Genetic diversity of <i>Pneumocystis jirovecii</i> from a cluster of cases of pneumonia in renal transplant patients: Cross‐sectional study

Ricci, Giannina; Santos, Daniel Wagner; Kovacs, Joseph A.; Nishikaku, Angela Satie; Sandes‐Freitas, Tainá Veras de; Rodrigues, Anderson Messias; Kutty, Geetha; Affonso, Regina; Silva, Hélio Tedesco; Medina‐Pestana, José Osmar; Franco, Marcello; Colombo, Arnaldo Lopes

doi:10.1111/myc.12823

Cited by 10 publications

(11 citation statements)

References 51 publications

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“…Furthermore, besides identifying the risk factors of PJP, it is necessary for kidney transplantation recipients to obtain effective prophylaxis against PJP, especially those with high risks of PJP, such as patient with acute rejection (AR), 6 certain genotypes of Pneumocystis jirovecii 7,8 or severe lymphopenia 9 after surgery. Trimethoprim‐sulfamethoxazole (TMP‐SMX) is considered to be the first choice for PJP prophylaxis, and the incidence of PJP after renal transplantation was significantly reduced by prophylactic use of TMP‐SMX.…”

Section: Introductionmentioning

confidence: 99%

The risk factor analysis and treatment experience in pneumocystis jirovecii pneumonia after kidney transplantation

Yang

Zhu

Liang

et al. 2021

Mycoses

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Background Pneumocystis jirovecii pneumonia (PJP) is an opportunistic infection among solid organ transplantation. The occurrence of PJP is dangerous and fatal if there is no early identification and sufficient treatment. Objective The aim of this study was to evaluate the risk factors and provide appropriate strategies of prophylaxis and treatment for PJP after kidney transplantation in our centre. Patients/Methods From January 2009 to December 2018, a total of 167 kidney transplantation recipients with pneumonia were enrolled, including 47 PJP patients as PJP group and 120 non‐PJP patients as control group. The clinical characteristics of the two groups were analysed retrospectively. Results Multivariate analysis showed that high total dosage of ATG [OR, 2.03; 95% CI, 1.12–3.68] and cytomegalovirus (CMV) infection were independent risk factors for PJP. Trimethoprim‐sulfamethoxazole (TMP‐SMX) (1.44 g q6h)–based treatment was used for 2 weeks, and its dosage and course were adjusted according to the therapeutic effect and side effects. Forty‐five cases were recovered after 3 months of follow‐up, and two patients died of respiratory failure. TMP‐SMX (0.48 g/day) prophylaxis was used for 3–6 months and prolonged to 7–8 months after treatment for acute rejection, which reduced the incidence of PJP compared with those without prophylaxis. Conclusion Our study suggests that the high total dosage of ATG and CMV infection indicate the increased risk of PJP. The strategies of prophylaxis and treatment for PJP after kidney transplantation in our centre were effective.

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Section: Introductionmentioning

confidence: 99%

The risk factor analysis and treatment experience in pneumocystis jirovecii pneumonia after kidney transplantation

Yang

Zhu

Liang

et al. 2021

Mycoses

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“…In Brazil, a pioneering study in PcP patients showed an absence of DHPS gene mutations. In contrast, a recent report described clusters of P. jirovecii with DHPS mutations among immunosuppressed patients following renal transplantation [32,33]. Among Colombian patients with PcP or PjC, DHPS mutations in respiratory samples were detected at a low rate [34].…”

Section: Developing Countriesmentioning

confidence: 86%

“…A prospective epidemiological study of PcP patients from three European cities showed nosocomial transmission of P. jirovecii that had mutations in the DHPS gene that could explain the high proportion of mutations in patients without exposure to sulfa drugs [19]. Additionally, possible nosocomial transmission has been investigated in other locations [33,87,88]. In France, longitudinal screening of patients with PcP and PjC suggested that circulation of Pneumocystis exists within hospitals [87], and more recently, the presence of Pneumocystis harboring DHPS mutant genotypes in the environment of a bronchoscopy unit has been described in Spain [88].…”

Section: Transmissionmentioning

confidence: 99%

Update on Dihydropteroate Synthase (DHPS) Mutations in Pneumocystis jirovecii

Horra

Friaza

Morilla

et al. 2021

JoF

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A Pneumocystis jirovecii is one of the most important microorganisms that cause pneumonia in immunosupressed individuals. The guideline for treatment and prophylaxis of Pneumocystis pneumonia (PcP) is the use of a combination of sulfa drug-containing trimethroprim and sulfamethoxazole. In the absence of a reliable method to culture Pneumocystis, molecular techniques have been developed to detect mutations in the dihydropteroate synthase gene, the target of sulfa drugs, where mutations are related to sulfa resistance in other microorganisms. The presence of dihydropteroate synthase (DHPS) mutations has been described at codon 55 and 57 and found almost around the world. In the current work, we analyzed the most common methods to identify these mutations, their geographical distribution around the world, and their clinical implications. In addition, we describe new emerging DHPS mutations. Other aspects, such as the possibility of transmitting Pneumocystis mutated organisms between susceptible patients is also described, as well as a brief summary of approaches to study these mutations in a heterologous expression system.

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“…Guarro et al identified a strain of Fusarium verticillioides from blood culture and F. solani from a skin biopsy, both from the same HIV-positive patient [77]. The DNA extracted from FFPE samples allowed Ricci et al to describe the molecular epidemiology of a cluster of Pneumocystis jirovecii pneumonia in renal transplant recipients, uncovering that 4 out 11 patients were infected by more than one genotype [78]. Ponzio et al have identified patients infected with various molecular siblings of Cryptococcus neoformans, such as VNI and VNII, isolated from infected patients' cerebrospinal fluid or blood [79].…”

Section: Discussionmentioning

confidence: 99%

A New Duplex PCR-Assay for the Detection and Identification of Paracoccidioides Species

Pinheiro

Pôssa

terra

et al. 2021

JoF

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Paracoccidioidomycosis (PCM) is a life-threatening systemic fungal infection caused by members of the Paracoccidioides brasiliensis complex and P. lutzii. Routine diagnoses of PCM down to the species level using classical mycological approaches are unspecific due to overlapping phenotypes. There is an urgent need for specific, sensitive, and cost-effective molecular tools to diagnose PCM. Variation among the exon-2 of the gp43 gene was exploited to design species-specific primer pairs to discriminate between members of the P. brasiliensis complex and P. lutzii in a duplex PCR assay. Primer-BLAST searches revealed highly species-specific primers, and no significant region of homology was found against DNA databases except for Paracoccidioides species. Primers PbraCx-F and PbraCx-R targeting P. brasiliensis DNA produced an amplicon of 308 bp, while primers Plu-F and Plu-R targeting P. lutzii DNA generated an amplicon of 142 bp. The lower limit of detection for our duplex PCR assay was 1 pg of gDNA. A panel of 62 Paracoccidioides revealed 100% specificity (AUC = 1.000, 95%CI 0.972–1.000, p < 0.0001) without cross-reacting with other medically relevant fungi or human DNA. As a proof of concept, we demonstrated the accurate identification of the P. brasiliensis complex (n = 7) or P. lutzii (n = 6) from a broad range of formalin-fixed, paraffin-embedded (FFPE) tissues of PCM patient’s organs. In four cases, FFPE PCR results confirmed, for the first time, co-infection due to P. brasiliensis (S1) and P. lutzii in the same biopsy. Our duplex PCR assay is useful to detect and differentiate members of the P. brasiliensis complex and P. lutzii, providing clinical laboratories with an important tool to be applied routinely, especially in atypical cases such as those featuring negative serology and positive mycological examination of clinical specimens as well as for the investigation of putative co-infection cases. This will likely benefit thousands of infected patients every year in a wide area of the Americas.

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Genetic diversity of Pneumocystis jirovecii from a cluster of cases of pneumonia in renal transplant patients: Cross‐sectional study

Cited by 10 publications

References 51 publications

The risk factor analysis and treatment experience in pneumocystis jirovecii pneumonia after kidney transplantation

The risk factor analysis and treatment experience in pneumocystis jirovecii pneumonia after kidney transplantation

Update on Dihydropteroate Synthase (DHPS) Mutations in Pneumocystis jirovecii

A New Duplex PCR-Assay for the Detection and Identification of Paracoccidioides Species

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