Pneumocystis pneumonia (PCP) is a life-threatening complication after allogeneic hematopoietic cell transplantation (allo-HCT). However, allo-HCT procedures have evolved toward older patients, unrelated donors, and reduced-intensity conditioning, possibly modifying the risks. Polymerase chain reaction (PCR), widely used nowadays, is more sensitive than microscopy diagnostic methods. This study aimed to assess the factors associated with PCP in allo-HCT recipients within 2 years of HCT and managed according to current procedures. This multicenter, nested case-control study included PCP cases diagnosed by PCR, cytology, or immunofluorescence on bronchoalveolar lavage fluid between 2016 and 2018. Two controls per case were selected from the ProMISe registry and matched for the center, transplant date, and underlying disease. Fifty-two cases and 104 controls were included among the 5452 patients who underwent allo-HCT in the participating centers. PCP occurred at a median of 11.5 months after transplantation. The mortality rate was 24% on day 30 after the PCP diagnosis and 37% on day 90. The clinical presentation and mortality rates of the 24 patients diagnosed using only PCR were not different from those diagnosed with microscopy methods. Our study demonstrates a substantial incidence of, and mortality from, PCP, after allogeneic HCT despite well-established prophylactic approaches. In our experience, PCP nowadays occurs later after transplant than previously reported, justifying the prolongation of prophylaxis after six months in many cases. Allo-HCT recipients diagnosed with PCR as the only PCP marker should benefit from specific treatment as for other patients.
- MeSH
- infekční nemoci * etiologie MeSH
- kostní dřeň MeSH
- lidé MeSH
- pneumocystová pneumonie * epidemiologie etiologie diagnóza MeSH
- rizikové faktory MeSH
- studie případů a kontrol MeSH
- transplantace hematopoetických kmenových buněk * škodlivé účinky metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
Cieľ: Pneumocystis jirovecii patril v minulosti do skupiny prvokov, ale v súčasnosti je taxonomicky zaradený do ríše húb. P. jirovecii je oportúnny patogén, zodpovedný za pneumocystovú pneumóniu s častými komplikáciami u imunokompromitovaných pacientov. Oneskorené začatie vhodnej liečby zvyšuje riziko úmrtia u pacientov s oslabenou imunitou. Cieľom práce bolo zistiť a zhodnotiť spoľahlivosť metód laboratórnej diagnostiky pneumocystózy používaných v rutinných laboratóriách ako aj výskyt tohto ochorenia u pacientov zo Slovenska za 19 rokov. Materiál a metódy: Diagnostika je založená na mikroskopickom dôkaze (farbenie podľa Giemsa a Gram-Weigerta) a detekcii DNA parazita klasickou alebo real-time PCR v bronchoalveolárnej laváži a spúte. Výsledky: Pneumocysty boli zistené u 190 osôb (5,7 %) z celého súboru pacientov. Onkologickí pacienti predstavovali najrizikovejšiu skupinu z hľadiska infekcie pneumocystami, čo sme potvrdili ich najvyšším podielom (57,9 %) z jedincov s pneumocystózou. Na základe binárneho klasifikačného testu sme vyhodnotili 33,7 % citlivosť a 100 % špecifickosť mikroskopického dôkazu v porovnaní s PCR. Molekulárne metódy sú v porovnaní s mikroskopickým dôkazom citlivejšie v detekcii P. jirovecii a v súčasnosti predstavujú spoľahlivý detekčný systém v diagnostike pneumocystózy. Záver: Vzhľadom na narastajúci počet imunokompromitovaných osôb je diagnostika P. jirovecii u pacientov s pľúcnymi komplikáciami nevyhnutná. To sa potvrdilo aj v našej štúdii, kde v priebehu rokov stúpal počet vyšetrení a záchytov tohto oportúnneho patogénu.
