Quantitative Pneumocystis jirovecii real-time PCR to differentiate disease from colonisation.

We studied a Pneumocystis jirovecii quantitative polymerase chain reaction (qPCR) for distinguishing P. jirovecii disease from colonisation. Eighty-two respiratory samples from 65 patients with qPCR results were analysed against a gold standard clinical diagnosis of Pneumocystis pneumonia. High inter-assay reproducibility using recombinant and clinical material was observed. Contemporaneous samples from the same patient displayed high variability (median difference 2.6 log10 copies/mL, IQR 2.1-3.1 log10 copies/mL). Despite this, area under the receiver operator characteristic curve was 0.8. An optimum cut-off of 2.8 log10 copies/mL (equivalent to CT of 34.0 cycles) had 59% sensitivity and 92% specificity. The median P. jirovecii load was 7.3 log10 copies/mL in HIV patients compared to 2.6 log10 copies/mL in non-HIV patients. Specificity was 100% in non-HIV patients with qPCR of >3.8 log10 copies/mL. qPCR was useful for distinguishing P. jirovecii disease from colonisation. A quantitative standard, standardisation of definitions and methods are required to improve the generalisability of results.

[Pneumocystis jirovecii pneumonia-an opportunistic infection undergoing change]. / Pneumocystis-jirovecii-Pneumonie ­ eine opportunistische Infektion im Wandel.

Pneumocystis jirovecii pneumonia (PcP) has for many years been reported mostly in human immunodeficiency virus-infected patients. Increasingly, it also affects other immunocompromised patients, e.g. after organ or allogeneic stem cell/bone marrow transplantation, patients with hematologic malignancies or autoimmune diseases. The diagnosis of PcP relies on a critical evaluation of clinical symptoms, risk factors, radiologic features and microbiological tests. High dose cotrimoxazole is the most effective therapeutic option. Rapid initiation is essential, since mortality is especially high in patients admitted to intensive care with respiratory failure. This article reviews the current epidemiology of PcP and highlights the diagnostic and therapeutic options. Recommendations for primary and secondary prophylaxis are summarized.

Challenging Alveolar Hemorrhage Complicating Pneumonia After Liver Transplantation: A Case Report.

Alveolar hemorrhage is a life-threatening clinical syndrome often initially thought to be atypical pneumonia. Association with hematopoietic stem cell transplantation is well studied, but not with solid organ transplantation. We report a case of a 54-year-old woman presented with fever and shortness of breath on the third posttransplant day after deceased donor liver transplantation. Imaging studies showed diffuse bilateral pulmonary infiltrates and a positive sequential bronchoalveolar lavage test was revealed during bronchoscopy. Cytomegalovirus antigenemia was present in 8/200,000 white blood cells; Aspergillus galactomannan and Pneumocystis jirovecii were also present. However, only Aspergillus hyphae were found in the sputum culture. Management strategy aimed to treat underlying infections, provide adequate respiratory support, and control inflammation. We proposed that diffuse alveolar hemorrhage should be considered as differential diagnosis in early pulmonary complications after liver transplantation. Early diagnosis and aggressive treatment protocol is the key for a good outcome.

The diagnosis of multiple opportunistic infections in advanced stage AIDS: when Ockham's Razor doesn't cut it

In the advanced stage of AIDS, the diagnosis of the opportunistic infections may be challenging due to the high risk of performing invasive diagnostic methods in a patient with a critical clinical condition, as well as the correct interpretation of the results of microbiological exams. One of the challenges for the diagnosis and treatment of the opportunistic infections is that they may occur concomitantly in the same patient and they may mimic each other, leading to a high discrepancy between clinical and autopsy diagnoses. We describe the case of a 52-year-old man who was hospitalized because of weight loss, anemia, cough, and hepatosplenomegaly. During the investigation, the diagnosis of AIDS was made, and the patient developed respiratory failure and died on the fourth day of hospitalization. At autopsy, disseminated non-tuberculosis mycobacteriosis was found, affecting mainly the organs of the reticuloendothelial system. Also, severe and diffuse pneumonia caused by multiple agents (Pneumocystis jirovecii, Histoplasma capsulatum, suppurative bacterial infection, non-tuberculosis mycobacteria, and cytomegalovirus) was seen in a morphological pattern that could be called "collision pneumonia." The lesson from this case, revealed by the autopsy, is that in advanced AIDS, patients often have multiple opportunistic infections, so the principle of Ockham's razor­that a single diagnosis is most likely the best diagnosis­fails in this clinical context.

