino-5-arylmethylpyrimidines containing an O-carboxylalkyloxy group in the aryl moiety are potent and selective inhibitors of the dihydrofolate reductase (DHFR) from opportunistic pathogens such as Pneumocystis carinii, the causative agent of Pneumocystis pneumonia in HIV/AIDS patients. In order to understand the structure-activity profile observed for a series of substituted dibenz[b,f]azepine antifolates, the crystal structures of mouse DHFR (mDHFR; a mammalian homologue) holo and ternary complexes with NADPH and the inhibitor 2,4-diamino-6-(2{prime}-hydroxydibenz[b,f]azepin-5-yl)methylpteridine were determined to 1.9 and 1.4 A resolution, respectively. Structural data for the ternary complex with the potent O-(3-carboxypropyl) inhibitor PT684 revealed no electron density for the O-carboxylalkyloxy side chain. The side chain was either cleaved or completely disordered. The electron density fitted the less potent hydroxyl compound PT684a. Additionally, cocrystallization of mDHFR with NADPH and the less potent 2{prime}-(4-carboxybenzyl) inhibitor PT682 showed no electron density for the inhibitor and resulted in the first report of a holoenzyme complex despite several attempts at crystallization of a ternary complex. Modeling data of PT682 in the active site of mDHFR and P. carinii DHFR (pcDHFR) indicate that binding would require ligand-induced conformational changes to the enzyme for the inhibitor to fit into the active site or that the inhibitor side chain would have to adopt an alternative binding mode to that observed for other carboxyalkyloxy inhibitors. These data also show that the mDHFR complexes have a decreased active-site volume as reflected in the relative shift of helix C (residues 59-64) by 0.6 A compared with pcDHFR ternary complexes. These data are consistent with the greater inhibitory potency against pcDHFR.

  14. Primary brain tumors treated with steroids and radiotherapy: Low CD4 counts and risk of infection

    SciTech Connect

    Hughes, Michael A.; Parisi, Michele; Grossman, Stuart; Kleinberg, Lawrence . E-mail: kleinla@jhmi.edu

    2005-08-01

    Purpose: Patients with primary brain tumors are often treated with high doses of corticosteroids for prolonged periods to reduce intracranial swelling and alleviate symptoms such as headaches. This treatment may lead to immunosuppression, placing the patient at risk of life-threatening opportunistic infections, such as Pneumocystis carinii pneumonia. The risk of contracting some types of infection may be reduced with prophylactic antibiotics. The purpose of this study was to determine the occurrence of low CD4 counts and whether monitoring CD4 counts during and after radiotherapy (RT) is warranted. Methods and Materials: CD4 counts were measured during RT in 70 of 76 consecutive patients with newly diagnosed Grade III and IV astrocytoma and anaplastic oligodendroglioma treated with corticosteroids and seen at the Johns Hopkins Hospital. Weekly CD4 measurements were taken in the most recent 25 patients. Prophylactic trimethoprim-sulfamethoxazole (160 mg/800 mg p.o. every Monday, Wednesday, and Friday) or dapsone (100 mg p.o. daily) in those with sulfa allergy was prescribed only if patients developed a low CD4 count. Carmustine chemotherapy wafers were placed at surgery in 23% of patients, evenly distributed between the groups. No patient received any other chemotherapy concurrent with RT. Results: CD4 counts decreased to <200/mm{sup 3} in 17 (24%) of 70 patients. For the 25 patients with weekly CD4 counts, all CD4 counts were >450/mm{sup 3} before RT, but 6 (24%) of 25 fell to <200/mm{sup 3} during RT. Patients with counts <200/mm{sup 3} were significantly more likely to be hospitalized (41% vs. 9%, p <0.01) and be hospitalized for infection (23% vs. 4%, p <0.05) during RT. Overall survival was not significantly different between the groups. All patients with low CD4 counts were treated with prophylactic antibiotics, and no patient developed Pneumocystis carinii pneumonia. No patients developed a serious adverse reaction to antibiotic therapy. The mean dose of

  15. The 13th International Workshops on Opportunistic Protists (IWOP13)

    PubMed Central

    CALDERON, ENRIQUE J.; CUSHION, MELANIE T.; XIAO, LIHUA; LORENZO-MORALES, JACOB; MATOS, OLGA; KANESHIRO, EDNA S.; WEISS, LOUIS M.

    2015-01-01

    The 13th International Workshops on Opportunistic Protists (IWOP-13) was held November 13 to 15, 2014 in Seville, Spain. The objectives of the IWOP meetings are to: (1) Serve as a forum for exchange of new information among active researchers concerning the basic biology, molecular genetics, immunology, biochemistry, pathogenesis, drug development, therapy, and epidemiology of these immunodeficiency associated pathogenic eukaryotic microorganisms that are seen in patients with AIDS; and (2) to foster the entry of new and young investigators into these underserved research areas. The IWOP meeting focuses on opportunistic protists; e.g. the free-living amoebae, Pneumocystis, Cryptosporidium, Toxoplasma, the Microsporidia, and kinetoplastid flagellates. This conference represents the major conference which brings together research groups working on these opportunistic pathogens. Progress has been achieved on understanding the biology of these pathogenic organisms, their involvement in disease causation in both immune deficient and immune competent hosts and is providing important insights into these emerging and reemerging pathogens. A continuing concern of the participants is the ongoing loss of scientific expertise and diversity in this research community. This decline is due to the small size of these research communities and an ongoing lack of understanding by the broader scientific community of the challenges and limitations faced by researchers working on these organisms, which makes these research communities very sensitive to declines in research funding. PMID:25923469

  16. Potential Impact of Co-Infections and Co-Morbidities Prevalent in Africa on Influenza Severity and Frequency: A Systematic Review

    PubMed Central

    Cohen, Adam L.; McMorrow, Meredith; Walaza, Sibongile; Cohen, Cheryl; Tempia, Stefano; Alexander-Scott, Marissa; Widdowson, Marc-Alain

    2015-01-01

    Infectious diseases and underlying medical conditions common to Africa may affect influenza frequency and severity. We conducted a systematic review of published studies on influenza and the following co-infections or co-morbidities that are prevalent in Africa: dengue, malaria, measles, meningococcus, Pneumocystis jirovecii pneumonia (PCP), hemoglobinopathies, and malnutrition. Articles were identified except for influenza and PCP. Very few studies were from Africa. Sickle cell disease, dengue, and measles co-infection were found to increase the severity of influenza disease, though this is based on few studies of dengue and measles and the measles study was of low quality. The frequency of influenza was increased among patients with sickle cell disease. Influenza infection increased the frequency of meningococcal disease. Studies on malaria and malnutrition found mixed results. Age-adjusted morbidity and mortality from influenza may be more common in Africa because infections and diseases common in the region lead to more severe outcomes and increase the influenza burden. However, gaps exist in our knowledge about these interactions. PMID:26068416

  17. A novel assay for drug-DNA binding mode, affinity, and exclusion number: scanning force microscopy.

    PubMed Central

    Coury, J E; McFail-Isom, L; Williams, L D; Bottomley, L A

    1996-01-01

    Determining the mode-of-binding of a DNA ligand is not always straightforward. Here, we establish a scanning force microscopic assay for mode-of-binding that is (i) direct: lengths of individual DNA-ligand complexes are directly measured; (ii) rapid: there are no requirements for staining or elaborate sample preparation; and (iii) unambiguous: an observed increase in DNA length upon addition of a ligand is definitive evidence for an intercalative mode-of-binding. Mode-of-binding, binding affinity, and site-exclusion number are readily determined from scanning force microscopy measurements of the changes in length of individual drug-DNA complexes as a function of drug concentration. With this assay, we resolve the ambiguity surrounding the mode of binding of 2,5-bis(4-amidinophenyl) furan (APF) to DNA and show that it binds to DNA by nonintercalative modes. APF is a member of an important class of aromatic dicationic drugs that show significant activity in the treatment of Pneumocystis carinii pneumonia, an opportunistic infection that is the leading cause of death in AIDS patients. Images Fig. 1 PMID:8901572

  18. Postmortem findings and opportunistic infections in HIV-positive patients from a public hospital in Peru

    PubMed Central

    Eza, Dominique; Cerrillo, Gustavo; Moore, David A.J.; Castro, Cecilia; Ticona, Eduardo; Morales, Domingo; Cabanillas, Jose; Barrantes, Fernando; Alfaro, Alejandro; Benavides, Alejandro; Rafael, Arturo; Valladares, Gilberto; Arevalo, Fernando; Evans, Carlton A.; Gilman, Robert H.

    2010-01-01

    There is a paucity of HIV autopsy data from South America and none that document the postmortem findings in patients with HIV/AIDS in Peru. The purpose of this autopsy study was to determine the spectrum of opportunistic infections and the causes of mortality in HIV-positive patients at a public hospital in Lima. Clinico-epidemiological information regarding HIV infection in Peru is also reviewed. Sixteen HIV-related hospital postmortems, performed between 1999 and 2004, were included in this retrospective analysis. The primary cause of death was established in 12 patients: one died of neoplasia and 11 of infectious diseases, including 3 from pulmonary infection, 7 from disseminated infection, and 2 from central nervous system infection (one case had dual pathology). Opportunistic infections were identified in 14 cases, comprising cytomegalovirus, histoplasmosis, cryptococcosis, toxoplasmosis, Pneumocystis pneumonia, aspergillosis, tuberculosis, varicella zoster virus, and cryptosporidiosis. Fourteen patients had at least one AIDS-related disease that had been neither clinically suspected nor diagnosed premortem. Moreover, 82% of the diagnoses considered to be of important clinical significance had not been suspected antemortem. The spectrum and frequency of certain opportunistic infections differed from other South American autopsy studies, highlighting the importance of performing HIV/AIDS postmortems in resource-limited countries where locally specific disease patterns may be observed. PMID:16979302

  19. Pyogranulomatous pleuropneumonia and mediastinitis in ferrets (Mustela putorius furo) associated with Pseudomonas luteola Infection.

    PubMed

    Martínez, J; Martorell, J; Abarca, M L; Olvera, A; Ramis, A; Woods, L; Cheville, N; Juan-Sallés, C; Moya, A; Riera, A; Soto, S

    2012-01-01

    Between 2008 and 2009, three pet ferrets from different sources presented with acute episode of dyspnoea. Cytological examination of pleural exudates revealed severe purulent inflammation with abundant clusters of rod-shaped microorganisms with a clear surrounding halo. Treatment was ineffective and the ferrets died 2-5 days later. Two ferrets were subjected to necropsy examination, which revealed pyothorax, mediastinal lymphadenopathy and multiple white nodules (1-2mm) in the lungs. Microscopical examination showed multifocal necrotizing-pyogranulomatous pleuropneumonia and lymphadenitis with aggregates of encapsulated microorganisms, some of which were positively stained by periodic acid-Schiff and alcian blue. In-situ hybridization for Pneumocystis spp., Ziehl-Neelsen staining and immunohistochemistry for distemper, coronavirus and influenza antigen were negative in all cases. Electron microscopically, the bacteria were 2-3 μm long with a thick electron-lucent capsule. Microbiology from one ferret yielded a pure culture of gram-negative bacteria identified phenotypically as Pseudomonas luteola. This speciation was later confirmed by 16S RNA gene amplification. PMID:21601873

  20. An estimate of the burden of serious fungal diseases in Greece.

    PubMed

    Gamaletsou, M N; Drogari-Apiranthitou, M; Denning, D W; Sipsas, N V

    2016-07-01

    Data on the epidemiology of serious fungal infections in Greece are scarce. Our aim was to calculate the burden of serious fungal diseases in Greece. A thorough literature search for papers reporting epidemiological data on serious fungal diseases in Greece was performed. Where no Greek data existed, we used a structured set of assumptions to estimate fungal disease burden, based on specific high-risk populations. Of the 10.8 million population, 85.5 % are adults and 27 % are over 60 years of age. The annual fungal disease estimates are as follows: 142,337 Greek women get recurrent vaginal thrush (2,632 cases/100,000 females); there are 889 cases of esophageal candidiasis (8.2 cases/100,000); annual incidence of Pneumocystis pneumonia is 112 cases; chronic pulmonary aspergillosis prevalence is 386 cases; there are 20,843 patients with allergic bronchopulmonary aspergillosis and 27,744 with severe asthma with fungal sensitization; candidaemia incidence is 541 cases (5.0/100,000); there are 81 cases of Candida peritonitis; invasive aspergillosis occurs in 1,125 patients. According to our calculations, 194,067 individuals (1.79 cases/100,000) in Greece suffer from serious fungal diseases each year. This is the first attempt to determine the burden of fungal diseases in Greece, and provides a crude estimate on its impact on public health. PMID:27086365

  1. Pilot trial of yttrium-90 ibritumomab tiuxetan consolidation following rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone chemotherapy in patients with limited-stage, bulky diffuse large B-cell lymphoma.

    PubMed

    Yang, Deok-Hwan; Kim, Won Seog; Kim, Seok Jin; Kim, Jin Seok; Kwak, Jae-Yong; Chung, Joo Seop; Oh, Sung Yong; Suh, Cheolwon; Lee, Je-Jung

    2012-05-01

    The clinical efficacy and safety of yttrium-90 ((90)Y)-ibritumomab tiuxetan consolidation treatment following rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) chemotherapy was investigated in patients with limited-stage and bulky diffuse large B-cell lymphoma (DLBCL). This prospective, multi-center, pilot trial included 21 patients who were newly diagnosed with stage I/II, bulky DLBCL and achieved a complete or partial response after six cycles of R-CHOP. The median size of bulky disease was 10.0 × 7.0 cm. After a median follow-up of 28.8 months, the overall response rate after (90)Y-ibritumomab tiuxetan consolidation treatment was 80.9%, including 4.8% partial response. However, six patients (28.6%) experienced a progression or relapse. The 3-year overall and progression-free survival rates were 85.0 ± 8.0% and 75.0 ± 9.7%, respectively. Grade 3-4 adverse events were mainly hematologic toxicities, such as thrombocytopenia (35%) and neutropenia (60%). One patient experienced grade 3 Pneumocystis carinii pneumonitis. Thus, (90)Y-ibritumomab tiuxetan consolidation following six cycles of R-CHOP resulted in an acceptable response with tolerable toxicity in patients with limited-stage and bulky DLBCL. PMID:22035417

  2. Infections Following Orthotopic Liver Transplantation

    PubMed Central

    Arnow, Paul M.

    1991-01-01

    The epidemiology of infections associated with orthotopic liver transplantation is summarized herein, and approaches to prophylaxis are outlined. Infection is a major complication following orthotopic liver transplantation, and more than half of transplant recipients develop at least one infection. The risk of infection is highest in the first month after transplantation, and the most common pathogens are bacteria and cytomegalovirus (CMV). Bacterial infections usually occur in the first month, arise in the abdomen, and are caused by aerobes. The peak incidence of CMV infection is late in the first month and early in the second month after transplantationn. CMV syndromes include fever and neutropenia, hepatitis, pneumonitis, gut ulceration, and disseminated infection. Other significant problems are Candida intraabdominal infection, Herpes simplex mucocutaneous infection or hepatitis, adenovirus hepatitis, and Pneumocystis carinii pneumonia. Prophylaxis of infection in liver transplant recipients has not been well-studied. Several different regimens of parenteral, oral absorbable, and/or oral non-absorbable antibiotics active against bacteria and yeast have been used at various centers, but no randomized controlled trials have been conducted. Selective bowel decontamination appears to be a promising approach to the prevention of bacterial and Candida infections, while oral acyclovir may be a relatively convenient and effective agent for CMV prophylaxis. PMID:1650245

  3. Dapsone induced acute photosensitivity dermatitis; a case report and review of literature.

    PubMed

    De, Dipankar; Dogra, Sunil; Kaur, Inderjit

    2007-12-01

    Dapsone is one of the main constituents of anti-leprosy treatment and has been in use for various dermatological and non-dermatological indications since the 1940s. Dapsone-induced photosensitivity is a rare complication. Only 11 cases seem to have been reported in the literature. We report a case of dapsone-induced photosensitivity in an Indian patient with leprosy, and briefly review the literature. Dapsone (diaminodiphenyl sulphone or DDS) is the most commonly used anti-leprosy drug since the 1940s. Apart from leprosy, it is used for various other infectious and non- infectious dermatoses as well as for prevention of Pneumocystis carinii pneumonia in HIV infected patients. It is one of the main constituents of multidrug therapy (MDT) in leprosy by virtue of its anti-mycobacterial properties. It acts by interference with folate metabolism. Because of its inhibitory effect in neutrophil chemotaxis and neutrophilic oxygen burst, it acts as a potent anti-inflammatory agent. Documented cutaneous adverse effects of dapsone include generalised maculopapular rash, exfoliative dermatitis, toxic epidermal necrolysis, erythema multiforme, erythema nodosum, pustular and acneiform skin eruptions. Photosensitivity dermatitis is a very rare side-effect of dapsone and to the best of our knowledge, only 11 cases have been reported in the literature to date. PMID:18309716

  4. Microbiological survey of mice (Mus musculus) purchased from commercial pet shops in Kanagawa and Tokyo, Japan

    PubMed Central

    HAYASHIMOTO, Nobuhito; MORITA, Hanako; ISHIDA, Tomoko; UCHIDA, Ritsuki; TANAKA, Mai; OZAWA, Midori; YASUDA, Masahiko; ITOH, Toshio

    2014-01-01

    Information regarding the prevalence of infectious agents in mice in pet shops in Japan is scarce. This information is particularly useful for minimizing the risk of potential transmission of infections to laboratory mice. Therefore, we surveyed infectious agents in mice from pet shops in Kanagawa and Tokyo, Japan. The survey was conducted in 28 mice from 5 pet shops to screen for 47 items (17 viruses, 22 bacteria and fungi, 10 parasites) using culture tests, serology, PCR, and microscopy. The most common viral agent detected was murine norovirus (17 mice; 60.7%), followed by Theiler’s murine encephalomyelitis virus (13 mice; 46.4%), and mouse hepatitis virus (12 mice; 42.8%). The most common agent amongst the bacteria and fungi was Pasteurella pneumotropica (10 mice; 35.7%), followed by Helicobacter ganmani and Pneumocystis murina (8 mice; 28.5%, for both). Tritrichomonas muris was the most common parasite (19 mice; 67.8%), followed by Spironucleus muris (13 mice; 46.4%), Aspiculuris tetraptera, and Syphacia obvelata (8 mice each; 28.5%). Remarkably, a zoonotic agent, Hymenolepis nana, was found in 7 mice (25%). Given these results, we suggest that the workers in laboratory animal facilities should recognize again the potential risks of mice outside of the laboratory animal facilities as an infectious source, and avoid keeping mice as pets or as feed for carnivorous reptiles as much as possible for risk management. PMID:25502736

  5. Diarylsulfones, a novel class of human immunodeficiency virus type 1 integrase inhibitors.

    PubMed Central

    Neamati, N; Mazumder, A; Zhao, H; Sunder, S; Burke, T R; Schultz, R J; Pommier, Y

    1997-01-01

    A majority of reported human immunodeficiency virus type 1 integrase (HIV-1 IN) inhibitors are polyhydroxylated aromatic compounds containing two phenyl rings separated by aliphatic or aromatic linkers. Most inhibitors possessing a catechol moiety exhibit considerable toxicity in cellular assays. In an effort to identify nonhydroxylated analogs, a series of aromatic sulfones were tested for their ability to inhibit the 3' processing and strand transfer steps that are necessary for HIV replication. Several aromatic sulfones have previously been shown to have moderate activity against HIV-1 reverse transcriptase in cellular assays; however, their inhibitory potencies against IN have not been explored. In the present study, the inhibitory effect of a series of sulfones and sulfonamides against IN was determined. Among 52 diaryl sulfones tested, 4 were determined to be highly potent (50% inhibitory concentration [IC50], 0.8 to 10 micrograms/ml), 5 had good potencies (IC50, 11 to 50 micrograms/ml), 10 showed moderate potencies (IC50, 51 to 100 micrograms/ml), and 33 were inactive (IC50, > 100 micrograms/ml) against IN. All of the active compounds exhibited similar potencies against HIV-2 IN. Sulfa drugs, used extensively in treating Pneumocystis carinii pneumonia, a leading cause of morbidity and mortality in AIDs patients, were also examined. Among 19 sulfonamides tested, sulfasalazine (IC50, 50 micrograms/ml) was the most potent. We conclude that potent inhibitors of IN can be designed based on the results presented in this study. PMID:9021196

  6. Aetiology of Pulmonary Symptoms in HIV-Infected Smear Negative Recurrent PTB Suspects in Kampala, Uganda: A Cross-Sectional Study

    PubMed Central

    Okwera, Alphonse; Bwanga, Freddie; Najjingo, Irene; Mulumba, Yusuf; Mafigiri, David K.; Whalen, Christopher C.; Joloba, Moses L.

    2013-01-01

    Introduction Previously treated TB patients with pulmonary symptoms are often considered recurrent TB suspects in the resource-limited settings, where investigations are limited to microscopy and chest x-ray. Category II anti-TB drugs may be inappropriate and may expose patients to pill burden, drug toxicities and drug-drug interactions. Objective To determine the causes of pulmonary symptoms in HIV-infected smear negative recurrent pulmonary tuberculosis suspects at Mulago Hospital, Kampala. Methods Between March 2008 and December 2011, induced sputum samples of 178 consented HIV-infected smear negative recurrent TB suspects in Kampala were subjected to MGIT and LJ cultures for mycobacteria at TB Reference Laboratory, Kampala. Processed sputum samples were also tested by PCR to detect 18S rRNA gene of P.jirovecii and cultured for other bacteria. Results Bacteria, M. tuberculosis and Pneumocystis jirovecii were detected in 27%, 18% and 6.7% of patients respectively and 53.4% of the specimens had no microorganisms. S. pneumoniae, M. catarrhalis and H. influenzae were 100% susceptible to chloramphenicol and erythromycin but co-trimoxazole resistant. Conclusion At least 81.5% of participants had no microbiologically-confirmed TB. However our findings call for thorough investigation of HIV-infected smear negative recurrent TB suspects to guide cost effective treatment. PMID:24312650

  7. Causes of death in renal transplant recipients: a study of 102 autopsies from 1968 to 1991.

    PubMed Central

    Reis, M A; Costa, R S; Ferraz, A S

    1995-01-01

    A study was conducted on 102 patients submitted to renal transplant who died and were autopsied at the University Hospital, Faculty of Medicine of Ribeirão Preto, Brazil, from 1968 to 1991. The cause of death, based on a review of medical records and autopsy reports, was assigned to one of the following categories: infectious (69.6%); cardiovascular (12.7%); gastrointestinal (7.8%); graft rejection (6.9%); tumoral (2.0%); and undetermined (1.0%). Among the 71 cases of death caused by infection, 28 (39.4%) showed disseminated agents involving two or more organs. Isolated pneumonia involved 17 patients (23.9%), followed by acute pyelonephritis in the transplanted kidney in 10 patients (14.1%). The most frequent agents were: bacteria (58.0%), divided into 'non-classified' (83.0%), Nocardia (10.6%) and Mycobacterium (6.4%); fungi (27.5%) represented by Cryptococcus (22.7%), Aspergillus, Candida and Pneumocystis carinii (18.1% each), Histoplasma (13.6%), Mucor and Paracoccidioides brasiliensis (4.5% each); viruses (6.2%) represented by Herpes simplex (60.0%); metazoa (5.0%, S. stercoralis), and protozoa (2.5%, T. cruzi). Cytomegalovirus (CMV) was identified in the lungs of 12 patients and was not directly correlated with death but was associated with other agents. In conclusion, immunodepressed patients such as renal transplant recipients should be carefully monitored for infection due to the high mortality rate. PMID:7884765

  8. The 13th International Workshops on Opportunistic Protists (IWOP13).

    PubMed

    Calderon, Enrique J; Cushion, Melanie T; Xiao, Lihua; Lorenzo-Morales, Jacob; Matos, Olga; Kaneshiro, Edna S; Weiss, Louis M

    2015-01-01

    The 13th International Workshops on Opportunistic Protists (IWOP-13) was held November 13-15, 2014 in Seville, Spain. The objectives of the IWOP meetings are to: (1) serve as a forum for exchange of new information among active researchers concerning the basic biology, molecular genetics, immunology, biochemistry, pathogenesis, drug development, therapy, and epidemiology of these immunodeficiency-associated pathogenic eukaryotic microorganisms that are seen in patients with AIDS and; (2) to foster the entry of new and young investigators into these underserved research areas. The IWOP meeting focuses on opportunistic protists; e.g. the free-living amoebae, Pneumocystis, Cryptosporidium, Toxoplasma, the Microsporidia, and kinetoplastid flagellates. This conference represents the major conference which brings together research groups working on these opportunistic pathogens. Progress has been achieved on understanding the biology of these pathogenic organisms, their involvement in disease causation in both immune deficient and immune competent hosts and is providing important insights into these emerging and reemerging pathogens. A continuing concern of the participants is the ongoing loss of scientific expertise and diversity in this research community. This decline is due to the small size of these research communities and an ongoing lack of understanding by the broader scientific community of the challenges and limitations faced by researchers working on these organisms, which makes these research communities very sensitive to declines in research funding. PMID:25923469

  9. Long-term outcomes to fludarabine and rituximab in Waldenström macroglobulinemia

    PubMed Central

    Branagan, Andrew R.; Ioakimidis, Leukothea; Soumerai, Jacob D.; Patterson, Christopher J.; Turnbull, Barry; Wasi, Parveen; Emmanouilides, Christos; Frankel, Stanley R.; Lister, Andrew; Morel, Pierre; Matous, Jeffrey; Gregory, Stephanie A.; Kimby, Eva

    2009-01-01

    We report the long-term outcome of a multicenter, prospective study examining fludarabine and rituximab in Waldenström macroglobulinemia (WM). WM patients with less than 2 prior therapies were eligible. Intended therapy consisted of 6 cycles (25 mg/m2 per day for 5 days) of fludarabine and 8 infusions (375 mg/m2 per week) of rituximab. A total of 43 patients were enrolled. Responses were: complete response (n = 2), very good partial response (n = 14), partial response (n = 21), and minor response (n = 4), for overall and major response rates of 95.3% and 86.0%, respectively. Median time to progression for all patients was 51.2 months and was longer for untreated patients (P = .017) and those achieving at least a very good partial response (P = .049). Grade 3 or higher toxicities included neutropenia (n = 27), thrombocytopenia (n = 7), and pneumonia (n = 6), including 2 patients who died of non–Pneumocystis carinii pneumonia. With a median follow-up of 40.3 months, we observed 3 cases of transformation to aggressive lymphoma and 3 cases of myelodysplastic syndrome/acute myeloid leukemia. The results of this study demonstrate that fludarabine and rituximab are highly active in WM, although short- and long-term toxicities need to be carefully weighed against other available treatment options. This study is registered at clinicaltrials.gov as NCT00020800. PMID:19015393

  10. Low absolute lymphocyte count and addition of rituximab confer high risk for interstitial pneumonia in patients with diffuse large B-cell lymphoma.