Aim: In the past, Pneumocystis jirovecii belonged to the Protozoa group, but is currently taxonomically included in the kingdom Fungi. P. jirovecii is an opportunistic pathogen, responsible for pneumocystis pneumonia with frequent complications of immunocompromised patients. Delayed initiation of appropriate therapy increases the risk of death in immunocompromised patient. The aim of this work was to determine and evaluate the reliability of methods of laboratory diagnosis of pneumocystosis used in routine laboratories as well as the occurrence of this disease in patients from Slovakia during 19 years. Material and Methods: The diagnosis is based on microscopic examination (Giemsa- and Gram-Weigert-staining) and detection of parasite DNA by classical or real-time PCR in bronchoalveolar lavage and sputum. Results: Pneumocysts were detected in 190 persons (5.7%) from the whole group of patients. Cancer patients represented the riskiest group in terms of pneumocystosis, which was confirmed by the highest percentage (57.9%) of individuals infected with P. jirovecii. Compared with the PCR, 33.7% sensitivity and 100% specificity of microscopy was calculated by using a binary classification test. Molecular methods are more sensitive in the detection of P. jirovecii compared to microscopic evidence and currently represent a reliable detection system in the diagnosis of pneumocystosis. Conclusion: In view of the increasing number of immunocompromised persons, diagnostics of P. jirovecii in patients with pulmonary complications is essential. This was also confirmed in our study, where the number of examinations and detection of this opportunistic pathogen increased over the years.
- MeSH
- bronchoalveolární lavážní tekutina mikrobiologie MeSH
- hostitel s imunodeficiencí MeSH
- imunosupresivní léčba škodlivé účinky MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- lidé MeSH
- Pneumocystis carinii * izolace a purifikace MeSH
- pneumocystová pneumonie diagnóza mikrobiologie MeSH
- Check Tag
- lidé MeSH
- Geografické názvy
- Slovenská republika MeSH
Těžké kombinované imunodeficience (SCID, severe combined immunodeficiencies) jsou skupinou onemocnění dětského věku s velmi závažnou prognózou. Vykytují se s frekvencí 1 na 40 000–100 000 dětí do jednoho roku věku. Včasná diagnóza je hlavním prognostickým faktorem úspěchu terapie. Neléčené končí fatálně. Kauzální léčbou je transplantace hematopoetických kmenových buněk. Od ledna 2022 v České republice probíhá pilotní projekt novorozeneckého screeningu SCID. Článek předkládá kazuistiky dvou pacientů se SCID diagnostikovaných v roce 2021 na našem pracovišti. První je 8měsíční chlapec přijatý pro bilaterální pneumonii s respirační insuficiencí. Jako původce byla stanovena Pneumocystis jiroveci. Stavu předcházelo období neprospívání a laboratorní nález lymfopenie. Doplněné imunologické vyšetření prokázalo těžkou hypogamaglobulinemii s poruchou tvorby specifických protilátek a T lymfopenii s nízkými aktivačními testy. Genetické vyšetření odhalilo X-vázanou formu SCID (defekt v genu pro receptor IL2; c. 925-13> G). Chlapec byl následně úspěšně transplantován. Druhá kazuistika 2měsíčního děvčátka hospitalizovaného pro těžkou infekci při současné pozitivitě viru SARS-CoV-2 s fatálním koncem. Post mortem byla zjištěna generalizovaná CMV infekce, těžká dysplazie thymu s nepřítomností T lymfocytů. Jako příčina byla stanovena autozomálně recesivní forma SCID s mutací genu pro receptor IL7 (bialelický defekt NM_002185.5: c.132 C> A, p.Ser44Arg, a c.514delG, p.Glu172Lysfs*10).