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

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.

Infección grave por Pneumocystis jirovecii en lactantes con síndrome de West tratados con hormona adrenocorticotropa intramuscular / Classification of structural lesions in magnetic resonance imaging. Surgical implications in drug-resistant epilepsy patients

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

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.

Trimethoprim-sulfamethoxazole treatment does not reverse obstructive pulmonary changes in pneumocystis-colonized nonhuman primates with SHIV infection.

BACKGROUND: Despite antiretroviral therapy and trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis, Pneumocystis pneumonia remains an important serious opportunistic infection in HIV-infected persons. Pneumocystis (Pc) colonization in HIV-infected individuals and in HIV-uninfected smokers is associated with chronic obstructive pulmonary disease (COPD). We previously developed a nonhuman primate model of HIV infection and Pc colonization and demonstrated that Pc colonization correlated with COPD development. In the present study, we examined kinetics of COPD development in non-human primate and tested the effect of Pc burden reduction on pulmonary function by TMP-SMX treatment. METHODS: Cynomolgus macaques (n = 16) were infected with simian/human immunodeficiency virus (SHIV89.6P), and natural Pc colonization was examined by nested polymerase chain reaction of serial bronchoalveolar lavage fluid and anti-Pc serology. RESULTS: Eleven of 16 monkeys became Pc colonized by 16 weeks post simian-human immunodeficiency virus (SHIV) infection. Pc colonization of SHIV-infected monkeys led to progressive declines in pulmonary function as early as 4 weeks after Pc detection. SHIV-infected and Pc-negative monkeys maintained normal lung function. At 25 weeks post-SHIV infection, TMP-SMX treatment was initiated in 7 Pc-positive (Pc+) (TMP: 20 mg/kg and SMX: 100 mg/kg, daily for 48 weeks) and 5 Pc-negative (Pc-) monkeys. Four SHIV+/Pc+ remained untreated for the duration of the experiment. Detection frequency of Pc in serial bronchoalveolar lavage fluid (P < 0.001), as well as plasma Pc antibody titers (P = 0.02) were significantly reduced in TMP-SMX-treated macaques compared with untreated. CONCLUSIONS: Reduction of Pc colonization by TMP-SMX treatment did not improve pulmonary function, supporting the concept that Pc colonization results in early, permanent obstructive changes in the lungs of immunosuppressed macaques.

Safety issues in vasculitis: infections and immunizations in the immunosuppressed host.

Infectious diseases are a significant cause of morbidity and mortality in immunosuppressed patients, including those with connective tissue diseases. Both disease and treatment contribute to a predisposition to infection in immunocompromised patients. Significant infection and morbidity occur in 25% to 50% of these patients with a median mortality of 5.2% due to common bacterial infections, such as pneumonia or bacteremia, and opportunistic fungal infections such as Pneumocystis. The lungs, skin, urinary tract, blood, and central nervous system are commonly affected. Pathogens such as Pneumocystis jirovecii, Histoplasma capsulatum, Aspergillus species, herpes zoster, JC virus, Nocardia asteroides, and Nocardia species are increasingly prevalent in immunocompromised patients. Improved recognition, diagnosis, and prevention of these infections are needed to enhance outcomes in these patients.

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

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

Molecular Adsorbents Recirculating System dialysis in children with cholestatic pruritus.

BACKGROUND: Cholestatic pruritus may severely compromise quality of life. The Molecular Adsorbents Recirculating System (MARS) allows removal of pruritogenic substances without exposure to foreign proteins. Pediatric data, however, are scant. METHODS: We retrospectively analyzed the efficacy of MARS in three boys with severe cholestatic pruritus. They received a total of 135 MARS sessions during 8, 4, and 13 months prior to liver transplantation. Total serum bilirubin and bile acids were monitored, and pruritus was assessed by a numerical rating scale (NRS 0 = no pruritus, 10 = maximal pruritus). RESULTS: MARS sessions were initially performed three times weekly at a mean duration of 6.3 ± 1.4 h. Sessions could be reduced to once weekly and once every other week in two patients. Pre-MARS plasma bile acid concentrations averaged 207 ± 67 µmol/l. They declined to 67 ± 9%, 48 ± 3%, 38 ± 14%, and 37 ± 5% of baseline within 2, 4, 6 and 8 h of therapy, respectively (all p < 0.05). The average interdialytic increase of plasma bile acids was 34 ± 33 µmol/l per day. Mean NRS score decreased from 6.5 ± 2.3 to 3.3 ± 2.9 (p < 0.01). Skin lesions from itching disappeared. All MARS treatments were well tolerated. CONCLUSION: MARS dialysis substantially reduces cholestatic pruritus in children refractory to pharmacological treatment.

