Pneumocystis Jirovecii Infection Research Articles

Low Titer Pneumocystis jirovecii Infections: More than Just Colonization?

Non-pneumonia Pneumocystis jirovecii colonization is thought to occur frequently in immunocompetent individuals. The aim was to analyze if P. jirovecii low-titer detections have more impact than just colonization. From our total cohort of patients for which P. jirovecii testing by qPCR was requested, we selected exclusively those that were fully immunocompetent. Patients were defined as fully immunocompetent if they did not receive immunosuppressive therapy, displayed regular antibody titers, and did not suffer from acquired, inherited or autoimmune diseases. Only those patients with complete medical records available were included. A retrospective analysis identified patients with P. jirovecii colonization and successful antibiotic therapy in response to laboratory pathogen detection. We identified 30 fully immunocompetent patients with P. jirovecii colonization suspected to suffer from infection with the pathogen, but with milder symptoms than pneumonia. All patients were successfully treated with cotrimoxazole against P. jirovecii and resolved from chronic cough and recurrent pulmonary infections. The fact that all patients displayed recovery from their clinical symptoms gives raise to the hypothesis that P. jirovecii infections may also occur in immunocompetent patients but with milder symptoms.

Mortality and its risk factors in Malawian children admitted to hospital with clinical pneumonia, 2001-12: a retrospective observational study.

Few studies have reported long-term data on mortality rates for children admitted to hospital with pneumonia in Africa. We examined trends in case fatality rates for all-cause clinical pneumonia and its risk factors in Malawian children between 2001 and 2012. Individual patient data for children (<5 years) with clinical pneumonia who were admitted to hospitals participating in Malawi's Child Lung Health Programme between 2001 and 2012 were recorded prospectively on a standardised medical form. We analysed trends in pneumonia mortality and children's clinical characteristics, and we estimated the association of risk factors with case fatality for children younger than 2 months, 2-11 months of age, and 12-59 months of age using separate multivariable mixed effects logistic regression models. Between November, 2012, and May, 2013, we retrospectively collected all available hard copies of yellow forms from 40 of 41 participating hospitals. We examined 113 154 pneumonia cases, 104 932 (92·7%) of whom had mortality data and 6903 of whom died, and calculated an overall case fatality rate of 6·6% (95% CI 6·4-6·7). The case fatality rate significantly decreased between 2001 (15·2% [13·4-17·1]) and 2012 (4·5% [4·1-4·9]; ptrend<0·0001). Univariable analyses indicated that the decrease in case fatality rate was consistent across most subgroups. In multivariable analyses, the risk factors significantly associated with increased odds of mortality were female sex, young age, very severe pneumonia, clinically suspected Pneumocystis jirovecii infection, moderate or severe underweight, severe acute malnutrition, disease duration of more than 21 days, and referral from a health centre. Increasing year between 2001 and 2012 and increasing age (in months) were associated with reduced odds of mortality. Fast breathing was associated with reduced odds of mortality in children 2-11 months of age. However, case fatality rate in 2012 remained high for children with very severe pneumonia (11·8%), severe undernutrition (15·4%), severe acute malnutrition (34·8%), and symptom duration of more than 21 days (9·0%). Pneumonia mortality and its risk factors have steadily improved in the past decade in Malawi; however, mortality remains high in specific subgroups. Improvements in hospital care may have reduced case fatality rates though a lack of sufficient data on quality of care indicators and the potential of socioeconomic and other improvements outside the hospital precludes adequate assessment of why case-fatality rates fell. Results from this study emphasise the importance of effective national systems for data collection. Further work combining this with data on trends in the incidence of pneumonia in the community are needed to estimate trends in the overall risk of mortality from pneumonia in children in Malawi. Bill & Melinda Gates Foundation.