Severe Combined Immunodeficiencies (SCID) are a group of childhood diseases with a very serious prognosis. They occur with a frequency of 1 in 40–100,000 children under one year of age. Early diagnosis is the main prognostic factor for the success of therapy. If left untreated, it is fatal. Causal treatment is haematopoietic stem cell transplantation. Since January 2022, a pilot newborns screening project for SCID has been running in the Czech Republic. This article presents case reports of two patients with SCID diagnosed in our department in 2021. The first is an 8-month-old boy hospitalized for bilateral pneumonia with respiratory insufficiency. Pneumocystis jiroveci was identified as the causative agent. The condition was preceded by a period of failure to thrive and laboratory findings of lymphopenia. Additional immunological examination revealed severe hypogammaglobulinemia with impaired specific antibody production and T lymphopenia with low activation tests. Genetic testing revealed an X-linked form of SCID (defect in the IL2 receptor gene; c.925-13>G). The boy was subsequently successfully transplanted. Second case report of a 2-month-old girl hospitalized for severe infection with concurrent SARS-CoV-2 positivity with fatal outcome. Post mortem findings were generalized CMV infection, severe thymic dysplasia with absence of T lymphocytes. The cause was determined to be an autosomal recessive form of SCID with mutation of the IL7 receptor gene (biallelic defect NM_002185.5: c.132C >A, p. Ser44Arg, a c.514delG, p. Glu172Lysfs*10).
- MeSH
- časná diagnóza MeSH
- COVID-19 diagnóza komplikace terapie MeSH
- fatální výsledek MeSH
- hemoragické poruchy diagnóza farmakoterapie MeSH
- kojenec MeSH
- lidé MeSH
- lymfopenie diagnóza MeSH
- pneumocystová pneumonie diagnóza farmakoterapie MeSH
- T-lymfocyty patologie MeSH
- těžká kombinovaná imunodeficience * diagnóza klasifikace terapie MeSH
- transplantace hematopoetických kmenových buněk MeSH
- Check Tag
- kojenec MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
POZOR! při kopírování abstrakt kontrolovat slova na konci řádků originálu!!!
POZOR! při kopírování abstrakt kontrolovat slova na konci řádků originálu!!!
- MeSH
- HIV infekce komplikace MeSH
- lidé MeSH
- pneumocystová pneumonie * diagnóza patofyziologie terapie MeSH
- rizikové faktory MeSH
- syndromy imunologické nedostatečnosti MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- MeSH
- imunosupresivní léčba škodlivé účinky MeSH
- lidé MeSH
- Pneumocystis carinii * patogenita MeSH
- pneumocystová pneumonie diagnóza farmakoterapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
Pulmonary pathology is common in HIV-infected individuals, but the possible role of the parasitic protist Toxoplasma gondii (Nicolle et Manceaux, 1908) is not completely known. The present account reports result of a retrospective cohort study. Medical cards of 907 HIV-positive people, which included 120 deceased patients, were analysed. During a three-year follow-up, the pulmonary pathology was diagnosed in 306 patients (33.7 ± 1.6%): pneumocystis pneumonia in 124 (13.7 ± 1.1%), primary pulmonary tuberculosis in 113 (12.5 ± 1.1%), bacterial pneumonia in 58 (6.4 ± 0.8%) toxoplasmosis pneumonia in two (0.2 ± 0.2%), and others. All patients were divided into two cohorts: 531 individuals seropositive for T. gondii and 376 seronegative ones. It has been found out that general lung pathology is more common in patients with seropositivity to T. gondii than in seronegative ones (43.3 ± 2.2% vs. 20.1 ± 2.0%, p < 0.001). The diagnosis of pneumocystis pneumonia was made ten times more often in the cohort of seropositive patients than in the cohort of seronegative ones (21.9 ± 1.8% vs. 2.1 ± 0.7%, respectively, p < 0.001) and in deceased patients of these cohorts it was 5.5 times more (45.1 ± 5.9% vs. 8.2 ± 3.9, respectively, p < 0.001). In patients with fatal outcome and seropositivity to T. gondii, the incidences of pneumocystis pneumonia increased by 23.2% (p < 0.001) and bacterial pneumonia by 12.4% (p < 0.05), whereas in seronegative individuals only pulmonary tuberculosis increased by 13.1% (p < 0.05) сompared with corresponding whole cohorts. Pearson's contingency coefficient showed the mean strength association between infection with T. gondii and incidence of pneumocystis pneumonia both in whole cohort (C = 0.272) and in patients with fatal outcomes (C = 0.368). In сonclusion, significantly increasing rate of pneumocystis pneumonia in patients with HIV/AIDS and T. gondii infection can be caused by certain synergism between T. gondii and Pneumocystis jirovecii and in some cases overdiagnosis pneumocystis pneumonia due to undiagnosed toxoplasmosis pneumonia.
