Evolución de las infecciones por Pneumocystis Jirovecii en el Hospital de Pediatría Juan P. Garrahan / Evolution of Pneumocystis Jirovecii infections at Hospital de Pediatría Juan P. Garrahan

Pneumocystis jirovecii es un hongo oportunista, causante de neumonía en huéspedes inmunocomprometidos. Es una infección grave con elevada tasa de mortalidad en pacientes oncohematológicos y receptores de trasplante de células progenitoras hematopoyéticas. La administración de corticosteroides es el principal factor de riesgo para adquirir esta infección. Actualmente las infecciones ocurren en aquellos pacientes que no reciben adecuada profilaxis. Las técnicas de diagnóstico molecular son las recomendadas por su elevada sensibilidad, especificidad y rapidez. La frecuencia global de P. jirovecii en pacientes inmunocomprometidos de nuestro hospital, durante el período evaluado fue de 4,8%, con una mortalidad global del 20%. Como factores de mal pronóstico se reportan la presencia de coinfecciones y la necesidad de asistencia respiratoria mecánica. Es importante la sospecha precoz en pacientes de riesgo, confirmada con un diagnóstico preciso mediante métodos moleculares para una intervención adecuada y oportuna (AU)

Pneumocystis jirovecii is an opportunistic fungus, causing pneumonia in immunocompromised hosts. It is a severe infection with a high mortality rate in oncology/hematology patients and hematopoietic stem cell transplant recipients. The administration of corticosteroids is the main risk factor for acquiring this infection. Currently infections occur in patients who do not receive adequate prophylaxis. Molecular diagnostic techniques are recommended because of their high sensitivity, specificity, and speed. In the study period, the overall incidence of P. jirovecii in immunocompromised patients at our hospital was 4.8%, with an overall mortality rate of 20%. Factors of a poor prognosis are the presence of coinfections and the need for mechanical respiratory assistance. Early suspicion in high-risk patients is important to confirm the diagnosis through molecular studies and start adequate and early treatment (AU)

(1→3)-ß-D-glucan testing for the detection of invasive fungal infections in immunocompromised or critically ill people.

BACKGROUND: Invasive fungal infections (IFIs) are life-threatening opportunistic infections that occur in immunocompromised or critically ill people. Early detection and treatment of IFIs is essential to reduce morbidity and mortality in these populations. (1→3)-ß-D-glucan (BDG) is a component of the fungal cell wall that can be detected in the serum of infected individuals. The serum BDG test is a way to quickly detect these infections and initiate treatment before they become life-threatening. Five different versions of the BDG test are commercially available: Fungitell, Glucatell, Wako, Fungitec-G, and Dynamiker Fungus. OBJECTIVES: To compare the diagnostic accuracy of commercially available tests for serum BDG to detect selected invasive fungal infections (IFIs) among immunocompromised or critically ill people. SEARCH METHODS: We searched MEDLINE (via Ovid) and Embase (via Ovid) up to 26 June 2019. We used SCOPUS to perform a forward and backward citation search of relevant articles. We placed no restriction on language or study design. SELECTION CRITERIA: We included all references published on or after 1995, which is when the first commercial BDG assays became available. We considered published, peer-reviewed studies on the diagnostic test accuracy of BDG for diagnosis of fungal infections in immunocompromised people or people in intensive care that used the European Organization for Research and Treatment of Cancer (EORTC) criteria or equivalent as a reference standard. We considered all study designs (case-control, prospective consecutive cohort, and retrospective cohort studies). We excluded case studies and studies with fewer than ten participants. We also excluded animal and laboratory studies. We excluded meeting abstracts because they provided insufficient information. DATA COLLECTION AND ANALYSIS: We followed the standard procedures outlined in the Cochrane Handbook for Diagnostic Test Accuracy Reviews. Two review authors independently screened studies, extracted data, and performed a quality assessment for each study. For each study, we created a 2 × 2 matrix and calculated sensitivity and specificity, as well as a 95% confidence interval (CI). We evaluated the quality of included studies using the Quality Assessment of Studies of Diagnostic Accuracy-Revised (QUADAS-2). We were unable to perform a meta-analysis due to considerable variation between studies, with the exception of Candida, so we have provided descriptive statistics such as receiver operating characteristics (ROCs) and forest plots by test brand to show variation in study results. MAIN RESULTS: We included in the review 49 studies with a total of 6244 participants. About half of these studies (24/49; 49%) were conducted with people who had cancer or hematologic malignancies. Most studies (36/49; 73%) focused on the Fungitell BDG test. This was followed by Glucatell (5 studies; 10%), Wako (3 studies; 6%), Fungitec-G (3 studies; 6%), and Dynamiker (2 studies; 4%). About three-quarters of studies (79%) utilized either a prospective or a retrospective consecutive study design; the remainder used a case-control design. Based on the manufacturer's recommended cut-off levels for the Fungitell test, sensitivity ranged from 27% to 100%, and specificity from 0% to 100%. For the Glucatell assay, sensitivity ranged from 50% to 92%, and specificity ranged from 41% to 94%. Limited studies have used the Dynamiker, Wako, and Fungitec-G assays, but individual sensitivities and specificities ranged from 50% to 88%, and from 60% to 100%, respectively. Results show considerable differences between studies, even by manufacturer, which prevented a formal meta-analysis. Most studies (32/49; 65%) had no reported high risk of bias in any of the QUADAS-2 domains. The QUADAS-2 domains that had higher risk of bias included participant selection and flow and timing. AUTHORS' CONCLUSIONS: We noted considerable heterogeneity between studies, and these differences precluded a formal meta-analysis. Because of wide variation in the results, it is not possible to estimate the diagnostic accuracy of the BDG test in specific settings. Future studies estimating the accuracy of BDG tests should be linked to the way the test is used in clinical practice and should clearly describe the sampling protocol and the relationship of time of testing to time of diagnosis.

