OPPORTUNISTIC INFECTIONS. PNEUMOCYSTIS INFECTION.
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The host response of CD28-deficient mice to Pneumocystis infection.
Pneumocystis infection leads to a life threatening pneumonia in susceptible individuals. While depletion or dysfunction of CD4+T cells is a key determinant of susceptibility to Pneumocystis, the host response that leads to resolution of infection or lung injury is less well understood. We had previously shown that mice deficient in the T cell costimulatory molecule CD28 are susceptible to infection with Pneumocystis. A detailed analysis revealed that they clear Pneumocystis with delayed kinetics. This is associated with an influx of naïve CD8+ T cells. Depletion of CD8+ T cells did not alter organism burden, suggesting these cells are not responsible for clearance. Analysis of the cytokine milieu demonstrated a consistent increase in mRNA for IL-10 and IFN-gamma in the CD28-deficient mice. These data suggest that CD28 function in important in the efficiency of the host response to Pneumocystis pneumonia.
Animals↗
Survival benefits of pulmonary cellular activation in AIDS patients with Pneumocystis infection.
Pneumocystis carinii pneumonia (PCP) is the most common life-threatening, opportunistic infection in patients with acquired immunodeficiency syndrome. Between 1984 and 1987, patients infected with human immunodeficiency virus (HIV) received bronchoalveolar lavages to confirm PCP diagnosis. Unstained slides containing bronchoalveolar cells from 20 of these patients were stored. Eight years after the last diagnostic bronchoalveolar lavage, blinded investigators immunohistochemically analyzed the unstained bronchoalveolar cells for the presence of proliferating cells and pneumocystic cysts. A significant association was found between the percentage of activated macrophages and patient survival after diagnostic bronchoalveolar lavage. On chart review, patients with higher CD4/CD8 ratios had significantly greater alveolar macrophage activation. The correlation of life span and pulmonary cellular activation in these cases (most predating retroviral therapy) suggests the importance of pulmonary cellular function to immunity and survival in patients infected with HIV.
AIDS-Related Opportunistic Infections↗
Pneumocystis infections: the iceberg?
Pneumocystis carinii pneumonia (PCP) is a well-recognized lung disease of immunocompromised patients, but the real impact of Pneumocystis infection in humans remains to be discovered. Pneumocystis represents probably one of the more frequent infectious agents faced by humans. Seroconversion revealed P. carinii primary infection in > 90% of infants and small children, but the infection source and the clinical or pathological changes associated with this first contact with the parasite remain unknown. Pneumocystis organisms are atypical microfungi able to attach specifically to type-I alveolar epithelial cells, and to proliferate, provoking severe pneumonitis. A deep impairment of cell-mediated immunity associated with changes in pulmonary surfactant make it possible for Pneumocystis to grow within the host. Alveolar type-II cell hypertrophy, macrophagic infiltrate and intra-alveolar foamy eosinophilic material are the most typical changes. CD4+ T-lymphocytes and interferon play a major role in host defense against P. carinii. Alveolar macrophages phagocytose P. carinii via the macrophage-mannose receptor and produce reactive free-radicals and nitric oxide under Pneumocystis stimulation. Furthermore, PCP is associated with an early decrease of surfactant phospholipids, increased hydrophilic surfactant protein (SP) levels and decreased hydrophobic SPs. Normal surfactant improves PCP, and consistently, it inhibits the parasite growth. New detection tools have revealed that hospitalized patients can be latently infected with Pneumocystis and that immunocompetent hosts develop transient Pneumocystis infections. Pneumocystis organisms circulate in human populations, being able to infect hosts with diverse susceptibility levels. In fact, airborne Pneumocystis infection can display a large spectrum of clinical presentations and most likely, we recognize at present only the tip of the iceberg.
Animals↗
High seroprevalence of Pneumocystis infection in Spanish children.
Pneumocystis infection occurs worldwide, and most individuals test seropositive for Pneumocystis early in childhood. Little is known about the epidemiology of this infection in western Europe. The seroprevalence of Pneumocystis infection in 233 Spanish children was determined in a community study by immunoblot analysis of sera. The overall seroprevalence was 73%, with an age-related increase from 52% at 6 years to 66% at 10 years and 80% at 13 years. The data indicated a high seroprevalence of Pneumocystis infection in healthy Spanish children, thereby demonstrating that this pathogen is widespread in southern Spain.
Adolescent↗
Quantitative real-time polymerase chain-reaction assay allows characterization of pneumocystis infection in immunocompetent mice.
Pneumocystis causes pneumonia in immunodeficient hosts but also likely causes infection in healthy hosts. To characterize infection in healthy mice, we developed and validated a real-time polymerase chain reaction assay for quantitation of Pneumocystis carinii f. sp. muris. In healthy mice exposed to Pneumocystis-infected animals, organisms were first detected at 2-3 weeks, peaked at 5-6 weeks, and were cleared by 7-9 weeks. The peak organism load in healthy animals was 2-3 logs lower than that in immunodeficient animals. This approach should facilitate studies of anti-Pneumocystis immune mechanisms in healthy hosts and provide insights into the development of Pneumocystis pneumonia in immunodeficient hosts.
Animals↗
Production of a monoclonal antibody using lymphocytes from Pneumocystis infected mice.
A colony of BALB/c mice maintained in a protected area of our laboratory was not infected with Pneumocystis carinii. During corticosteroid treatment, animals became infected by exposure to infected mice. After four months of corticosteroid treatment, BALB/c mice developed severe pneumocystosis. Stopping of treatment was associated with: (i) high mortality of mice, (ii) decreased lung parasite level and (iii) appearance of anti-P. carinii antibodies in survivors. A monoclonal antibody (MAb) 4F2 was obtained by immortalisation of spleen lymphocytes of a female BALB/c mouse 3 months after the cessation of corticosteroid treatment. The MAb 4F2 recognized a 210-220 kDa mouse P. carinii antigen, but did not react with rat-, rabbit- or human-derived P. carinii. This MAb reacted with all stages of mouse P. carinii.
Animals↗
Pneumocystis infection in macaque monkeys: Macaca fuscata fuscata and Macaca fascicularis.
Retrospective examination of lungs from 128 monkey necropsies was attempted for Pneumocystis infection using special strains, including toluidine blue-O and Gomori's methenamine silver nitrate. Four Japanese monkeys (7.7%), Macaca fuscata fuscata, and one crab-eating monkey (7.7%), Macaca fascicularis, were found to have Pneumocystis infection. The organism was found in young and infant animals. At the time of death, one infant and two young monkeys were debilitated and/or emaciated. Pneumocystis infection was considered an important lesion which could have caused reduced respiratory function in two of the Japanese monkeys, but constituted only an incidental finding in the others.
Animals↗
Association between human-Pneumocystis infection and small-cell lung carcinoma.
BACKGROUND: Tobacco smoking is the most important but not the only risk factor in lung carcinoma. There is evidence that certain infections, which cause chronic inflammatory reactions, can also induce tumour development. It has recently been shown that patients with chronic pulmonary diseases present a high rate of subclinical Pneumocystis infection, and that the latter is able to induce inflammatory responses and alveolar cell alterations. The possible role of Pneumocystis infection in the development of lung neoplasms thus deserves consideration. MATERIAL AND METHODS: Polymerase chain reaction has been used to analyze the presence of DNA of two independent loci of the Pneumocystis genome: the mitochondrial region (mtLSU rRNA) and the gene encoding for the dihydropteroate synthase enzyme, in paraffin-embedded tissue blocks of 10 cases of small cell lung carcinoma (SCLC) and 10 cases of nonsmall cell lung carcinoma (NSCLC) with similar demographic and clinical characteristics. Five cases without lung pathology, and two cases of Pneumocystis pneumonia were also analyzed as controls. RESULTS: DNA of the microorganism was found in all the cases of SCLC but in only two of the NSCLC, and in none of the controls without pulmonary disease - thus implying a statistically significant association (P < 0.0001) between subclinical Pneumocystis infection and SCLC. CONCLUSIONS: While the nature of this association is not clear, it nevertheless constitutes an important finding - either the infection is specifically facilitated by this tumour or induces the development of this type of neoplasm in combination with other factors. Eur J Clin Invest 2004; 34 (3): 229-335
Adult↗
[The host-opportunistic protozoa system. The dissemination of Pneumocystis infection in white rats under the influence of drug-induced and biological immunosuppression].
The main purpose of the present study is the investigation of relationships of Pneumocystis carinii with the organism of white rat Wistar, which is natural carrier of this parasite. The series of experiments has shown that the immunosuppressor Tricort-40 (corticosteroid of prolonged activity) in a short time reactivates the Pneumocystis infection. The parasites have been observed in a great number in the lungs and rarely in the liver. The reactivation and dissemination of the Pneumocystis infection have been achieved constantly and with great expression by the combined immunosuppression of rats, by the medicamentous immunosuppression (injection of T-40) and biological one (infection with amastigotes Leishmania infantum). The developing mixed-infection (with pneumocysts and leishmania) could be the basis for the parasitocenological relationships.
AIDS-Related Opportunistic Infections↗
Factors influencing Pneumocystis infection in the immunocompromised rat.
A compromised immune system is the primary predisposing condition for Pneumocystis infection. Factors that contribute to this underlying state of immunosuppression are poorly understood. The presence of common rodent viruses and the role of anti-Pneumocystis antibodies on the progression of natural infection in the corticosteroid-treated rat model of Pneumocystis pneumonia were evaluated. The development and intensity of infection were not affected by the presence or absence of antibodies to these viruses or to major Pneumocystis antigens. A significant increase in survival of Pneumocystis-infected viral antibody-positive rats was observed when these rats were housed under barrier conditions.
Animals↗
[Inhalation pneumonia presenting as a pneumocystis infection].
A case of Pneumocystis carinii pneumonia is presented. Following presentation a chronic alveolitis was uncovered, which was due to ultimately repeated and prolonged inhalation of sweets containing gum arabic. The diagnosis was confirmed by a trans-bronchial biopsy and by chemical analysis of centrifugation of the alveolar lavage deposit. After cessation of the inhalation the progress was satisfactory both in terms of clinical status and lung function measurement.
Gum Arabic↗
[Latent pneumocystis infection revealed after introduction of highly active antiretroviral therapy].
INTRODUCTION: Soon after the introduction of antiretroviral therapy for HIV infection, some patients may develop an inflammatory immune reconstitution syndrome, in the presence of clinically unsuspected infection. CASE REPORT: We describe a 31 year old patient, who presented with a lymphoid interstitial pneumonia associated with HIV infection. Unexpectedly, 15 days after the beginning of antiretroviral therapy, he developed a worsening of his respiratory function due to Pneumocystis infection. CONCLUSION: The appearance or aggravation of pulmonary symptoms, after highly active antiretroviral therapy has been initiated should lead to suspicion of an opportunist infection. Specific sampling must be considered.
Adult↗
Detection of HIV protease inhibitors in alveolar epithelial lining fluid: relevance for modulation of pneumocystis infection in the course of HAART.
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AIDS-Related Opportunistic Infections↗
Similar genotypes of Pneumocystis jirovecii in different forms of Pneumocystis infection.
This study describes the genotyping of Pneumocystis jirovecii organisms isolated from three groups of patients that developed diverse forms of P. jirovecii infection; the patients were monitored in the same French hospital. Forty archival specimens from 13 adults with Pneumocystis pneumonia, eight adults colonized by P. jirovecii and 19 immunocompetent infants infected with the fungus contemporaneously with a bronchiolitis episode were analysed retrospectively. Genotyping was performed by analysis of sequences of the internal transcribed spacer (ITS)1 and ITS2 regions, and of the dihydropteroate synthase (DHPS) locus. At the ITS regions, a high diversity of genotypes, identical main genotypes (B(1)a(3) and B(2)a(1)) and the occurrence of mixed infections (more than one genotype) were observed in the three patient groups. At the DHPS locus, the results indicated the presence of mutants in the two adult groups, as well as in the infant group. Consequently, at these two independent genomic regions, P. jirovecii isolates from patients who developed different forms of infection and who lived in the same geographical region presented common characteristics. These results suggest that patients infected with P. jirovecii, whatever the form of infection they present, are part of a common human reservoir for P. jirovecii.
Adult↗
The effect of corticosteroid treatment on the cell surface glycocalyx of the rat pulmonary alveolus: relevance to the host-parasite relationship in pneumocystis carinii infection.
Pneumocystis carinii infection is characterized by the attachment of P. Carinii to host alveolar type I cell and propagation of the organism with corticosteroid administration. We have examined the effects of corticosteroids on the cell surface glycocalyx of the pulmonary alveolus in rats by ultrastructural histochemistry using cationized ferritin, ruthenium red and concanavalin A-horseradish peroxidase techniques. In rats treated for 4 and 6 weeks, the amount of the alveolar cell surface glycocalyx was markedly decreased by all three techniques. The changes were most pronounced at the cell surface of the type I pneumocyte, and this may be important in the pathogenesis of P. carinii pneumonia.
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[The host-opportunistic protozoa system. The incidence of mixed infections (Pneumocystis and cytomegalovirus) in children living in radionuclide-contaminated areas].
The purpose of our study was to determine the influence of ionized radiation onto the frequency of mixed infections (P. carinii and Cytomegalovirus) in children inhabitants of the settlements affected with radionuclide after Chernobyl accident. Two groups of children were under survey. 1) 103 inhabitants of Novozybkov (Bryansk Province, Russia) and 38 patients under observation in Moscow paediatric hospital from another affected villages (5-15 Ci/km2) were examined serologically by the diagnostic system "Pneumo-test" and "Cytomegatest" (Nyarmedic, Moscow, Russia). Cut-off titers for P. carinii were IgM-1: 200, IgG-1: 20, for CMV IgG-1: 200, 2) Retrospective study of 563 patients with respiratory pathology and 1809 died children after acute pneumonia during 14 years period. Sputum and mucus of the patients taken by laryngoscopy and bronchoscopy were studied for P. carinii by microscopy, the section of lungs--histologically. The sediments of urine and saliva were examined for CMV by microscopy and section of different organs_-histologically. Examinations were performed by one and the same highly qualified pathologist. The results of the study were as follows. 1. Of 563 children examined for both P. carinii and CMV 186 (33%) were positive for P. carinii and 189 (33.7%) for CMV. Both pathogens were found in 46 children (8.2%), mainly among 1-2 and 6-12 month age (8.5 and 14.5%, respectively). Retrospective analysis of 1809 autopsy results shows, that in 73 cases (4%) were found only P. carinii, in 200 (11.1%) only CMV and in 24 (1.3%) two pathogens simultaneously. 2. Of 103 children surveyed serologically P. carinii monoinfection was found in 7 (8.8%), CMV-in 25 (24.3%) and coinfection in 55 (53.4%). Estimated frequency for coinfection (if combination of two infections were to be accidental) should equal 46.8%. In control group consisted of 30 children from clean Moscow region the rate of coinfection was 16.7% and estimated rate 15% (the difference between empiric and estimated rates are statistically significant, t > 4). Thus it is clear that the rate of coinfection of P. carinii and CMV is always high either in clean or in affected by ionized radiation regions. This rate determined by microscopy was higher in patients (8.2%) than in autopsy cases (1.3%) and much higher in children from affected region (53.3%) than in control (16.7%), being determined serologically. Separate interest present geometric mean titers found in the cases of coinfection. The titer for anti-CMV IgG in children from affected regions was rather high (5884 vs. 1246 in control) and on the contrary titers for anti-P. carinii IgM and IgG were lower than in control (512 vs. 1245 and 58 vs. 159 respectively). We are incline to interpret the results of our study as evidence of increased susceptibility to P. carinii and CMV in those children whose immune system was suppressed by premorbid factors or ionized radiation and peculiar symbiotic relationships of P. carinii and CMV resulting in enhancement of their infectiousness.
Autopsy↗
Pneumocystis infection masquerading as diffuse alveolar damage: a potential source of diagnostic error.
The nonspecific histopathologic changes of diffuse alveolar damage (DAD) were the only findings in nine of 17 lung biopsy specimens containing Pneumocystis carinii infection. Because of the frequent absence of the classically described intra-alveolar frothy material, special stains for organisms should be performed on all biopsy specimens from immunocompromised patients that show DAD, and the diagnosis of Pneumocystis infection should not be discarded unless careful search for organisms using special stains is negative.
Adult↗