Pneumocystis infection and the pathogenesis of chronic obstructive pulmonary disease.

With increases in the immunocompromised patient population and aging of the HIV+ population, the risk of serious fungal infections and their complications will continue to rise. In these populations, infection with the fungal opportunistic pathogen Pneumocystis jirovecii remains a leading cause of morbidity and mortality. Infection with Pneumocystis (Pc) has been shown to be associated with the development of chronic obstructive pulmonary disease (COPD) in human subjects with and without HIV infection and in non-human primate models of HIV infection. In human studies and in a primate model of HIV/Pc co-infection, we have shown that antibody response to the Pc protein, kexin (KEX1), correlates with protection from colonization, Pc pneumonia, and COPD. These findings support the hypothesis that immunity to KEX1 may be critical to controlling Pc colonization and preventing or slowing development of COPD.

Gastrectomy and chemotherapy with S-1 for gastric cancer in a patient with acquired immunodeficiency syndrome.

Total gastrectomy and chemotherapy with S-1 after surgery were performed in a 50-year-old woman with gastric cancer associated with acquired immunodeficiency syndrome (AIDS). She was given a diagnosis of gastric cancer at the lesser curvature of the body of the stomach, and distal gastrectomy was performed in December 2004. The postoperative course was eventful, with persistent high fever of unknown origin after surgery and infiltrative shadows in the bilateral lung fields showing on CT scan. Polymerase chain reaction (PCR) for pneumocystis carinii on bronchoscopy was positive, serum HIV antibody was positive, HIV-RNA was 2.2 × 10(5) copies/ml, and the serum CD4 lymphocyte level was 25/mm(3) on postoperative day 28. She was given a diagnosis of pneumocystis carinii with AIDS. Pneumocystis carinii and fever improved immediately when ST mixture and highly active antiretroviral therapy (HAART) were performed. After 3 months, the serum CD4 lymphocyte level was elevated to 125/mm(3), and she underwent total gastrectomy because cancer cells at the cut end of the resected stomach were positive microscopically. The postoperative course was uneventful, and she underwent adjuvant chemotherapy with S-1 because the serum CD4 lymphocyte level was 568/mm(3). S-1 therapy was continued for 2 years (each course consisting of 2 weeks of administration followed by 2 weeks off) while performing HAART and monitoring CD4 lymphocyte levels. No side effects such as decreases in white blood cell counts or CD4 lymphocyte levels were seen during S-1 therapy. She is alive and well without recurrence of gastric cancer 5 years after initial gastrectomy.

Pneumocystis jirovecii colonization in patients with systemic autoimmune diseases: prevalence, risk factors of colonization and outcome.

OBJECTIVES: To determine the rate and identify risk factors of Pneumocystis jirovecii (P. jirovecii) colonization among patients with systemic autoimmune diseases. METHODS: We conducted an observational study in patients with systemic autoimmune diseases in an internal medicine department. Each week, five patients with systemic diseases were randomly selected for colonization screening. Patients complaining of recent respiratory symptoms were excluded. P. jirovecii PCR was performed on induced sputum samples. Univariate and multivariate logistic regression analyses of clinical and biological data were performed to determine predictors of Pneumocystis colonization. Pneumocystis pneumonia occurrence in P. jirovecii-positive PCR patients was recorded during a 1-year follow-up. RESULTS: P. jirovecii was detected in 11/67 (16%) subjects. Comparing the features in P. jirovecii-positive and P. jirovecii-negative PCR patients, only male gender was significantly associated with Pneumocystis colonization. In multivariate analysis with regard to gender, the higher prevalence of P. jirovecii colonization in men was largely explained by higher daily CSs [odds ratio (OR) = 1.6; 95% CI 1.1, 2.3] and lower total lymphocyte level (OR = 0.9; 95% CI 0.8, 0.99). No P. jirovecii-positive PCR patient developed Pneumocystis pneumonia during the 1-year follow-up, but corticosteroid amounts were significantly lower at the end of follow-up than on inclusion. CONCLUSION: This is the first study on P. jirovecii colonization in patients with systemic autoimmune diseases. We found a high prevalence of colonization and identified CS therapy and lymphocyte counts as risk factors for colonization. We recommend screening for P. jirovecii colonization in patients with systemic autoimmune diseases receiving immunosuppressant treatment. Further studies are needed to determine the role of subclinical colonization in disease transmission and the persistence of Pneumocystis colonization.

