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Investigation of outbreaks of Pneumocystis jirovecii pneumonia in two Scottish renal units

Published:November 18, 2016DOI:https://doi.org/10.1016/j.jhin.2016.11.005

      Summary

      Pneumocystis jirovecii is recognized as an opportunistic pathogen. In recent years, human-to-human transmission of P. jirovecii has been demonstrated. However, outbreaks of P. jirovecii infections are not well defined because the epidemiological setting that facilitates transmission is not fully understood. This article describes two outbreaks of P. jirovecii pneumonia (PCP) in renal transplant patients in the West of Scotland. In total, 25 patients in two geographically contiguous locations were affected. Allele B was identified as the dominant type, along with allele A3. It was not possible to determine the exact reason for clustering of cases, although the outpatient clinic setting featured in one of the outbreaks. The outbreaks ceased with the use of trimethoprim-sulphamethoxazole prophylaxis; the target populations that received prophylaxis were different in the two outbreaks. Infection control teams should be alert to the possibility of outbreaks of PCP.

      Keywords

      Introduction

      Pneumocystis jirovecii was first described in guinea pig and rat lungs in 1909.
      • Morris A.
      • Norris K.A.
      Colonization by Pneumocystis jirovecii and its role in disease.
      The organism, which is ubiquitous in the environment, was initially classified as a parasite, and was subsequently reclassified as a fungus in 1988. P. jirovecii is a well-described pathogen in patients with human immunodeficiency virus (HIV), and was a leading cause of morbidity and mortality in this group in the 1980s. However, in more recent years, it has declined in patients with HIV but emerged in other immunosuppressed patient groups, particularly the renal transplant population. Factors that may have contributed to this increase include increasing immunosuppression, an increase in the prevalent transplant population, greater awareness with improved diagnostics, enhanced transmission between susceptible hosts, and variations in prophylaxis protocols.
      • Maini R.
      • Henderson K.L.
      • Sheridan E.A.
      • et al.
      Increasing pneumocystis pneumonia, England, UK, 2000–2010.
      The epidemiology of P. jirovecii infection is not fully understood. In one study, most individuals were found to be exposed in early childhood, with >80% of children having detectable antibodies by four years of age.
      • Morris A.
      • Norris K.A.
      Colonization by Pneumocystis jirovecii and its role in disease.
      Potential modes of transmission of the organism are re-activation of latent carriage, environmental exposure or interhuman transmission, as evidenced by typing of cases during recent clusters.
      • Maini R.
      • Henderson K.L.
      • Sheridan E.A.
      • et al.
      Increasing pneumocystis pneumonia, England, UK, 2000–2010.
      Most cases of P. jirovecii pneumonia (PCP) are now believed to be a result of recent acquisition.
      • Choukri F.
      • Menotti J.
      • Sarfati C.
      • et al.
      Quantification and spread of Pneumocystis jirovecii in the surrounding air of patients with pneumocystis pneumonia.
      In the absence of prophylaxis, PCP occurs in approximately 3.8% of renal transplant recipients; the risk is four times higher in the first year post transplant, with a mortality rate of up to 49%.
      • Le Gal S.
      • Damiani C.
      • Rouillé A.
      • et al.
      A cluster of pneumocystis infections among renal transplant recipients: molecular evidence of colonized patients as potential infectious sources of Pneumocystis jirovecii.
      The European Renal Association recommends prophylaxis for PCP for at least four months post transplant.
      • EBPG Expert Group on Renal Transplantation
      European best practice guidelines for renal transplantation. Section IV: Long-term management of the transplant recipient. IV.7.1 Late infections. Pneumocystis carinii pneumonia.
      The UK Renal Association states that all patients should receive three to six months of trimethoprim-sulphamethoxazole (TMP-SMX) 480mg daily.
      • Baker R.
      • Jardine A.
      • Andrews P.
      Postoperative care of the kidney transplant recipient..
      This article describes two outbreaks of PCP amongst renal transplant and non-transplant renal patients receiving immunosuppression in two renal units in hospitals in the West of Scotland from October 2012 to May 2015, along with measures taken to limit transmission. Twenty-five patients across two health boards in the region developed PCP during this period.