- MeSH
- dospělí MeSH
- HIV infekce komplikace MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- pneumocystová pneumonie mikrobiologie MeSH
- retrospektivní studie MeSH
- Toxoplasma fyziologie MeSH
- toxoplazmóza parazitologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: Since the beginning of the HIV epidemic in resource-rich countries, Pneumocystis jirovecii pneumonia (PjP) is one of the most frequent opportunistic AIDS-defining infections. The Collaboration of Observational HIV Epidemiological Research Europe (COHERE) has shown that primary Pneumocystis jirovecii Pneumonia (PjP) prophylaxis can be safely withdrawn in patients with CD4 counts of 100 to 200 cells/µL if plasma HIV-RNA is suppressed on combination antiretroviral therapy. Whether this holds true for secondary prophylaxis is not known, and this has proved difficult to determine due to the much lower population at risk. METHODS: We estimated the incidence of secondary PjP by including patient data collected from 1998 to 2015 from the COHERE cohort collaboration according to time-updated CD4 counts, HIV-RNA and use of PjP prophylaxis in persons >16 years of age. We fitted a Poisson generalized additive model in which the smoothed effect of CD4 was modelled by a restricted cubic spline, and HIV-RNA was stratified as low (<400), medium (400 to 10,000) or high (>10,000copies/mL). RESULTS: There were 373 recurrences of PjP during 74,295 person-years (py) in 10,476 patients. The PjP incidence in the different plasma HIV-RNA strata differed significantly and was lowest in the low stratum. For patients off prophylaxis with CD4 counts between 100 and 200 cells/µL and HIV-RNA below 400 copies/mL, the incidence of recurrent PjP was 3.9 (95% CI: 2.0 to 5.8) per 1000 py, not significantly different from patients on prophylaxis in the same stratum (1.9, 95% CI: 0.1 to 3.7). CONCLUSIONS: HIV viraemia importantly affects the risk of recurrent PjP. In virologically suppressed patients on ART with CD4 counts of 100 to 200/µL, the incidence of PjP off prophylaxis is below 10/1000 py. Secondary PjP prophylaxis may be safely withheld in such patients. While European guidelines recommend discontinuing secondary PjP prophylaxis only if CD4 counts rise above 200 cells/mL, the latest US Guidelines consider secondary prophylaxis discontinuation even in patients with a CD4 count above 100 cells/µL and suppressed viral load. Our results strengthen and support this US recommendation.