Neumonía severa fatal por Pneumocistis jirovecii e Influenza A en un paciente con dermatomiositis amiopática y síndrome antisintetasa

Tradicionalmente, la neumonía por Pneumocistis jirovecii se ha relacionado con pacientes en estado de inmunodeficiencia marcada, principalmente con infección por virus de inmunodeficiencia humana (VIH). Sin embargo, dada la presencia de ciertas condiciones clínicas como el cáncer, los síndromes linfoproliferativos, los trasplantes (en especial los de órgano sólido), las enfermedades autoinmunes y el uso de medicamentos inmunosupresores para el manejo de estas condiciones, las infecciones por Pneumocistis jirovecii son cada vez más frecuentes a pesar de la profilaxis, que en los países en desarrollo no se cumple a cabalidad en todos los pacientes, lo cual genera mayor morbimortalidad en poblaciones vulnerables. A esto se suma el que las coinfecciones en pacientes inmunosuprimidos son una situación común que empeora su pronóstico. En esta oportunidad se presenta el caso de un paciente con infección por Pneumocistis jirovecii e Influenza A, quien tenía de base diagnóstico de dermatomiositis amiopática y síndrome antisintetasa en tratamiento con esteroides e inmunosupresores.

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

AbstractOmenn 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.

Pneumocystis jirovecii Infection of the Liver Presenting With Acutely Elevated Liver Functions Tests

Introduction: AIDS related Pneumocystis Jirovecii [PJ] typically presents as a pulmonary infection. Liver involvement is thought to be rare and has previously been described in a case of hepatic and splenic infiltration of PJ1 and after discovery on antemortem liver biopsy.2 We report a rare case of acute hepatocellular injury with cholestasis in a patient with PJ infiltration seen on liver biopsy. Early diagnosis and treatment led to rapid recovery in this case. Case Presentation: A 38 year old African American man presented with nausea, vomiting and dry cough of 1 week duration. He had a past medical history of untreated HIV. He had a prior hospitalization 3 days ago with similar symptoms, and due to concern for pneumonia he was started on levofloxacin and Bactrim. He denied recent travel history and had no localizing findings on physical examination. His HIV RNA viral load was 79593 copies/ml and CD4 count was 12. CXR and CT revealed bilateral upper lobe ground glass opacities and cystic changes suspicious for pneumocystis pneumonia. Liver function tests were normal on admission however during this hospitalization, became increasingly abnormal with an alkaline phosphatase of 260, while AST and ALT increased to 1506 and 859. Total bilirubin remained normal. Initially this was presumed to be due to drug related liver injury possibly from Bactrim and Fluconazole, however after all potentially offending agents were discontinued, his liver function tests continued to worsen. Liver biopsy was performed which showed patchy areas of hepatocellular necrosis Fig 1 and stained positive for PJ Fig 2. Due to concern for Bactrim related liver injury, the patient was treated with alternative medications: Primaquine and Clindamycin. His liver enzymes improved and patient was discharged to complete a total of 21 days course of PJ directed antimicrobial therapy. Patient was also started back on HIV retroviral therapy Raltegravir and Emtricitabin-Tenofovir.Figure 1Figure 2Discussion: PJ is notorious for causing severe atypical pneumonia in AIDS. Our case highlights an important fact that disseminated PJ, although rare, should be considered as a possible cause of acutely worsening liver function tests in immune compromised patients. Early diagnosis and treatment is crucial and can lead to dramatic clinical improvement and decrease overall morbidity and mortality.

Anti-CD20 antibody therapy and susceptibility to Pneumocystis pneumonia.

Anti-CD20 antibody therapy has been a useful medication for managing non-Hodgkin's lymphoma as well as autoimmune diseases characterized by autoantibody generation. CD20 is expressed during most developmental stages of B lymphocytes; thus, CD20 depletion leads to B-lymphocyte deficiency. As the drug has become more widely used, there has been an increase in the number of case reports of patients developing Pneumocystis pneumonia. The role of anti-CD20 in Pneumocystis jirovecii infection is under debate due to the fact that most patients receiving it are on a regimen of multiple immunosuppressive medications. To address the specific role of CD20 depletion in host immunity against Pneumocystis, we examined a murine anti-CD20 depleting antibody. We demonstrated that anti-CD20 alone is permissive for Pneumocystis infection and that anti-CD20 impairs components of type II immunity, such as production of interleukin-4 (IL-4), IL-5, and IL-13 by whole-lung cells, in response to Pneumocystis murina. We also demonstrated that CD4(+) T cells from mice treated with anti-CD20 during Pneumocystis infection are incapable of mounting a protective immune response when transferred into Rag1(-/-) mice. Thus, CD20(+) cells are critical for generating protective CD4(+) T-cell immune responses against this organism.

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

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.

Consensus guidelines for diagnosis, prophylaxis and management of Pneumocystis jirovecii pneumonia in patients with haematological and solid malignancies, 2014.

Pneumocystis jirovecii infection (PJP) is a common cause of pneumonia in patients with cancer-related immunosuppression. There are well-defined patients who are at risk of PJP due to the status of their underlying malignancy, treatment-related immunosuppression and/or concomitant use of corticosteroids. Prophylaxis is highly effective and should be given to all patients at moderate to high risk of PJP. Trimethoprim-sulfamethoxazole is the drug of choice for prophylaxis and treatment, although several alternative agents are available.

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.

The role of rapid diagnostic tests in managing adults with pneumonia in low-resource settings.

In well-resourced settings the systematic use of rapid diagnostics tests (e.g. pneumococcal urinary antigen test) that define the causal pathogen to direct therapy has not resulted in significantly improved outcomes in adults withpneumonia. The management of pneumonia in many low-resource settings is complicated by a substantial burden of tuberculosis and HIV-associated opportunistic infections, in addition to the usual spectrum of pathogens seenin well-resourced settings. Clinical features alone do not reliably distinguish between these different aetiologiesand physicians often have to treat empirically. Given the limitations in diagnostic laboratory capability present inmost low-resource settings, rapid and point-of-care diagnostic tests could become valuable tools to guide treatment decisions. Pneumococcal and Legionella urinary antigen tests are specific and moderately sensitive, but their utilityin low-resource settings is uncertain. The Xpert MTB/RIF (Cepheid, USA) platform and rapid assays for urinary lipoarabinomannan can substantially speed up tuberculosis diagnosis; the current challenge is to translate this intoearlier treatment and hopefully improve patient outcome. In HIV-infected patients, 1-3-β-D-glucan is a serum marker of Pneumocystis jirovecii infection with excellent sensitivity. Further studies are needed to assess the clinical utilityand cost-effectiveness of these rapid diagnostic assays when they are incorporated into treatment algorithms.

Thrombotic thrombocytopenic purpura due to anti-ADAMTS13 antibodies in multiple myeloma

Thrombotic thrombocytopenic purpura (TTP) is a particularly serious form of thrombotic microangiopathy (TMA) due to the risk of multiple organ dysfunction. Several etiological factors such as infection, auto-immune disease, certain medications and cancers have been associated with TTP. A 74-year-old hypertensive woman with a history of thromboembolic disease was hospitalized for acute kidney injury (AKI) associated with pneumonia. Initial investigations were suggestive of Pneumocystis jirovecii infection and myeloma cast nephropathy. Several days later, the patient presented features of TTP. Von Willebrand factor-cleaving protease activity was less than 5% with a high level of IgG antibody directed against ADAMTS13. Treatment consisted of monthly 4-day cycles of dexamethasone and melphalan in combination with plasmapheresis and resulted in a favorable outcome. Three years after ceasing treatment, the patient presented no signs of hemolysis, but required chronic hemodialysis. The association of TMA, especially TTP, and multiple myeloma is exceptional. The authors report such a case that induced irreversible renal damage, but with stable clinical and laboratory parameters with a follow-up of 4 years.