A followup study of asymptomatic carriers of Pneumocystis jiroveci during immunosuppressive therapy for rheumatoid arthritis.

OBJECTIVE: To examine the preventive effects of prophylaxis against Pneumocystis jiroveci-induced pneumonia (PCP) in patients receiving immunosuppressive therapy for rheumatoid arthritis (RA) who are colonized by this organism. METHODS: We performed molecular testing by polymerase chain reaction (PCR) for P. jiroveci on induced sputum or bronchoalveolar lavage fluids of 82 patients with RA. During primary prophylaxis, asymptomatic carriers of this organism were examined by high-resolution computed tomography and PCR every 2 weeks. RA patients who had developed PCP received PCR tests every week. Once negative results were obtained, PCR testing was scheduled at Months 1, 3, and 6, followed by reexaminations every 6 months. RESULTS: We found 9 cases of asymptomatic carriage of P. jiroveci. All the carriers had received low doses of methotrexate. Upon introduction of PCP prophylaxis, 5 cases tested negative for PCR within 1 month. Three carriers developed PCP before starting prophylaxis, but these tested negative for PCR after short periods (1-2 weeks) of PCP treatment. Once P. jiroveci was eradicated, all cases maintained negative PCR results during followup without prophylactic intervention, even after resuming immunosuppressive therapy. One patient refused PCP prophylaxis, but no PCP developed. CONCLUSION: RA patients with asymptomatic carriage of P. jiroveci benefited from short-term prophylaxis against PCP. Positive PCR results appeared to be predictive of future development of PCP in RA patients. Identification of P. jiroveci carriers will encourage prompt introduction of PCP prophylaxis when rheumatologists consider immunosuppressive therapy for RA.

Neumotórax en pacientes infectados con el virus de la inmunodeficiencia humana / Pneumothorax in human immunodeficiency virus infected patients

Introducción. El sistema respiratorio continúa siendo un sitio común de deterioro en los pacientes con el virus de la inmunodeficiencia humana (VIH). Entre sus manifestaciones está el neumotórax por causas traumáticas e infecciosas y que es una causa de agravamiento para estos pacientes. El presente estudio pretende identificar y caracterizar el comportamiento de un conjunto de variables en pacientes con VIH con esta complicación. Material y método. Se realizó un estudio observacional descriptivo del tipo de serie de casos. De los registros clínicos se obtuvieron las variables deseadas. Resultados. El 91,67% eran varones, la media de edad fue 32,17 años. Las principales causas del neumotórax fueron infecciosas, particularmente neumonía por Pneumocystis jirovecii y cateterismo venoso profundo. El 33,3% de los pacientes presentó fuga de aire persistente (con significación estadística) y 2 casos, sepsis pleural. Fallecieron 4 pacientes, todos con insuficiencia respiratoria aguda y bronconeumonía bacteriana. Conclusiones. Fueron mayoría los varones en la tercera década de la vida, enfermos de sida. Las principales causas de neumotórax fueron las infecciosas y la cateterización de la vena subclavia. La inmunodeficiencia tuvo un papel pronóstico relevante en la evolución y el desenlace del enfermo. La pleurostomía mínima sigue siendo la primera opción de tratamiento en estos pacientes debido a un precario estado general que contraindica un proceder mayor. La complicación más frecuente fue la fuga de aire persistente, que fue significativa como factor de mal pronóstico en la evolución de los pacientes. Prevalecieron, como causas de muerte, la insuficiencia respiratoria aguda y la bronconeumonía bacteriana bilateral (AU)