- MeSH
- dospělí MeSH
- HIV infekce * komplikace farmakoterapie MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- Pneumocystis carinii * MeSH
- pneumocystová pneumonie * epidemiologie prevence a kontrola MeSH
- počet CD4 lymfocytů MeSH
- viremie epidemiologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Evropa MeSH
- MeSH
- antiretrovirové látky terapeutické užití MeSH
- dospělí MeSH
- HIV infekce * diagnóza MeSH
- klinické laboratorní techniky metody MeSH
- lidé MeSH
- mozková toxoplazmóza * diagnóza farmakoterapie MeSH
- neurozobrazování metody MeSH
- Pneumocystis carinii izolace a purifikace MeSH
- pneumocystová pneumonie diagnóza farmakoterapie MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Quantitative real-time PCR (qPCR) is increasingly used to detect Pneumocystis jirovecii for the diagnosis of Pneumocystis pneumonia (PCP), but there are differences in the nucleic acids targeted, DNA only versus whole nucleic acid (WNA), and also the target genes for amplification. Through the Fungal PCR Initiative, a working group of the International Society for Human and Animal Mycology, a multicenter and monocenter evaluation of PCP qPCR assays was performed. For the multicenter study, 16 reference laboratories from eight different countries, performing 20 assays analyzed a panel consisting of two negative and three PCP positive samples. Aliquots were prepared by pooling residual material from 20 negative or positive- P. jirovecii bronchoalveolar lavage fluids (BALFs). The positive pool was diluted to obtain three concentrations (pure 1:1; 1:100; and 1:1000 to mimic high, medium, and low fungal loads, respectively). The monocenter study compared five in-house and five commercial qPCR assays testing 19 individual BALFs on the same amplification platform. Across both evaluations and for all fungal loads, targeting WNA and the mitochondrial small sub-unit (mtSSU) provided the earliest Cq values, compared to only targeting DNA and the mitochondrial large subunit, the major surface glycoprotein or the beta-tubulin genes. Thus, reverse transcriptase-qPCR targeting the mtSSU gene could serve as a basis for standardizing the P. jirovecii load, which is essential if qPCR is to be incorporated into clinical care pathways as the reference method, accepting that additional parameters such as amplification platforms still need evaluation.
- MeSH
- bronchoalveolární lavážní tekutina mikrobiologie MeSH
- diagnostické techniky molekulární metody normy MeSH
- DNA fungální genetika MeSH
- kvantitativní polymerázová řetězová reakce normy MeSH
- lidé MeSH
- Pneumocystis carinii genetika MeSH
- pneumocystová pneumonie diagnóza mikrobiologie MeSH
- senzitivita a specificita MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- hodnotící studie MeSH
- multicentrická studie MeSH
The present study aims to evaluate the diagnostic yield of bronchoalveolar lavage (BAL) fluid in patients with hematological malignancies and describe the most common pathogens detected in BAL fluid (BALF.) An analysis of 480 BALF samples was performed in patients with hematological malignancies over a period of 7 years. The results of culture methods, PCR, and immunoenzymatic sandwich microplate assays for Aspergillus galactomannan (GM) in BALF were analyzed. Further, the diagnostic thresholds for Aspergillus GM and Pneumocystis jiroveci were also calculated. Microbiological findings were present in 87% of BALF samples. Possible infectious pathogens were detected in 55% of cases; 32% were classified as colonizing. No significant difference in diagnostic yield or pathogen spectrum was found between non-neutropenic and neutropenic patients. There was one significant difference in BALF findings among intensive care units (ICU) versus non-ICU patients for Aspergillus spp. (22% versus 9%, p = 0.03). The most common pathogens were Aspergillus spp. (n = 86, 33% of BAL with causative pathogens) and Streptococcus pneumoniae (n = 46, 18%); polymicrobial etiology was documented in 20% of cases. A quantitative PCR value of > 1860 cp/mL for Pneumocystis jirovecii was set as a diagnostic threshold for pneumocystis pneumonia. The absorbance index of GM in BALF of 0.5 was set as a diagnostic threshold for aspergillosis. The examination of BAL fluid revealed the presence of pathogen in more than 50% of cases and is, therefore, highly useful in this regard when concerning pulmonary infiltrates.
- MeSH
- Aspergillus genetika izolace a purifikace patogenita MeSH
- bronchoalveolární lavážní tekutina mikrobiologie MeSH
- DNA fungální genetika MeSH
- dospělí MeSH
- hematologické nádory komplikace mikrobiologie MeSH
- jednotky intenzivní péče MeSH
- lidé středního věku MeSH
- lidé MeSH
- mannany analýza MeSH
- mladiství MeSH
- mladý dospělý MeSH
- neutropenie mikrobiologie MeSH
- Pneumocystis carinii genetika izolace a purifikace patogenita MeSH
- pneumocystová pneumonie diagnóza mikrobiologie MeSH
- retrospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Streptococcus pneumoniae genetika izolace a purifikace patogenita MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH