scholarly journals High Prevalence of Pneumocystis jirovecii Dihydropteroate Synthase Gene Mutations in Patients with a First Episode of Pneumocystis Pneumonia in Santiago, Chile, and Clinical Response to Trimethoprim-Sulfamethoxazole Therapy

2016 ◽  
Vol 61 (2) ◽  
Author(s):  
Carolina A. Ponce ◽  
Magali Chabé ◽  
Claudio George ◽  
Alejandra Cárdenas ◽  
Luisa Durán ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Latin American ◽  
Clinical History ◽  
Pneumocystis Pneumonia ◽  
Pneumocystis Jirovecii ◽  
First Episode ◽  
Sulfa Drugs ◽  
Content Type ◽  
Dihydropteroate Synthase ◽  
High Prevalence

ABSTRACT Mutations in the dihydropteroate synthase (DHPS) gene of Pneumocystis jirovecii are associated with the failure of sulfa prophylaxis. They can develop by selection in patients receiving sulfa drugs or be acquired via person-to-person transmission. DHPS mutations raise concern about the decreasing efficacy of sulfa drugs, the main available therapeutic tool for Pneumocystis pneumonia (PCP). The prevalence of Pneumocystis DHPS mutations was examined in Pneumocystis isolates from 56 sulfa-prophylaxis-naive adults with a first episode of PCP from 2002 to 2010 in Santiago, Chile. Their clinical history was reviewed to analyze the effect of these mutations on response to trimethoprim-sulfamethoxazole (TMP-SMX) therapy and outcome. Mutant genotypes occurred in 22 (48%) of 46 HIV-infected patients and in 5 (50%) of 10 HIV-uninfected patients. Compared to patients with a wild-type genotype, those with mutant genotypes were more likely to experience sulfa treatment-limiting adverse reactions and to have a twice-longer duration of mechanical ventilation if mechanically ventilated. Specific genotypes did not associate with death, which occurred in none of the HIV-infected patients and in 50% of the non-HIV-infected patients. Chile has a high prevalence of DHPS mutations, which were presumably acquired through interhuman transmission because patients were not on sulfa prophylaxis. These results contrast with the low prevalence observed in other Latin American countries with similar usage of sulfa drugs, suggesting that additional sources of resistant genotypes may be possible. The twice-longer duration of mechanical ventilation in patients with mutant DHPS genotypes suggests a decreased efficacy of TMP-SMX and warrants collaborative studies to assess the relevance of DHPS mutations and further research to increase therapeutic options for PCP.

scholarly journals Low Prevalence of Pneumocystis pneumonia (PCP) but High Prevalence of Pneumocystis dihydropteroate synthase (dhps) Gene Mutations in HIV-Infected Persons in Uganda

PLoS ONE ◽  
2012 ◽  
Vol 7 (11) ◽  
pp. e49991 ◽  
Author(s):  
Steve M. Taylor ◽  
Steven R. Meshnick ◽  
William Worodria ◽  
Alfred Andama ◽  
Adithya Cattamanchi ◽  
...  
Keyword(s):  
Gene Mutations ◽  
Pneumocystis Pneumonia ◽  
Dihydropteroate Synthase ◽  
High Prevalence ◽  
Dhps Gene ◽  
Low Prevalence

Severity and outcome of HIV-associated Pneumocystis pneumonia containing Pneumocystis jirovecii dihydropteroate synthase gene mutations

AIDS ◽  
2005 ◽  
Vol 19 (8) ◽  
pp. 801-805 ◽  
Author(s):  
Kristina Crothers ◽  
Charles B Beard ◽  
Joan Turner ◽  
Gena Groner ◽  
Melissa Fox ◽  
...  
Keyword(s):  
Gene Mutations ◽  
Pneumocystis Pneumonia ◽  
Pneumocystis Jirovecii ◽  
Dihydropteroate Synthase

Detection of Pneumocystis jirovecii dihydropteroate synthase polymorphisms in patients with Pneumocystis pneumonia

2005 ◽  
Vol 37 (10) ◽  
pp. 766-771 ◽  
Author(s):  
M. C Costa ◽  
J Gaspar ◽  
K Mansinho ◽  
F Esteves ◽  
F Antunes ◽  
...  
Keyword(s):  
Pneumocystis Pneumonia ◽  
Pneumocystis Jirovecii ◽  
Dihydropteroate Synthase

scholarly journals Update on Dihydropteroate Synthase (DHPS) Mutations in Pneumocystis jirovecii

2021 ◽  
Vol 7 (10) ◽  
pp. 856
Author(s):  
Carmen de la Horra ◽  
Vicente Friaza ◽  
Rubén Morilla ◽  
Juan Delgado ◽  
Francisco J. Medrano ◽  
...  
Keyword(s):  
Expression System ◽  
Pneumocystis Pneumonia ◽  
Molecular Techniques ◽  
Pneumocystis Jirovecii ◽  
Clinical Implications ◽  
Heterologous Expression System ◽  
Sulfa Drug ◽  
Dihydropteroate Synthase ◽  
The World ◽  
Approaches To Study

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.

scholarly journals Immunization with Pneumocystis Cross-Reactive Antigen 1 (Pca1) Protects Mice against Pneumocystis Pneumonia and Generates Antibody to Pneumocystis jirovecii

2016 ◽  
Vol 85 (4) ◽  
Author(s):  
Brenda L. Tesini ◽  
Terry W. Wright ◽  
Jane E. Malone ◽  
Constantine G. Haidaris ◽  
Martha Harber ◽  
...  
Keyword(s):  
Pneumocystis Carinii ◽  
Surface Protein ◽  
Pneumocystis Pneumonia ◽  
Negative Control ◽  
Cross Reactivity ◽  
Pneumocystis Jirovecii ◽  
Content Type ◽  
Life Threatening ◽  
Potential Vaccine ◽  
Preventive Methods

ABSTRACT Pneumocystis pneumonia (PcP) is a life-threatening infection that affects immunocompromised individuals. Nearly half of all PcP cases occur in those prescribed effective chemoprophylaxis, suggesting that additional preventive methods are needed. To this end, we have identified a unique mouse Pneumocystis surface protein, designated Pneumocystis cross-reactive antigen 1 (Pca1), as a potential vaccine candidate. Mice were immunized with a recombinant fusion protein containing Pca1. Subsequently, CD4+ T cells were depleted, and the mice were exposed to Pneumocystis murina. Pca1 immunization completely protected nearly all mice, similar to immunization with whole Pneumocystis organisms. In contrast, all immunized negative-control mice developed PcP. Unexpectedly, Pca1 immunization generated cross-reactive antibody that recognized Pneumocystis jirovecii and Pneumocystis carinii. Potential orthologs of Pca1 have been identified in P. jirovecii. Such cross-reactivity is rare, and our findings suggest that Pca1 is a conserved antigen and potential vaccine target. The evaluation of Pca1-elicited antibodies in the prevention of PcP in humans deserves further investigation.

A study of the psychotropic prescriptions of people attending an addiction service in England

2013 ◽  
Vol 6 (2) ◽  
pp. 54-65 ◽  
Author(s):  
Adejoke Obirenjeyi Oluyase ◽  
Duncan Raistrick ◽  
Yasir Abbasi ◽  
Veronica Dale ◽  
Charlie Lloyd
Keyword(s):  
Design Methodology ◽  
Psychotropic Medications ◽  
First Episode ◽  
Content Type ◽  
High Prevalence ◽  
Addiction Service ◽  
Other Substances ◽  
Prescribing Practice ◽  
The Uk ◽  
Service Data

PurposeThe purpose of this paper is to examine the prescribed psychotropic medications taken by newly referred people with a range of substance use disorders (SUD) who attend a specialist community addiction service.Design/methodology/approachAnonymised data on newly referred people (n=1,537) with SUD attending a specialist community addiction service for their first episode of treatment between August 2007 and July 2010 were obtained from the database of the service. Data were cleaned and the percentage of people taking prescribed psychotropic medications at their first episode of treatment was calculated.FindingsMore than half (56.1 percent) of people attending the service were taking prescribed antidepressants and anxiolytics at their first episode of treatment whilst 15.2 percent of people were taking prescribed antipsychotics. Alcohol and opioids were the primary referral substances for 77.4 percent and 15.2 percent of people respectively. People referred for “other” substances (cannabis, stimulants, sedatives, hallucinogens, solvents and polydrug use) made up the remaining 7.5 percent and had the highest percentage of prescribed psychotropics (antipsychotics=47 percent, antidepressants and anxiolytics=64.3 percent) compared to those referred for alcohol and opioids (p<0.0005).Originality/valueTo the best of the authors’ knowledge, this is the first study of psychotropic prescribing among people with a range of SUD in the UK. The high prevalence of psychotropic prescribing raises questions about the appropriateness of these prescriptions and calls for scrutiny of prescribing practice in this group of people.

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