[Pneumocystis jirovecii and quantitative PCR: Pneumonia or colonization?] / Pneumocytis jirovecii et PCR quantitative : pneumonie ou colonisation à Pneumocystis jirovecii ?

BACKGROUND: Quantitative PCR to detect Pneumocystis jirovecii (Pj) is a new tool for the diagnosis of Pneumocystis jirovecii pneumonia (PJP). The yield of this technique, in cases of low fungal burden, when the standard technique using immunofluorescence (IF) is negative, needs to be evaluated. METHODS: We retrospectively reviewed the charts of all patients with a positive PCR but negative IF test (PCR+/IF-) in bronchoalveolar lavage (BAL) fluid performed over one year. We used an algorithm based on underlying immunosuppression, clinical picture, thoracic CT scan appearances, existence of an alternative diagnosis and the patient's outcome on treatment. Using this, each case was classified as probable PJP, possible PJP or colonization. RESULTS: Among the 416 BAL performed, 48 (12%) were PCR+/IF- and 43 patients were analyzed. Patients were mostly male (56%) with a median age of 60 years. Thirty-five (84%) were immunocompromised: 4 (9%) HIV-infected patients, 26 (60%) with hematologic or solid organ cancer, 3 (7%) were renal transplant recipients. Seven (16%) were classified as probable PPJ and 9 (21%) as possible PJP. Patients with a probable or possible PJP were more frequently admitted to the ICU (P<0.02) and had higher risk of death (P<0.01) when compared to those with colonization. Median PCR levels were very low and were not different between PJP or colonized patients (P=0.23). CONCLUSIONS: Among patients with a positive Pj PCR in BAL but with negative IF, only 37% had probable or possible PJP and PCR could not discriminate PJP from colonization.

Pneumocystis jirovecii infection of bilateral adrenal glands in an immunocompetent adult: a case report.

Pneumocystis jirovecii (PJ) infection is one of the most common opportunistic infections occurring in patients with HIV/AIDS and other immunocompromised states. It is not known to cause clinically significant illness in immunocompetent hosts. We report a 48-year-old HIV-negative, diabetic male who presented with fever and adrenal insufficiency. Abdominal sonography and PET-CT revealed bilateral enlarged adrenal glands with peripheral enhancement and central necrosis. An endoscopic ultrasound-guided fine-needle aspiration cytology of the left adrenal gland demonstrated well-defined, round cysts of PJ. There was no evidence of pulmonary involvement. The response to first-line treatment was poor and the patient responded to second-line treatment for Pneumocystis infection.

[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 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.

[Extrapulmonary pneumocystosis: a case report]. / Neumocistosis extrapulmonar: comunicación de un caso.

We report a case of a middle-age male patient, with newly HIV infection in AIDS stage diagnosis, no comorbitidies, who was hospitalized for subacute malaise, fever, self-limited unproductive cough and no bloody chronic diarrea. The diagnosis of Pneumocystis jiroveci pneumonia was performed by imagenological suspicion and stains of cysts of this pathogen with bronchoalveolar lavage samples. Treatment was initiated with oral cotrimoxazole and starting HAART with good clinical outcome. Concomitantly, an etiologic study was conducted for chronic diarrhea and through histopathological examination of colonic mucosa, numerous extracellular cystic structures Pneumocystis characteristics were observed, performing the diagnosis of extrapulmonary pneumocystosis. Extrapulmonary pneumocystosis is a rare cause of P. jiroveci infection, requires a high index of suspicion and should be approached in HIV patients with severe AIDS which is common in co-infection of various infections and is peremptory to make an etiologic diagnosis and early treatment.

Neumocistosis extrapulmonar: comunicación de un caso / Extrapulmonary pneumocystosis: a case report

We report a case of a middle-age male patient, with newly HIV infection in AIDS stage diagnosis, no comorbitidies, who was hospitalized for subacute malaise, fever, self-limited unproductive cough and no bloody chronic diarrea. The diagnosis of Pneumocystis jiroveci pneumonia was performed by imagenological suspicion and stains of cysts of this pathogen with bronchoalveolar lavage samples. Treatment was initiated with oral cotrimoxazole and starting HAART with good clinical outcome. Concomitantly, an etiologic study was conducted for chronic diarrhea and through histopathological examination of colonic mucosa, numerous extracellular cystic structures Pneumocystis characteristics were observed, performing the diagnosis of extrapulmonary pneumocystosis. Extrapulmonary pneumocystosis is a rare cause of P. jiroveci infection, requires a high index of suspicion and should be approached in HIV patients with severe AIDS which is common in co-infection of various infections and is peremptory to make an etiologic diagnosis and early treatment.

Comunicamos el caso de un varón de edad mediana, con diagnóstico reciente de infección por VIH en etapa SIDA, sin otras co-morbilidades, y cuadro subagudo de compromiso del estado general, fiebre, tos poco productiva autolimitada y diarrea crónica no sanguinolenta. Se realizó el diagnóstico de neumonía por Pneumocystis jiroveci mediante sospecha imagenológica y tinción de quistes de este patógeno en muestras de lavado broncoalveolar. Se inició tratamiento con cotrimoxazol y TARV con buena evolución clínica. En forma concomitante se realizó el estudio etiológico de diarrea crónica y a través del estudio histopatológico de mucosa colónica se observaron numerosas estructuras quísticas extracelulares, características de Pneumocystis por lo que se realizó el diagnóstico de neumocistosis extrapulmonar. La neumocistosis extrapulmonar es una causa infrecuente de infección por P. jiroveci, que requiere un alto índice de sospecha en pacientes con VIH e inmunocompromiso grave, en los cuales es frecuente la co-infección de infecciones oportunistas. Es perentorio realizar un diagnóstico etiológico y tratamiento precoz.

Extra-pulmonary Pneumocystis jiroveci infection: a case report

In physical examination abdominal tenderness, gate disturbance and penile herpetic lesions were detected. Decreased disc height at T11-T12 level was detected in chest X-ray. Abdominal sonography and CT scan revealed hypo dense lesions in Lt left Lobe of liver and multiple hypo dense splenic and pancreatic lesions, ascitis, Lt left sided pleural effusion, thickening of jejuneal mucosa and edema of bowel wall. Vertebral body lesion and paravertebral abscess, bony calvarial involvement and adjacent extra axial brain lesion were observed in imaging were other findings. RNA analysis for HIV was positive. Vertebral lesion biopsy and aspiration of splenic lesion were performed and pathology revealed Pneumocystis jirovecii suggestive of extra pulmonary Pneumocystis carinii infection.

Extra-pulmonary Pneumocystis jiroveci infection: a case report.

In physical examination abdominal tenderness, gate disturbance and penile herpetic lesions were detected. Decreased disc height at T11-T12 level was detected in chest X-ray. Abdominal sonography and CT scan revealed hypo dense lesions in Lt left Lobe of liver and multiple hypo dense splenic and pancreatic lesions, ascitis, Lt left sided pleural effusion, thickening of jejuneal mucosa and edema of bowel wall. Vertebral body lesion and paravertebral abscess, bony calvarial involvement and adjacent extra axial brain lesion were observed in imaging were other findings. RNA analysis for HIV was positive. Vertebral lesion biopsy and aspiration of splenic lesion were performed and pathology revealed Pneumocystis jirovecii suggestive of extra pulmonary Pneumocystis carinii infection.

Update on pulmonary Pneumocystis jirovecii infection in non-HIV patients.

Pneumocystis jirovecii is the only fungus of its kind to be pathogenic in humans. It is primarily responsible for pneumonia (PJP). The key to understanding immune defences has focused on T-cells, mainly because of the HIV infection epidemic. Patients presenting with PJP all have a CD4 count below 200/mm(3). The introduction of systematic primary prophylaxis and the use of new anti-retroviral drugs have significantly reduced the incidence of this disease in the HIV-infected population, mainly in developed countries. The increasingly frequent use of corticosteroids, chemotherapy, and other immunosuppressive drugs has led to an outbreak of PJP in patients not infected by HIV. These patients presenting with PJP have more rapid and severe symptoms, sometimes atypical, leading to delay the initiation of a specific anti-infective therapy, sometimes a cause of death. However, the contribution of new diagnostic tools and a better understanding of patients at risk should improve their survival.

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.

Coinfección pulmonar por Aspergillus fumigatus y Pneumocystis jirovecii en un paciente con VIH-SIDA / Lung coinfection by Aspergillus fumigatus and Pneumocystis jirovecii in an HIV-AIDS patient

Se presenta un caso de coinfección pulmonar por Aspergillus fumigatus y Pneumocystis jirovecii en un paciente con VIH-SIDA. Se diagnosticó con TAC pulmonar, visualización directa con KOH 20 por ciento, tinción de Gomori-Grocott y cultivo del LBA, galactomanano en sangre y de LBA. Se discuten los factores de riesgo, diagnóstico y tratamiento para cada infección.

We report a case of lung coinfection by Aspergillus fumigatus and Pneumocystis jirovecii in a patient with HIV-AIDS. Was diagnosed with lung TAC, direct visualization with KOH 20 percent, Gomori- Grocott staining and culture of BAL, galactomannan in blood and BAL. We discuss risk factors, diagnosis and treatment for each infection.

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.

Pneumocystis jirovecii: cien años de historia / Pneumocystis jirovecii: one hundred years of history

Introducción: Pneumocystis jirovecii es uno de los patógenos oportunistas más importantes que afectan a individuos con síndrome de inmunodeficiencia adquirida y pacientes inmunodeprimidos por otras causas. A pesar de haber sido observado por primera vez hace más de 100 años, se desconocen aún muchos aspectos importantes de su biología y de la morbilidad que produce. Objetivo: en este trabajo se pretende presentar una actualización sobre los principales aspectos de la historia, la epidemiología y la biología de P. jirovecii, así como de la enfermedad que produce. Conclusiones: se han publicado varios artículos de revisión desde su descubrimiento que brindan detalles y elementos novedosos del microorganismo, sin embargo, pocos son los manuscritos encontrados en la literatura de habla hispana que aborden esta problemática.

Introduction: Pneumocystis jirovecii is one of the most important opportunistic pathogens affecting AIDS individuals and immunodepressive patients. In spite of the fact that it was observed one hundred years ago for the first time, many fundamental aspects of its biology and the morbidity it causes are still unknown. Objective: this paper was aimed at presenting updating on the main aspects of the history, the epidemiology and the biology of P. jirovecii and the disease it causes. Conclusions: a number of review articles have been published since the discovery, all of which provide details and novel elements of the microorganism. However, few original papers dealing with this problem have been found in the Spanish literature.

[Presence of Pneumocystis carinii and Pneumocystis wakefieldiae DNA in the extrapulmonary tissues of immunocompromised laboratory rats]. / Wystepowanie DNA Pneumocystis carinii i Pneumocystis wakefieldiae w tkankach pozaplucnych szczurów laboratoryjnych poddawanych immunosupresji.

Fungi of the genus Pneumocystis are opportunistic pathogens which cause lethal pneumonia in immunocompromised hosts. Those fungi may also invade other visceral organs where they induce lesions, although, the pathways or mechanisms of the in vivo infection are still unknown. The corticosteroid-treated rat model was used to evaluate the course of extrapulmonary pneumocystosis. Liver, kidney, spleen, and mesenteric lymph nodes of 16 rats were examined for the presence of mtLSU gene fragments of P. carinii and P. wakefieldiae using the nested PCR method. Pneumocystis DNA was detected in 26 organ samples of which 17 contained both species (P. carinii and P. wakefieldiae) and 9 contained only P. carinii. Positive samples were received from 10 rats examined after 6-9 weeks of immunosuppression. The highest percentage of positive samples (62.5%) was obtained among examined visceral lymph nodes. Pneumocystis DNA was detected in the blood serum of two rats with no traces of the DNA in their internal organs. Conversely, Pneumocystis DNA was found in the internal organs of two other rats, although their serum samples were negative. The average number of Pneumocystis cysts in the lungs of animals in which extrapulmonary infection was detected was 3.4 per one microscopic view field. In the case of animals where the infection was limited to the lung tissue this number was almost two times lower (1.8 cysts per one microscopic view field). An analysis of the results of the presently reported experiment showed that massive Pneumocystis infection in the lungs makes it more likely that Pneumocystis will spread to other internal organs. This spread probably takes place via the lymphatic vessels. The extrapulmonary foci may contain either P. carinii alone, or both pathogens: P. carinii and P. wakefieldiae.