Opportunistic Infections Due to Inflammatory Bowel Disease Therapy

The use of biological agents and immunomodulators for inflammatory bowel disease (IBD) has remarkably improved disease management in the current era but at the same time has increased the risk of infectious complications. Patients with IBD on corticosteroids, immunomodulators, and biological agents are considered immunocompromised and are at risk for opportunistic infections. These are infections caused by organisms that take advantage of a weakened immune system, and cause disease, when they ordinarily would cause mild illness or no disease in an immunocompetent host. Risk factors for opportunistic infections include malnutrition, older age, congenital immunodeficiency, HIV infection, chronic diseases, and use of corticosteroids, immunomodulators, and anti-tumor necrosis factor alpha therapy. Apart from immunosuppressive medications and older age, there is only indirect evidence for above risk factors contributing directly to opportunistic infection risk in patients with IBD. Opportunistic infections in patients with IBD include viral infections (herpes viruses, human papillomavirus, influenza virus, and JC virus), bacterial infections (tuberculosis, nocardiosis, Clostridium difficile infection, pneumococcal infection, legionellosis, and listeriosis), fungal infections (histoplasmosis, cryptococcosis, Pneumocystis jirovecii infection, aspergillosis, and candidiasis), and parasite infections (Strongyloides stercoralis). Although these infections lead to high morbidity and mortality, only a minority of patients with IBD develop opportunistic infections. Currently, we lack a test to accurately predict patients at risk of opportunistic infection, and future research needs to focus on biomarkers or predictive models for risk stratification. Until such a test is developed, we need to screen, prevent, diagnose, and treat opportunistic infections in all patients with IBD in a timely manner.

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

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.

Calculation skills for nurses: Co-trimoxazole

T topic of calculation skills this month is dosage calculation using co-trimoxazole. The licensed indications for co-trimoxazole are restricted because of serious side effects, including blood dyscrasias and StevensJohnson syndrome, to the treatment of and prophylaxis against serious infections such as Pneumocystis jirovecii (previously known as Pneumocystis carinii) pneumonia. However, it is also used to treat toxoplasmosis and nocardiosis. It may be used to treat acute exacerbations of chronic bronchitis and urinary tract infections in adults and acute otitis media in children only where bacteriological testing shows good evidence of sensitivity to this drug combination (1-part trimethoprim with 5-parts sulfamethoxazole) and where there are good reasons to select this drug combination over a single drug alternative. Prophylactic use is common in immunocompromised patients, including those with human immunodeficiency virus (HIV) or those receiving chemotherapy or organ transplantation, to reduce the risk of opportunistic infection. The British National Formulary (BNF) (Joint Formulary Committee, 2013) recommends a treatment dose by mouth or by intravenous (IV) infusion for Pneumocystis jirovecii infection in adults (and children over 4 weeks old) of 120 mg/kg daily in two to four divided doses for 14–21 days. However, the BNF for Children 2013–2014, the preferred reference source for children, gives the amount per dose for oral/IV treatment as 60 mg/kg every 12 hours for 14– 21 days for children aged 1 month to 18 years. It states that the total daily dose can alternatively be divided into 3–4 divided doses and the oral route is preferred. In the adult BNF, the prophylactic dose is related to age rather than weight. In the BNF for Children 2013–14, the oral/IV prophylactic dose is stated for children aged 1 month to 18 years as 450 mg/m (maximum 960 mg) twice daily for three days of the week, to be given either consecutively or on alternate days. In patients with renal impairment, the dose is reduced to half the normal dose in adults and children if the estimated glomerular filtration rate (eGFR) is 15–30 ml/min/1.73 m. If the eGFR is less than 15 ml/min/1.73 Alison Eggleton

Legionella pneumophila and Pneumocystis jirovecii Coinfection in an Infant Treated With Adrenocorticotropic Hormone for Infantile Spasm

We describe an 8-month-old infant with infantile spasms treated with adrenocorticotropic hormone (ACTH) who presented with fatal Legionella pneumophila and Pneumocystis jirovecii infection. Emphasis is placed on the ensuing immunosuppression and infectious sequelae of ACTH therapy. Given that ACTH therapy may increase the risk of fatal infection, patients undergoing such treatment should be closely monitored, with particular attention paid to the functioning of the immune system.

Mixed Pneumocystis and Cryptococcus Cutaneous Infection Histologically Mimicking Xanthoma

Cutaneous Pneumocystis jirovecii infection is rare. It is thought that the disease emerges from a latent infection delivered via hematogenous and/or lymphatic dissemination from a primary lung infection in immunocompromised individuals. A 32-year-old human immunodeficiency virus-positive male was admitted for headache and vomiting. He was diagnosed with meningitis due to Cryptococcus neoformans and sputum tested positive for Pneumocystis. Six months later, he presented with a slightly crusted yellowish brown plaque and 2 similar but smaller papules with telangiectasia near the right angle of the mouth. Biopsy of the area featured histiocytes expanded by foamy cytoplasm as in a xanthoma except that the vacuoles were coarser. Special stains ultimately demonstrated the characteristic disks of Pneumocystis accompanied by a minor component of budding yeasts (Cryptococcus) in the same fields. This case illustrates the utility of adequate special stains in recognizing a mixed cutaneous infection, particularly in human immunodeficiency virus-positive patients, when microscopy presents an odd xanthoma-like lesion.

Incidence of Pneumocystis Jirovecii Infection and Duration of Prophylaxis After Allogeneic Stem Cell Transplantation

Incidence of Pneumocystis Jirovecii Infection and Duration of Prophylaxis After Allogeneic Stem Cell Transplantation

Pneumocystis jirovecii infection: an emerging threat to patients with rheumatoid arthritis.

Accompanying the increased use of biologic and non-biologic antirheumatic agents, patients with RA have been exposed to an increased risk of Pneumocystis jirovecii infection, which causes acute fulminant P. jirovecii pneumonia (PCP). Mortality in this population is higher than in HIV-infected individuals. Several guidelines and recommendations for HIV-infected individuals are available; however, such guidelines for RA patients remain less clear. Between 2006 and 2008 we encountered a clustering event of P. jirovecii infection among RA outpatients. Through our experience with this outbreak and a review of the recent medical literature regarding asymptomatic colonization and its clinical significance, transmission modes of infection and prophylaxis of PCP, we have learned the following lessons: PCP outbreaks among RA patients can occur through person-to-person transmission in outpatient facilities; asymptomatic carriers serve as reservoirs and sources of infection; and short-term prophylaxis for eradication of P. jirovecii is effective in controlling PCP outbreaks among RA outpatients.

Molecular evidence of Pneumocystis jirovecii reinfection in a haemato-oncology patient

For many years Pneumocystis pneumonia was thought to be caused by the reactivation of a latent infection, but several studies have demonstrated that Pneumocystis jirovecii infection can be acquired de novo. On the basis of our results obtained from a patient with recurrent pneumocystosis, we support the hypothesis that recurrent episodes are caused by reinfection.

A Cluster of Pneumocystis Infections Among Renal Transplant Recipients: Molecular Evidence of Colonized Patients as Potential Infectious Sources of Pneumocystis jirovecii

Eighteen renal transplant recipients (RTRs) developed Pneumocystis jirovecii infections at the renal transplantation unit of Brest University Hospital (Brest, Brittany, France) from May 2008 through April 2010, whereas no cases of P. jirovecii infection had been diagnosed in this unit since 2002. This outbreak was investigated by identifying P. jirovecii types and analyzing patient encounters. The identification of P. jirovecii internal transcribed spacer (ITS) types was performed on P. jirovecii isolates from the 18 RTRs (12 patients with Pneumocystis pneumonia [PCP], 6 colonized patients), 22 unlinked control patients (18 patients with PCP, 4 colonized patients), and 69 patients (34 patients with PCP, 35 colonized patients) with contemporaneously diagnosed P. jirovecii infections in the Brest geographic area. A transmission map was drawn up. Its analysis was combined with the results of P. jirovecii typing. P. jirovecii ITS type identification was successful in 14 of 18 RTRs, 15 of 22 control patients, and 48 of the 69 patients. Type Eg was the most frequent type in the 3 patient groups. However, its frequency was significantly higher in the first patient group than in the 2 other groups (P < .05 and P < .01, respectively). Fourteen encounters between RTRs who harbored an identical type were observed. Ten patients were considered as possible index patients, of whom 3 were colonized by the fungus, and 7 presented PCP. The results provide to our knowledge the first data on the role of colonized patients as potential sources of P. jirovecii in a context of nosocomial acquisition of the fungus.