    PubMed

    Huang, Yu-Chung; Liu, Chia-Jen; Liu, Chun-Yu; Pai, Jih-Tung; Hong, Ying-Chung; Teng, Hao-Wei; Hsiao, Liang-Tsai; Chao, Ta-Chung; Gau, Jyh-Pyng; Liu, Jin-Hwang; Hsu, Hui-Chi; Chiou, Tzeon-Jye; Chen, Po-Min; Yu, Yuan-Bin; Tzeng, Cheng-Hwai

    2011-10-01

    Several small-scale studies have reported pulmonary toxicity among patients with diffuse large B-cell lymphoma (DLBCL) receiving rituximab-containing chemotherapy, though whether the use of rituximab predisposes to interstitial pneumonia (IP) remains unclear. This retrospective study was intended to identify the characteristics and risk factors of IP in patients with DLBCL. Between 2000 and 2009, 529 consecutive patients with DLBCL receiving first-line tri-weekly COP- or CHOP-based chemotherapy with or without rituximab were enrolled as subjects. IP was defined as diffuse pulmonary interstitial infiltrates found on computed tomography scans in conjunction with respiratory symptoms. IP was observed in 26 patients (4.9%), six of whom were confirmed with Pneumocystis jirovecii pneumonia. The median number of chemotherapy courses before IP was four cycles. Using multivariate analysis, absolute lymphocyte count less than 1×10(9)/l at diagnosis [odds ratio (OR) 2.75, p=0.014] and the addition of rituximab to chemotherapy (OR 4.56, p=0.003) were identified as independent risk factors for IP. In conclusion, the incidence of IP is increased in patients with DLBCL receiving rituximab-containing chemotherapy. Specific subgroups with lymphopenia at diagnosis may justify close scrutiny to detect pulmonary complications. PMID:21647583

  11. Parasite epigenetics and immune evasion: lessons from budding yeast

    PubMed Central

    2013-01-01

    The remarkable ability of many parasites to evade host immunity is the key to their success and pervasiveness. The immune evasion is directly linked to the silencing of the members of extended families of genes that encode for major parasite antigens. At any time only one of these genes is active. Infrequent switches to other members of the gene family help the parasites elude the immune system and cause prolonged maladies. For most pathogens, the detailed mechanisms of gene silencing and switching are poorly understood. On the other hand, studies in the budding yeast Saccharomyces cerevisiae have revealed similar mechanisms of gene repression and switching and have provided significant insights into the molecular basis of these phenomena. This information is becoming increasingly relevant to the genetics of the parasites. Here we summarize recent advances in parasite epigenetics and emphasize the similarities between S. cerevisiae and pathogens such as Plasmodium, Trypanosoma, Candida, and Pneumocystis. We also outline current challenges in the control and the treatment of the diseases caused by these parasites and link them to epigenetics and the wealth of knowledge acquired from budding yeast. PMID:24252437

  12. Extrapulmonary pneumocystosis.

    PubMed Central

    Ng, V L; Yajko, D M; Hadley, W K

    1997-01-01

    Extrapulmonary pneumocystosis is an exceedingly rare complication of Pneumocystis carinii pneumonia (PCP). Prior to the advent of the human immunodeficiency virus type 1 (HIV-1) epidemic, only 16 cases of extrapulmonary pneumocystosis in individuals who were immunocompromised by a variety of underlying diseases had been reported. Since the beginning of the HIV-1 and related PCP epidemic, at least 90 cases of extrapulmonary pneumocystosis have been reported. This review briefly presents a history of the discovery of P. carinii and its recognition as a human pathogen, the controversy regarding its taxonomy, and the epidemiology of this organism. A more detailed analysis of the incidence of extrapulmonary pneumocystosis in HIV-1-infected individuals and its occurrence despite widespread prophylaxis for PCP with either aerosolized pentamidine or systemic dapsone-trimethoprim is presented. The clinical features of published cases of extrapulmonary pneumocystosis in non-HIV-1-infected individuals are summarized and contrasted with those in HIV-1 infected individuals. The diagnosis of extrapulmonary pneumocystosis is discussed, and because clinical microbiologists and pathologists are the key individuals in establishing the diagnosis, the characteristic microscopic morphology of P. carinii as its appears when stained with a variety of stains is presented and reviewed. The review concludes with a brief discussion of treatments for extrapulmonary pneumocystosis. PMID:9227859

  13. Significant improvement following combination treatment with mefloquine and mirtazapine in a patient with progressive multifocal leukoencephalopathy after allogeneic peripheral blood stem cell transplantation.

    PubMed

    Yoshida, Hitoshi; Ohshima, Kenji; Toda, Jun; Kusakabe, Shinsuke; Masaie, Hiroaki; Yagi, Toshinari; Ishikawa, Jun

    2014-01-01

    We report a case of a 40-year-old female who developed progressive multifocal leukoencephalopathy (PML), which is associated with JC virus reactivation, after allogeneic hematopoietic cell transplantation. As she had been suffering from graft-versus-host disease and lung damage after pneumocystis pneumonia, the administration of calcineurin inhibitor and steroid could not be discontinued. However, she showed a favorable improvement in clinical symptoms and imaging findings after treatment with the anti-malarial drug, mefloquine and a serotonin receptor blocker, mirtazapine. Continuation of the treatment for eight months finally led to the clearance of the JC virus from her cerebrospinal fluid. She currently shows no neurological disturbance and has resumed her daily activities. PML due to the severe immunosuppressive condition has been reported as a fatal complication after allo-SCT. Our case suggests that combination treatment with mefloquine and mirtazapine may be of great value for the treatment for PML patients in the post allo-SCT setting, although it is difficult to say whether the combination treatment alone led to improvement. Further clinical study is needed to clarify the efficacy of these drugs for the treatment of PML. PMID:24264833

  14. Review of zoonotic parasites in medical and veterinary fields in the Republic of Korea.

    PubMed

    Youn, Heejeong

    2009-10-01

    Zoonotic parasites are animal parasites that can infect humans. The major zoonotic protozoa in the Republic of Korea are Babesia bovis, Chilomastix mesnili, Cryptosporidium parvum, Endolimax nana, Entamoeba coli, Entamoeba hitolytica, Giardia lamblia, Iodamoeba bütschlii, Pneumocystis carinii, Sarcocystis cruzi, and Toxoplasma gondii. The major zoonotic helminths in Korea include trematodes, cestodes, and nematodes. Trematodes are Clonorchis sinensis, Echinostoma hortense, Echinostoma spp., Fasciola hepatica, Heterophyes nocens, Metagonimus yokogawai, and Paragonimus westermani. Cestodes are Diphyllobothrium latum, Dipylidium caninum, Echinococcus granulosus, Hymenolepis nana, Raillietina tetragona, sparganum (Spirometra spp.), Taenia saginata, T. solium, and T. asiatica. Nematodes are Ancylostoma caninum, Brugia malayi, Capillaria hepatica, Dirofilaria immitis, Gnathostoma dololesi, Gnathostoma spinigerum, Loa loa, Onchocerca gibsoni, Strongyloides stercoralis, Thelazia callipaeda, Trichinella spiralis, Trichostrongylus orientalis, Trichuris trichiura, and Trichuris vulpis. The one arthropod is Sarcoptes scabiei. Many of these parasites have disappeared or were in decline after the 1990's. Since the late 1990's, the important zoonotic protozoa have been C. parvum, E. nana, E. coli, E. hitolytica, G. lamblia, I. buetschlii, P. carinii and T. gondii. The important zoonotic helminths have been C. sinensis, H. nocens, M. yokogawai, P. westermani, D. latum, T. asiatica, sparganum, B. malayi, T. orientalis, T. callipaeda and T. spiralis. However, outbreaks of these parasites are only in a few endemic areas. The outbreaks of Enterobius vermicularis and head lice, human parasites, have recently increased in the kindergartens and primary schools in the Republic of Korea. PMID:19885329

  15. The reversed halo sign: update and differential diagnosis.

    PubMed

    Godoy, M C B; Viswanathan, C; Marchiori, E; Truong, M T; Benveniste, M F; Rossi, S; Marom, E M

    2012-09-01

    The reversed halo sign is characterised by a central ground-glass opacity surrounded by denser air-space consolidation in the shape of a crescent or a ring. It was first described on high-resolution CT as being specific for cryptogenic organising pneumonia. Since then, the reversed halo sign has been reported in association with a wide range of pulmonary diseases, including invasive pulmonary fungal infections, paracoccidioidomycosis, pneumocystis pneumonia, tuberculosis, community-acquired pneumonia, lymphomatoid granulomatosis, Wegener granulomatosis, lipoid pneumonia and sarcoidosis. It is also seen in pulmonary neoplasms and infarction, and following radiation therapy and radiofrequency ablation of pulmonary malignancies. In this article, we present the spectrum of neoplastic and non-neoplastic diseases that may show the reversed halo sign and offer helpful clues for assisting in the differential diagnosis. By integrating the patient's clinical history with the presence of the reversed halo sign and other accompanying radiological findings, the radiologist should be able to narrow the differential diagnosis substantially, and may be able to provide a presumptive final diagnosis, which may obviate the need for biopsy in selected cases, especially in the immunosuppressed population. PMID:22553298

  16. A Rare Mechanism of Hyponatremia in HIV Disease

    PubMed Central

    Madariaga, Hector; Kumar, Aswini; Khanna, Apurv

    2015-01-01

    Patient: Male, 25 Final Diagnosis: Corticosteroid reistance Symptoms: Weakness Medication: — Clinical Procedure: Diagnosis Specialty: Nephrology Objective: Unusual clinical course Background: Hyponatremia is the most common disorder of body fluid and electrolyte balance in clinical practice. It is associated with increased morbidity, mortality, and length of hospital stay. Little is known about the relationship between hyponatremia and HIV disease. It is thought that hyponatremia in HIV is associated with a syndrome of inappropriate ADH secretion (SIADH), volume depletion, and adrenal insufficiency. Another common association is with Pneumocystis jirovecii (PCP). In early 1990s, there were several reports linking hyponatremia and HIV disease. It was found that these patients with acquired immune deficiency syndrome (AIDS) had abnormal adrenal cortical function. Additionally, these patients showed an abnormally elevated baseline cortisol level and a blunted response to cosyntropin. Case Report: Here, we present the case of an HIV patient presenting with hyponatremia and a physical examination suggestive of hypovolemia. Laboratory tests revealed urinary loss of sodium in the setting of normal serum cortisol level. The patient responded well to the administration of a mineralocorticoid hormone. Conclusions: Glucocorticoid resistance is an unusual cause of hyponatremia, and needs to be identified and treated accordingly. PMID:26436215

  17. Pentamidine analogs as inhibitors of [3H]MK-801 and [3H]ifenprodil binding to rat brain NMDA receptors

    PubMed Central

    Berger, Michael L.; Maciejewska, Dorota; Vanden Eynde, Jean Jacques; Mottamal, Madhusoodanan; Żabiński, Jerzy; Kaźmierczak, Paweł; Rezler, Mateusz; Jarak, Ivana; Piantanida, Ivo; Karminski-Zamola, Grace; Mayence, Annie; Rebernik, Patrick; Kumar, Arvind; Ismail, Mohamed A.; Boykin, David W.; Huang, Tien L.

    2016-01-01

    The anti-protozoal drug pentamidine is active against opportunistic Pneumocystis pneumonia, but in addition has several other biological targets, including the NMDA receptor (NR). Here we describe the inhibitory potencies of 76 pentamidine analogs at 2 binding sites of the NR, the channel binding site labeled with [3H]MK-801 and the [3H]ifenprodil binding site. Most analogs acted weaker at the ifenprodil than at the channel site. The spermine-sensitivity of NR inhibition by the majority of the compounds was reminiscent of other long-chain dicationic NR blockers. The potency of the parent compound as NR blocker was increased by modifying the heteroatoms in the bridge connecting the 2 benzamidine moieties and also by integrating the bridge into a seven-membered ring. Docking of the 45 most spermine-sensitive bisbenzamidines to a recently described acidic interface between the N-terminal domains of GluN1 and GluN2B mediating polyamine stimulation of the NR revealed the domain contributed by GluN1 as the most relevant target. PMID:26117647

  18. The burden of serious human fungal infections in Brazil.

    PubMed

    Giacomazzi, Juliana; Baethgen, Ludmila; Carneiro, Lilian C; Millington, Maria Adelaide; Denning, David W; Colombo, Arnaldo L; Pasqualotto, Alessandro C

    2016-03-01

    In Brazil, human fungal infections are prevalent, however, these conditions are not officially reportable diseases. To estimate the burden of serious fungal diseases in 1 year in Brazil, based on available data and published literature. Historical official data from fungal diseases were collected from Brazilian Unified Health System Informatics Department (DATASUS). For fungal diseases for which no official data were available, assumptions of frequencies were made by estimating based on published literature. The incidence (/1000) of hospital admissions for coccidioidomycosis was 7.12; for histoplasmosis, 2.19; and for paracoccidioidomycosis, 7.99. The estimated number of cryptococcal meningoencephalitis cases was 6832. Also, there were 4115 cases of Pneumocystis pneumonia in AIDS patients per year, 1 010 465 aspergillosis and 2 981 416 cases of serious Candida infections, including invasive and non-invasive diseases. In this study, we demonstrate that more than 3.8 million individuals in Brazil may be suffering from serious fungal infections, mostly patients with malignant cancers, transplant recipients, asthma, previous tuberculosis, HIV infection and those living in endemic areas for truly pathogenic fungi. The scientific community and the governmental agencies should work in close collaboration in order to reduce the burden of such complex, difficult-to-diagnose and hard to treat diseases. PMID:26691607

  19. Review of Zoonotic Parasites in Medical and Veterinary Fields in the Republic of Korea

    PubMed Central

    2009-01-01

    Zoonotic parasites are animal parasites that can infect humans. The major zoonotic protozoa in the Republic of Korea are Babesia bovis, Chilomastix mesnili, Cryptosporidium parvum, Endolimax nana, Entamoeba coli, Entamoeba hitolytica, Giardia lamblia, Iodamoeba bütschlii, Pneumocystis carinii, Sarcocystis cruzi, and Toxoplasma gondii. The major zoonotic helminths in Korea include trematodes, cestodes, and nematodes. Trematodes are Clonorchis sinensis, Echinostoma hortense, Echinostoma spp., Fasciola hepatica, Heterophyes nocens, Metagonimus yokogawai, and Paragonimus westermani. Cestodes are Diphyllobothrium latum, Dipylidium caninum, Echinococcus granulosus, Hymenolepis nana, Raillietina tetragona, sparganum (Spirometra spp.), Taenia saginata, T. solium, and T. asiatica. Nematodes are Ancylostoma caninum, Brugia malayi, Capillaria hepatica, Dirofilaria immitis, Gnathostoma dololesi, Gnathostoma spinigerum, Loa loa, Onchocerca gibsoni, Strongyloides stercoralis, Thelazia callipaeda, Trichinella spiralis, Trichostrongylus orientalis, Trichuris trichiura, and Trichuris vulpis. The one arthropod is Sarcoptes scabiei. Many of these parasites have disappeared or were in decline after the 1990's. Since the late 1990's, the important zoonotic protozoa have been C. parvum, E. nana, E. coli, E. hitolytica, G. lamblia, I. buetschlii, P. carinii and T. gondii. The important zoonotic helminths have been C. sinensis, H. nocens, M. yokogawai, P. westermani, D. latum, T. asiatica, sparganum, B. malayi, T. orientalis, T. callipaeda and T. spiralis. However, outbreaks of these parasites are only in a few endemic areas. The outbreaks of Enterobius vermicularis and head lice, human parasites, have recently increased in the kindergartens and primary schools in the Republic of Korea. PMID:19885329

  20. Burden of serious fungal infections in Belgium.

    PubMed

    Lagrou, Katrien; Maertens, Johan; Van Even, Ellen; Denning, David W

    2015-10-01

    We aimed to estimate the total number of serious fungal infections occurring yearly in Belgium. The number of cryptococcal infections was retrieved from the National Reference Center for Mycosis. Populations at risk and fungal infections frequencies in these populations were used to estimate incidence or prevalence of other fungal infections. The Belgian population consists of 11.10 million people. Cryptococcal meningitis is rare. In all, 15 of the 1227 newly diagnosed HIV/AIDS cases presented with Pneumocystis jirovecii pneumonia. This accounts for ±14% of total PCP cases (n = 120). The incidence of candidaemia is estimated as 5/100,000 resulting in 555 cases and 213 deaths. A total number of 675 invasive aspergillosis cases and ≥169 deaths attributed to this infection were calculated. Chronic pulmonary aspergillosis is estimated to be prevalent in 662 cases. Allergic bronchopulmonary aspergillosis cases were estimated to be 23,119 applying a 2.5% and 15% rate in adult asthma and cystic fibrosis patients respectively. Severe asthma with fungal sensitisation cases was estimated to be 30,402. There were 174,760 women with recurrent Candida vaginitis assuming a 6% rate in women aged between 15 and 50. Approximately 233,000 people of the Belgian population (2.1%) are estimated to suffer from a fungal infection on a yearly basis. PMID:26449500

  1. [Associated infections in acute bronchopulmonary infections in children].

    PubMed

    Lykova, E A; Vorob'ev, A A; Bokovoĭ, A G; Karazhas, N V; Evseeva, L F

    2003-01-01

    A total of 189 children with bacterial complications of the acute respiratory viral infection (ARVI)--primarily with pneumonia and bronchitis--were dynamically examined for typical and atypical pneumotropic causative agents of the infection process (Mycoplasma pneumoniae, Chlamydia spp., Streptococcus pneumoniae, Haemophilus influenzae, Pneumocystis carini, and Citomegalovirus). A high frequency rate of the associative infection involving mycoplasmas and pneumocysts was registered (45-50%); it was lower in the cases involving Chlamydias, hemophilic bacteria, pneumococcus, and cytomegalovirus--up to 25-30%. No sharp difference was found between the indices of an infection degree and those of an active clinical infectious process involving the same pneumotropic agent: the biggest difference was observed in Chlamydia infections (9.4%) and the lowest one--in mycoplasma infections (3%). A dynamic comparison of different classes of immunoglobulins revealed that, in acute bronchitis and pneumonias, the Chlamydia and cytomegalovirus infections are, primarily, of the persistent nature; the hemophilic and pneumocystic infections are of a mixed nature; and the pneumococcus one is of the acute nature. The Mycoplasma infection, which is more often encountered in pre-school children, is of the primary type with a trend towards a prolonged clinical course. All pneumonias had a typical clinical course; the clinical picture was compared in 128 patients with the etiological factor (including a description of characteristic symptoms). PMID:12861708

  2. Refractory kaposiform hemangioendothelioma that expressed vascular endothelial growth factor receptor (VEGFR)-2 and VEGFR-3: a case report.

    PubMed

    Saito, Mari; Gunji, Yuji; Kashii, Yoshifumi; Odaka, Jun; Yamauchi, Tadahiko; Kanai, Nobuyuki; Momoi, Mariko Y

    2009-03-01

    This report describes the case of a 10-month-old boy who was diagnosed to have kaposiform hemangioendothelioma (KHE) with Kasabach-Merritt syndrome (KMS), which is a rare pediatric vascular tumor with a high mortality rate. Although both KHE with KMS were resistant to various therapies, such as oral prednisolone, sclerotherapy, and chemotherapy, repeated radiation therapy with methylprednisolone pulse therapy did reduce the volume of KHE and improved the symptoms of KMS. Unfortunately, a regrowth of KHE with KMS was observed 4 months after the cessation of treatment and the patient thereafter died from an intracranial hemorrhage and Pneumocystis carinii pneumonia, which is a complication related to repetitive radiation and steroid therapy. A histopathologic examination of autopsy specimens confirmed a diagnosis of KHE and immunohistologic staining was positive for vascular endothelial growth factor receptor (VEGFR)-2 and VEGFR-3. These findings may provide the rationale to further investigate the role of VEGFRs in the pathogenesis of KHE and also to elucidate its prognostic value, along with the application of inhibitors for VEGFRs for the treatment of refractory KHE. PMID:19262246

  3. Kinetic characterization of the first step of the ribozyme-catalyzed trans excision-splicing reaction.

    PubMed

    Dotson, P Patrick; Sinha, Joy; Testa, Stephen M

    2008-06-01

    Group I introns catalyze the self-splicing reaction, and their derived ribozymes are frequently used as model systems for the study of RNA folding and catalysis, as well as for the development of non-native catalytic reactions. Utilizing a group I intron-derived ribozyme from Pneumocystis carinii, we previously reported a non-native reaction termed trans excision-splicing (TES). In this reaction, an internal segment of RNA is excised from an RNA substrate, resulting in the covalent reattachment of the flanking regions. TES proceeds through two consecutive phosphotransesterification reactions, which are similar to the reaction steps of self-splicing. One key difference is that TES utilizes the 3'-terminal guanosine of the ribozyme as the first-step nucleophile, whereas self-splicing utilizes an exogenous guanosine. To further aid in our understanding of ribozyme reactions, a kinetic framework for the first reaction step (substrate cleavage) was established. The results demonstrate that the substrate binds to the ribozyme at a rate expected for simple helix formation. In addition, the rate constant for the first step of the TES reaction is more than one order of magnitude lower than the analogous step in self-splicing. Results also suggest that a conformational change, likely similar to that in self-splicing, exists between the two reaction steps of TES. Finally, multiple turnover is curtailed because dissociation of the cleavage product is slower than the rate of chemistry. PMID:18479464

  4. Correlation of Parasite Load Determined by Quantitative PCR to Clinical Outcome in a Heart Transplant Patient with Disseminated Toxoplasmosis▿

    PubMed Central

    Patrat-Delon, Solène; Gangneux, Jean-Pierre; Lavoué, Sylvain; Lelong, Bernard; Guiguen, Claude; le Tulzo, Yves; Robert-Gangneux, Florence

    2010-01-01

    Disseminated toxoplasmosis is a life-threatening infection in transplant recipients, which results either from reactivation of latent infection or from organ-transmitted primary infection. Preventive measures and diagnostic screening methods differ between countries and are related to the seroprevalence of Toxoplasma spp. in the general population. Here we report a case of disseminated toxoplasmosis in a heart transplant recipient with previous immunity that occurred after cotrimoxazole prophylaxis for the prevention of Pneumocystis jirovecii pneumonia was stopped. Quantitative PCR proved useful for the diagnosis and monitoring of Toxoplasma infection. Decreasing parasitic burdens in sequential samples of cerebrospinal fluid, blood, and bronchoalveolar lavage fluid correlated with a favorable outcome and allowed modulation of the immunosuppressive drug regimen. The duration of anti-Toxoplasma treatment and the need for maintenance prophylaxis are discussed, as well as prophylaxis for solid-organ transplant recipients. Although a rare event in heart transplant recipients, Toxoplasma reactivation must be investigated promptly, since early treatment improves the prognosis. PMID:20463167

  5. Linear plasmid vector for cloning of repetitive or unstable sequences in Escherichia coli.

    PubMed

    Godiska, Ronald; Mead, David; Dhodda, Vinay; Wu, Chengcang; Hochstein, Rebecca; Karsi, Attila; Usdin, Karen; Entezam, Ali; Ravin, Nikolai

    2010-04-01

    Despite recent advances in sequencing, complete finishing of large genomes and analysis of novel proteins they encode typically require cloning of specific regions. However, many of these fragments are extremely difficult to clone in current vectors. Superhelical stress in circular plasmids can generate secondary structures that are substrates for deletion, particularly in regions that contain numerous tandem or inverted repeats. Common vectors also induce transcription and translation of inserted fragments, which can select against recombinant clones containing open reading frames or repetitive DNA. Conversely, transcription from cloned promoters can interfere with plasmid stability. We have therefore developed a novel Escherichia coli cloning vector (termed 'pJAZZ' vector) that is maintained as a linear plasmid. Further, it contains transcriptional terminators on both sides of the cloning site to minimize transcriptional interference between vector and insert. We show that this vector stably maintains a variety of inserts that were unclonable in conventional plasmids. These targets include short nucleotide repeats, such as those of the expanded Fragile X locus, and large AT-rich inserts, such as 20-kb segments of genomic DNA from Pneumocystis, Plasmodium, Oxytricha or Tetrahymena. The pJAZZ vector shows decreased size bias in cloning, allowing more uniform representation of larger fragments in libraries. PMID:20040575

  6. Successful Treatment of Life-Threatening Interstitial Lung Disease Secondary to Antisynthetase Syndrome Using Rituximab: A Case Report and Review of the Literature.

    PubMed

    Dasa, Osama; Ruzieh, Mohammed; Oraibi, Omar

    2016-01-01

    We are presenting a case of antisynthetase syndrome (ASS) that manifested with severe interstitial pneumonitis in the presence of anti-Jo-1 and Ro (SSA) antibodies. Our patient developed respiratory failure with high oxygen requirements despite treatment by high-dose steroids. The patient was then treated with rituximab. This treatment led to significant improvement in the patient condition, with resolution of the ground glass opacities on high-resolution computerized tomography and near normalization of pulmonary function tests. In this communication, we performed a literature review and summarized previous reports pertinent to using of rituximab to treat interstitial lung disease (ILD) secondary to ASS by searching the PubMed database from 1980 to 2014. We were able to find 14 reports that included total of 45 patients with ILD secondary to ASS. A significant improvement in ILD was reported in the majority of reported patients who received rituximab, while there was only 1 mortality-related to Pneumocystis jirovecii pneumonia. Rituximab treatment was tolerated well in the majority of cases. It is our conclusion that rituximab can be considered a therapeutic option in ILD secondary to ASS based on our experience with this case and the currently available evidence in the literature. Nevertheless, there is a need for additional controlled studies to assess the efficacy and safety of rituximab in ILD secondary to ASS compared with other immunosuppressive regimens. PMID:25830868

  7. Tobacco use and cessation in HIV-infected individuals

    PubMed Central

    Wewers, Mary Ellen; Ferketich, Amy; Diaz, Philip

    2013-01-01

    Synopsis The smoking prevalence estimates among HIV-infected individuals range from 40%-84%; much higher than the overall adult prevalence in the United States. Characteristics that are associated with smokers who are HIV-positive include drug and alcohol abuse, psychiatric comorbidities, and lower education and socioeconomic status. There are important health implications for HIV-infected smokers, including bacterial and Pneumocystis pneumonia, tuberculosis, COPD, lung cancer and coronary artery disease. To date, there have been few tobacco dependence treatment trials conducted among HIV-infected smokers. Most have used nicotine replacement therapy but abstinence rates were low. A recent preliminary study found the use of varenicline to be well tolerated and it may increase abstinence rates with HIV-infected individuals. Recommendations for future research include examining underlying factors that contribute to persistent smoking and barriers to abstinence, identifying ways to increase motivation for quit attempts, increasing the number of multi-centered, two-arm tobacco dependence treatment trials, and using highly efficacious first-line pharmacotherapy in tobacco dependence treatment intervention studies. Addressing the above-mentioned research gaps will help to reduce the tobacco-related disease burden of HIV-infected individuals in the future. PMID:23702169

  8. Disseminated histoplasmosis in an HIV patient with CD4 count of 1 cell/µL

    PubMed Central

    Tella, Sri Harsha; Abuzaid, Ahmed

    2014-01-01

    We report a case of a young woman with advanced HIV/AIDS who presented with a short duration of fever and shortness of breath, with no recent travel history or previous hospitalisation, accompanied by non-specific abdominal symptoms and suspicious upper gastrointestinal bleed. Her CD4 count was 1 cell/μL raising the suspicious for various opportunistic aetiologies. The initial suspicion was for pneumocystis pneumonia (PCP) and the patient was treated empirically with antimicrobials. Peripheral smear findings, urinary antigen tests and bronchoalveolar lavage (BAL) were suggestive of disseminated histoplasmosis. PCP was ruled out in BAL. Transabdominal imaging was concerning for periaortic lymphadenopathy raising the suspicion of occult malignancy. Endoscopic evaluation of her digestive tract was unrevealing. Endoscopic ultrasound fine-needle aspiration (EUS-FNA) confirmed histoplasmosis. She received a liposomal amphotericin B for 10 days followed by itraconazole with significant improvement. Her CD4 count was found to be the lowest reported count with a single opportunistic pathogen. PMID:25139916

  9. Assignment of the human macrophage mannose receptor gene (MRC1) to 10p13 by in situ hybridization and PCR-based somatic cell hybrid mapping

    SciTech Connect

    Eichbaum, Q.; Clerc, P.; Bruns, G.

    1994-08-01

    Tissue macrophages form a latticework beneath epithelial surfaces and play a pivotal role in first line host defense. The macrophage mannose receptor is highly expressed on these terminally differentiated cells, but is not expressed on circulating monocytes. Although originally defined as an endocytic receptor, the predominant physiological role for this 170-kDa transmembrane protein appears to be phagocytosis of microorganisms, such as Candida albicans and Pneumocystis carinii. The characterization of cDNAs that encode the human and mouse mannose receptors reveals that the ectodomain contains a cysteine-rich NH{sub 2} domain that appears to resemble the b subunit of ricin D. This domain is followed by a fibronectin type 2 domain. A tandem array of eight carbohydrate recognition domains bear approximately 30% homology to one another. A short hydrophobic region is followed by a 45-amino-acid cytoplasmic tail. Comparison of the human and mouse encoded proteins reveals an average homology of 80%. Of interest is the fact that the murine and human genes both span about 70 kb that contains 30 exons interrupted by 29 introns. The position of the introns and the size of the exons are identical in the mouse and human genes. 15 refs., 2 figs.

  10. Infections in solid-organ transplant recipients.

    PubMed Central

    Patel, R; Paya, C V

    1997-01-01

    Solid-organ transplantation is a therapeutic option for many human diseases. Infections are a major complication of solid-organ transplantation. All candidates should undergo a thorough infectious-disease screening prior to transplantation. There are three time frames, influenced by surgical factors, the level of immunosuppression, and environmental exposures, during which infections of specific types most frequently occur posttransplantation. Most infections during the first month are related to surgical complications. Opportunistic infections typically occur from the second to the sixth month. During the late posttransplant period (beyond 6 months), transplantation recipients suffer from the same infections seen in the general community. Opportunistic bacterial infections seen in transplant recipients include those caused by Legionella spp., Nocardia spp., Salmonella spp., and Listeria monocytogenes. Cytomegalovirus is the most common cause of viral infections. Herpes simplex virus, varicella-zoster virus, Epstein-Barr virus and others are also significant pathogens. Fungal infections, caused by both yeasts and mycelial fungi, are associated with the highest mortality rates. Mycobacterial, pneumocystis, and parasitic diseases may also occur. PMID:8993860

  11. sup 111 In-labeled nonspecific immunoglobulin scanning in the detection of focal infection

    SciTech Connect

    Rubin, R.H.; Fischman, A.J.; Callahan, R.J.; Khaw, B.A.; Keech, F.; Ahmad, M.; Wilkinson, R.; Strauss, H.W. )

    1989-10-05

    We performed radionuclide scanning after the intravenous injection of human IgG labeled with indium-111 in 128 patients with suspected focal sites of inflammation. Localization of 111In-labeled IgG correlated with clinical findings in 51 infected patients (21 with abdominal or pelvic infections, 11 with intravascular infections, 7 with pulmonary infections, and 12 with skeletal infections). Infecting organisms included gram-positive bacteria, gram-negative bacteria, Pneumocystis carinii, Mycoplasma pneumoniae, and Candida albicans. No focal localization of 111In-labeled IgG was observed in 63 patients without infection. There were five false negative results, and nine results were unusable. Serial scans were carried out in eight patients: continued localization correctly predicted relapse in six, and the absence of localization indicated resolution in two. To determine whether 111In-labeled IgG localization was specific for inflammation, we studied 16 patients with cancer. Focal localization occurred in 13 of these patients (5 with melanomas, 5 with gynecologic cancers, and 1 each with lymphoma, prostate cancer, and malignant fibrous histiocytoma). No localization was seen in patients with renal or colon cancer or metastatic medullary carcinoma of the thyroid. We conclude that 111In-labeled IgG imaging is effective for the detection of focal infection and that serial scans may be useful in assessing therapeutic efficacy. This technique may also be helpful in the evaluation of certain cancers.

  12. Proceedings of the 2013 National Toxicology Program Satellite Symposium

    PubMed Central

    Elmore, Susan A.; Boyle, Michael C.; Boyle, Molly H.; Cora, Michelle C.; Crabbs, Torrie A.; Cummings, Connie A.; Gruebbel, Margarita M.; Johnson, Crystal L.; Malarkey, David E.; McInnes, Elizabeth F.; Nolte, Thomas; Shackelford, Cynthia C.; Ward, Jerrold M.

    2014-01-01

    The 2013 annual National Toxicology Program (NTP) Satellite Symposium, entitled “Pathology Potpourri” was held in Portland, Oregon in advance of the Society of Toxicologic Pathology's 32nd annual meeting. The goal of the NTP Symposium is to present current diagnostic pathology or nomenclature issues to the toxicologic pathology community. This article presents summaries of the speakers' presentations, including diagnostic or nomenclature issues that were presented, along with select images that were used for audience voting and discussion. Some lesions and topics covered during the symposium included a caudal tail vertebra duplication in mice; nephroblastematosis in rats; ectopic C cell tumor in a hamster; granular cell aggregates/tumor in the uterus of a hamster; Pneumocystis carinii in the lung of a rat; iatrogenic chronic inflammation in the lungs of control rats; hepatoblastoma arising within an adenoma in a mouse; humoral hypercalcemia of benignancy in a transgenic mouse; acetaminophen induced hepatoxicity in rats; electron microscopy images of iatrogenic intraerythrocytic inclusions in transgenic mice; questionable hepatocellular degeneration/cell death/artifact in rats; atypical endometrial hyperplasia in rats; malignant mixed Müllerian tumors/carcinosarcomas in rats; differential diagnoses of proliferative lesions the intestine of rodents; and finally obstructive nephropathy caused by melamine poisoning in a rat. PMID:24334674

  13. Lung parasites of shrews from Pennsylvania.

    PubMed

    Laakkonen, J; Haukisalmi, V; Merritt, J F

    1997-04-01

    We examined lung parasites of three species of soricids, Sorex cinereus (n = 58), Sorex fumeus (n = 23) and Blarina brevicauda (n = 45) collected from Pennsylvania (USA), from 1990 to 1995. Yeast-like cells of Hisfoplasma capsulatum var. capsulatum were found in lung sections stained with Grocott's modification of Gomori's methenamine silver, periodic acid-Schiff, Giemsa, and hematoxylin-eosin in two (3%) S. cinereus, eight (35%) S. fumeus and two (4%) B. brevicauda. The number of spores of H. capsulatum in the lungs was low and no inflammatory reaction was evident. The infection was not disseminated to other organs. This is the first report of H. capsulatum infection in any species of shrews of the genus Sorex and the prevalence in S. fumeus was remarkably high compared to those reported for other wild mammals. A nematode, possibly Angiostrongylus michiganensis, was found in the lungs of one S. fumeus on necropsy and in a stained lung section of one S. cinereus. In both cases the host was also infected with the fungus. Pneumocystis carinii, which is the most common lung parasite in Sorex araneus (the numerically dominant Eurasian species of shrew), was not found in any of the North American species of shrew examined in this study. PMID:9131560

  14. Terms used by nurses to describe patient problems: can SNOMED III represent nursing concepts in the patient record?

    PubMed Central

    Henry, S B; Holzemer, W L; Reilly, C A; Campbell, K E

    1994-01-01

    OBJECTIVE: To analyze the terms used by nurses in a variety of data sources and to test the feasibility of using SNOMED III to represent nursing terms. DESIGN: Prospective research design with manual matching of terms to the SNOMED III vocabulary. MEASUREMENTS: The terms used by nurses to describe patient problems during 485 episodes of care for 201 patients hospitalized for Pneumocystis carinii pneumonia were identified. Problems from four data sources (nurse interview, intershift report, nursing care plan, and nurse progress note/flowsheet) were classified based on the substantive area of the problem and on the terminology used to describe the problem. A test subset of the 25 most frequently used terms from the two written data sources (nursing care plan and nurse progress note/flowsheet) were manually matched to SNOMED III terms to test the feasibility of using that existing vocabulary to represent nursing terms. RESULTS: Nurses most frequently described patient problems as signs/symptoms in the verbal nurse interview and intershift report. In the written data sources, problems were recorded as North American Nursing Diagnosis Association (NANDA) terms and signs/symptoms with similar frequencies. Of the nursing terms in the test subset, 69% were represented using one or more SNOMED III terms. PMID:7719788

  15. [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

  16. THE PATIENT-DOCTOR-PSYCHOLOGIST TRIANGLE IN A CASE Of SEVERE IMUNOSUPRESSION IN THE HIV INFECTION.

    PubMed

    Manciuc, Carmen; Filip-Ciubotaru, Florina; Badescu, Aida; Duceag, Letiţia Doina; Largu, Alexandra Maria

    2016-01-01

    In the last two years the Romanian adult population infected with the human immunodeficiency virus (HIV) has increased due to sexual transmission, both heterosexual and homosexual. The case presented is that of a 33 year-old man, admitted to the Infectious Diseases Hospital in Iasi with acute respiratory failure and a confirmation of Kaposi's sarcoma. Tests later proved positive for HIV, the patient being included in the stage AIDS C3 (acute immunodeficiency syndrome). The respiratory failure was suspected to be caused by Pneumocystis carinii and cotrimoxazol therapy, oxygen therapy and anti-retroviral therapy were established. He was also referred to the oncology hospital for treatment of Kaposi's sarcoma. The patient's adherence to therapy was influenced by a strong doctor-patient relationship, as well as by psychological counseling and support. Creating a functional doctor-patient-psychologist team is key throughout the HIV-positive patient's existence, for supporting long term adherence to therapy and acceptance of the diagnosis. This case highlights the need for a strong psychosocial compartment in every medical center that deals with HIV-infected individuals. PMID:27125083

  17. Review: Chemical and structural modifications of pulmonary collectins and their functional consequences.

    PubMed

    Atochina-Vasserman, Elena N; Beers, Michael F; Gow, Andrew J

    2010-06-01

    The lung is continuously exposed to inhaled pathogens (toxic pollutants, micro-organisms, environmental antigens, allergens) from the external environment. In the broncho-alveolar space, the critical balance between a measured protective response against harmful pathogens and an inappropriate inflammatory response to harmless particles is discerned by the innate pulmonary immune system. Among its many components, the surfactant proteins and specifically the pulmonary collectins (surfactant proteins A [SP-A] and D [SP-D]) appear to provide important contributions to the modulation of host defense and inflammation in the lung. Many studies have shown that multimerization of SP-A and SP-D are important for efficient local host defense including neutralization and opsonization of influenza A virus, binding Pneumocystis murina and inhibition of LPS-induced inflammatory cell responses. These observations strongly imply that oligomerization of collectins is a critical feature of its function. However, during the inflammatory state, despite normal pool sizes, chemical modification of collectins can result in alteration of their structure and function. Both pulmonary collectins can be altered through proteolytic inactivation, nitration, S-nitrosylation, oxidation and/or crosslinking as a consequence of the inflammatory milieu facilitated by cytokines, nitric oxide, proteases, and other chemical mediators released by inflammatory cells. Thus, this review will summarize recent developments in our understanding of the relationship between post-translational assembly of collectins and their modification by inflammation as an important molecular switch for the regulation of local innate host defense. PMID:20423921

  18. The natural history of human immunodeficiency virus infection: a five year study in a London cohort of homosexual men.

    PubMed Central

    Kelly, G E; Stanley, B S; Weller, I V

    1990-01-01

    Progression rates from asymptomatic to symptomatic Human Immunodeficiency Virus (HIV) infection according to the CDC classification were prospectively studied in a cohort of 172 seropositive homosexual and bisexual men. The median follow-up time was 4 years. The progression from data of entry to the study to any group IV disease was 56% (SE 7%) at 5 years. However, the progression from an estimated date of seroconversion to any group IV disease was 36% (SE 4%) at 5 years. This was more than double the progression rate to AIDS-14% (SE 3%) at 5 years calculated in the same way. There were no differences in progression to AIDS from group IV A (systemic symptoms such as unexplained fever, weight loss or persistent diarrhoea) and group IV C-2 (oral candida or oral hairy leukoplakia). Progression rates to AIDS were significantly lower (p = 0.02) in patients who were under 25 years of age at entry than in those over 25. A review of progression rates to AIDS among homosexual cohorts shows that they tend to be higher than in cohorts of haemophiliac patients, in the early stage of infection. However, when Pneumocystis carinii pneumonia is the outcome measure, progression rates in all studies are remarkably similar. PMID:2133371

  19. Detection of abnormalities in febrile AIDS patients with In-111-labeled leukocyte and Ga-67 scintigraphy

    SciTech Connect

    Fineman, D.S.; Palestro, C.J.; Kim, C.K.; Needle, L.B.; Vallabhajosula, S.; Solomon, R.W.; Goldsmith, S.J.

    1989-03-01

    Thirty-six patients with acquired immunodeficiency syndrome (AIDS), who were febrile but without localizing signs, underwent indium-111 leukocyte scintigraphy 24 hours after injection of labeled white blood cells (WBCs) and were restudied 48 hours after injection of gallium-67 citrate. Fifty-six abnormalities were identified as possible sources of the fever; 27 were confirmed with biopsy. Of these 27, 15 were identified only on In-111 WBC scans (including colitis, sinusitis, and focal bacterial pneumonia); six, only on Ga-67 scans (predominantly Pneumocystis carinii pneumonia and lymphadenopathy); and six, on both studies (predominantly pulmonary lesions). In-111 WBC scanning revealed 21 of 27 abnormalities (78%) and gallium scanning, 12 of 27 (44%). If only one scintigraphic study has been performed, particularly with Ga-67, a significant number of lesions would not have been detected. The authors believe radionuclide evaluation of the febrile AIDS patient without localizing signs should begin with In-111 WBC scintigraphy. Gallium scanning may be used depending on results of In-111 WBC scans or if there is a high index of suspicion for P carinii pneumonia.

  20. Diagnostic implications of Ga-67 chest-scan patterns in human immunodeficiency virus-seropositive patients

    SciTech Connect

    Kramer, E.L.; Sanger, J.H.; Garay, S.M.; Grossman, R.J.; Tiu, S.; Banner, H.

    1989-03-01

    Consecutive gallium-67 scans (n = 237) of 180 human immunodeficiency virus-seropositive patients with suspected pulmonary infections were evaluated for intensity and pattern of gallium distribution. Scan findings were correlated with the history, chest radiographic findings, and clinicopathologic diagnoses. Pneumocystis carinii pneumonia (PCP) occurred significantly more often with heterogeneous diffuse uptake than with homogeneous diffuse uptake. Heterogeneous diffuse uptake had an 87% positive predictive value for PCP, which was higher than that of other patterns. Localized pulmonary uptake was most commonly due to bacterial pneumonia or PCP; ill-defined, perihilar uptake, to cytomegalovirus or PCP; and focal (lymph node) uptake, to tuberculosis or lymphoma. The positive predictive value of any pulmonary uptake for lung pathology was 93%, and the negative predictive value of a negative scan was 96%. These findings confirm the utility of gallium scanning in the detection of lung pathology related to acquired immunodeficiency syndrome, particularly PCP. Furthermore, identification of a diffuse pattern may permit the use of a less invasive test more specifically directed at the confirmation of a diagnosis of PCP.

  1. Outpatient supportive therapy after induction to remission therapy in adult acute myelogenous leukaemia (AML) is feasible: a multicentre study.

    PubMed

    Ruiz-Argüelles, G J; Apreza-Molina, M G; Alemán-Hoey, D D; Gómez-Almaguer, D; Marín-López, A; Mercado-Díaz, L

    1995-01-01

    Twenty-four adult patients with AML were treated with standard "7 + 3" chemotherapy. After administering the myeloablative drugs in the hospital, patients were instructed to continue their supportive treatment on an outpatient basis; they received ciprofloxacin, cotrimoxasole and itraconazole vo until the absolute granulocyte count rose above 1 x 10(9)/l. Platelet concentrates were given every other day until the platelet count rose above 20 x 10(9)/l. Complete remission (CR) was obtained in 87%. Fever developed in 29% and 2 cases were complicated by indwelling-catheter-related Pseudomona aeruginosa septicaemia, 1 Entamoeba hystolytica enteritis and 1 Pneumocystis carinii pneumonia; these patients were hospitalized to treat these infections specifically. In no case was the infection fatal. The median disease free-survival (DFS) was 17 months, 12-month DFS was 66%, and 30-month DFS was 17%. Our calculations have shown that 1700 USD/patient were saved by avoiding prolonged hospitalization; this may provide not only economical, but also psychological advantages to patients. PMID:7859871

  2. DNA Double-Strand Breaks and Telomeres Play Important Roles in Trypanosoma brucei Antigenic Variation

    PubMed Central

    2015-01-01

    Human-infecting microbial pathogens all face a serious problem of elimination by the host immune response. Antigenic variation is an effective immune evasion mechanism where the pathogen regularly switches its major surface antigen. In many cases, the major surface antigen is encoded by genes from the same gene family, and its expression is strictly monoallelic. Among pathogens that undergo antigenic variation, Trypanosoma brucei (a kinetoplastid), which causes human African trypanosomiasis, Plasmodium falciparum (an apicomplexan), which causes malaria, Pneumocystis jirovecii (a fungus), which causes pneumonia, and Borrelia burgdorferi (a bacterium), which causes Lyme disease, also express their major surface antigens from loci next to the telomere. Except for Plasmodium, DNA recombination-mediated gene conversion is a major pathway for surface antigen switching in these pathogens. In the last decade, more sophisticated molecular and genetic tools have been developed in T. brucei, and our knowledge of functions of DNA recombination in antigenic variation has been greatly advanced. VSG is the major surface antigen in T. brucei. In subtelomeric VSG expression sites (ESs), VSG genes invariably are flanked by a long stretch of upstream 70-bp repeats. Recent studies have shown that DNA double-strand breaks (DSBs), particularly those in 70-bp repeats in the active ES, are a natural potent trigger for antigenic variation in T. brucei. In addition, telomere proteins can influence VSG switching by reducing the DSB amount at subtelomeric regions. These findings will be summarized and their implications will be discussed in this review. PMID:25576484

  3. Proceedings of the 2013 National Toxicology Program Satellite Symposium.

    PubMed

    Elmore, Susan A; Boyle, Michael C; Boyle, Molly H; Cora, Michelle C; Crabbs, Torrie A; Cummings, Connie A; Gruebbel, Margarita M; Johnson, Crystal L; Malarkey, David E; McInnes, Elizabeth F; Nolte, Thomas; Shackelford, Cynthia C; Ward, Jerrold M

    2014-01-01

    The 2013 annual National Toxicology Program (NTP) Satellite Symposium, entitled "Pathology Potpourri," was held in Portland, Oregon, in advance of the Society of Toxicologic Pathology's 32nd annual meeting. The goal of the NTP Symposium is to present current diagnostic pathology or nomenclature issues to the toxicologic pathology community. This article presents summaries of the speakers' presentations, including diagnostic or nomenclature issues that were presented, along with select images that were used for audience voting and discussion. Some lesions and topics covered during the symposium included a caudal tail vertebra duplication in mice; nephroblastematosis in rats; ectopic C cell tumor in a hamster; granular cell aggregates/tumor in the uterus of a hamster; Pneumocystis carinii in the lung of a rat; iatrogenic chronic inflammation in the lungs of control rats; hepatoblastoma arising within an adenoma in a mouse; humoral hypercalcemia of benignancy in a transgenic mouse; acetaminophen-induced hepatotoxicity in rats; electron microscopy images of iatrogenic intraerythrocytic inclusions in transgenic mice; questionable hepatocellular degeneration/cell death/artifact in rats; atypical endometrial hyperplasia in rats; malignant mixed Müllerian tumors/carcinosarcomas in rats; differential diagnoses of proliferative lesions of the intestine of rodents; and finally obstructive nephropathy caused by melamine poisoning in a rat. PMID:24334674

  4. Autoimmunity and dysmetabolism of human acquired immunodeficiency syndrome.

    PubMed

    Huang, Yan-Mei; Hong, Xue-Zhi; Xu, Jia-Hua; Luo, Jiang-Xi; Mo, Han-You; Zhao, Hai-Lu

    2016-06-01

    Acquired immunodeficiency syndrome (AIDS) remains ill-defined by lists of symptoms, infections, tumors, and disorders in metabolism and immunity. Low CD4 cell count, severe loss of body weight, pneumocystis pneumonia, and Kaposi's sarcoma are the major disease indicators. Lines of evidence indicate that patients living with AIDS have both immunodeficiency and autoimmunity. Immunodeficiency is attributed to deficits in the skin- and mucosa-defined innate immunity, CD4 T cells and regulatory T cells, presumably relating human immunodeficiency virus (HIV) infection. The autoimmunity in AIDS is evident by: (1) overproduction of autoantibodies, (2) impaired response of CD4 cells and CD8 cells, (3) failure of clinical trials of HIV vaccines, and (4) therapeutic benefits of immunosuppression following solid organ transplantation and bone marrow transplantation in patients at risk of AIDS. Autoantibodies are generated in response to antigens such as debris and molecules de novo released from dead cells, infectious agents, and catabolic events. Disturbances in metabolic homeostasis occur at the interface of immunodeficiency and autoimmunity in the development of AIDS. Optimal treatments favor therapeutics targeting on the regulation of metabolism to restore immune homeostasis. PMID:26676359

  5. The Spectrum of Infectious Diseases in Kidney Transplantation: A Review of the Classification, Pathogens and Clinical Manifestations.

    PubMed

    Anastasopoulos, Nikolaos-Andreas; Duni, Anila; Peschos, Dimitrios; Agnantis, Niki; Dounousi, Evangelia

    2015-01-01

    Kidney transplantation is the treatment-of-choice for a significant number of patients with end-stage renal disease. Renal transplant recipients (RTRs) benefit from a longer life expectancy, with a better quality of life. Despite, recent accomplishments in the field of kidney transplantation, both short- and long-term, surgical and medical complications still exist. Among these complications, cardiovascular disease, carcinogenesis and infections are the most important. Infectious diseases constitute the most common complications after renal transplantation and the second most common cause of death among RTRs with a functioning graft. Theoretically, all infectious pathogens could cause disease in immunocompromised RTRs, yet among these, one could identify more important ones, such as the Enterobacteriaceae, causing urinary tract infections; pneumonia due to Pneumocystis jirovecii; Candida species which cause invasive fungal infections; herpes viruses; hepatitis viruses and parasites. Early diagnosis and effective treatment are key elements in salvaging both the allograft and the patient. However, clinical manifestations and diagnosis of such infectious diseases are not easily identified due to the altered state of immune response of the RTR. Thus, apart from possessing a deep knowledge of the etiology and the treatment options in each case, transplant physicians should also always remain alert when dealing with RTRs. PMID:26130786

  6. 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

  7. Omenn syndrome associated with a functional reversion due to a somatic second-site mutation in CARD11 deficiency

    PubMed Central

    Fuchs, Sebastian; Rensing-Ehl, Anne; Pannicke, Ulrich; Lorenz, Myriam R.; Fisch, Paul; Jeelall, Yogesh; Rohr, Jan; Speckmann, Carsten; Vraetz, Thomas; Farmand, Susan; Schmitt-Graeff, Annette; Krüger, Marcus; Strahm, Brigitte; Henneke, Philipp; Enders, Anselm; Horikawa, Keisuke; Goodnow, Christopher; Schwarz, Klaus

    2015-01-01

    Omenn syndrome (OS) is a severe immunodeficiency associated with erythroderma, lymphoproliferation, elevated IgE, and hyperactive oligoclonal T cells. A restricted T-cell repertoire caused by defective thymic T-cell development and selection, lymphopenia with homeostatic proliferation, and lack of regulatory T cells are considered key factors in OS pathogenesis. We report 2 siblings presenting with cytomegalovirus (CMV) and Pneumocystis jirovecii infections and recurrent sepsis; one developed all clinical features of OS. Both carried homozygous germline mutations in CARD11 (p.Cys150*), impairing NF-κB signaling and IL-2 production. A somatic second-site mutation reverting the stop codon to a missense mutation (p.Cys150Leu) was detected in tissue-infiltrating T cells of the OS patient. Expression of p.Cys150Leu in CARD11-deficient T cells largely reconstituted NF-κB signaling. The reversion likely occurred in a prethymic T-cell precursor, leading to a chimeric T-cell repertoire. We speculate that in our patient the functional advantage of the revertant T cells in the context of persistent CMV infection, combined with lack of regulatory T cells, may have been sufficient to favor OS. This first observation of OS in a patient with a T-cell activation defect suggests that severely defective T-cell development or homeostatic proliferation in a lymphopenic environment are not required for this severe immunopathology. PMID:26289640

  8. Human Immunodeficiency Virus Infection and Host Defense in the Lungs.

    PubMed

    Charles, Tysheena P; Shellito, Judd E

    2016-04-01

    Immunosuppression associated with human immunodeficiency virus (HIV) infection impacts all components of host defense against pulmonary infection. Cells within the lung have altered immune function and are important reservoirs for HIV infection. The host immune response to infected lung cells further compromises responses to a secondary pathogenic insult. In the upper respiratory tract, mucociliary function is impaired and there are decreased levels of salivary immunoglobulin A. Host defenses in the lower respiratory tract are controlled by alveolar macrophages, lymphocytes, and polymorphonuclear leukocytes. As HIV infection progresses, lung CD4 T cells are reduced in number causing a lack of activation signals from CD4 T cells and impaired defense by macrophages. CD8 T cells, on the other hand, are increased in number and cause lymphocytic alveolitis. Specific antibody responses by B-lymphocytes are decreased and opsonization of microorganisms is impaired. These observed defects in host defense of the respiratory tract explain the susceptibility of HIV-infected persons for oropharyngeal candidiasis, bacterial pneumonia, Pneumocystis pneumonia, and other opportunistic infections. PMID:26974294

  9. Neglected tropical diseases of Namibia: unsolved mysteries.

    PubMed

    Noden, Bruce H; van der Colf, Berta E

    2013-01-01

    Neglected tropical diseases (NTDs) are diseases most commonly found in settings of poverty and are responsible for the morbidity and/or mortality of millions each year. As an upper-middle income country, Namibia is not normally considered to have many NTDs but published reports indicate the possible presence of over 30. Because much of the data is buried in historical studies published before Independence in 1990, there is a risk of losing valuable information on which to build current and future integrated public health strategies. The purpose of this review, therefore, is to bring together these significant fragments to identify existing knowledge gaps which need to be addressed to build effective control, prevention, and even elimination strategies. The review focuses on intestinal helminthes, schistosomes/snail 'vectors', viruses (Rift Valley Fever, Crimean Congo Hemorrhagic Fever, rabies), protozoa (Leishmania, Toxoplasma, Amoeba, Giardia), bacteria (Rickettsia, Ehrlichia, Leptospira, Coxiella, Brucella, and Borrelia), fungi (Pneumocystis) and myiasis. Each NTD speaks to the possible need for surveillance and the creation of integrated disease risk maps, linking prevalence of related NTDs with environmental and ecological factors to assist control and prevention efforts. The predominance of zoonotic disease suggests a need to integrate veterinary and public health components as the national public health surveillance system is established. PMID:23006744

  10. Omenn syndrome associated with a functional reversion due to a somatic second-site mutation in CARD11 deficiency.

    PubMed

    Fuchs, Sebastian; Rensing-Ehl, Anne; Pannicke, Ulrich; Lorenz, Myriam R; Fisch, Paul; Jeelall, Yogesh; Rohr, Jan; Speckmann, Carsten; Vraetz, Thomas; Farmand, Susan; Schmitt-Graeff, Annette; Krüger, Marcus; Strahm, Brigitte; Henneke, Philipp; Enders, Anselm; Horikawa, Keisuke; Goodnow, Christopher; Schwarz, Klaus; Ehl, Stephan

    2015-10-01

    Omenn syndrome (OS) is a severe immunodeficiency associated with erythroderma, lymphoproliferation, elevated IgE, and hyperactive oligoclonal T cells. A restricted T-cell repertoire caused by defective thymic T-cell development and selection, lymphopenia with homeostatic proliferation, and lack of regulatory T cells are considered key factors in OS pathogenesis. We report 2 siblings presenting with cytomegalovirus (CMV) and Pneumocystis jirovecii infections and recurrent sepsis; one developed all clinical features of OS. Both carried homozygous germline mutations in CARD11 (p.Cys150*), impairing NF-κB signaling and IL-2 production. A somatic second-site mutation reverting the stop codon to a missense mutation (p.Cys150Leu) was detected in tissue-infiltrating T cells of the OS patient. Expression of p.Cys150Leu in CARD11-deficient T cells largely reconstituted NF-κB signaling. The reversion likely occurred in a prethymic T-cell precursor, leading to a chimeric T-cell repertoire. We speculate that in our patient the functional advantage of the revertant T cells in the context of persistent CMV infection, combined with lack of regulatory T cells, may have been sufficient to favor OS. This first observation of OS in a patient with a T-cell activation defect suggests that severely defective T-cell development or homeostatic proliferation in a lymphopenic environment are not required for this severe immunopathology. PMID:26289640

  11. Estimating the burden of fungal disease in Vietnam.

    PubMed

    Beardsley, J; Denning, D W; Chau, N V; Yen, N T B; Crump, J A; Day, J N

    2015-10-01

    Data regarding the prevalence of fungal infections in Vietnam are limited yet they are likely to occur more frequently as increasingly sophisticated healthcare creates more iatrogenic risk factors. In this study, we sought to estimate baseline incidence and prevalence of selected serious fungal infections for the year 2012. We made estimates with a previously described actuarial method, using reports on the incidence and prevalence of various established risk factors for fungal infections from Vietnam, or similar environments, supplemented by personal communications. Global data were used if local data were unavailable. We estimated 2,352,748 episodes of serious fungal infection occurred in Vietnam in 2012. Frequent conditions included recurrent vaginal candidiasis (3893/100,000 women annually), tinea capitis (457/100,000 annually) and chronic pulmonary aspergillosis (61/100,000/5 year period). We estimated 140 cases of cryptococcal meningitis, 206 of penicilliosis and 608 of Pneumocystis jirovecii pneumonia. This is the first summary of Vietnamese fungal infections. The majority of severe disease is due to Aspergillus species, driven by the high prevalence of pulmonary tuberculosis. The AIDS epidemic highlights opportunistic infections, such as penicilliosis and cryptococcosis, which may complicate immunosuppressive treatments. These estimates provide a useful indication of disease prevalence to inform future research and resource allocation but should be verified by further epidemiological approaches. PMID:26449514

  12. Bacterial Respiratory Infections Complicating Human Immunodeficiency Virus.

    PubMed

    Feldman, Charles; Anderson, Ronald

    2016-04-01

    Opportunistic bacterial and fungal infections of the lower respiratory tract, most commonly those caused by Streptococcus pneumoniae (the pneumococcus), Mycobacterium tuberculosis, and Pneumocystis jirovecii, remain the major causes of mortality in those infected with human immunodeficiency virus (HIV). Bacterial respiratory pathogens most prevalent in those infected with HIV, other than M. tuberculosis, represent the primary focus of the current review with particular emphasis on the pneumococcus, the leading cause of mortality due to HIV infection in the developed world. Additional themes include (1) risk factors; (2) the predisposing effects of HIV-mediated suppression on pulmonary host defenses, possibly intensified by smoking; (3) clinical and laboratory diagnosis, encompassing assessment of disease severity and outcome; and (4) antibiotic therapy. The final section addresses current recommendations with respect to pneumococcal immunization in the context of HIV infection, including an overview of the rationale underpinning the current "prime-boost" immunization strategy based on sequential administration of pneumococcal conjugate vaccine 13 and pneumococcal polysaccharide vaccine 23. PMID:26974299

  13. The Critically Ill Kidney Transplant Recipient: A Narrative Review.

    PubMed

    Canet, Emmanuel; Zafrani, Lara; Azoulay, Élie

    2016-06-01

    Kidney transplantation is the most common solid organ transplantation performed worldwide. Up to 6% of kidney transplant recipients experience a life-threatening complication that requires ICU admission, chiefly in the late posttransplantation period (≥ 6 months). Acute respiratory failure and septic shock are the main reasons for ICU admission. Cardiac pulmonary edema, bacterial pneumonia, acute graft pyelonephritis, and bloodstream infections account for the vast majority of diagnoses in the ICU. Pneumocystis jirovecii pneumonia is the most common opportunistic infection, and one-half of the patients so infected require mechanical ventilation. The incidence of cytomegalovirus visceral infections in the era of preemptive therapy has dramatically decreased. Drug-related neutropenia, sirolimus-related pneumonitis, and posterior reversible encephalopathy syndrome are among the most common immunosuppression-associated toxic effects. Importantly, the impact of critical illness on graft function is worrisome. Throughout the ICU stay, acute kidney injury is common, and about 40% of the recipients require renal replacement therapy. One-half of the patients are discharged alive and free from dialysis. Hospital mortality can reach 30% and correlates with acute illness severity and reason for ICU admission. Transplant characteristics are not predictors of short-term survival. Graft survival depends on pre-ICU graft function, disease severity, and renal toxicity of ICU investigations and treatments. PMID:26836919

  14. Pulmonary Kaposi sarcoma and disseminated Mycobacterium genavense infection in an HIV-infected patient.

    PubMed

    Tribuna, Cindy; Ângela, Cristina; Eira, Isabel; Carvalho, Alexandre

    2015-01-01

    We report a case of Kaposi sarcoma (KS) and disseminated infection by Mycobacterium genavense in a 40-year-old HIV-positive man with CD4+ T-cell count 5/µL. He presented with anorexia, diarrhoea, cachexia and multiple firm violaceous nodules distributed over the face, neck and upper and lower extremities. Biopsy of a skin nodule was performed, confirming KS. Immunoperoxidase staining for human herpesvirus 8 was strongly positive. Endoscopic examination revealed erosive duodenopathy. Multiple biopsy samples showed numerous acid-fast bacilli at direct microscopic examination. Real-time PCR (RT-PCR) identified M. genavense. A CT scan showed diffuse pulmonary infiltrates with a 'tree-in-bud' appearance, striking splenomegaly and abdominal lymphadenopathy. A bronchoscopy was performed, revealing typical Kaposi's lesions in the upper respiratory tract. RT-PCR of bronchial aspirate identified M. genavense and Pneumocystis jirovecii. Despite treatment with highly active antiretroviral therapy, antimycobacterial therapy and trimethoprim/sulfamethoxazole, the outcome was fatal. PMID:26452414

  15. [Infection due to Mycobacterium bovis in common variable immunodeficiency].

    PubMed

    Herrera-Sánchez, Diana Andrea; Castilla-Rodríguez, Jaisel Luz; Castrejón-Vázquez, María Isabel; Vargas-Camaño, María Eugenia; Medina-Torres, Edgar Alejandro; Blancas-Galicia, Lizbeth; Espinosa-Padilla, Sara Elva

    2015-01-01

    Common variable immunodeficiency (CVID) is an heterogeneous group of disorders characterized by impaired antibody production. It shows a wide spectrum of manifestations including severe and recurrent respiratory infections (Streptococcus pneumoniae, Haemophilus) and gastrointestinal (Campylobacter jejuni, rotavirus and Giardia lamblia). Viral infections caused by herpes zoster, cytomegalovirus (CMV) and hepatitis C are rare. The opportunistic agents such as CMV, Pneumocystis jirovecii, cryptococcus and atypical mycobacteria have been reported as isolated cases. This paper reports the case of a 38-year-old female patient, who began six years before with weight loss of 7 kg in six months, fatigue, weakness, sweating, fever and abdominal pain. Furthermore, patient had intestinal obstruction and abdominal CT showed mesenteric lymph growth. The mesenteric lymph node biopsy revealed positives Mycobacterium PCR, Ziehl-Neelsen staining and culture for M. bovis. In the laparotomy postoperative period was complicated with nosocomial pneumonia, requiring mechanical ventilation and tracheostomy. Two years later, she developed right renal abscess that required surgical drainage, once again with a positive culture for Mycobacterium bovis. She was referred to highly specialized hospital and we documented panhypogammaglobulinemia and lymphopenia. Secondary causes of hypogammaglobulinemia were ruled out and common variable immunodeficiency (CVID) was confirmed, we started IVIG replacement. Four years later she developed mixed cellularity Hodgkin's lymphoma. Until today she continues with IVIG and chemotherapy. This report of a patient with CVID and Mycobacterium bovis infection, a unusual association, shows the cellular immunity susceptibility in this immunodeficiency, additional to the humoral defect. PMID:25758115

  16. Microbiological survey of mice (Mus musculus) purchased from commercial pet shops in Kanagawa and Tokyo, Japan.

    PubMed

    Hayashimoto, Nobuhito; Morita, Hanako; Ishida, Tomoko; Uchida, Ritsuki; Tanaka, Mai; Ozawa, Midori; Yasuda, Masahiko; Itoh, Toshio

    2015-01-01

    Information regarding the prevalence of infectious agents in mice in pet shops in Japan is scarce. This information is particularly useful for minimizing the risk of potential transmission of infections to laboratory mice. Therefore, we surveyed infectious agents in mice from pet shops in Kanagawa and Tokyo, Japan. The survey was conducted in 28 mice from 5 pet shops to screen for 47 items (17 viruses, 22 bacteria and fungi, 10 parasites) using culture tests, serology, PCR, and microscopy. The most common viral agent detected was murine norovirus (17 mice; 60.7%), followed by Theiler's murine encephalomyelitis virus (13 mice; 46.4%), and mouse hepatitis virus (12 mice; 42.8%). The most common agent amongst the bacteria and fungi was Pasteurella pneumotropica (10 mice; 35.7%), followed by Helicobacter ganmani and Pneumocystis murina (8 mice; 28.5%, for both). Tritrichomonas muris was the most common parasite (19 mice; 67.8%), followed by Spironucleus muris (13 mice; 46.4%), Aspiculuris tetraptera, and Syphacia obvelata (8 mice each; 28.5%). Remarkably, a zoonotic agent, Hymenolepis nana, was found in 7 mice (25%). Given these results, we suggest that the workers in laboratory animal facilities should recognize again the potential risks of mice outside of the laboratory animal facilities as an infectious source, and avoid keeping mice as pets or as feed for carnivorous reptiles as much as possible for risk management. PMID:25502736

  17. Hemolytic anemia in two patients with glioblastoma multiforme: A possible interaction between vorinostat and dapsone.

    PubMed

    Lewis, Jennifer A; Petty, William J; Harmon, Michele; Peacock, James E; Valente, Kari; Owen, John; Pirmohamed, Munir; Lesser, Glenn J

    2015-06-01

    Patients undergoing treatment for glioblastoma multiforme are routinely placed on prophylactic treatment for Pneumocystis jirovecii pneumonia because of significant therapy-induced lymphopenia. In patients with sulfa allergies, dapsone prophylaxis is often used due to its efficacy, long half-life, cost effectiveness, and general safety at low doses. However, dapsone may uncommonly induce a hemolytic anemia, particularly in patients deficient of glucose-6-phosphate dehydrogenase. This hemolysis is thought to be a result of oxidative stress on red blood cells induced by dapsone metabolites which produce reactive oxygen species that disrupt the red blood cell membrane and promote splenic sequestration. A single case report of dapsone-induced hemolytic anemia in a patient with glioblastoma multiforme has been reported. We present two patients with glioblastoma multiforme who developed severe hemolytic anemia shortly after initiating therapy with vorinostat, a pan-active histone deacetylase inhibitor, while on prophylactic dapsone. There are several potential mechanisms by which histone deacetylase inhibition may alter dapsone metabolism including changes in hepatic acetylation or N-glucuronidation leading to an increase in the bioavailability of dapsone's hematotoxic metabolites. In addition, vorinostat may lead to increased hemolysis through inhibition of heat shock protein-90, a chaperone protein that maintains the integrity of the red blood cell membrane cytoskeleton. The potential interaction between dapsone and vorinostat may have important clinical implications as more than 10 clinical trials evaluating drug combinations with vorinostat in patients with malignant glioma are either ongoing or planned in North America. PMID:24576944

  18. Synthesis and biological activities of tricyclic conformationally restricted tetrahydropyrido annulated furo[2,3-d]pyrimidines as inhibitors of dihydrofolate reductases.

    PubMed

    Gangjee, A; Elzein, E; Queener, S F; McGuire, J J

    1998-04-23

    The synthesis of seven 2,4-diamino-5,6,7,8-tetrahydro-7-substituted pyrido[4',3':4,5]furo[2,3-d]pyrimidines 1-6 are reported as nonclassical antifolate inhibitors of dihydrofolate reductase (DHFR) and compound 7 as a classical antifolate inhibitor of tumor cells in culture. The compounds were designed as conformationally restricted analogues of trimetrexate. The synthesis was accomplished from the cyclocondensation of 3-bromo-4-piperidone with 2, 4-diamino-6-hydroxypyrimidine to afford regiospecifically 2, 4-diamino-5,6,7,8-tetrahydropyrido[4',3':4,5]furo[2, 3-d]pyrimidine-7-hydrobromide (16). This in turn was alkylated with the appropriate benzyl halide to afford the target compounds 1-6. The classical antifolate 7 utilized 4-(chloromethyl)benzoyl-l-glutamic acid diethyl ester (17) instead of the benzyl halide for alkylation, followed by saponification to afford 7. Compounds 1-6 showed moderate inhibitory potency against DHFR from Pneumocystis carinii, Toxoplasma gondii, Mycobacterium avium, and rat liver. The classical analogue 7 was 88-fold more potent against M. avium DHFR than against rat liver DHFR. The classical analogue was also inhibitory against the growth of tumor cells, CCRF-CEM, and FaDu, in culture. PMID:9554874

  19. Phase I Safety and Pharmacokinetics Study of Micronized Atovaquone in Human Immunodeficiency Virus-Infected Infants and Children

    PubMed Central

    Hughes, Walter; Dorenbaum, Alejandro; Yogev, Ram; Beauchamp, Belinda; Xu, Jing; McNamara, James; Moye, John; Purdue, Lynette; van Dyke, Russell; Rogers, Michael; Sadler, Brian; Group, The Pediatric Aids Clinical Trials

    1998-01-01

    A phase I dose-escalating safety and pharmacokinetic study evaluated an oral suspension of micronized atovaquone (m-atovaquone) in infants and children stratified into age groups from 1 month to 12 years of age. Dosages of 10, 30, and 45 mg/kg of body weight/day were evaluated as single daily doses over a period of 12 days. Steady-state concentrations in plasma were determined on day 12, and single postdose concentrations were measured on days 1, 3, 5, 7, 9, 13, 15, 18, 21, and 24. Prior studies with adults suggest that the average plasma atovaquone concentration of 15 μg/ml is associated with therapeutic success in more than 95% of patients with Pneumocystis carinii pneumonitis. The results showed m-atovaquone to be safe and well tolerated. Dosages of 30 mg/kg/day were adequate to achieve an average steady-state concentration of greater than 15 μg/ml in children ages 1 to 3 months and 2 to 12 years, but a dosage of 45 mg/kg/day was needed to reach this concentration in infants 3 to 24 months of age. The oral suspension of atovaquone is safe and well tolerated in children. A single daily dose of 30 mg/kg provides bioavailability considered adequate for therapy of P. carinii pneumonia, but infants between 3 and 24 months of age may require a dosage of 45 mg/kg/day. PMID:9624466

  20. Infection as a complication of heart transplantation.

    PubMed

    Linder, J

    1988-01-01

    Infection and cardiac rejection are the most significant causes of morbidity and mortality after heart transplantation. At some transplant centers, more than half of the early transplantation-related deaths are the result of infection. The infectious agents may be transmitted to the host by means of the allograft, through blood transfusion, by nosocomial or environmental routes, or they may represent endogenous microbial flora or reactivation of a prior infection. The frequency of infectious complications is generally related to the degree of immunosuppressive therapy required to prevent graft rejection. Both the composition of the immunosuppressive regimen and the dosage of the immunosuppressive drugs affect the infection rate. Recent protocols, employing a combination of cyclosporine, steroids, and azathioprine cause less toxicity and lower infection rates than protocols that rely solely on cyclosporine and steroids or protocols utilized in the 1970s, which did not contain cyclosporine. A literature review of data reported from 12 transplant centers, encompassing 384 patients who received their transplantation in the era of cyclosporine, revealed infections in 221 patients (57.6%), with 20 infection-related deaths (5.2%). All classes of microorganisms infected the heart transplant recipients. The most frequent agents included staphylococci, gram-negative enteric, Nocardia (bacterial); Aspergillus, Candida, Cryptococcus (fungal); cytomegalovirus, herpes simplex, herpes zoster (viral); and Pneumocystis carinii, Toxoplasma gondii (protozoal). The respiratory tract, urinary tract, and skin were the most common sites of infection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3058911

  1. Diagnosis of nosocomial pneumonia.

    PubMed

    Bamberger, D M

    1988-06-01

    Nosocomial pneumonia occurs in 0.6% of hospitalized patients. The usual causative agents are gram-negative bacilli, Staphylococcus aureus, Streptococcus pneumoniae, and anaerobic bacteria. In immunocompromised hosts, the differential diagnosis also includes fungi, mycobacteria, viruses, Nocardia, and Pneumocystis carinii. Important risk factors for the development of nosocomial pneumonia include prolonged mechanical ventilation, thoracic or upper abdominal surgery, altered mental status, underlying immunosuppression, chronic obstructive pulmonary disease, and the use of antacids or histamine type 2 blockers. Colonization of the oropharynx and tracheal secretions with gram-negative aerobic bacteria is common in hospitalized patients with or without pneumonia. The diagnosis of nosocomial pneumonia is usually based on the clinical features of dyspnea, cough, fever, purulent sputum production, new pulmonary infiltrates, hypoxemia, and leukocytosis. However, the clinician must recognize that the presence of these features is neither sensitive nor specific in the diagnosis of nosocomial pneumonia. Microbiologic diagnosis is also difficult because blood cultures are usually negative, and cultures of tracheal secretions, although usually sensitive, are not specific. Invasive procedures may prove useful, but most have yet to be studied in large groups of patients with nosocomial pneumonia. PMID:3041515

  2. HIV infection in Malaysia: a report of cases seen at the University Hospital, Kuala Lumpur.

    PubMed

    Ismail, R; Doi, S; Naganathna, N

    1995-12-01

    The spread of HIV infection into Malaysia is estimated to have occurred in the early 1980's. The first case of AIDS was reported here in 1986. As of March 31, 1994, the numbers have increased to 8049 HIV positive individuals detected in the country. The risk behaviours among those tested positive were intravenous drug use in 77.2%, sexual transmission in 4.5%, while the remainder are still under investigation. Pediatric AIDS constitutes 0.2% of positives. The high prevalence among intravenous drug users (IVDU) is likely to be due to mandatory testing for HIV upon entry to rehabilitation centres. The trend of HIV infection in this country seems to be highest amongst the intravenous drug users. The increasing number of HIV infected prostitutes and heterosexuals in our population is worrying. Since 1986, a total of 104 HIV positive individuals have been treated at the University Hospital, Kuala Lumpur, Malaysia. Of these, 25 have died and of those still alive, 5 have symptomatic disease. The most common AIDS-defining illness is Pneumocystis carinii pneumonia. Education programmes have been developed targeting the various high risk groups and the general population. PMID:8668046

  3. Age-related presence of selected viral and bacterial pathogens in paraffin-embedded lung samples of dogs with pneumonia.

    PubMed

    Wöhrer, Daniela; Spergser, Joachim; Bagrinovschi, Gabriela; Möstl, Karin; Weissenböck, Herbert

    2016-03-01

    The aim of this retrospective study was to detect selected pathogens in pneumonic lung tissue of dogs of different age groups by immunohistochemistry (IHC), in situ hybridisation (ISH) or polymerase chain reaction (PCR) in order to get information about their involvement in pneumonia formation. In archived formalin-fixed and paraffin wax-embedded lung samples from 68 cases with the clinical and histologic diagnosis of pneumonia the histological pattern of pneumonia was re-evaluated and the samples were further investigated for the following infectious agents: canine distemper virus (CDV), canine adenovirus type 2 (CAV-2), canine respiratory coronavirus (CRCoV), Bordetella (B.) bronchiseptica, Pasteurella (P.) multocida, Mycoplasma spp., and Pneumocystis spp. In 47.1% of the samples at least one of the featured respiratory pathogens was detected. In 31.3% of these positive samples more than one pathogen could be found. The correct detection of CDV had been achieved in ten out of eleven positive cases (90.9%) upon initial investigation, but the presence of bacterial pathogens, like B. bronchiseptica (10 cases) and P. multocida (17 cases) had been missed in all but one case. While CDV and CRCoV infections were exclusively found in dogs younger than one year, the vast majority of infections with P. multocida and B. bronchiseptica were both common either in dogs younger than 4 months or older than one year. Thus, this retrospective approach yielded valuable data on the presence, absence and prevalence of certain respiratory pathogens in dogs with pneumonia. PMID:26919147

  4. [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

  5. First Line of Defense: Innate Cell-Mediated Control of Pulmonary Aspergillosis

    PubMed Central

    Espinosa, Vanessa; Rivera, Amariliz

    2016-01-01

    Mycotic infections and their effect on the human condition have been widely overlooked and poorly surveilled by many health organizations even though mortality rates have increased in recent years. The increased usage of immunosuppressive and myeloablative therapies for the treatment of malignant as well as non-malignant diseases has contributed significantly to the increased incidence of fungal infections. Invasive fungal infections have been found to be responsible for at least 1.5 million deaths worldwide. About 90% of these deaths can be attributed to Cryptococcus, Candida, Aspergillus, and Pneumocystis. A better understanding of how the host immune system contains fungal infection is likely to facilitate the development of much needed novel antifungal therapies. Innate cells are responsible for the rapid recognition and containment of fungal infections and have been found to play essential roles in defense against multiple fungal pathogens. In this review we summarize our current understanding of host-fungi interactions with a focus on mechanisms of innate cell-mediated recognition and control of pulmonary aspergillosis. PMID:26973640

  6. Differences in difficulty adjudicating clinical events in patients with advanced HIV disease.

    PubMed

    Eisenbud, R; Assmann, S F; Kalish, L A; van Der Horst, C; Collier, A C

    2001-09-01

    Adjudication of clinical events is often used as a quality assurance method in clinical research. During the design of the Viral Activation Transfusion Study (a clinical trial in patients with advanced HIV disease), a set of study endpoints was defined (primarily AIDS-defining conditions), criteria for confirmation of each event type were developed, and an adjudication procedure was established. The adjudication process included 1) an initial review of documentation of each event by two independent reviewers, 2) the opportunity to request additional information, 3) a second review either of additional documentation or of cases in which there was disagreement on first review, and 4) the consultation of a third reviewer if there was still disagreement. Overall, of 288 reported endpoints, 30% required additional documentation or more than one review, and 16% were not confirmed at the end of the adjudication process. However, these percentages varied widely over different types of events. For example, of 30 reported nonophthalmalogic cytomegalovirus events, 37% required additional documentation and 40% were not confirmed. In contrast, every one of 17 reported Pneumocystis cariini pneumonias were confirmed with no requirement for additional documentation. The results can be used to help design endpoint documentation and adjudication procedures for other studies, thereby improving data quality and reducing costs. PMID:11579276

  7. 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

  8. Preventing secondary infections among HIV-positive persons.

    PubMed Central

    Filice, G A; Pomeroy, C

    1991-01-01

    Secondary infectious diseases contribute substantially to morbidity and mortality of people infected with human immunodeficiency virus (HIV). The authors developed comprehensive, practical recommendations for prevention of infectious complications in HIV-infected people. Recommendations are concerned with the pathogens that are more common or more severe in HIV-infected people. Several infectious complications can be prevented by avoiding ingestion of contaminated food or water. Zoonoses can be prevented by precautions to be taken in contacts with animals. The risk of several fungal diseases can be reduced if activities likely to lead to inhalation of spores are avoided. HIV-infected people should be advised how to lower adverse health effects of travel, especially international travel. The potential for infectious complications of sexual activity and illicit drug use should be stressed, and recommendations to reduce the risk are discussed. Recommendations for use of vaccines in HIV-infected people are reviewed. Blood CD4+ lymphocyte concentrations, tuberculin skin testing, Toxoplasma serology, and sexually transmitted disease screening should be performed in certain subsets of HIV-infected people. Guidelines for chemoprophylaxis against Pneumocystis carinii and tuberculosis are presented. Recent data suggest that intravenous immunoglobulin therapy may prevent bacterial infections in HIV-infected children. PMID:1910184

  9. Microbial antigenic variation mediated by homologous DNA recombination.

    PubMed

    Vink, Cornelis; Rudenko, Gloria; Seifert, H Steven

    2012-09-01

    Pathogenic microorganisms employ numerous molecular strategies in order to delay or circumvent recognition by the immune system of their host. One of the most widely used strategies of immune evasion is antigenic variation, in which immunogenic molecules expressed on the surface of a microorganism are continuously modified. As a consequence, the host is forced to constantly adapt its humoral immune response against this pathogen. An antigenic change thus provides the microorganism with an opportunity to persist and/or replicate within the host (population) for an extended period of time or to effectively infect a previously infected host. In most cases, antigenic variation is caused by genetic processes that lead to the modification of the amino acid sequence of a particular antigen or to alterations in the expression of biosynthesis genes that induce changes in the expression of a variant antigen. Here, we will review antigenic variation systems that rely on homologous DNA recombination and that are found in a wide range of cellular, human pathogens, including bacteria (such as Neisseria spp., Borrelia spp., Treponema pallidum, and Mycoplasma spp.), fungi (such as Pneumocystis carinii) and parasites (such as the African trypanosome Trypanosoma brucei). Specifically, the various DNA recombination-based antigenic variation systems will be discussed with a focus on the employed mechanisms of recombination, the DNA substrates, and the enzymatic machinery involved. PMID:22212019

  10. Paediatric feather duvet hypersensitivity pneumonitis.

    PubMed

    Jordan, Louise E; Guy, Emma

    2015-01-01

    A previously well 12-year-old boy was admitted with a second insidious episode of dyspnoea, dry cough, anorexia, weight loss and chest pain. At admission, he had an oxygen requirement, significantly impaired lung function and reduced exercise tolerance. Initial forced expiratory volume in 1 s was 26%; a 3 min exercise test stopped at 1 min 50 when saturations dropped to 85%. CT scan showed ground-glass nodularity with lymphadenopathy. Bronchoalveolar lavage (BAL) for Pneumocystis carinii pneumonia and viruses were negative, and microbiology results for the BAL were reported in the absence of histology. This is because at the time the BAL samples were collected, a lung biopsy was performed. The biopsy was consistent with hypersensitivity pneumonitis. Echo was normal and CT pulmonary angiography negative. After taking a thorough history, exposure to feather duvets prior to each episode was elicited. IgG of avian precipitants was raised at 10.6 mgA/L (normal <10 mgA/L). Clinical improvement began with avoidance of exposure, while the boy was an inpatient. Antigen avoidance continued on discharge. He continues to improve since discharge. The condition was diagnosed as hypersensitivity pneumonitis secondary to exposure to antigens from feather duvets. PMID:26113584

  11. Molecular and Nonmolecular Diagnostic Methods for Invasive Fungal Infections

    PubMed Central

    Arvanitis, Marios; Anagnostou, Theodora; Fuchs, Beth Burgwyn; Caliendo, Angela M.

    2014-01-01

    SUMMARY Invasive fungal infections constitute a serious threat to an ever-growing population of immunocompromised individuals and other individuals at risk. Traditional diagnostic methods, such as histopathology and culture, which are still considered the gold standards, have low sensitivity, which underscores the need for the development of new means of detecting fungal infectious agents. Indeed, novel serologic and molecular techniques have been developed and are currently under clinical evaluation. Tests like the galactomannan antigen test for aspergillosis and the β-glucan test for invasive Candida spp. and molds, as well as other antigen and antibody tests, for Cryptococcus spp., Pneumocystis spp., and dimorphic fungi, have already been established as important diagnostic approaches and are implemented in routine clinical practice. On the other hand, PCR and other molecular approaches, such as matrix-assisted laser desorption ionization (MALDI) and fluorescence in situ hybridization (FISH), have proved promising in clinical trials but still need to undergo standardization before their clinical use can become widespread. The purpose of this review is to highlight the different diagnostic approaches that are currently utilized or under development for invasive fungal infections and to identify their performance characteristics and the challenges associated with their use. PMID:24982319

  12. Phylogenetic Analysis of Lacazia loboi Places This Previously Uncharacterized Pathogen within the Dimorphic Onygenales

    PubMed Central

    Herr, Roger A.; Tarcha, Eric J.; Taborda, Paulo R.; Taylor, John W.; Ajello, Libero; Mendoza, Leonel

    2001-01-01

    Lacazia loboi is the last of the classical fungal pathogens to remain a taxonomic enigma, primarily because it has resisted cultivation and only causes cutaneous and subcutaneous infections in humans and dolphins in the New World tropics. To place it in the evolutionary tree of life, as has been done for the other enigmatic human pathogens Pneumocystis carinii and Rhinosporidium seeberi, we amplified its 18S small-subunit ribosomal DNA (SSU rDNA) and 600 bp of its chitin synthase-2 gene. Our phylogenetic analysis indicated that L. loboi is the sister taxon of the human dimorphic fungal pathogen Paracoccidioides brasiliensis and that both species belong with the other dimorphic fungal pathogens in the order Onygenales. The low nucleotide variation among three P. brasiliensis 18S SSU rDNA sequences contrasts with the surprising amount of nucleotide differences between the two sequences of L. loboi used in this study, suggesting that the nucleic acid epidemiology of this hydrophilic pathogen will be rewarding. PMID:11136789

  13. Epidemiology, aetiology and management of childhood acute community-acquired pneumonia in developing countries--a review.

    PubMed

    Falade, A G; Ayede, A I

    2011-12-01

    Childhood acute community-acquired pneumonia is one of the leading causes of morbidity and mortality in developing countries. In children who have not received prior antibiotic therapy, the main bacterial causes of clinical pneumonia in developing countries are Streptococcus pneumoniae and Haemophilus influenzae type b (Hib), and the main viral cause is respiratory syncytial virus (RSV), but estimates of their relative importance vary in different settings. The only vaccines for the prevention of bacterial pneumonia (excluding vaccines for pertussis and measles) are Hib and pneumococcal conjugate vaccines (PCV). In children with human immunodeficiency virus (HIV) infection, bacterial infection remains a major cause of pneumonia mortality; however, Pneumocystis jirovecii and Mycobacterium tuberculosis are important causes of pneumonia in them. Studies of bacterial aetiology of acute pneumonia in severely malnourished children have implicated Klebsiella pneumoniae, Staphylococcus aureus, S. pneumoniae, Escherichia coli, and H. influenzae, with very few data on the role of respiratory viruses and tuberculosis. Studies of neonatal sepsis suggest that Gram-negative enteric organisms, particularly Klebsiella spp., and Gram-positive organisms, mainly pneumococcus, group b Streptococcus and S. aureus are causes of neonatal pneumonia. Many of the developing countries that ranked high in pneumonia mortality are preparing to introduce new pneumonia vaccines with support from Global Alliance for Vaccine and Immunization (GAVI Alliance), plan for the expansion of community-based case management and have ambitious plans for strengthening health systems. Assurance that these plans are implemented will require funding and continued public attention to pneumonia, which will help contribute to a substantial decline in childhood pneumonia deaths. PMID:22783679

  14. Good's Syndrome Patients Hospitalized for Infections: A Single-Center Retrospective Study.

    PubMed

    Sun, Xuefeng; Shi, Juhong; Wang, Mengzhao; Xu, Kaifeng; Xiao, Yi

    2015-11-01

    Good's syndrome (GS) is a rare combination of thymoma and hypogammaglobulinemia, resulting in immunodeficiency. Patients with GS are highly susceptible to bacterial infection, particularly encapsulated bacterial infection in upper and lower respiratory tracts. Good's syndrome patients with moderate-to- severe infection are often hospitalized. Clinical features of GS patients remain to be characterized.Patients with the discharge diagnosis of GS and simultaneous infection from Peking Union Medical College Hospital between January 2001 and July 2015 were retrospectively analyzed.Among 14 hospitalized GS patients, 12 of them were admitted for severe infections. Mean patient age was 56.7 + 10.1 years. Average concentrations of serum IgG, IgA, and IgM were 2.3 + 1.9 g/L, 0.28 + 0.28 g/L, and 0.06 + 0.07 g/L, respectively. Respiratory and intestinal tracts were the most common sites for infection, which occurred in 7 and 4 patients, respectively. Pathogens identified in 10 patients included cytomegalovirus in 5 patients, Pneumocystis jirovecii, Clostridium difficile in 2 patients, Klebsiella pneumonia in 2 patients, and Streptococcus pneumonia and Hemophilus influenza in 1 patient. Ten patients were treated with antibiotics and immunoglobulin replacement. Only 1 patient who was on immunosuppressant therapy died from P. jirovecii pneumonia.Infection was the most frequent cause for hospitalization of GS patients. Both respiratory and intestinal tracts were the most common sites of infection. Cytomegalovirus and P. jirovecii represented 2 common opportunistic pathogens isolated from hospitalized GS patients with infections. PMID:26632723

  15. Prospective Study of Bevacizumab Plus Temozolomide in Patients With Advanced Neuroendocrine Tumors

    PubMed Central

    Chan, Jennifer A.; Stuart, Keith; Earle, Craig C.; Clark, Jeffrey W.; Bhargava, Pankaj; Miksad, Rebecca; Blaszkowsky, Lawrence; Enzinger, Peter C.; Meyerhardt, Jeffrey A.; Zheng, Hui; Fuchs, Charles S.; Kulke, Matthew H.

    2012-01-01

    Purpose Both tyrosine kinase inhibitors targeting the vascular endothelial growth factor (VEGF) receptor and bevacizumab, a monoclonal antibody targeting VEGF, have antitumor activity in neuroendocrine tumors (NETs). Temozolomide, an oral analog of dacarbazine, also has activity against NETs when administered alone or in combination with other agents. We performed a phase II study to evaluate the efficacy of temozolomide in combination with bevacizumab in patients with locally advanced or metastatic NETs. Patients and Methods Thirty-four patients (56% with carcinoid, 44% with pancreatic NETs) were treated with temozolomide 150 mg/m2 orally per day on days 1 through 7 and days 15 through 21, together with bevacizumab at a dose of 5 mg/kg per day intravenously on days 1 and 15 of each 28-day cycle. All patients received prophylaxis against Pneumocystis carinii and varicella zoster. Patients were followed for toxicity, biochemical and radiologic response, and survival. Results The combination of temozolomide and bevacizumab was associated with anticipated grade 3 to 4 toxicities, including lymphopenia (53%) and thrombocytopenia (18%). Although the overall radiographic response rate was 15% (five of 34), response rates differed between patients with pancreatic NETs (33%; five of 15) and those with carcinoid tumors (zero of 19). The median progression-free survival was 11.0 months (14.3 months for pancreatic NETs v 7.3 months for carcinoid tumors). The median overall survival was 33.3 months (41.7 months for pancreatic NETs v 18.8 months for carcinoid tumors). Conclusion Temozolomide and bevacizumab can be safely administered together in patients with advanced NETs, and the combination regimen appears promising for patients with pancreatic NETs. Studies evaluating the relative contributions of these two agents to the observed antitumor activity are warranted. PMID:22778320

  16. Incidence of Opportunistic Infections and the Impact of Antiretroviral Therapy Among HIV-Infected Adults in Low- and Middle-Income Countries: A Systematic Review and Meta-analysis

    PubMed Central

    Low, Andrea; Gavriilidis, Georgios; Larke, Natasha; B-Lajoie, Marie-Renee; Drouin, Olivier; Stover, John; Muhe, Lulu; Easterbrook, Philippa

    2016-01-01

    Background. To understand regional burdens and inform delivery of health services, we conducted a systematic review and meta-analysis to evaluate the effect of antiretroviral therapy (ART) on incidence of key opportunistic infections (OIs) in human immunodeficiency virus (HIV)–infected adults in low- and middle-income countries (LMICs). Methods. Eligible studies describing the cumulative incidence of OIs and proportion on ART from 1990 to November 2013 were identified using multiple databases. Summary incident risks for the ART-naive period, and during and after the first year of ART, were calculated using random-effects meta-analyses. Summary estimates from ART subgroups were compared using meta-regression. The number of OI cases and associated costs averted if ART was initiated at a CD4 count ≥200 cells/µL were estimated using Joint United Nations Programme on HIV/AIDS (UNAIDS) country estimates and global average OI treatment cost per case. Results. We identified 7965 citations, and included 126 studies describing 491 608 HIV-infected persons. In ART-naive patients, summary risk was highest (>5%) for oral candidiasis, tuberculosis, herpes zoster, and bacterial pneumonia. The reduction in incidence was greatest for all OIs during the first 12 months of ART (range, 57%–91%) except for tuberculosis, and was largest for oral candidiasis, Pneumocystis pneumonia, and toxoplasmosis. Earlier ART was estimated to have averted 857 828 cases in 2013 (95% confidence interval [CI], 828 032–874 853), with cost savings of $46.7 million (95% CI, $43.8–$49.4 million). Conclusions. There was a major reduction in risk for most OIs with ART use in LMICs, with the greatest effect seen in the first year of treatment. ART has resulted in substantial cost savings from OIs averted. PMID:26951573

  17. Development of spray dried liposomal dry powder inhaler of Dapsone.

    PubMed

    Chougule, Mahavir; Padhi, Bijay; Misra, Ambikanandan

    2008-01-01

    This investigation was undertaken to evaluate practical feasibility of site specific pulmonary delivery of liposomal encapsulated Dapsone (DS) dry powder inhaler for prolonged drug retention in lungs as an effective alternative in prevention of Pneumocystis carinii pneumonia (PCP) associated with immunocompromised patients. DS encapsulated liposomes were prepared by thin film evaporation technique and resultant liposomal dispersion was passed through high pressure homogenizer. DS nano-liposomes (NLs) were separated by ultra centrifugation and characterized. NLs were dispersed in phosphate buffer saline (PBS) pH 7.4 containing different carriers like lactose, sucrose, and hydrolyzed gelatin, and 15% L-leucine as antiadherent. The resultant dispersion was spray dried and spray dried formulation were characterized to ascertain its performance. In vitro pulmonary deposition was assessed using Andersen Cascade Impactor as per USP. NLs were found to have average size of 137 +/- 15 nm, 95.17 +/- 3.43% drug entrapment, and zeta potential of 0.8314 +/- 0.0827 mV. Hydrolyzed gelatin based formulation was found to have low density, good flowability, particle size of 7.9 +/- 1.1 microm, maximum fine particle fraction (FPF) of 75.6 +/- 1.6%, mean mass aerodynamic diameter (MMAD) 2.2 +/- 0.1 microm, and geometric standard deviation (GSD) 2.3 +/- 0.1. Developed formulations were found to have in vitro prolonged drug release up to 16 h, and obeys Higuchi's Controlled Release model. The investigation provides a practical approach for direct delivery of DS encapsulated in NLs for site specific controlled and prolonged release behavior at the site of action and hence, may play a promising role in prevention of PCP. PMID:18446460

  18. Effect of Bacterial Pneumonia on Lung SIV Replication in Alcohol Consuming SIV Infected Rhesus Macaques

    PubMed Central

    Nelson, Steve; Happel, Kyle I.; Zhang, Ping; Myers, Leann; Dufour, Jason P.; Bagby, Gregory J.

    2013-01-01

    Background Opportunistic infections in HIV-infected persons have been shown to increase the rate of HIV replication. In populations where prophylaxis against Pneumocystis pneumonia is utilized, bacterial pneumonia is now the leading cause of lower respiratory tract infection in HIV+ patients. Our prior studies have shown that chronic alcohol consumption in simian demarcated immunodeficiency virus (SIV) infected rhesus macaques increases plasma viral load set point and accelerates progression to end-stage AIDS. While chronic alcohol abuse is well-known to increase the incidence and severity of bacterial pneumonia, the impact of alcohol consumption on local and systemic SIV/HIV burden during lung infection is unknown. Therefore, we utilized the macaque SIV infection model to examine the effect of chronic ethanol feeding on SIV burden during the course of pulmonary infection with Streptococcus pneumoniae, the most commonly identified etiology of bacterial pneumonia in HIV+ and HIV- persons in developed countries. Methods Alcohol was administered starting 3 months before SIVMac251 inoculation to the end of the study via an indwelling intragastric catheter to achieve a plasma alcohol concentration of 50–60 mM. Control animals received isocaloric sucrose. Four months after SIV infection, the right lung was inoculated with 2 × 106 CFU S. pneumoniae. Results Leukocyte recruitment into the lung, pulmonary bacterial clearance, and clinical course were similar between ethanol and control groups. While plasma SIV viral load was similar between groups post-pneumonia, chronic ethanol-fed macaques showed a prolonged increase in SIV RNA in bronchoalveolar lavage (BAL) fluid. Alveolar macrophages isolated from ethanol-fed macaques one day post-pneumonia showed greater nuclear factor kappa beta (NF-kB) activation. Conclusions This study indicates that chronic ethanol feeding results in enhanced local, but not systemic, SIV replication following pneumococcal pneumonia. Increased

  19. [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

  20. Pharmacokinetics of Dapsone Administered Daily and Weekly in Human Immunodeficiency Virus-Infected Children

    PubMed Central

    Mirochnick, Mark; Cooper, Ellen; McIntosh, Ken; Xu, Jing; Lindsey, Jane; Jacobus, David; Mofenson, Lynne; Sullivan, John L.; Dankner, Wayne; Frenkel, Lisa M.; Nachman, Sharon; Wara, Diane W.; Johnson, Daniel; Bonagura, Vincent R.; Rathore, Mobeen H.; Cunningham, Coleen K.; McNamara, James

    1999-01-01

    Although dapsone is a commonly used alternative agent for prophylaxis against Pneumocystis carinii pneumonia in children intolerant to trimethoprim-sulfamethoxazole, there are few data that describe dapsone pharmacokinetics in children. We studied dapsone pharmacokinetics in 30 children (median age, 2.8 years; age range, 0.3 to 12 years) receiving a new proprietary liquid preparation by three dosing regimens (1 mg/kg of body weight daily, 2 mg/kg daily, or 4 mg/kg weekly). Dosing of children with 2 mg/kg daily or 4 mg/kg weekly resulted in peak concentrations equivalent to those reached in adults receiving 100-mg tablets daily. For the entire population, the median half-life was 22.2 h (range, 7.1 to 40.3 h), the median oral clearance was 0.0365 liter/kg/h (range, 0.0104 to 0.1021 liter/kg/h), and the median oral apparent volume of distribution was 1.13 liters/kg (range, 0.50 to 2.32 liters/kg). The median dapsone oral clearance was significantly increased in those infants less than 2 years of age compared to the oral clearance in those over 2 years of age (0.0484 versus 0.0278 liter/kg/h; P = 0.011). These data suggest that absorption of this liquid preparation is adequate and that the concentrations in the sera of children receiving 2 mg/kg daily or 4 mg/kg weekly are equivalent to those seen in adults receiving standard dapsone dosing. Dapsone oral clearance appears to be increased in children under 2 years of age. PMID:10543733

  1. Extra-pulmonary aspects of acquired pulmonary alveolar proteinosis as predicted by granulocyte-macrophage colony-stimulating factor-deficient mice.

    PubMed

    Seymour, John F

    2006-01-01

    Granulocyte-macrophage colony-stimulating factor (GM-CSF)-/- mice are an invaluable model for exploring the effects of systemic GM-CSF deficiency. Their lung phenotype exactly reproduces the abnormalities seen in human pulmonary alveolar proteinosis (PAP). However, GM-CSF-/- mice also have significant systemic functional abnormalities. These include immune defects which result in a reduced susceptibility to a range of experimentally induced autoimmune disorders. These immunological defects are also functionally manifest as an impaired ability to resolve a range of infections under certain conditions, usually implicating cellular effectors, including Listeria, Group B streptococcus, adenovirus, Pneumocystis carinii, and malaria. These observations are consistent with the known propensity for patients with PAP to develop a range of opportunistic infections. Conversely, the diminished immunological response to inflammatory stimuli may be beneficial in some settings by limiting inflammatory cell recruitment and pro-inflammatory mediator-release. GM-CSF-/- mice also have distinct fertility defects, manifest as reduced litter size and an increased rate of early fetal loss. These observations may be clinically relevant for women affected by PAP and further support the evaluation of the role of GM-CSF in human reproduction. These observations reinforce the importance of clinicians viewing PAP as a state of systemic functional GM-CSF deficiency, albeit with prominent pulmonary manifestations, rather than purely a 'lung disease'. These systemic manifestations of GM-CSF deficiency should also be considered when deciding on the choice between pulmonary or systemic delivery of GM-CSF as therapy for PAP, as only systemic drug delivery has the potential capacity to correct the systemic manifestations of GM-CSF deficiency in these patients. PMID:16423263

  2. The 12th International Workshops on Opportunistic Protists (IWOP-12)

    PubMed Central

    Weiss, Louis M.; Cushion, Melanie T.; Didier, Elizabeth; Xiao, Lihua; Marciano-Cabral, Francine; Sinai, Anthony P.; Matos, Olga; Calderon, Enrique J.; Kaneshiro, Edna S.

    2013-01-01

    The 12th International Workshops on Opportunistic Protists (IWOP-12) was held in August 2012 in Tarrytown, New York. The objectives of the IWOP meetings are to: (1) serve as a forum for exchange of new information among active researchers concerning the basic biology, molecular genetics, immunology, biochemistry, pathogenesis, drug development, therapy, and epidemiology of these immunodeficiency-associated pathogenic eukaryotic microorganisms that are seen in patients with AIDS and (2) foster the entry of new and young investigators into these underserved research areas. The IWOP meeting focuses on opportunistic protists, e.g. the free-living amoebae, Pneumocystis, Cryptosporidium, Toxoplasma, the Microsporidia, and kinetoplastid flagellates. This conference represents the major conference that brings together research groups working on these opportunistic pathogens. Slow but steady progress is being achieved on understanding the biology of these pathogenic organisms, their involvement in disease causation in both immune-deficient and immune-competent hosts, and is providing critical insights into these emerging and reemerging pathogens. This IWOP meeting demonstrated the importance of newly developed genomic level information for many of these pathogens and how analysis of such large data sets is providing key insights into the basic biology of these organisms. A great concern is the loss of scientific expertise and diversity in the research community due to the ongoing decline in research funding. This loss of researchers is due to the small size of many of these research communities and a lack of appreciation by the larger scientific community concerning the state of art and challenges faced by researchers working on these organisms. PMID:23560871

  3. Diffuse lung uptake (DLU) on Ga-67 scintigraph: Clinical, radiologic and pathologic correlation

    SciTech Connect

    Sy, W.M.; Seo, I.S.; Vieira, J.; Zaman, M.

    1985-05-01

    Review, analysis and correlation (clinical, radiologic and pathologic) of 29 consecutive adults (16 drug addicts and/or homosexuals) with DLU on Ga-67 scintigraph were made. Diffuse increased uptake of at least 75% of both lungs was considered as DLU. WFOF cameras were used to obtain 24 to 96 hr. scintigraphs after IV injection of 3-5 mCi of Ga-67 citrate. In 26, tissue diagnosis established: pneumocystis carinii (PC) 15, miliary tuberculosis (TB) 3, sarcoidosis (SR) 3, drug-induced toxicity 2, and toxoplasmosis (TX), primary hyperparathyroidism and nonspecific lymphocytic pneumonia-one each. In two with breast and one with esophageal carcinomas, no lung tissue diagnosis was sought. Concurrent chest x-rays were negative in 16, but in 7/16, lung infiltrate was later documented. An average of 31 days elapsed before x-rays became positive in four with PC, 7 days in two with TB, and 22 days in one with TX. In 13, concurrent x-rays showed lung infiltrate, but in 6, only subtle, localized rather than diffuse infiltrate was noted. Fourteen of 29 had at least two Ga-67 studies. In 12 (7 PC, 2 TB, 3 SR) of 14 whose repeat studies showed significant to total disappearance of DLU, all did well clinically. In two whose initial studies were negative or equivocal, they became clinically worse when the repeat study showed DLU. In three others (2 PC, 1 TX) who died, their single studies recorded intense DLU. DLU on gallium scintigraph indicated a variety of pathology. In 55.2%, gallium scintigraph predated x-ray findings by a few days to weeks. In 20.3%, x-ray findings were only subtle or localized. Scintigraphic changes correlated well with the clinical courses in various diseases.

  4. Epidemiology of HIV-Associated Lung Disease in the United States.

    PubMed

    Fitzpatrick, Meghan; Brooks, John T; Kaplan, Jonathan E

    2016-04-01

    The epidemiology of HIV infection and its pulmonary complications in the United States has evolved significantly over nearly 20 years since the advent of combination antiretroviral therapy. While infectious complications are less of a threat to patients whose immune systems have been restored, many HIV-infected persons in the United States remain at high risk for opportunistic infection because they are unaware of their HIV infection, have difficulty maintaining linkage to care, or maintain inadequate viral control. Bacterial pneumonia and Pneumocystis pneumonia remain significantly more prevalent among HIV-infected persons, and together with seasonal influenza are areas where public health efforts to increase antiretroviral therapy, appropriate prophylaxis, and vaccination may decrease burden of disease. Noninfectious pulmonary complications of chronic HIV infection are increasingly recognized in the United States and elsewhere. Chronic obstructive pulmonary disease, asthma, pulmonary hypertension, sleep-disordered breathing, and primary lung cancer may all be more common among persons with HIV; of concern, disease burden in U.S. HIV-infected persons may be underestimated due to lack of diagnostic testing for these conditions. Smoking is among the most prevalent preventable causes of morbidity and mortality affecting persons living with HIV infection, and has particular import to pulmonary disease. As of 2009, 42% of HIV-infected adults in medical care in the United States smoked tobacco (over twice the national rate in the general population). Successful efforts to promote smoking cessation among HIV-infected persons are of critical importance to decrease the burden of chronic pulmonary disease. PMID:26974297

  5. 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

  6. 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

  7. Relevance of nucleic acid amplification techniques for diagnosis of respiratory tract infections in the clinical laboratory.

    PubMed Central

    Ieven, M; Goossens, H

    1997-01-01

    Clinical laboratories are increasingly receiving requests to perform nucleic acid amplification tests for the detection of a wide variety of infectious agents. In this paper, the efficiency of nucleic acid amplification techniques for the diagnosis of respiratory tract infections is reviewed. In general, these techniques should be applied only for the detection of microorganisms for which available diagnostic techniques are markedly insensitive or nonexistent or when turnaround times for existing tests (e.g., viral culture) are much longer than those expected with amplification. This is the case for rhinoviruses, coronaviruses, and hantaviruses causing a pulmonary syndrome, Bordetella pertussis, Chlamydia pneumoniae, Mycoplasma pneumoniae, and Coxiella burnetii. For Legionella spp. and fungi, contamination originating from the environment is a limiting factor in interpretation of results, as is the difficulty in differentiating colonization and infection. Detection of these agents in urine or blood by amplification techniques remains to be evaluated. In the clinical setting, there is no need for molecular diagnostic tests for the diagnosis of Pneumocystis carinii. At present, amplification methods for Mycobacterium tuberculosis cannot replace the classical diagnostic techniques, due to their lack of sensitivity and the absence of specific internal controls for the detection of inhibitors of the reaction. Also, the results of interlaboratory comparisons are unsatisfactory. Furthermore, isolates are needed for susceptibility studies. Additional work remains to be done on sample preparation methods, comparison between different amplification methods, and analysis of results. The techniques can be useful for the rapid identification of M. tuberculosis in particular circumstances, as well as the rapid detection of most rifampin-resistant isolates. The introduction of diagnostic amplification techniques into a clinical laboratory implies a level of proficiency for

  8. Ophthalmic manifestations of HIV in the highly active anti-retroviral therapy era.

    PubMed

    Mowatt, L

    2013-01-01

    HIV-related eye disease can be classified as retinal HIV microangiopathy, opportunistic infections, neuro-ophthalmic manifestations and unusual malignancies. There is a 52-100% lifetime accumulative risk of HIV patients developing eye problems. Seventy-seven per cent of patients with ocular manifestations of HIV had CD4 counts < 200 cells/μL. Cytomegalovirus (CMV) is the most prevalent opportunistic infection, however, Africa has a low incidence of this, and more commonly squamous cell carcinoma, compared to the western hemisphere. Due to highly active antiretroviral therapy (HAART), the anti-CMV therapy may be discontinued if the CD4+ T cell count is > 100 cells/μL for a minimum of three months. Despite HAART, patients with a CD4 count < 50 cells/μL have a similar risk of developing CMV retinitis as compared to the pre-HAART era. Opportunistic infections include CMV, herpetic retinopathy (progressive outer retinal necrosis - PORN), less commonly toxoplasmosis, pneumocystis and cryptococcus. Malignancies associated with HIV include Kaposi's sarcoma and conjunctival squamous cell carcinoma. Cranial nerve palsies, optic disc swelling and atrophy are characteristic neuro-ophthalmic features. They usually occur secondary to meningitis/encephalitis (from cryptococcus and tuberculosis). With the advent of HAART, new complications have developed in CMV retinitis: immune recovery uveitis (IRU) and cystoid macula oedema (CMO). Immune recovery uveitis occurs in 71% of patients if HAART is started before the induction of the anti-CMV treatment. However, this is reduced to 31% if HAART is started after the induction treatment. Molluscum contagiosum and Kaposi's sarcoma can spontaneously resolve on HAART. Highly active anti-retroviral therapy has reduced the frequencies of opportunistic infections and improved the remission duration in HIV patients. PMID:24756590

  9. Estimated Burden of Serious Fungal Infections in Jamaica by Literature Review and Modelling

    PubMed Central

    Gugnani, HC; Denning, DW

    2015-01-01

    ABSTRACT Objective: Jamaica is one of the largest countries in the Caribbean with a population of 2 706 500. Prevalence of human immunodeficiency virus (HIV) in Jamaica is high, while that of tuberculosis (TB) is recorded to be low. In this study, we have estimated the burden of serious fungal infections and some other mycoses in Jamaica. Methods: All published papers reporting on rates of fungal infections in Jamaica and the Caribbean were identified through extensive search of the literature. We also extracted data from published papers on epidemiology and from the World Health Organization (WHO) TB Programme and UNAIDS. Chronic pulmonary aspergillosis (CPA), allergic bronchopulmonary aspergillosis (ABPA) and severe asthma with fungal sensitization (SAFS) rates were derived from asthma and TB rates. Where there were no available data on some mycoses, we used specific populations at risk and frequencies of fungal infection of each to estimate national prevalence. Results: Over 57 600 people in Jamaica probably suffer from serious fungal infections each year, most related to ‘fungal asthma’ (ABPA and SAFS), recurrent vulvovaginal candidiasis and AIDS-related opportunistic infections. Histoplasmosis is endemic in Jamaica, though only a few clinical cases are known. Pneumocystis pneumonia is frequent while cryptococcosis and aspergillosis are rarely recorded. Tinea capitis was common in children. Recurrent vulvovaginal candidiasis is very common (3154/100 000) and candidaemia occurs. Subcutaneous mycoses such as chromoblastomycosis and mycetoma also seem to be relatively common. Conclusion: Local epidemiological studies are urgently required to validate or modify these estimates of serious fungal infections in Jamaica. PMID:26426178

  10. Recent trends in the spectrum of opportunistic infections in human immunodeficiency virus infected individuals on antiretroviral therapy in South India

    PubMed Central

    Shahapur, Praveen R.; Bidri, Rajendra C.

    2014-01-01

    Background: Opportunistic infections (OI) are the major cause of morbidity and mortality among human immunodeficiency virus (HIV) infected individuals. The pattern of OIs differs widely, hence it is necessary to correlate spectrum of OIs and CD4 counts among HIV infected individuals in specific localities. Materials and Methods: The present study describes the clinical and laboratory profiles of different OIs among 55 HIV seropositive patients. CD4 count was estimated and antiretroviral therapy (ART) was started in 27 patients as per National Acquired Immunodeficiency Syndrome Control Organization guidelines. These 27 patients were classified into stage 1, stage 2 and stage 3 based on CD4 counts of >500 cells/μl, 200-499 cells/μl and <200 cells/μl respectively. The OIs presented by respective groups were documented. Results: Pulmonary tuberculosis was found to be the most common OI constituting 43.6% of all cases followed by candidiasis (30.9%), cryptosporidial diarrhea (21.8%), herpes zoster (16.3%), cryptococcal meningitis (3.63%), Pneumocystis jirovecii pneumonia (1.81%), and other miscellaneous infections (23.6%). Only 1 patient was found in stage I while 13 patients each were grouped in stage II or stage III. The mean CD4 count in our study population who were on ART was 230 ± 150 cells/µl. Conclusion: The pattern of OIs among our study group did not differ significantly from patients not receiving ART. The effect of ART on CD4 count differs from patient to patient based on the degree of depletion of CD4 count before the initiation of ART, drug adherence, concomitant OIs and their treatment. PMID:25097422

  11. The Impact of Opportunistic Infections on Clinical Outcome and Healthcare Resource Uses for Adult T Cell Leukaemia

    PubMed Central

    Maeda, Toshiki; Babazono, Akira; Nishi, Takumi; Yasui, Midori; Matsuda, Shinya; Fushimi, Kiyohide; Fujimori, Kenji

    2015-01-01

    We examined the impact of opportunistic infections on in-hospital mortality, hospital length of stay (LOS), and the total cost (TC) among adult T-cell leukaemia (ATL) patients. In this retrospective cohort study, we identified 3712 patients with ATL using national hospital administrative data. Analysed opportunistic infections included Aspergillus spp., Candida spp., cytomegalovirus (CMV), herpes simplex virus (HSV), pneumocystis pneumonia (PCP), tuberculosis, varicella zoster virus (VZV), Cryptococcus spp., nontuberculous mycobacteria, and Strongyloides spp. Multilevel logistic regression analysis for in-hospital mortality and a multilevel linear regression analysis for LOS and TC were employed to determine the impact of opportunistic infections on clinical outcomes and healthcare resources. We found ATL patients infected with CMV had significantly higher in-hospital mortality (adjusted odds ratio (AOR) 2.29 [1.50–3.49] p < 0.001), longer LOS (coefficient (B): 0.13 [0.06–0.20] p < 0.001) and higher TC (B: 0.25 [0.17–0.32] p < 0.001) than those without CMV. Those with CAN and PCP were associated with a lower in-hospital mortality rate (AOR 0.72 [0.53–0.98] p = 0.035 and 0.54[0.41–0.73] p < 0.001, respectively) than their infections. VZV was associated with longer LOS (B: 0.13 [0.06–0.19] p < 0.001), while aspergillosis, HSV, or VZV infections were associated with higher TC (B: 0.16 [0.07–0.24] p < 0.001, 0.12 [0.02–0.23] p = 0.025, and 0.17 [0.10–0.24] p < 0.001, respectively). Our findings reveal that CMV infection is a major determinant of poor prognosis in patients affected by ATL. PMID:26274925

  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. Clinical features of HIV/AIDS patients presenting to an inner city clinic in Ho Chi Minh City, Vietnam.

    PubMed

    Klotz, Stephen A; Nguyen, Hao Cong; Van Pham, Tam; Nguyen, Liem Thanh; Ngo, Dong Thi Anh; Vu, Son Nhoc

    2007-07-01

    An outpatient HIV clinic was opened in March 2005 in Binh Thanh District, a poor section of Ho Chi Minh City, Vietnam. Over 1500 patients were seen in the first year. The average age of patients was 27 years. Men represented 77% of the clinic population, women, 23% and children under the age of 16 years of age, 5% of the population. The most common risk factor among men was being an injecting drug user (IDU), 76%, and among women, being married to an IDU HIV-positive man, 35%. Physical signs of disease were uncommon: lymphadenopathy in 24% and hepatomegaly and splenomegaly in 4% and 3%, respectively. Men and women were anaemic at presentation, with a mean haemoglobin of 11.9 g/dL and 11.1 g/dL, respectively. An overwhelming majority of patients had profound immunodeficiency. The mean CD4+ cell count was 164 cells/mL and the median was 69 cells/mL. No correlation was found between the World Health Organization's stage of disease and the CD4+ cell count. Thus, the former is a poor predictor of immunity in this population. Data regarding opportunistic infections diagnosed at the first visit were studied. Candidiasis of the oral pharynx, oesophagus or vagina was found in 34.5% of the patients, and pulmonary and extrapulmonary tuberculosis was found in 32% of the patients. Pneumocystis carinii pneumonia (PCP) was diagnosed in only 3% of the patients. Cotrimoxazole prophylaxis is advocated for HIV-infected Vietnamese, but the incidence of PCP is negligible and resources could be spent elsewhere. The various opportunistic infections seen in this resource-poor clinic setting is likely to be a pattern of presentation of HIV-infected Vietnamese for some time to come. PMID:17623507

  14. 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

  15. 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

  16. Early mortality and cause of deaths in patients using HAART in Brazil and the United States

    PubMed Central

    Grinsztejn, Beatriz; Veloso, Valdilea G.; Friedman, Ruth K.; Moreira, Ronaldo I.; Luz, Paula M.; Campos, Dayse P.; Pilotto, José H.; Cardoso, Sandra W.; Keruly, Jeanne C.; Moore, Richard D.

    2013-01-01

    Objective: To compare the early mortality pattern and causes of death among patients starting HAART in Brazil and the United States. Methods: We analyzed the combined data from two clinical cohorts followed at the Johns Hopkins AIDS Service in Baltimore, United States, and the Evandro Chagas Clinical Research Institute AIDS Clinic in Rio de Janeiro, Brazil. Participants included those who entered either cohort between 1999 and 2007 and were antiretroviral naive. Follow-up was at 1 year since HAART initiation. Cox proportional hazards regression analysis was used to assess the role of the city on the risk of death. Results: A total of 859 and 915 participants from Baltimore and Rio de Janeiro, respectively, were included. In Rio de Janeiro, 64.7% of deaths occurred within 90 days of HAART initiation; in Baltimore, 48.9% occurred between 180 and 365 days. AIDS-defining illness (61.8%) and non-AIDS-defining illness (55.6%) predominated as causes of death in Rio de Janeiro and Baltimore, respectively. Risk of death was similar in both cities (hazard ratio 1.04; P value=0.95) after adjusting for CD4+ T cell count, age, sex, HIV risk group, prior AIDS-defining illness, and Pneumocystis jirovecii pneumonia and Mycobacterium avium prophylaxis. Individuals with CD4+ T cell count less than or equal to 50 cells/μl (hazard ratio 4.36; P = 0.001) or older (hazard ratio, 1.03; P = 0.03) were more likely to die. Conclusion: Although late HIV diagnosis is a problem both in developed and developing countries, differences in the timing and causes of deaths clearly indicate that, besides interventions for early HIV diagnosis, different strategies to curb early mortality need to be tailored in each country. PMID:19770698

  17. Post-transplantation Infections in Bolivia.

    PubMed

    Arze, S; Arze, L; Abecia, C

    2016-03-01

    Over 26 years, we found 46 infectious episodes in 350 kidney transplant recipients. Fifteen were urinary tract infections, recurrent in 4 patients. There were 8 cytomegalovirus infections, three of them fatal when intravenous (IV) ganciclovir was not available. Seven patients had a reactivation of tuberculosis (TB) in the pleura, cervical spine, lumbar spine, knee, ankle, skin and peritoneum, respectively, and were all resolved satisfactorily with conventional anti-TB therapy. Three patients transplanted before routine prophylaxis with the use of acyclovir developed an extensive herpes zoster infection in the 1st 6 months after transplantation, which was resolved with the use of oral acyclovir, and 1 had a disseminated herpes simplex infection resolved with the use of IV acyclovir. Three patients transplanted before routine prophylaxis with trimethoprim sulfa developed Pneumocystis carinii pneumonia in the 1st 6 months after transplantation, which was fatal in one of them. In 2 patients, we found a Nocardia infection, confined to the lung, which was cured in one of the cases and systemic and fatal in the other. Two patients transplanted before routine prophylaxis with the use of nystatin developed esophageal candidiasis in the 1st 6 months after transplantation. One patient developed infective endocarditis in a stenotic bicuspid aortic valve and died 10 years later after another incident of infective endocarditis at the prosthetic aortic valve. Two patients developed an extensive condyloma at the penis, perianal region, and perineum owing to human papillomavirus, requiring extensive surgical resection and podophyllin applications. Another patient developed fatal post-transplantation lymphoproliferative disease due to Epstein-Barr virus infection 15 years after transplantation. One patient developed a severe and fatal mucocutaneous leishmaniasis with no response to conventional antimonial therapy. It is interesting to note that despite Chagas disease being endemic

  18. Introduction and immunopathogenesis of acquired immune deficiency syndrome

    PubMed Central

    Sudharshan, S

    2008-01-01

    India has a large number of patients with acquired immune deficiency syndrome (AIDS), the third largest population of this group in the world. This disease was first described in patients with Pneumocystis pneumonia in 1981. Ocular lesions can occur at any stage of the disease but are more commonly seen at the late stages. Human immunodeficiency virus (HIV), the causative agent of AIDS is a retrovirus with RNA genome and a unique ′Reverse transcriptase enzyme′ and is of two types, HIV-1 and 2. Most human diseases are caused by HIV-1. The HIV-1 subtypes prevalent in India are A, B and C. They act predominantly by reducing the CD4+ cells and thus the patient becomes susceptible to opportunistic infections. High viral titers in the peripheral blood during primary infection lead to decrease in the number of CD4+ T lymphocytes. Onset of HIV-1-specific cellular immune response with synthesis of HIV-1 specific antibodies leads to the decline of plasma viral load and chronification of HIV-1 infection. However, the asymptomatic stage of infection may lead to persistent viral replication and a rapid turnover of plasma virions which is the clinical latency. During this period, there is further decrease in the CD4+ counts which makes the patient′s immune system incapable of controlling opportunistic pathogens and thus life-threatening AIDS-defining diseases emerge. Advent of highly active antiretroviral treatment (HAART) has revolutionized the management of AIDS though there is associated increased development of immune recovery uveitis in a few of these patients. PMID:18711263

  19. Human immunodeficiency virus (HIV)-related pulmonary complications in pregnancy.

    PubMed

    Saade, G R

    1997-08-01

    With changes in the demographics of human immunodeficiency virus (HIV) infection, women and children are becoming the fastest growing group of newly infected patients. With longer survival after HIV infection, more women infected with HIV are becoming pregnant. Pulmonary disease is one of the most common presenting conditions in an AIDS-defining illness. Pneumocystis carini pneumonia and tuberculosis are the most common disorders that herald the onset of AIDS. They are also the most frequently encountered HIV-related pulmonary complications during pregnancy. Others have been rarely reported during pregnancy and include fungal infections (Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitus), bacterial infections (Haemophilus influenzae and Streptococcus pneumoniae along with Pseudomona aeruginosa), viral infections (CMV), opportunistic neoplasms (Kaposi's sarcoma, lymphoma) and miscellaneous conditions peculiar to HIV-infected individuals (nonspecific interstitial pneumonitis, lymphoid interstitial pneumonitis, isolated pulmonary hypertension, and pulmonary edema secondary to cardiac disease or drug abuse). Most of the data regarding the pulmonary complications of HIV infection come from studies in nonpregnant patients. The extent to which pregnancy affects the course of respiratory disease in HIV infection and vice versa is not well documented. Clinical presentation is usually not altered by pregnancy. Except for minor modifications mainly related to potential fetal effects, the diagnostic work-up and management are similar to those in the nonpregnant patient. The most important effect of pregnancy on these conditions remains the delay in diagnosis and treatment. A high index of suspicion should, therefore, be maintained. In addition, most prophylactic measures recommended in nonpregnant HIV-infected individuals also apply to pregnant women. PMID:9298723

  20. Pharmacokinetics and metabolism of the prodrug DB289 (2,5-bis[4-(N-methoxyamidino)phenyl]furan monomaleate) in rat and monkey and its conversion to the antiprotozoal/antifungal drug DB75 (2,5-bis(4-guanylphenyl)furan dihydrochloride).

    PubMed

    Midgley, Ian; Fitzpatrick, Karen; Taylor, Lynne M; Houchen, Tara L; Henderson, Simon J; Wright, Sarah J; Cybulski, Zbigniew R; John, Brian A; McBurney, Alan; Boykin, David W; Trendler, Kerri L

    2007-06-01

    DB289 (pafuramidine maleate; 2,5-bis[4-(N-methoxyamidino)phenyl]furan monomaleate) is a prodrug of DB75 (furamidine dihydrochloride; 2,5-bis(4-guanylphenyl)furan dihydrochloride), an aromatic dication related to pentamidine that has demonstrated good efficacy against African trypanosomiasis, Pneumocystis carinii pneumonia, and malaria, but lacks adequate oral availability. The pharmacokinetics and metabolism of 14C-DB289 have been investigated in rat and monkey after oral and intravenous administration. Oral doses were well absorbed (approximately 50-70%) and effectively converted to DB75 in both species but subject to first-pass metabolism and hepatic retention, limiting its systemic bioavailability to 10 to 20%. Clearance of DB289 approximated the liver plasma flow and its large volume of distribution was consistent with extensive tissue binding. Plasma protein binding of DB289 was 97 to 99% in four animal species and humans, but that of DB75 was noticeably less and more species- and concentration-dependent. Together, prodrug and active metabolite accounted for less than 20% of the plasma radioactivity after an oral dose, but DB75 was the major radiochemical component in key organs such as brain and liver and was largely responsible for the persistence of 14C in the body. The predominant route of excretion of radioactivity was via the feces, although biliary secretion was not particularly extensive. High-performance liquid chromatography and liquid chromatography-mass spectrometry investigations showed that the formation of DB75 from the prodrug involved the sequential loss of the two N-methoxy groups, either directly or by O-demethylation followed by reduction of the resulting oxime to the amidine. It was estimated that almost half of an oral dose of DB289 to rats and about one-third of that to monkeys was metabolized to DB75. PMID:17360833

  1. Trimethoprim/Sulfamethoxazole-Induced Severe Lactic Acidosis

    PubMed Central

    Bulathsinghala, Marie; Keefer, Kimberly; Van de Louw, Andry

    2016-01-01

    Abstract Propylene glycol (PG) is used as a solvent in numerous medications, including trimethoprim/sulfamethoxazole (TMP/SMX) and lorazepam, and is metabolized in the liver to lactic acid. Cases of lactic acidosis related to PG toxicity have been described and always involved large doses of benzodiazepines and PG. We present the first case of severe lactic acidosis after a 3-day course of TMP/SMX alone, involving allegedly safe amounts of PG. A 31-year-old female with neurofibromatosis and pilocytic astrocytoma, receiving temozolomide and steroids, was admitted to the intensive care unit for pneumonia and acute respiratory failure requiring intubation. Her initial hemodynamic and acid–base statuses were normal. She was treated with intravenous TMP/SMX for possible Pneumocystis jirovecii pneumonia and was successfully extubated on day 2. On day 3, she developed tachypnea and arterial blood gas analysis revealed a severe metabolic acidosis (pH 7.2, PCO2 19 mm Hg, bicarbonates 8 mEq/L) with anion gap of 25 mEq/L and lactate of 12.1 mmol/L. TMP/SMX was discontinued and the lactate decreased to 2.9 mmol/L within 24 hours while her plasma bicarbonates normalized, without additional intervention. The patient never developed hypotension or severe hypoxia, and her renal and liver functions were normal. No other cause for lactic acidosis was identified and it resolved after TMP/SMX cessation alone, suggesting PG toxicity. Although PG-related lactic acidosis is well recognized after large doses of lorazepam, clinicians should bear in mind that TMP/SMX contains PG as well and should suspect PG toxicity in patients developing unexplained metabolic acidosis while receiving TMP/SMX. PMID:27124045

  2. [Positive HIV (human immunodeficiency virus) serology in the pregnant woman: current data on its management. Apropos of a continuous series of 56 cases].

    PubMed

    Constantopoulos, P; Gabaude, B; Duforestel, T; Fuzibet, J G; Mourey, C; Lefebvre, J C; Cassuto, J P; Gillet, J Y

    1987-01-01

    56 cases of pregnant women with a positive HIV serology were reported in 20 months at the Maternity of the Nice Hospital Center. In 10 cases, there were clinical signs of the disease (9 ARC-Syndrome, one case of AIDS). The predisposing factor was most of the time drug addiction, 53 cases (94.5%) and one case occurred after a blood transfusion. In the majority of the cases (52%) the pregnancy was pursued because of the late term or the patient's decision. A therapeutic abortion was performed in 12 instances (25%) and an interruption before 12 weeks of amenorrhea in 15 cases. 24 women delivered. The obstetrical complications were frequent with especially a fetal death in utero, five premature deliveries and fifteen hypotrophies. A severe infectious complication (septicemia, pneumopathy secondary to Pneumocystis carinii) was observed in 9 cases, a marked thrombopenia causing profuse post-partum haemorrhages in one case. Finally, one woman died 35 days after delivery. The study of the consequences on the child is incomplete because of insufficient follow-up: all children were sero-positive at birth and among thirteen children aged between 12 to 20 months, there were one death, one AIDS syndrome, 4 ARC-syndrome, 4 sero-positive and 3 sero-negative. The notion of HIV sero-positivity in a pregnant woman presents serious problems for the obstetrician. Decompensation of the disease during the pregnancy is uncertain but it is now confirmed that the child is affected, and this is a well established fact. These important consequences lead to propose, at this time a therapeutic interruption of pregnancy when possible, depending on the term, and when accepted by the patient. PMID:3478787

  3. Acquired immunodeficiency syndrome (AIDS) with lymphocytic interstitial pneumonitis (LIP) in a multi transfused child with thalassemia major.

    PubMed

    Sen, S; Goyal, R S; Kumar, A; Pande, I; Khare, S D; Chattopadhya, D; Malaviya, A N

    1992-11-01

    -trimoxazole for prophylaxis against Pneumocystis carinii infection. PMID:1294497

  4. Survival after diagnosis of AIDS: a prospective observational study of 2625 patients. Royal Free/Chelsea and Westminster Hospitals Collaborative Group.

    PubMed Central

    Mocroft, A.; Youle, M.; Morcinek, J.; Sabin, C. A.; Gazzard, B.; Johnson, M. A.; Phillips, A. N.

    1997-01-01

    OBJECTIVE: To estimate median survival and changes in survival in patients diagnosed as having AIDS. DESIGN: Prospective observational study. SETTING: Clinics in two large London hospitals. SUBJECTS: 2625 patients with AIDS seen between 1982 and July 1995. MAIN OUTCOME MEASURES: Survival, estimated using lifetable analyses, and factors associated with survival, identified from Cox proportional hazards models. RESULTS: Median survival (20 months) was longer than previous estimates. The CD4 lymphocyte count at or before initial AIDS defining illness decreased significantly over time from 90 x 10(6)/1 during 1987 or earlier to 40 x 10(6)/1 during 1994 and 1995 (P < 0.0001). In the first three months after diagnosis, patients in whom AIDS was diagnosed after 1987 had a much lower risk of death (relative risk 0.44, 95% confidence interval 0.22 to 0.86; P = 0.017) than patients diagnosed before 1987. When the diagnosis was based on oesophageal candidiasis or Kaposi's sarcoma, patients had a lower risk of death than when the diagnosis was based on Pneumocystis carinii pneumonia (0.21 (0.07 to 0.59). P = 0.0030 and 0.37 (0.16 to 0.83), P = 0.016). Three months after AIDS diagnosis, the risk of death was similar in patients whose diagnosis was made after and before 1987 (1.02 (0.79 to 1.31), P = 0.91). There were no differences in survival between patients diagnosed during 1988-90, 1991-3, or 1994-5. CONCLUSIONS: In later years, patients were much more likely to survive their initial illness, but long term survival has remained poor. The decrease in CD4 lymphocyte count at AIDS diagnosis indicates that patients are being diagnosed as having AIDS at ever more advanced stages of immunodeficiency. PMID:9040386

  5. Altered natural history of AIDS-related opportunistic infections in the era of potent combination antiretroviral therapy.

    PubMed

    Jacobson, M A; French, M

    1998-01-01

    Since potent HIV protease inhibitor drugs became widely available in early 1996, many HIV clinical specialists have noted a marked decrease in the occurrence of AIDS-related opportunistic infections, and some specialists have reported unusual clinical presentations and manifestations of previously common opportunistic infections. In this article, we will review (1) the available data regarding recent trends in AIDS-related opportunistic infections incidence and manifestations, (2) clinical and immunologic evidence that potent combination antiretroviral therapy can alter the natural history of these opportunistic infections, and (3) the implications of these findings for current patient management practice and future clinical and immunologic research. As a preface to this review, however, it is important to acknowledge that any evaluation of the potential benefit of potent combination antiretroviral therapy in reducing the risk of serious opportunistic infections can be confounded by the concomitant use of prophylactic antimicrobial agents co-administered to prevent specific opportunistic infections. For example, it is standard clinical practice to administer trimethoprim-sulfamethoxazole (or another agent if trimethoprim-sulfamethoxazole cannot be tolerated) to patients with an absolute CD4 lymphocyte count < 200 cells/microliters, unexplained chronic fever or a history of oropharyngeal candidiasis. Similarly, specific antimicrobial prophylaxis to prevent disseminated Mycobacterium avium complex (MAC) infection in patients with absolute CD4 counts < 50 cells/microliters is also a widely recommended guideline. Although the relative efficacies of specific antimicrobial prophylaxis regimens in preventing the most common life- and sight-threatening opportunistic infectious complications of AIDS [Pneumocystis carinii pneumonia (PCP), disseminated MAC infection, and cytomegalovirus (CMV) retinitis] are now well established, these relative efficacies were established in

  6. Trimethoprim/Sulfamethoxazole-Induced Severe Lactic Acidosis: A Case Report and Review of the Literature.

    PubMed

    Bulathsinghala, Marie; Keefer, Kimberly; Van de Louw, Andry

    2016-04-01

    Propylene glycol (PG) is used as a solvent in numerous medications, including trimethoprim/sulfamethoxazole (TMP/SMX) and lorazepam, and is metabolized in the liver to lactic acid. Cases of lactic acidosis related to PG toxicity have been described and always involved large doses of benzodiazepines and PG. We present the first case of severe lactic acidosis after a 3-day course of TMP/SMX alone, involving allegedly safe amounts of PG.A 31-year-old female with neurofibromatosis and pilocytic astrocytoma, receiving temozolomide and steroids, was admitted to the intensive care unit for pneumonia and acute respiratory failure requiring intubation. Her initial hemodynamic and acid-base statuses were normal. She was treated with intravenous TMP/SMX for possible Pneumocystis jirovecii pneumonia and was successfully extubated on day 2. On day 3, she developed tachypnea and arterial blood gas analysis revealed a severe metabolic acidosis (pH 7.2, PCO2 19 mm Hg, bicarbonates 8 mEq/L) with anion gap of 25 mEq/L and lactate of 12.1 mmol/L. TMP/SMX was discontinued and the lactate decreased to 2.9 mmol/L within 24 hours while her plasma bicarbonates normalized, without additional intervention. The patient never developed hypotension or severe hypoxia, and her renal and liver functions were normal. No other cause for lactic acidosis was identified and it resolved after TMP/SMX cessation alone, suggesting PG toxicity.Although PG-related lactic acidosis is well recognized after large doses of lorazepam, clinicians should bear in mind that TMP/SMX contains PG as well and should suspect PG toxicity in patients developing unexplained metabolic acidosis while receiving TMP/SMX. PMID:27124045

  7. Antipneumocystis activity of water-soluble lipopeptide L-693,989 in rats.

    PubMed Central

    Schmatz, D M; Powles, M A; McFadden, D C; Pittarelli, L; Balkovec, J; Hammond, M; Zambias, R; Liberator, P; Anderson, J

    1992-01-01

    Water-soluble lipopeptide L-693,989 was evaluated for its antipneumocystis activity in rats. Rats from colonies with latent Pneumocystis carinii infections were immunosuppressed with dexamethasone for 6 weeks to facilitate the development of acute P. carinii pneumonia (PCP). After 6 weeks, the rats were maintained on dexamethasone and were treated twice daily for 4 days with various concentrations of L-693,989. At a dose of 0.15 mg/kg of body weight, the compound effectively eliminated 90% of the cysts in 4 days. Trophozoite forms of P. carinii were still present in these animals, as determined by using a P. carinii-specific DNA probe. A 3-week therapy study showed that the trophozoite load did not expand during treatment and that the trophozoites already present at the initiation of therapy appeared to persist. This may be a consequence of the stage specificity of the compound for cyst development and the severe immunosuppressive effects of dexamethasone on rats. When evaluated as a daily parenteral prophylactic agent, L-693,989 was effective in preventing the development of both P. carinii cysts and trophozoites, demonstrating its potential for use in prophylaxis and implying that the cyst stage of P. carinii is an obligatory step in trophozoite multiplication. The foamy exudate commonly associated with P. carinii infections was absent in the lungs of rats on prophylaxis. The compound was also evaluated via oral administration and was found to have a 90% effective dose of 32 mg/kg for therapy of acute infections and 5 mg/kg for daily prophylaxis. Images PMID:1416888

  8. Disparities in the Magnitude of Human Immunodeficiency Virus-related Opportunistic Infections Between High and Low/Middle-income Countries: Is Highly Active Antiretroviral Therapy Changing the Trend?

    PubMed

    Iroezindu, M O

    2016-01-01

    Opportunistic infections (OIs) cause significant morbidity/mortality in human immunodeficiency virus (HIV)-infected individuals globally. Disparities between high-income countries (HICs) and low/middle-income countries (LMICs) in the magnitude of HIV-related OIs in pre-highly active antiretroviral therapy (HAART) populations was reviewed, and HAART-induced decline in OIs was further compared between the two settings. Studies published in English from onset of HIV epidemic up to December 2013 were searched in PubMed, Google, Google Scholar, and African Journal online. An article was included if (a) the study was conducted in HIC or LMIC, (b) the age of the participants was ≥12 years, (c) the HAART status of the participants was stated, and (d) various types of OIs were investigated. In predominantly pre-HAART populations, the incidence and prevalence of overall HIV-related OIs in HIC ranged from 5.5 to 50.0 per 100 person-years (PY) and 27.4-56.7%, respectively. In LMIC, the respective overall incidence and prevalence of OIs were 12.2-93.9 per 100 PY and 32.0-77.7%. Pneumocystis jirovecii pneumonia, candidiasis, Cytomegalovirus disease, Mycobacterium avium complex disease, and Kaposi's sarcoma were the most frequent OIs in HICs while tuberculosis, candidiasis, chronic diarrhea, and cryptococcosis were predominant in LMICs. The introduction of HAART led to substantial reduction in the incidence of OIs with more impressive percentage decline in HICs (43-97%) compared to 30-79% in LMICs. Disparities in the magnitude of HIV-related OIs between HICs and LMICs are evident both in the pre-HAART and post-HAART era. Efforts to optimize HAART-induced decline in HIV-related OIs should become a global health priority irrespective of prevailing socioeconomic circumstances. PMID:27144071

  9. Clinical manifestations and outcome of patients with human immunodeficiency virus infection at tertiary care teaching hospital

    PubMed Central

    Patil, Virendra Chandrashekhar; Patil, Harsha V.

    2016-01-01

    Background: AIDS has become chronic illness which is well treated with antiretroviral therapy and management of opportunistic infections (OIs). Aims and Objectives: The study clinical profile and outcome of human immunodeficiency virus (HIV) seropositive patients. Materials and Methods: This was retrospective observational study carried out over a period of 1 year (January 2011–December 2011). All HIV patients admitted in medicine ward, and ICU were enrolled. Statistical analysis was performed using SSPE statistical software trial version 11. The P< 0.05 was considered as statistically significant. Results: Of total 111 patients with a diagnosis of HIV/AIDS, 75 (67.56%) were male and 36 (32.43%) were female patients. A total 52 (46.84%) patients presented with respiratory manifestations, of them 23 (44.23%) had pulmonary tuberculosis (TB), 6 (11.53%) had tubercular effusion, and 3 (5.76%) had Pneumocystis jirovecii pneumonia. Respiratory manifestations including pulmonary TB were the most common presentation (P< 0.001). Total 27 (24.32%) patients were presented with the neurological manifestation of them 8 (29.62%) had a cerebro-vascular accident, 5 (18.51%) had cryptococcal meningitis, 4 (14.81%) had tubercular meningitis, and 1 (3.70%) had progressive multifocal leukoencephalopathy. Total 12 (38.70%) had acute gastroenteritis 6 (19.35%) had oral candidiasis, 8 (25%) had general tonic clonic seizure and 7 (21.87%) had pyrexia of unknown origin, 6 (18.75%) had septicemia, 6 (18.75%) had acute renal failure, and 6 (94.11%) had anemia. A total 11 (9.90%) patients succumbed. Conclusions: Overall respiratory manifestations were the common presentation in a present cohort of HIV seropositive patients and TB was the most common OI and the cerebrovascular accident was the most common neurological manifestation. PMID:27190411

  10. HIV and/or AIDS-related deaths and modifiable risk factors: A descriptive study of medical admissions at Oshakati Intermediate Hospital in Northern Namibia

    PubMed Central

    Mgori, N.K.

    2015-01-01

    Background High rates of HIV infection have decreased life expectancy in many African countries. Regardless of worldwide efforts to escalate treatment, care and prevention strategies, the number of deaths due to AIDS-related disorders is still high. Local healthcare workers suspect that there are modifiable factors in the care of HIV and/or AIDS patients which can be identified and improved. Aim To describe the HIV and/or AIDS-related causes of adult mortality and identify modifiable factors amongst patients admitted to Oshakati Intermediate Hospital, northern Namibia. Methods Data was extracted retrospectively and coded using the modified CoDe protocol for AIDS. Modifiable factors relating to the patient, health system or clinical care were identified using a standardised data collection tool. Results A total of 177 HIV and/or AIDS patients were identified, 94 (53.1%) were male and 120 (68%) had a CD4 count of less than 200 cells/mL. The common HIV-related causes of death were tuberculosis (25.9%), renal failure (15.8%), Pneumocystis jirovecii pneumonia (11.3%), cryptococcal meningitis (9%), HIV wasting syndrome (7.9%) and AIDS-defining malignancy (7.9%). The analysis revealed 281 modifiable factors; patient-related factors were the most common (153 [54.4%]), followed by health system factors (97 [34.5%]) and healthcare personnel factors (31 [11%]). Conclusion Our findings have highlighted the challenges in overall HIV and/or AIDS inpatient care and surrounding primary care facilities. The identification of specific modifiable factors can be used to reduce mortality by providing training as well as rational monitoring, planning and resource allocation.

  11. Thoracic Diseases Associated with HIV Infection in the Era of Antiretroviral Therapy: Clinical and Imaging Findings

    PubMed Central

    Prabhu, Somnath J.; Crothers, Kristina; Stern, Eric J.; Godwin, J. David; Pipavath, Sudhakar N.

    2014-01-01

    The human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) pandemic has entered its 4th decade. Since the introduction of combination antiretroviral therapy (ART) in 1996, the number of AIDS-related deaths has plateaued worldwide. Today, owing to the effectiveness of ART, the HIV-infected population is aging and HIV infection has become a chronic illness. Non-AIDS comorbidities are increasing, and the spectrum of HIV-related thoracic diseases is evolving. In developed countries, bacterial pneumonia has become more common than Pneumocystis pneumonia. Its imaging appearance depends on the responsible organism, most commonly Streptococcus pneumoniae. Mycobacterium tuberculosis continues to be a major threat. Its imaging patterns vary depending on CD4 count. Primary lung cancer and Hodgkin lymphoma are two important non–AIDS-defining malignancies that are increasingly encountered at chest imaging. Human herpesvirus 8, also known as Kaposi sarcoma–associated herpesvirus (KSHV), is strongly linked to HIV-related diseases, including Kaposi sarcoma, multicentric Castleman disease, KSHV inflammatory cytokine syndrome, and primary effusion lymphoma. Immune reconstitution inflammatory syndrome is a direct complication of ART whose manifestations vary with the underlying disease. Given the high rate of smoking among HIV-infected patients, chronic obstructive pulmonary disease is another important cause of morbidity and mortality. A high degree of suspicion is required for the early diagnosis of pulmonary arterial hypertension and lymphocytic interstitial pneumonia, given their nonspecific manifestations. Finally, multilocular thymic cyst manifests as a cystic anterior mediastinal mass. Recognition of the clinical and radiologic manifestations of these less traditional HIV-related diseases can expedite diagnosis and treatment in the ART era. © RSNA, 2014 PMID:25019430

  12. Diminazene aceturate--An antiparasitic drug of antiquity: Advances in pharmacology & therapeutics.

    PubMed

    da Silva Oliveira, George Laylson; de Freitas, Rivelilson Mendes

    2015-12-01

    Diminazene aceturate (C14H15N7.2C4H7NO3) is an aromatic diamidine that was developed more than six decades ago and has been marketed until today for the control of trypanosomiasis. In recent years, however, this trypanocidal compound has been extensively studied with respect to its therapeutic potential and has consequently attracted much interest for the development of further research. The objective of this study was to conduct a systematic review on diminazene aceturate regarding its pharmacological properties. In this way, databases were searched for articles (ScienceDirect, Scopus, PubMed, Web of Science and SciFinder) and patents (INPI, USPTO, WIPO, DPMA, SIPO, DERWENT, CIPO and EPO). For the development of this review, 115 articles and 22 patents were selected and analyzed. It was thus possible to highlight several researches that have investigated alternatives in order to improve success in the treatment of animal trypanosomiasis, by using new drugs in associations with diminazene aceturate, as well as looking for new pharmacological applications for this compound, such as leishmanicidal, amebicidal, anti-pneumocystis, anti-rheumatoid arthritis, antihypertensive agent, and mainly as an activator of angiotensin-converting enzyme 2. Another pharmacological property still little studied is the inhibition of acid-sensitive ion channels (ASIC1a, ASIC1b, ASIC2a and ASIC3), which are related to the development of various diseases. Collectively, these studies conducted by several research groups extend the use of diminazene aceturate beyond the antitrypanosomal activity and suggest promising new applications. PMID:26470648

  13. 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

  14. Consensus definitions of 14 severe acute toxic effects for childhood lymphoblastic leukaemia treatment: a Delphi consensus.

    PubMed

    Schmiegelow, Kjeld; Attarbaschi, Andishe; Barzilai, Shlomit; Escherich, Gabriele; Frandsen, Thomas Leth; Halsey, Christina; Hough, Rachael; Jeha, Sima; Kato, Motohiro; Liang, Der-Cherng; Mikkelsen, Torben Stamm; Möricke, Anja; Niinimäki, Riitta; Piette, Caroline; Putti, Maria Caterina; Raetz, Elizabeth; Silverman, Lewis B; Skinner, Roderick; Tuckuviene, Ruta; van der Sluis, Inge; Zapotocka, Ester

    2016-06-01

    Although there are high survival rates for children with acute lymphoblastic leukaemia, their outcome is often counterbalanced by the burden of toxic effects. This is because reported frequencies vary widely across studies, partly because of diverse definitions of toxic effects. Using the Delphi method, 15 international childhood acute lymphoblastic leukaemia study groups assessed acute lymphoblastic leukaemia protocols to address toxic effects that were to be considered by the Ponte di Legno working group. 14 acute toxic effects (hypersensitivity to asparaginase, hyperlipidaemia, osteonecrosis, asparaginase-associated pancreatitis, arterial hypertension, posterior reversible encephalopathy syndrome, seizures, depressed level of consciousness, methotrexate-related stroke-like syndrome, peripheral neuropathy, high-dose methotrexate-related nephrotoxicity, sinusoidal obstructive syndrome, thromboembolism, and Pneumocystis jirovecii pneumonia) that are serious but too rare to be addressed comprehensively within any single group, or are deemed to need consensus definitions for reliable incidence comparisons, were selected for assessment. Our results showed that none of the protocols addressed all 14 toxic effects, that no two protocols shared identical definitions of all toxic effects, and that no toxic effect definition was shared by all protocols. Using the Delphi method over three face-to-face plenary meetings, consensus definitions were obtained for all 14 toxic effects. In the overall assessment of outcome of acute lymphoblastic leukaemia treatment, these expert opinion-based definitions will allow reliable comparisons of frequencies and severities of acute toxic effects across treatment protocols, and facilitate international research on cause, guidelines for treatment adaptation, preventive strategies, and development of consensus algorithms for reporting on acute lymphoblastic leukaemia treatment. PMID:27299279

  15. Identification of Cryptosporidium parvum Dihydrofolate Reductase Inhibitors by Complementation in Saccharomyces cerevisiae

    PubMed Central

    Brophy, Victoria Hertle; Vasquez, John; Nelson, Richard G.; Forney, John R.; Rosowsky, Andre; Sibley, Carol Hopkins

    2000-01-01

    There is a pressing need for drugs effective against the opportunistic protozoan pathogen Cryptosporidium parvum. Folate metabolic enzymes and enzymes of the thymidylate cycle, particularly dihydrofolate reductase (DHFR), have been widely exploited as chemotherapeutic targets. Although many DHFR inhibitors have been synthesized, only a few have been tested against C. parvum. To expedite and facilitate the discovery of effective anti-Cryptosporidium antifolates, we have developed a rapid and facile method to screen potential inhibitors of C. parvum DHFR using the model eukaryote, Saccharomyces cerevisiae. We expressed the DHFR genes of C. parvum, Plasmodium falciparum, Toxoplasma gondii, Pneumocystis carinii, and humans in the same DHFR-deficient yeast strain and observed that each heterologous enzyme complemented the yeast DHFR deficiency. In this work we describe our use of the complementation system to screen known DHFR inhibitors and our discovery of several compounds that inhibited the growth of yeast reliant on the C. parvum enzyme. These same compounds were also potent or selective inhibitors of the purified recombinant C. parvum DHFR enzyme. Six novel lipophilic DHFR inhibitors potently inhibited the growth of yeast expressing C. parvum DHFR. However, the inhibition was nonselective, as these compounds also strongly inhibited the growth of yeast dependent on the human enzyme. Conversely, the antibacterial DHFR inhibitor trimethoprim and two close structural analogs were highly selective, but weak, inhibitors of yeast complemented by the C. parvum enzyme. Future chemical refinement of the potent and selective lead compounds identified in this study may allow the design of an efficacious antifolate drug for the treatment of cryptosporidiosis. PMID:10722506

  16. Lung deposition of nebulised pentamidine in children.

    PubMed Central

    O'Doherty, M J; Thomas, S H; Gibb, D; Page, C J; Harrington, C; Duggan, C; Nunan, T O; Bateman, N T

    1993-01-01

    BACKGROUND: Nebulised pentamidine is effective for preventing Pneumocystis carinii pneumonia in adults with acquired immunodeficiency syndrome. The nebuliser dose required to produce equivalent lung concentrations of pentamidine in children is unknown. This study was performed to measure pulmonary pentamidine deposition in children and to relate this to age, ventilation pattern, and body size. METHODS: Nebulised pentamidine (50 mg in 6 ml saline) was administered to 12 children (including one with lymphocytic interstitial pneumonitis) and to six adults with human immunodeficiency virus infection using a Respirgard II nebuliser. Technetium-99m labeled colloidal human serum albumin was used as an indirect marker for pentamidine and deposition in the lungs was detected by a gamma camera. RESULTS: Absolute deposition of pentamidine was not related to age, height, weight, spirometry, or ventilation characteristics. Deposition, as a mean (SD) percentage of nebuliser output, was similar in children aged 8-11 years (5.5(2.4)%), teenagers aged 12-15 years (7.2(2.2)%) and adults (7.1(2.6)%). Aerosol concentration within the lungs (% nebuliser output deposited/predicted total lung capacity) was therefore higher in children (1.9(1.5)%/1) and teenagers (1.9(0.7)%/1) than in adults (1.0(0.7%)/1), and was negatively correlated with height (r = -0.69) and weight (r = -0.50). Deposition of aerosol in the region of the large central airways was particularly marked in children. Small reductions in forced expiratory volume in one second and forced vital capacity after treatment did not differ significantly between adults and children and visual analogue scores of subjective adverse effects did not vary with age. CONCLUSIONS: These results suggest that children probably require lower nebuliser pentamidine doses to produce lung pentamidine concentrations equivalent to those found to be effective for preventing P carinii pneumonia in adults using the Respirgard II nebuliser. PMID:8497819

  17. 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

  18. L’évaluation et le traitement du nourrisson exposé au virus d’immunodéficience humaine de type 1

    PubMed Central

    2004-01-01

    RÉSUMÉ Dans les pays industrialisés, des soins et un traitement sont offerts aux femmes enceintes et aux nourrissons, afin de faire chuter à 2 % ou moins le taux d’infection périnatale au virus d’immunodéficience humaine de type 1 (VIH-1). Le pédiatre joue un rôle de premier plan dans la prévention de la transmission du VIH-1 de la mère à l’enfant par le dépistage des nourrissons exposés au VIH dont l’infection au VIH de la mère n’a pas été diagnostiquée avant l’accouchement. Il prescrit une prophylaxie antirétrovirale à ces nourrissons, afin de réduire le risque d’acquisition de l’infection au VIH-1 et d’en éviter le plus possible la transmission par le lait maternel. De plus, le pédiatre peut soigner les nourrissons exposés au VIH-1 en les surveillant pour obtenir un dépistage précoce de l’infection au VIH-1 et évaluer les toxicités à court et à long terme de l’exposition aux antirétroviraux, assurer une chimioprophylaxie de la pneumonie à Pneumocystis et soutenir les familles qui vivent avec une infection au VIH-1, grâce à des conseils thérapeutiques aux parents ou aux soignants.

  19. Animal model of mucosally transmitted human immunodeficiency virus type 1 disease: intravaginal and oral deposition of simian/human immunodeficiency virus in macaques results in systemic infection, elimination of CD4+ T cells, and AIDS.

    PubMed

    Joag, S V; Adany, I; Li, Z; Foresman, L; Pinson, D M; Wang, C; Stephens, E B; Raghavan, R; Narayan, O

    1997-05-01

    Chimeric simian/human immunodeficiency virus (SHIV) consists of the env, vpu, tat, and rev genes of human immunodeficiency virus type 1 (HIV-1) on a background of simian immunodeficiency virus (SIV). We derived a SHIV that caused CD4+ cell loss and AIDS in pig-tailed macaques (S. V. Joag, Z. Li, L. Foresman, E. B. Stephens, L. J. Zhao, I. Adany, D. M. Pinson, H. M. McClure, and O. Narayan, J. Virol. 70:3189-3197, 1996) and used a cell-free stock of this virus (SHIV(KU-1)) to inoculate macaques by the intravaginal route. Macaques developed high virus burdens and severe loss of CD4+ cells within 1 month, even when inoculated with only a single animal infectious dose of the virus by the intravaginal route. The infection was characterized by a burst of virus replication that peaked during the first week following intravenous inoculation and a week later in the intravaginally inoculated animals. Intravaginally inoculated animals died within 6 months, with CD4+ counts of <30/microl in peripheral blood, anemia, weight loss, and opportunistic infections (malaria, toxoplasmosis, cryptosporidiosis, and Pneumocystis carinii pneumonia). To evaluate the kinetics of virus spread, we inoculated macaques intravaginally and euthanized them after 2, 4, 7, and 15 days postinoculation. In situ hybridization and immunocytochemistry revealed cells expressing viral RNA and protein in the vagina, uterus, and pelvic and mesenteric lymph nodes in the macaque euthanized on day 2. By day 4, virus-infected cells had disseminated to the spleen and thymus, and by day 15, global elimination of CD4+ T cells was in full progress. Kinetics of viral replication and CD4+ loss were similar in an animal inoculated with pathogenic SHIV orally. This provides a sexual-transmission model of human AIDS that can be used to study the pathogenesis of mucosal infection and to evaluate the efficacy of vaccines and drugs directed against HIV-1. PMID:9094679

  20. 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

  1. β-d-Glucan Testing Is Important for Diagnosis of Invasive Fungal Infections

    PubMed Central

    Doern, Christopher D.

    2013-01-01

    Invasive fungal infections are a significant cause of morbidity and mortality in patients who receive immunosuppressive therapy, such as solid organ and hematopoietic stem cell transplant (HSCT) recipients. Many of the fungi associated with these infections are angioinvasive and are best diagnosed by visualizing the organism in or culturing the organism from deep tissue. However, obtaining such tissue often requires an invasive procedure. Many HSCT recipients are thrombocytopenic, making such procedure too risky because of potential bleeding complications. Additionally, positive blood cultures are rare for patients with angioinvasive fungal infections, making this diagnostic strategy of little value. Undiagnosed fungal infections in these patient populations are a significant cause of mortality. Prophylactic use of antifungal agents, such as the echinocandins, during periods of neutropenia or graft-versus-host disease may prevent some fungal infections but increase the risk for others. Detection of fungal antigens in body fluids, including cryptococcus capsular polysaccharide, histoplasma antigen, galactomannan, and β-d-glucan, is viewed as being clinically useful for at least the presumptive diagnosis of invasive fungal infections. β-d-Glucan is an attractive antigen in that it is found in a broad range of fungal agents, including the commonly encountered agents Candida spp., Aspergillus spp., and Pneumocystis jirovecii. Cross-reactions with certain hemodialysis filters, beta-lactam antimicrobials, and immunoglobulins, which raise concerns about false-positive tests, have also been described. As a result, the use of this testing must be closely monitored. In this point-counterpoint, we have asked Elitza Theel, who directs the Infectious Disease Serology Laboratory at the Mayo Clinic, to address why she believes that this test has value in the diagnosis of invasive fungal infections. We have asked Christopher Doern, Director of Clinical Microbiology at Children

  2. (1, 3)-β-D-glucan assay for diagnosing invasive fungal infections in critically ill patients with hematological malignancies

    PubMed Central

    Azoulay, Elie; Guigue, Nicolas; Darmon, Michael; Mokart, Djamel; Lemiale, Virginie; Kouatchet, Achille; Mayaux, Julien; Vincent, François; Nyunga, Martine; Bruneel, Fabrice; Rabbat, Antoine; Bretagne, Stéphane; Lebert, Christine; Meert, Anne-Pascale; Benoit, Dominique; Pene, Frédéric

    2016-01-01

    Invasive fungal infections (IFIs) are life-threatening complications of hematological malignancies that must be diagnosed early to allow effective treatment. Few data are available on the performance of serum (1–3)-β-D-glucan (BG) assays for diagnosing IFI in patients with hematological malignancies admitted to the intensive care unit (ICU). In this study, 737 consecutive patients with hematological malignancies admitted to 17 ICUs routinely underwent a BG assay at ICU admission. IFIs were diagnosed using standard criteria applied by three independent specialists. Among the 737 patients, 439 (60%) required mechanical ventilation and 273 (37%) died before hospital discharge. Factors known to alter BG concentrations were identified in most patients. IFIs were documented in 78 (10.6%) patients (invasive pulmonary aspergillosis, n = 54; Pneumocystis jirovecii pneumonia, n = 13; candidemia, n = 13; and fusarium infections, n = 3). BG concentrations (pg/mL) were higher in patients with than without IFI (144 (77–510) vs. 50 (30–125), < 0.0001). With 80 pg/mL as the cutoff, sensitivity was 72%, specificity 65%, and area-under-the-curve 0.74 (0.68–0.79). Assuming a prevalence of 10%, the negative and positive predictive values were 94% and 21%. By multivariable analysis, factors independently associated with BG > 80 pg/mL were IFI, admission SOFA score, autologous bone-marrow or hematopoietic stem-cell transplantation, and microbiologically documented bacterial infection. In conclusion, in unselected critically ill hematology patients with factors known to affect serum BG, this biomarker showed only moderate diagnostic performance and rarely detected IFI. However, the negative predictive value was high. Studies are needed to assess whether a negative BG test indicates that antifungal de-escalation is safe. PMID:26910891

  3. [Analysis of Cases with Elevated Blood (1->3)-β-D-glucan in Relation to an Infection Marker, Neutrophil CD64 Expression].

    PubMed

    Hashimoto, Atsushi; Matsui, Toshihiro

    2015-11-01

    (1->3)-β-D-glucan (BDG) is a constituent of the fungal cell wall and its blood level is known as a marker of fungal infection including pneumocystis pneumonia (PCP). Meanwhile, peripheral blood neutrophil CD64 expression (CD64) is upregulated in various infections. We analyzed patients with positive BDG (cut off 11.0 pg/mL) and those whose CD64 was measured simultaneously. In patients who visited our hospital from 2005 to 2011, BDG was measured in 3,960 samples. The number of positive samples were 441 obtained from 185 patients. In patients with positive BDG, the initial BDG was 24.3 [16.4-70.5] pg/mL (median [interquartile range]). Positive BDG samples were derived mainly from the department of Rheumatology or that of Allergy and Respirology. Common primary diseases were rheumatoid arthritis (RA) or other connective tissue diseases, followed by malignancy, none (only abnormal chest X-ray) and bronchial asthma. The rates of afebrile patients, patients on immunosuppressive therapy and those with a normal range of white blood cell count were 63.7%, 50.9% and 40.8%, respectively. The main causes of positive BDG were PCP (n = 38, 20.5%) and non-PCP mycosis (n = 48, 25.9%, including 26 cases of aspergillosis). Others (99 patients, 53.6%) had positive BDG of unknown origin and 53 of them ameliorated spontaneously, most of whom could have been examples of pseudo-positive BDG. The number of deceased patients was 57 (30.8%) consisting of 9 PCP, 16 non-PCP mycosis and others. The median initial positive BDG levels in patients with PCP, non-PCP mycosis and others were 49.9, 28.9 and 19.7pg/mL, respectively. The positive rate of CD64 (cut off 2,000 molecules/cell) measured simultaneously with initial positive BDG was 77.8%. In RA patients with PCP, 94.7% of them had positive CD64 and the levels of CD64 were significantly higher than those in RA patients with bacterial pneumonia (median 9,386 vs 4,399 molecules/cell) in that same period. The positive rate of CD64 was lower in

  4. Costs of HIV+/AIDS at CD4+ counts disease stages based on treatment protocols.

    PubMed

    Gable, C B; Tierce, J C; Simison, D; Ward, D; Motte, K

    1996-08-01

    We report treatment protocols for HIV+/AIDS patients by CD4+ counts (T-lymphocyte cells/mm3: > or = 500, 499-200, 199-50, and < 50) as a tool to provide better definition and to project annual costs (total charges for services) and lifetimes costs for HIV+/AIDS. The treatment protocols, derived from the literature and an HIV+/AIDS Physician Panel, defined the resource use associated with antiretroviral therapy and opportunistic disease prophylaxis and treatment. Resource use costs were derived from the published literature, insurance database, Medicare fee schedules, surveys, and the Physician Panel. At CD4+ counts, the rates of opportunistic diseases were derived from the Physician Panel experience; the mean occupancy times were derived from the literature. The sensitivity analysis indicated stability of the lifetime costs to variation in mean occupancy times, rates of opportunistic diseases, rates of adverse events (AE), and costs. The total annual costs (1995 dollars) of HIV+/AIDS patients ranged from $1,934 (> or = 500), $6,015 (200-499), and $9,031 (50-199), to $25,239 ( < 50). The annual costs of opportunistic diseases are esophageal candidiasis (EC) ($2,194), tuberculosis (TB) ($2,924), cryptococcal meningitis (CM) ($17,264), toxoplasmosis ($17,631), Mycobacterium avium complex (MAC) (+20,153), Non-Hodgkin's lymphoma (NHL) ($22,329), wasting syndrome ($26,676), central nervous system (CNS) lymphoma ($27,333), Pneumocystis carinii pneumonia (PCP) [mild ($3,545), moderate ($4,889), and severe ($32,609)], Kaposi' sarcoma (KS) [mild/moderate ($5,902), and severe ($10,744)], and cytomegalovirus (CMV) retinitis ($100,337). The projected lifetime costs of HIV+/AIDS are $94,726 (annual costs $7,645). Our lower lifetime costs as compared with recent estimates may be due to including resources only for HIV+/AIDS-related treatment and not for non-HIV+/AIDS conditions, as well as reduced resource use resulting from more efficient diagnostic and therapeutic techniques

  5. 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

  6. [Why are AIDS patients frequently visually impaired?].

    PubMed

    Fabricius, E M

    1996-01-01

    Patients with HIV infection and, above all, patients with full-blown AIDS can get a variety of ocular diseases as well as some cerebral maladies which have an influence on ocular functions. First there are hematogenous opportunistic infections of the retina or the choroid. The cytomegalovirus [CMV] retinitis was found in nearly 20% of all AIDS patients. Without treatment this disease destroys the retina completely, and the involved eye becomes blind. This can be prevented by modern therapeutic strategies in most of the cases. Other infections affecting the retina are toxoplasmosis, systemic varizella zoster or herpes simplex virus infections, syphilis or, seldom, fungal or bacterial pathogens. The choroid mainly can be infested by mycobacteria, cryptococci and pneumocystis carinii. Early detection and treatment of all inflammations are necessary. The anterior eye can be affected by a sicca syndrome and various superficial infections but also noninfectious inflammation. The anterior uvea can be involved in various opportunistic infections of the posterior eye segment. An HIV-associated isolated anterior uveitis has been described in earlier stages of the HIV infection. Treatment of mycobacterial infections with rifabutin can cause an anterior uveitis as well. 1 to 2% of HIV-infected persons suffer from a zoster ophthalmicus with more severe keratitis than it occurs in immunocompetent persons. Last but not least, there are various cerebral affections which can cause visual disturbances. So the optic nerve can be involved in various forms of retinitic or meningoencephalitic processes, of ischemic mechanisms or elevated intracranial pressure. Neuroophthalmological symptoms also include homonymous hemianopsia caused by foci of cerebral toxoplasmosis, progressive multifocal leucencephalopathy or primary intracerebral malignant lymphoma situated in the central neuron of the afferent visual pathway. A variety of oculomotor abnormalities can be caused by a great variety of

  7. 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

  8. 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

  9. Association between Highly Active Antiretroviral Therapy and Type of Infectious Respiratory Disease and All-Cause In-Hospital Mortality in Patients with HIV/AIDS: A Case Series

    PubMed Central

    Báez-Saldaña, Renata; Villafuerte-García, Adriana; Cruz-Hervert, Pablo; Delgado-Sánchez, Guadalupe; Ferreyra-Reyes, Leticia; Ferreira-Guerrero, Elizabeth; Mongua-Rodríguez, Norma; Montero-Campos, Rogelio; Melchor-Romero, Ada; García-García, Lourdes

    2015-01-01

    Background Respiratory manifestations of HIV disease differ globally due to differences in current availability of effective highly active antiretroviral therapy (HAART) programs and epidemiology of infectious diseases. Objective To describe the association between HAART and discharge diagnosis and all-cause in-hospital mortality among hospitalized patients with infectious respiratory disease and HIV/AIDS. Material and Methods We retrospectively reviewed the records of patients hospitalized at a specialty hospital for respiratory diseases in Mexico City between January 1st, 2010 and December 31st, 2011. We included patients whose discharge diagnosis included HIV or AIDS and at least one infectious respiratory diagnosis. The information source was the clinical chart. We analyzed the association between HAART for 180 days or more and type of respiratory disease using polytomous logistic regression and all-cause hospital mortality by multiple logistic regressions. Results We studied 308 patients, of whom 206 (66.9%) had been diagnosed with HIV infection before admission to the hospital. The CD4+ lymphocyte median count was 68 cells/mm3 [interquartile range (IQR): 30–150]. Seventy-five (24.4%) cases had received HAART for more than 180 days. Pneumocystis jirovecii pneumonia (PJP) (n = 142), tuberculosis (n = 63), and bacterial community-acquired pneumonia (n = 60) were the most frequent discharge diagnoses. Receiving HAART for more than 180 days was associated with a lower probability of PJP [Adjusted odd ratio (aOR): 0.245, 95% Confidence Interval (CI): 0.08–0.8, p = 0.02], adjusted for sociodemographic and clinical covariates. HAART was independently associated with reduced odds (aOR 0.214, 95% CI 0.06–0.75) of all-cause in-hospital mortality, adjusting for HIV diagnosis previous to hospitalization, age, access to social security, low socioeconomic level, CD4 cell count, viral load, and discharge diagnoses. Conclusions HAART for 180 days or more was associated

  10. Immune reconstitution inflammatory syndrome: incidence and implications for mortality

    PubMed Central

    Novak, Richard M.; Richardson, James T.; Buchacz, Kate; Chmiel, Joan S.; Durham, Marcus D.; Palella, Frank J.; Wendrow, Andrea; Wood, Kathy; Young, Benjamin; Brooks, John T.

    2015-01-01

    Objective To describe incidence of immune reconstitution inflammatory syndrome (IRIS) and its association with mortality in a large multisite US HIV-infected cohort applying an objective, comprehensive definition. Design We studied 2 610 patients seen during 1996–2007 who initiated or resumed highly active combination antiretroviral therapy (cART) and, during the next 6 months, demonstrated a decline in plasma HIV-RNA viral load of at least 0.5 log10 copies/ml or an increase of at least 50% in CD4 cell count per microliter. We defined IRIS as the diagnosis of a type B or C condition [as per the Centers for Disease Control and Prevention (CDC) 1993 AIDS case definition] or any new mucocutaneous disorder during this same 6-month period. Methods We assessed the incidence of IRIS and evaluated risk factors for IRIS using conditional logistic regression and for all-cause mortality using proportional hazards models. Results We identified 370 cases of IRIS (in 276 patients). Median and nadir CD4 cell counts at cART initiation were 90 and 43 cells/μl, respectively; median viral load was 2.7 log10 copies/ml. The most common IRIS-defining diagnoses were candidiasis (all forms), cytomegalovirus infection, disseminated Mycobacterium avium intracellulare, Pneumocystis pneumonia, varicella zoster, Kaposi’s sarcoma and non-Hodgkin lymphoma. Only one case of Mycobacterium tuberculosis was observed. IRIS was independently associated with CD4 cell count less than 50 cells/μl vs. at least 200 cells/μl [odds ratio (OR) 5.0] and a viral load of at least 5.0 log10 copies vs. less than 4.0 log10 copies (OR 2.3). IRIS with a type B-defining or type C-defining diagnosis approximately doubled the risk for all-cause mortality. Conclusion In this large US-based HIV-infected cohort, IRIS occurred in 10.6% of patients who responded to effective ART and contributed to increased mortality. PMID:22233655

  11. Risk factors for AIDS-defining illnesses among a population of poorly adherent people living with HIV/AIDS in Atlanta, Georgia.

    PubMed

    Chow, Jeremy Y; Alsan, Marcella; Armstrong, Wendy; del Rio, Carlos; Marconi, Vincent C

    2015-01-01

    In order to achieve the programmatic goals established in the National HIV/AIDS Strategy, virologic suppression remains the most important outcome within the HIV care continuum for individuals receiving antiretroviral therapy (ART). Therefore, clinicians have dedicated substantial resources to improve adherence and clinic retention for individuals on ART; however, these efforts should be focused first on those most at risk of morbidity and mortality related to AIDS. Our study aimed to characterize the factors that are associated with AIDS-defining illnesses (ADIs) amongst people living with HIV (PLHIV) who are poorly adherent or retained in care in order to identify those at highest risk of poor clinical outcomes. We recruited 99 adult PLHIV with a history of poor adherence to ART, poor clinic attendance, or unsuppressed viral load (VL) from the Infectious Disease Program (IDP) of the Grady Health System in Atlanta, Georgia between January and May 2011 to participate in a survey investigating the acceptability of a financial incentive for improving adherence. Clinical outcomes including the number of ADI episodes in the last five years, VLs, and CD4 counts were abstracted from medical records. Associations between survey items and number of ADIs were performed using chi-square analysis. In our study, 36.4% of participants had ≥1 ADI in the last five years. The most common ADIs were Pneumocystis jirovecii pneumonia, recurrent bacterial pneumonia, and esophageal candidiasis. Age <42.5 years (OR 2.52, 95% CI = 1.08-5.86), male gender (OR 3.51, 95% CI = 1.08-11.34), CD4 nadir <200 cells/µL (OR 11.92, 95% CI = 1.51-94.15), unemployment (OR 3.54, 95% CI = 1.20-10.40), and travel time to clinic <30 minutes (OR 2.80, 95% CI = 1.20-6.52) were all significantly associated with a history of ≥1 ADI in the last five years. Awareness of factors associated with ADIs may help clinicians identify which poorly adherent PLHIV are at highest risk of HIV-related morbidity. PMID

  12. Risk Factors for Mortality from Acute Lower Respiratory Infections (ALRI) in Children under Five Years of Age in Low and Middle-Income Countries: A Systematic Review and Meta-Analysis of Observational Studies

    PubMed Central

    Sonego, Michela; Pellegrin, Maria Chiara; Becker, Genevieve; Lazzerini, Marzia

    2015-01-01

    Objective To evaluate risk factors for death from acute lower respiratory infections (ALRI) in children in low- and middle-income countries. Design Systematic review and meta-analysis. Study selection Observational studies reporting on risk factors for death from ALRI in children below five years in low- and middle income countries. Data sources Medline, Embase, Global Health Library, Lilacs, and Web of Science to January 2014 Risk of bias assessment Quality In Prognosis Studies tool with minor adaptations to assess the risk of bias; funnel plots and Egger's test to evaluate publication bias. Results Out of 10655 papers retrieved, 77 studies from 39 countries (198359 children) met the inclusion criteria. Host and disease characteristics more strongly associated with ALRI mortality were: diagnosis of very severe pneumonia as per WHO definition (odds ratio 9.42, 95% confidence interval 6.37‒13.92); age below two months (5.22, 1.70‒16.03); diagnosis of Pneumocystis Carinii (4.79, 2.67 ‒ 8.61), chronic underlying diseases (4.76, 3.27‒ 6.93); HIV/AIDS (4.68, 3.72‒5.90); and severe malnutrition (OR 4.27, 3.47‒5.25). Socio-economic and environmental factors significantly associated with increased odds of death from ALRI were: young maternal age (1.84, 1.03‒3.31); low maternal education (1.43, 1.13‒1.82); low socio-economic status (1.62, 1.32‒2.00); second-hand smoke exposure (1.52, 1.20 to 1.93); indoor air pollution (3.02, 2.11‒4.31). Immunisation (0.46, 0.36‒0.58) and good antenatal practices (0.50, 0.31‒0.81) were associated with decreased odds of death. Conclusions Host and disease characteristics as well as socio-economic and environmental determinants affect the risk of death from ALRI in children. Together with the prevention and treatment of chronic diseases, interventions to modify underlying risk factors such as poverty, lack of female education, and poor environmental conditions, should be considered among the strategies to reduce ALRI

  13. Time to HAART Initiation after Diagnosis and Treatment of Opportunistic Infections in Patients with AIDS in Latin America

    PubMed Central

    Crabtree-Ramírez, Brenda; Caro-Vega, Yanink; Shepherd, Bryan E.; Grinsztejn, Beatriz; Wolff, Marcelo; Cortes, Claudia P.; Padgett, Denis; Carriquiry, Gabriela; Fink, Valeria; Jayathilake, Karu; Person, Anna K.; McGowan, Catherine; Sierra-Madero, Juan

    2016-01-01

    Background Since 2009, earlier initiation of highly active antiretroviral therapy (HAART) after an opportunistic infection (OI) has been recommended based on lower risks of death and AIDS-related progression found in clinical trials. Delay in HAART initiation after OIs may be an important barrier for successful outcomes in patients with advanced disease. Timing of HAART initiation after an OI in “real life” settings in Latin America has not been evaluated. Methods Patients in the Caribbean, Central and South America network for HIV Epidemiology (CCASAnet) ≥18 years of age at enrolment, from 2001–2012 who had an OI before HAART initiation were included. Patients were divided in an early HAART (EH) group (those initiating within 4 weeks of an OI) and a delayed HAART (DH) group (those initiating more than 4 weeks after an OI). All patients with an AIDS-defining OI were included. In patients with more than one OI the first event reported was considered. Calendar trends in the proportion of patients in the EH group (before and after 2009) were estimated by site and for the whole cohort. Factors associated with EH were estimated using multivariable logistic regression models. Results A total of 1457 patients had an OI before HAART initiation and were included in the analysis: 213 from Argentina, 686 from Brazil, 283 from Chile, 119 from Honduras and 156 from Mexico. Most prevalent OI were Tuberculosis (31%), followed by Pneumocystis pneumonia (24%), Invasive Candidiasis (16%) and Toxoplasmosis (9%). Median time from OI to HAART initiation decreased significantly from 5.7 (interquartile range [IQR] 2.8–12.1) weeks before 2009 to 4.3 (IQR 2.0–7.1) after 2009 (p<0.01). Factors associated with starting HAART within 4 weeks of OI diagnosis were lower CD4 count at enrolment (p-<0.001), having a non-tuberculosis OI (p<0.001), study site (p<0.001), and more recent years of OI diagnosis (p<0.001). Discussion The time from diagnosis of an OI to HAART initiation has

  14. Steroids are a risk factor for Kaposi's sarcoma-immune reconstitution inflammatory syndrome and mortality in HIV infection

    PubMed Central

    Fernández-Sánchez, Mónica; Iglesias, María C.; Ablanedo-Terrazas, Yuria; Ormsby, Christopher E.; Alvarado-de la Barrera, Claudia; Reyes-Terán, Gustavo

    2016-01-01

    Objectives: To investigate the association between Kaposi's sarcoma-associated immune reconstitution inflammatory syndrome (KS-IRIS) and mortality, with the use of glucocorticoids in HIV-infected individuals. Design: Case–control study. Methods: We reviewed the medical records of 145 individuals with HIV-associated Kaposi's sarcoma receiving antiretroviral therapy. The association of different variables with KS-IRIS and Kaposi's sarcoma-related mortality was explored by univariate and multivariate analyses. The main exposure of interest was the use of glucocorticoids. We also compared the time to KS-IRIS and the time to death of individuals treated with glucocorticoids vs. those nontreated with glucocorticoids, and the time to death of individuals with KS-IRIS vs. those without KS-IRIS by hazards regression. Results: Sixty of 145 individuals received glucocorticoids (41.4%) for the management or suspicion of Pneumocystis jirovecii pneumonia. Fifty individuals had KS-IRIS (37%). The use of glucocorticoids was more frequent in individuals with KS-IRIS than in those without KS-IRIS (54.9 vs. 36.47%, P = 0.047). Kaposi's sarcoma-related mortality occurred in 17 cases (11.7%), and glucocorticoid use was more frequent in this group (76.47 vs. 36.7%, P = 0.003). Glucocorticoid use was a risk factor for mortality (adjusted odds ratio = 4.719, 95% confidence interval = 1.383–16.103, P = 0.0132), and was associated with shorter periods to KS-IRIS (P = 0.03) and death (P = 0.0073). KS-IRIS was a risk factor for mortality (P = 0.049). Conclusion: In HIV-infected individuals, the use of glucocorticoids is a risk factor for KS-IRIS and Kaposi's sarcoma-associated mortality. In addition, KS-IRIS is a risk factor for mortality. Therefore, glucocorticoid administration in this population requires careful consideration based on individualized risk–benefit analysis. PMID:26636923

  15. Serum immunoglobulin E levels in human immunodeficiency virus-infected children with pneumonia.

    PubMed

    Zar, Heather J; Latief, Zeino; Hughes, Jane; Hussey, Gregory

    2002-10-01

    Elevated serum immunoglobulin E (IgE) levels have been reported in association with human immunodeficiency virus (HIV) infection in adults, but there is little information in children. The aim of the present study was to compare serum IgE levels in HIV-positive and -negative children hospitalized with pneumonia in South Africa and to investigate whether IgE may be useful as a marker of specific infections or prognosis in HIV-infected children. History, examination, blood tests, and induced sputum or bronchoalveolar lavage were carried out. Of 122 children [45% female, median age 8 months (3-20 months)], 81 were infected with HIV. A history of allergy or asthma was present in three children (two of whom were HIV positive). Serum IgE was higher in HIV-infected children [83 (33-147) vs. 29 (6-113) IU/l; p = 0.011] as was immunoglobulin G (IgG) [49 (37-63) vs. 27.5 (23-34) g/l; p < 0.001]. CD4 lymphocytes [600 (330-1,210) vs. 1,900 (1,500-3,030) cells/ micro l], percentage CD4 cells [13.6 (9.4-20.3) vs. 40.1 (31.1-44.9)] and CD4 : CD8 ratio [0.3 (0.2-0.4) vs. 2 (1.4-2.8)] were lower in HIV-positive children (p < 0.001 for all). Bacteremia occurred in 12 (10%) children; other specific pathogens identified included Mycobacterium tuberculosis in eight (7%) and Pneumocystis carinii in nine (7%). There was no correlation with CD4 count, CD4 : CD8 ratio, or the presence of specific pathogens, and IgE level. In-hospital mortality (11%) did not correlate with IgE levels. HIV-infected children with pneumonia have higher serum IgE compared with seronegative patients. In HIV-positive children, IgE levels did not correlate with the degree of immunosuppression or with outcome. PMID:12431191

  16. TB-HIV co-infection: a catastrophic comradeship.

    PubMed

    Narendran, G; Swaminathan, S

    2016-04-01

    The symbiotic association of tuberculosis (TB) and HIV poses a challenge to human survival. HIV complicates every aspect of TB including presentation, diagnosis and treatment. HIV-TB patients encounter unique problems like drug-drug interactions, cumulative toxicity, immune reconstitution inflammatory syndrome (IRIS), lower plasma drug levels and emergence of drug resistance during treatment despite adherence. TB may also be overdiagnosed in HIV due to a number of diseases that closely resemble TB. Notable among them are non-tuberculous mycobacteria, Pneumocystis Jirovecii and Nocardia. Even though diagnostic procedures have improved over the years, patients in developing countries usually seek health care at later stage of the disease. Research data ascertains the duration of therapy for TB to be 6 months with rifampicin and isoniazid, reinforced with ethambutol and pyrazinamide in the first 2 months. The schedule of therapy is still debatable with daily regimens being preferred in the context of HIV. Many reasons exist for persistence of Mycobacterium Tuberculosis (M.TB) in sputum, or delayed-clearance of TB from sputum smears in HIV, apart from emergence of drug resistance and non-compliance. Acquired rifampicin resistance (ARR) is a unique phenomenon complicating HIV-associated TB when an intermittent regimen of antituberculosis therapy (ATT) is used without timely initiation of highly active antiretroviral therapy (HAART), especially in patients harbouring isoniazid-resistant strains Immune restoration is often incomplete ('swiss cheese' pattern) even with effective HAART if not started early. Immune reconstitution inflammatory syndrome (IRIS) is the paradoxical worsening of the patient's condition often with radiological deterioration, due to an enhanced immune response with HAART. IRIS occurs despite an effective virological suppression and a favourable response to ATT. The incidence of IRIS in HIV has reached up to 54%, requiring utilization of experts

  17. 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

  18. HIV infection and maternal and child health.

    PubMed

    Ramachandran, P

    1988-01-01

    Collaborative studies to determine the consequences of pregnancy in HIV infected women have been begun in the last 2 years. Both HIV and HIV antibodies pass through the placenta, and 30-50% of infants born to HIV infected mothers are infected in utero. In developed countries it is feasible to screen pregnant women in high risk groups for HIV positivity. In developing countries, where heterosexual transmission is the main route of infection, there are no high risk groups, and it is not feasible to screen all pregnant women. Some data have shown that HIV infection in pregnancy is associated with intrauterine growth retardation, low birth weight, and high infant mortality. There is no evidence that cesarean section reduces infection in neonates, and it should not be performed on HIV infected women. By 1987 almost 1.5% of AIDS cases in the US were in vertically infected infants. In Africa also the main factor in HIV in infancy is vertical transmission. AIDS in infancy follows 1 of 2 distinct patterns: failure to thrive and death from Pneumocystis carinii pneumonia within the 1st year or else apparent health during infancy but death from opportunistic infections by age 3. HIV infection in childhood is uncommon and can usually be traced to blood transfusions or unsterilized needles used for vaccinations. Neurological symptoms often develop early in children. Breast feeding probably does not infect any infants who have not already been infected in utero, and in developing counties breast feeding is still the best assurance of total nutrition. Pooled, unpasteurized milk banks, on the other hand, represent an unnecessary danger, and milk donors should be screened. Since there is no evidence that routine immunization accelerates the course of HIV infection, and since mass screening is not feasible in developing countries, the World Health Organization recommends that routine immunizations be continued. Since the best protection from in utero HIV infection is the use of

  19. A special report: four-year study of a boy with combined immune deficiency maintained in strict reverse isolation from birth.

    PubMed

    1977-01-01

    A 4-year study of a boy with combined immune deficiency is presented, and the impact of this disease on various aspects of his growth and development is examined. There is no evidence of immune deficiency in either parent or in the genetic background on the maternal side. Three children of a brother of the mother's father may have had immune deficiencies but two have grown to be teenagers with no problems. Another died. At autopsy, however, lymph nodes appeared normal. The deceased older brother had severe combined immune deficiency (SCID). The autopsy findings showed Pneumocystis carinii pneumonia to be the direct cause of death and these findings contributed to the diagnosis of SCID. After a successful germ-free birth, the male infant (DV) was placed in the isolator. Laboratory tests were normal except that the x-rays showed no thymic shadow, his absolute lymphocyte count ranged from 399-440/mm and the lymphocytes showed no proliferative response to phytohemagglutinin (PHA). Specific tests showed the antibody-producing immune system and the cell-mediated immune system to be severely defective. The patient's lymphocytes elicited positive responses by lymphocytes from father, mother, and sister. Subsequent search in national and international tissue-typing laboratories has shown four HLA matches but none has been nonreactive in mixed lymphocyte culture (MLC). therefore, this patient has remained in isolation to the present; now he is 4 years old. Approximately 35 species of microorganisms, mostly transient contaminants, have been isolated, taking into account that the same organism may have been identified under different names in different laboratories. Those isolated frequently and in sufficiently high concentration to indicate colonization have been speciated as follows: anaerobes-Propionibacterium acnes, Lactobacillus catenaforme (disappeared spontaneously), Bacteroides oralis ss. elongatus, Clostridium (perenne, hastiforme, bifermentans), Bacteroides

  20. [Detection of Echinococcus granulosus and Echinococcus multilocularis in cyst samples using a novel single tube multiplex real-time polymerase chain reaction].

    PubMed

    Can, Hüseyin; İnceboz, Tonay; Caner, Ayşe; Atalay Şahar, Esra; Karakavuk, Muhammet; Döşkaya, Mert; Çelebi, Fehmi; Değirmenci Döşkaya, Aysu; Gülçe İz, Sultan; Gürüz, Yüksel; Korkmaz, Metin

    2016-04-01

    Cystic echinococcosis (CE) and alveolar echinococcosis (AE) caused by Echinococcus granulosus and Echinococcus multilocularis, respectively, are important helminthic diseases worldwide as well as in our country. Epidemiological studies conducted in Turkey showed that the prevalence of CE is 291-585/100.000. It has also been showed that the seroprevalence of AE is 3.5%. For the diagnosis of CE and AE, radiological (ultrasonography, computed tomography, magnetic resonance) and serological methods, in addition to clinical findings, are being used. The definitive diagnosis relies on pathological examination When the hydatid cysts are sterile or does not contain protoscolex, problems may occur during pathological discrimination of E.granulosus and E.multilocularis species. In this study, we aimed to develop a novel multiplex real-time polymerase chain reaction (M-RT-PCR) targeting mitochondrial 12S rRNA gene of E.granulosus and E.multilocularis using Echi S (5'-TTTATGAATATTGTGACCCTGAGAT-3') and Echi A (5'-GGTCTTAACTCAACTCATGGAG-3') primers and three different probes; Anchor Ech (5'-GTTTGCCACCTCGATGTTGACTTAG-fluoroscein-3'), Granulosus (5'-LC640-CTAAGGTTTTGGTGTAGTAATTGATATTTT-phosphate-3') and Multilocularis (5'-LC705-CTGTGATCTTGGTGTAGTAGTTGAGATT-phosphate-3') that will enable the diagnosis of CE and AE in same assay. During M-RTR-PCR, plasmids containing E.granulosus (GenBank: AF297617.1) and E.multilocularis (GenBank: NC_000928.2) mitochondrial 12S rRNA regions were used as positive controls. Cysts samples of patients which were pathologically confirmed to be CE (n: 10) and AE (n: 15) and healthy human DNA samples (n: 25) as negative control as well as DNA samples of 12 different parasites (Taenia saginata, Hymenolepis nana, Trichuris trichiura, Fasciola hepatica, Enterobius vermicularis, Toxoplasma gondii, Pneumocystis jirovecii, Trichomonas vaginalis, Cryptosporidium hominis, Strongyloides stercoralis, Plasmodium falciparum, Plasmodium vivax) were used to develop M

  1. Update on HIV/AIDS in Thailand.

    PubMed

    Ruxrungtham, K; Phanuphak, P

    2001-06-01

    Thailand experienced its first case of AIDS in 1984. Approximately 800,000 Thais were infected with HIV in 1995 and 1 million Thais became infected by the year 2000. There have been 5 major epidemic waves: among male homosexuals (started 1984-5), intravenous drug users (started 1988), female commercial sex workers (started 1989), male clients (started 1990), and housewives and the newborn (started 1991). Approximately 96 per cent of HIV-1 infected Thais carried recombinant subtype A/E, the rest carried B'. In a male seroconvertors cohort of 235 cases, median time to show CD4 <200 cells/microL was 6.8 years. Five years survival was significantly lower than that of the other subtype B seroconvertors study, i.e., 82 per cent compared to 90 per cent. Interestingly, 13.5 per cent of seronegative Thais showed homozygous SDF1-3'A polymorphism, which suggests that approximately one-tenth of Thais may become long-term non-progressors after HIV-1 infection. Primary HIV infection syndrome is rare among Thai patients (1.1%). In contrast, it was 50-90 per cent in Western cohorts. In early symptomatic patients, one-third developed pruritic pappular eruptions (PPEs). In advanced stage, disseminated tuberculosis, Pneumocystis carinii pneumonia (PCP), cryptococcosis, and esophageal candidiasis are commonly found. In Northern Thailand, however, Penicillium marneffei infection or penicillosis is more common than cryptococcosis. The recent understanding of HIV pathogenesis suggests that HIV eradication is unlikely to be achievable with current strategies. Several National HIV treatment guidelines including the Thai guideline have been recommended treatment with triple antiretroviral regimen when patients become symptomatics or CD4+ <200. Current development of antiretroviral therapy which includes new agents, new formulas, and pharmacokinetic enhancements, is directed to better potency, higher genetic resistant barrier, less pill burden, and once a day dosing. These will ultimately

  2. Antifungal Activities and Cytotoxicity Studies of Six New Azasordarins

    PubMed Central

    Herreros, Esperanza; Almela, Maria Jesus; Lozano, Sonia; Gomez De Las Heras, Federico; Gargallo-Viola, Domingo

    2001-01-01

    GW 471552, GW 471558, GW 479821, GW 515716, GW 570009, and GW 587270 are members of a new family of sordarin derivatives called azasordarins. The in vitro activities of these compounds were evaluated against clinical isolates of yeasts, including Candida albicans, Candida non-albicans, and Cryptococcus neoformans strains. Activities against Pneumocystis carinii, Aspergillus spp., less common molds, and dermatophytes were also investigated. Azasordarin derivatives displayed significant activities against the most clinically important Candida species, with the exception of C. krusei. Against C. albicans, including fluconazole-resistant strains, MICs at which 90% of the isolates tested are inhibited (MIC90s) were 0.002 μg/ml with GW 479821, 0.015 μg/ml with GW 515716 and GW 587270, and 0.06 μg/ml with GW 471552, GW 471558, and GW 570009. The MIC90s of GW 471552, GW 471558, GW 479821, GW 515716, GW 570009, and GW 587270 were 0.12, 0.12, 0.03, 0.06, 0.12, and 0.06 μg/ml, respectively, against C. tropicalis and 4, 0.25, 0.06, 0.25, 0.5, and 0.5 μg/ml, respectively, against C. glabrata. In addition, some azasordarin derivatives (GW 479821, GW 515716, GW 570009, and GW 58720) were active against C. parapsilosis, with MIC90s of 2, 4, 4, and 1 μg/ml, respectively. The compounds were extremely potent against P. carinii, showing 50% inhibitory concentrations of ≤0.001 μg/ml. However Cryptococcus neoformans was resistant to all compounds tested (MIC > 16 μg/ml). These azasordarin derivatives also showed significant activity against emerging fungal pathogens, which affect immunocompromised patients, such as Rhizopus arrhizus, Blastoschizomyces capitatus, and Geotrichum clavatum. Against these organisms, the MICs of GW 587270 ranged from 0.12 to 1 μg/ml, those of GW 479821 and GW 515716 ranged from 0.12 to 2 μg/ml, and those of GW 570009 ranged from 0.12 to 4 μg/ml. Against Fusarium oxysporum, Scedosporium apiospermum, Absidia corymbifera, Cunninghamella

  3. Penetration of anti-infective agents into pulmonary epithelial lining fluid: focus on antifungal, antitubercular and miscellaneous anti-infective agents.

    PubMed

    Rodvold, Keith A; Yoo, Liz; George, Jomy M

    2011-11-01

    on the magnitude of ELF concentrations of antitubercular agents. Subjects who were slow acetylators had higher plasma and ELF concentrations of isoniazid than those who were fast acetylators. Penetration of dapsone into ELF was very good, with the range of mean ELF to plasma concentration ratios being 0.65-2.91 at individual sampling times over 48 hours. Once-daily dosing of aerosolized pentamidine resulted in higher concentrations in BAL fluid than after intravenous administration. The mean BAL concentrations at 15-32 days after once- or twice-monthly administration of aerosolized pentamidine 300 and 600 mg ranged from 6.5 to 28.4 ng/mL. No differences in pentamidine BAL concentrations were observed in symptomatic patients who developed Pneumocystis jirovecii pneumonia compared with patients who did not. Zanamivir concentrations in ELF were similar in magnitude (range 141-326 ng/mL) following administration by continuous intravenous infusion (3 mg/hour), oral inhalation (10 mg every 12 hours) and intravenous bolus (200 mg every 12 hours). Data from case reports have suggested that concentrations of nelfinavir and saquinavir in ELF are undetectable, whereas tipranavir and lopinavir had measureable ELF concentrations (2.20 μmol/L and 14.4 μg/mL, respectively) when these protease inhibitors were co-administrated with ritonavir. While the clinical significance of ELF or BAL concentrations remains unknown for this group of anti-infective agents, the knowledge of drug penetration into the extracellular space of the lung should assist in re-evaluating and designing specific dosing regimens for use against potential pathogens. PMID:21973267

  4. Synthesis of 5-methyl-5-deaza nonclassical antifolates as inhibitors of dihydrofolate reductases and as potential antipneumocystis, antitoxoplasma, and antitumor agents.

    PubMed

    Gangjee, A; Shi, J; Queener, S F; Barrows, L R; Kisliuk, R L

    1993-10-29

    A series of 2,4-diamino-5-methyl-6-(anilinomethyl)pyrido[2,3-d]pyrimidines 4-9 were synthesized as 5-deaza nonclassical antifolates containing trimethoxy, dichloro-, or trichlorophenyl substitutions and a N-H, N-CH3, or N-CHO at the 10-position. The compounds were evaluated as inhibitors of dihydrofolate reductases (DHFR) from Pneumocystis carinii (P. carinii), Toxoplasma gondii (T. gondii), rat liver (RL), and Lactobacillus casei (L. casei); as inhibitors of T. gondii and P. carinii cell growth in culture; and as antitumor agents. The compounds were prepared by modifications of procedures for classical 5-deaza folates. 2,4-Diamino-5-methyl-6-[(3',4',5'-trimethoxy-N- methylanilino)methyl]pyrido[2,3-d]pyrimidine (5a) exhibited high potency as well as selectivity (compared to RL DHFR) for P. carinii and T. gondii DHFR. Compound 5a is one of the most potent and selective nonclassical folate inhibitors of T. gondii DHFR known. The N-10 formyl analogue 2,4-diamino-5-methyl-6-[(N-formyl-3',4',5'-trimethoxyanilino) methyl]pyrido-[2,3-d]pyrimidine (6a) had decreased potency, but it maintained high selectivity for T. gondii DHFR. The corresponding chloro-substituted analogues maintained potency or had decreased potency; N-10 substitution did not increase potency or selectivity to the extent observed in the 3',4',5'-trimethoxy series. Partial reduction of the B ring to afford the dihydro analogue 2,4-diamino-5-methyl-6-[(N-formyl-3',4',5'-trimethoxyanilino) methyl]-5,8-dihydropyrido[2,3-d]pyrimidine (7), its 5,6,7,8-tetrahydropyrido[2,3-d]pyrimidine analogue 8, and 2,4-diamino-5-methyl-6-[(3',4',5'-trimethoxyanilino)methyl]-5,6,7, 8- tetrahydropyrido[2,3-d]pyrimidine (9) resulted in a significant decrease in potency. In T. gondii cell culture inhibitory studies, 2,4-diamino-5-methyl-6-[(3',4',5'- trimethoxyanilino)methyl]pyrido[2,3-d]pyrimidine (4a), 5a, and 6a were less potent compared to their DHFR inhibitory potencies. Against P. carinii cells in culture, 4a and 5a at 10

  5. HIV infection in children--impact upon ENT doctors.

    PubMed

    Hoare, Simon

    2003-12-01

    The global epidemic of HIV infection remains appalling. By 2001, there were an estimated 1.4 million HIV-infected children, with 4.5 million deaths. In the UK, paediatric cases are clustered around population centres where there are high concentrations of infected immigrant adults, and to a lesser extent, areas where IV drug abuse is common. The highest incidence remains in London and the southeast. With the national redistribution of immigrant and refugee families, any doctor in any specialty may expect to be involved with children who are HIV positive, or have clinical AIDS. The majority of children are infected vertically, i.e. infection of the infant from an infected mother in the pre-, peri-, or post-natal periods. Rates of transmission vary from 15-20% in the developed countries. Children with HIV infection may have their primary presentation to ENT doctors, who should have appropriate thresholds for suspecting the diagnosis. The most common presenting features include persistent generalised lymphadenopathy, hepatosplenomegaly, chronic/recurrent diarrhoea, poor growth, and fever. Fifteen to twenty percent of untreated children will present with an AIDS-defining illness by 12 months, typically with Pneumocystis pneumonia at approximately 3-4 months of age. Seventy percent of perinatally infected children will exhibit some signs or symptoms by 12 months Without treatment, the median age to progression to AIDS is approximately 6 years, and 25-30% will have died by this age. The median age of death is approximately 9 years. Children may also present with repeated/unusual ear infections, sinus disease (inc. mastoiditis), tonsillitis, orbital/peri-orbital cellulitis, oral candidiasis, and dental infections. Infections with streptococcus pneumoniae and group A streptococcus are common, and often progress to severe systemic infection with an appreciable mortality. Infections may be due to unusual pathogens such as Pseudomonas, 'typical' and atypical Mycobacteria