Introduction. The respiratory system still continues to be a common place which deteriorates in HIV patients. Among the signs and symptoms, is the occurrence of a pneumothorax due to trauma and infections and is a cause of aggravation for these patients. The present study attempts to identify and characterise the behaviour of a group of variables in HIV patients with this complication. Material and method. An observational, descriptive case series study was carried out. The desired variables were obtained from clinical records. Results. Of the total number, 91.67% were males, and the mean age was 32.17 years. The main causes of pneumothorax were infections, particularly due to Pneumocystis jirovecii and deep venous catheterisation. A persistent statistically significant air leak was present in 33.3% of patients and two cases of pleural sepsis. Four patients died, all with acute respiratory failure and bacterial bronchopneumonia. Conclusions. The majority were males in the third decade of life, AIDS patients. The main causes of the pneumothorax were infections and catheterisation of the subclavian vein. Immunodepression played a significant prognostic role in the progression and outcome of the patient. Minimum pleurotomy continues to be the first treatment option in these patients, due to their precarious general state which contraindicates a major procedure. The most frequent complication was the persistent air leak, being a significant indicator of a poor prognosis in the progress of these patients. Causes of death such as acute respiratory failure and bilateral bronchopneumonia prevailed (AU)

Otic pneumocystosis in acquired immune deficiency syndrome.

AIDS-associated otic pneumocystosis is rare. Of 14 cases documented mainly as case reports up to now, only 1 has been reported in the surgical pathology literature. We report 6 males, mean age of 32.3 years, with external auditory canal masses and otorrhea. Two biopsies contained a predominance of granulation tissue with a mixed inflammatory cell infiltrate and elusive foci of foamy exudate. In contrast, 4 biopsies demonstrated conspicuous angiocentric mantles of stippled, foamy exudate. Fibrin was noted in intravascular, perivascular, and intervascular locations. One biopsy demonstrated bordering of the foamy exudate by a palisaded granulomatous reaction, with adjacent discrete giant cell-containing granulomas. Special stains confirmed trophozoites and cysts within the foamy exudate. Review of 2 initial "nondiagnostic" biopsies confirmed granulation tissue and necrotic debris in which Pneumocystis jiroveci was identified in focal foamy exudate. After the diagnosis of otic pneumocystosis, all patients were initiated on trimethoprim-sulfamethoxazole. One patient also had dapsone. Two patients succumbed to pulmonary tuberculosis and 2 were lost to follow-up. One patient with pneumocystis pneumonia did not return for follow-up after 6 weeks. One patient experienced complete resolution of the mass on medical therapy, and is disease free for 4 years. Heightened recognition of the characteristic foamy exudate in an unconventional location remains the gold standard in the timely diagnosis of this eminently treatable disease. In all patients, otic pneumocystosis served as the sentinel of underlying HIV infection and AIDS.

Extrapulmonary Pneumocystis carinii infection in an AIDS patient: a case report.

BACKGROUND: Extrapulmonary Pneumocystis carinii (EPC) infection is an uncommon condition, regardless of HIV status, and can occur as a complication of P carinii pneumonia (PCP). However, PCP is the most common severe opportunistic infection in patients with AIDS. The incidence of EPC is variable, and in HIV-1-infected individuals it has been estimated to be 0.06-2.5%. CASE: A case of generalized lymphadenopathy was referred to us for fine needle aspiration cytology (FNAC). The patient was a 9-year-old boy who had a toxic facies and manifested multiple skin lesions all over the body. Fever was present during the examination. HIV status was confirmed from the history and test report. FNAC was done from a cervical lymph node and smears stained with hematoxylin-eosin and with Giemsa and Papanicolaou stain. The presence of P carinii was suspected in Giemsa- and hematoxylin-eosin-stained smears, and silver methenamine stain was used to confirm the diagnosis. Fungal spores were seen as small, spherical cysts of variable sizes, more or less the size of erythrocytes. The diagnosis was thus established as EPC infection. CONCLUSION: Lymph node involvement is the most common site of pneumocystosis in AIDS patients. Fine needle aspiration diagnosis of EPC infection is a possibility in such cases with lymphadenopathy and must be included in the differential diagnosis of lymph node swellings in AIDS.