      Methods

      Setting

      The outbreaks took place in two regional nephrology units within acute hospital settings in the West of Scotland. The renal unit at Western Infirmary, Glasgow has 61 beds across three wards comprising of four-bedded and single rooms. Transplant clinics are situated at several hospitals across the city. The renal service at University Hospital Crosshouse is based at the John Lynch dialysis unit and in two inpatient wards. At University Hospital Crosshouse, there are two separate clinics for renal transplant and non-transplant patients, but they share a common waiting area. All patients at University Hospital Crosshouse are transplanted at Glasgow renal transplant unit and receive follow-up at the Glasgow unit for up to one year following transplantation.

      Time course

      The outbreak at Western Infirmary lasted from October 2012 until May 2013. This was followed by an outbreak at University Hospital Crosshouse between November 2014 and May 2015.

      Case definition

      The case definition was any renal transplant patient with a respiratory illness consistent with PCP and detectable P. jirovecii in sputum, throat swab or bronchoalveolar lavage by polymerase chain reaction (PCR).

      Existing prophylaxis and immunosuppressant protocols

      At both units, all renal transplant patients receive prophylaxis for PCP with TMP-SMX for three months post transplant. There are no situations whereby prophylaxis for PCP would normally be re-instated after that. The standard immunosuppressive regime is prednisolone, tacrolimus and mycophenolate mofetil.

      Identification and typing methods

      PCR was used to identify PCP. The West of Scotland Specialist Virology Centre (WoSSVC) undertook multi-locus sequence typing (MLST) for typing the strains. The internal transcribed spacer (ITS)-1 sequence is located on the nuclear ribosomal ribonucleic acid (rRNA) operon between the genes of 18S rRNA and 5.8S rRNA, and shows a high level of polymorphism that has been used for genetic typing applications. The amount of polymorphism at the mt26s rRNA locus is substantially less than that reported for ITS; nevertheless, the variation observed in this second locus has helped address a number of important epidemiological questions.
      Respiratory samples positive for P. jirovecii were extracted using the Easymag Nucleisens (Biomerieux- Marcy-l'Étoile, France) extraction platform. Genotyping of P. jirovecii-positive specimens was performed using the MLST method described previously.
      • Hauser P.M.
      • Francioli P.
      • Bille J.
      • Telenti A.
      • Blanc D.S.
      Typing of Pneumocystis carinii f. sp. hominis by single-strand conformation polymorphism of four genomic regions.
      However, based on previous outbreak investigations in both Belfast and Liverpool, the WoSSVC chose to sequence the ITS and the mt26sRNA regions alone as these regions were most sensitive and discriminatory.
      • Curran T.
      • McCaughey C.
      • Coyle P.V.
      Pneumocystis jirovecii multilocus genotyping profiles in Northern Ireland.
      • Thomas S.
      • Vivancos R.
      • Corless C.
      • Wood G.
      • Beeching N.J.
      • Beadsworth M.B.
      Increasing frequency of Pneumocystis jirovecii pneumonia in renal transplant recipients in the United Kingdom: clonal variability, clusters, and geographic location.
      The ITS and mt26sRNA regions were amplified by nested PCR using Roche Expand High Fidelity Roche Master Mix (Roche-Basel, Switzerland) using the reaction and cycling conditions and primer concentrations as described in the protocol. Following electrophoresis on a 1.2% gel, the relevant-sized DNA amplicons (ITS1 204bp, mt26S 347bp) were purified using QIAquick Gel Extraction Kit (Qiagen-Hilden, Germany) and eluted in 50μL of AE buffer (Qiagen- Hilden, Germany). Purified products were sequenced on a ABI3130XL capillary sequencer (ABI - Carlsbad, California, USA) using the Big Dyes v3.1 sequencing kit (ABI - Carlsbad, California, USA). Sequence analysis was performed with SeqMan Version 5.08 (DNASTAR). The obtained sequences were compared with P. jirovecii reference gene sequences for each gene (Accession No. U07220 for ITS1, M58605 for mt26S) and alleles were determined. Of the 25 isolates, one was not available for typing.

      Results

      Description of incident and cases

      Western Infirmary, Glasgow

      In February 2013, the infection control team was alerted to three concurrent PCP infections amongst renal transplant patients. A lookback exercise was performed and this identified eight renal patients diagnosed with PCP between October 2012 and February 2013. Data from the WoSSVC that performed PCR testing confirmed that there had been no PCP-positive renal transplant patients in 2010, and there had only been one case in 2011. The finding of eight positive results was therefore deemed to represent a significant increase in this patient population. Importantly, there had been no change in PCP testing methods during this time, and no increase in the number of samples being sent which may have indicated raised awareness. Subsequently during the course of the investigation and from February to May 2013, a further six cases of PCP were identified, taking the total number of cases in this incident to 14.
      All patients had a history of renal transplantation and had received immunosuppression with prednisolone, tacrolimus and mycophenolate mofetil. In addition, all had received the recommended prophylaxis for PCP with TMP-SMX. None remained on TMP-SMX prophylaxis at the time of infection. No patients had significant bacteriology results at the same time as the PCP diagnosis. The interval from transplant to positive result ranged from eight months to 15 years. Only two patients had acquired PCP within one year of renal transplant. Seven patients were identified as having cytomegalovirus (CMV) infection post transplantation but not concurrently with PCP. Seven of the 14 patients had also experienced one or more episodes of post-transplant rejection. The 30-day crude mortality rate in the outbreak at Western Infirmary was 14% (two of 14 patients).

      University Hospital Crosshouse

      In January 2015, a cluster of patients were identified with PCP. Four patients were diagnosed with PCP between November 2014 and January 2015, which was higher than expected. A further seven patients were identified between February and May 2015, bringing the total to 11 patients under the care of the renal unit [seven renal transplant patients and four non-renal-transplant patients (but one heart transplant patient)]. All patients were attending the renal outpatient clinic and were on immunosuppression. The investigation was expanded to include outpatient attendance and non-renal patients. The interval from transplant to positive result ranged from 32 months to 28 years. Two patients had detectable CMV in bronchoalveolar lavage, but CMV was below the level of quantification in blood samples in both patients. The 30-day crude mortality at University Hospital Crosshouse was 54.5% (six of 11 patients).

      Infection control investigation and measures

      Western Infirmary, Glasgow

      The infection control investigation concentrated on mapping of patients and investigation of potential common sources. Extensive mapping of inpatient and outpatient activity took place and timelines were created. This included admission to the renal wards, and attendance at outpatient renal, radiology, cardiology, rheumatology, dermatology and respiratory clinics. There was no evidence of any crossover during inpatient hospital stay. However, several patients had attended the same renal transplant outpatient clinic on the same day. This clinic was situated in a newly built facility in north Glasgow. The clinic was visited by infection control staff and noted to be clean and uncluttered. However, the clinic waiting area was small and, as evidenced on the day of the visit, patients were in close proximity to one another. When identified as PCP positive during their inpatient stay, patients were isolated in single-room accommodation. If this was not possible, transplant or immunosuppressed individuals were not nursed in close proximity to positive cases. Recommended cleaning with a chlorine-based detergent was carried out daily. Surgical masks were worn by staff, and FFP3 masks were worn for aerosol-generating procedures. Ongoing surveillance was put in place by the infection control team for further cases. Patients were not known to have social contact with each other. Prophylaxis was not instituted for the entire renal transplant patient population; however, the prophylaxis policy was reviewed to include the identified risk factors.

      University Hospital Crosshouse

      At University Hospital Crosshouse, suspected or confirmed PCP patients in the renal ward were isolated in single rooms and nursed with droplet precautions, including use of surgical masks by staff for all close contact to prevent temporary colonization and potential transmission to other patients. Patients in the general medical wards were not necessarily placed under isolation. Staff members caring for the patients were not excluded from caring for other patients not infected with P. jirovecii. All renal transplant patients were advised to notify the transplant administrator of any respiratory symptoms. Patients at University Hospital Crosshouse were noted to have social contact with each other. Social events included a pantomime at Christmas, summer picnics and patient support group meetings, held monthly. At the outbreak investigation meeting at University Hospital Crosshouse, it was decided that all renal transplant patients and non-transplant patients attending renal clinics and being treated with immunosuppressive drugs would be offered prophylaxis with TMP-SMX. Patients who were intolerant to TMP-SMX or in whom TMP-SMX was contradicted were offered atovaquone or dapsone. Patient information leaflets were prepared explaining the situation and the need for prophylaxis. The leaflet provided the patients with a contact number in cases they needed to seek advice. A decision was made to offer prophylaxis for a period of six months. Following cessation of prophylaxis, an enhanced surveillance system was put in place whereby every laboratory request for testing for P. jirovecii was followed up by the microbiology department. At University Hospital Crosshouse, a detailed timeline of hospital and outpatient attendance was developed for all renal and non-renal patients to determine potential points of contact. This was further refined when typing results became available. There were only two occasions where two patients who were infected with the same allele type could be matched in time and place. In the first instance, the index case (Patient 14) and the exposed case (Patient 16) attended the same outpatient clinic on the same day. However, it was 53 and 76 days, respectively, before a positive PCP sample was obtained for each patient. Both were infected with Allele B. The second instance where two patients (Patient 20 and Patient 21) could be matched in time and place related to infection with allele A3. Although the patients attended different clinics, they shared a waiting area within the outpatient department. This occurred six days before the index case tested positive for PCP, and 37 days before the exposed case tested positive for PCP. There were a further seven instances where two renal patients could be matched in time and place; however, one of the pair had an isolate that did not amplify. A number of these instances were mutually exclusive as the exposed patient had contact with more than one source patient and more than one allele type. There were no links established between the renal and non-renal patients. The evidence for cross-transmission within either the inpatient or outpatient healthcare setting was limited and could not explain the majority of infections.
      Typing was performed on 24 of the 25 positive PCP cases (Table I). From the Western Infirmary subset, six of 13 patients typed had the same genotype (allele B), three patients had a different type (allele A3), and four samples did not amplify and therefore could not be typed. Eight background cases were also typed (i.e. PCP positives in a non-renal population). Of these background patients, one had the same two PCP alleles as found in the outbreak patients. At University Hospital Crosshouse, typing was performed successfully in nine of 11 patients. Allele B was identified in five patients and allele A3 in was identified in four patients. Seven background cases were also subjected to typing: four were typed as allele B and three could not be typed.
      Table Imt26SRNA and ITS1 alleles in 24 patients (Patients 1–13 at Western Infirmary and Patients 14–24 at University Hospital Crosshouse)
      Renalmt26SRNA alleleITS1 allele
      Patient 1DNADNA
      Patient 2DNADNA
      Patient 3Allele 8Allele B
      Patient 4Allele 8DNA
      Patient 5DNADNA
      Patient 6Allele 8Allele A3
      Patient 7DNADNA
      Patient 8Allele 8Allele B
      Patient 9Allele 8Allele B
      Patient 10Allele 8Allele B
      Patient 11Allele 8Allele A3
      Patient 12Allele 8Allele B
      Patient 13Allele 8Allele B
      Patient 14Allele 8Allele B
      Patient 15Allele 8Allele B
      Patient 16Allele 8Allele B
      Patient 17Allele 8Allele B
      Patient 18Allele 8Allele A3
      Patient 19DNADNA
      Patient 20Allele 8Allele A3
      Patient 21Allele 8Allele A3
      Patient 22Allele 8Allele A3
      Patient 23DNADNA
      Patient 24Allele 8Allele B

      Risk factor analysis

      Risk factor analysis was performed as part of this investigation, matching the 14 cases in Glasgow with controls to give a total of 28 transplant patients for analysis. Cases were matched according to age at time of transplant and date of transplant. There were 16 males (57.14%) and 12 (42.86%) females. The mean age was 49.5 years (range 35–64 years). Univariate matched analysis was performed (Table II). The main finding was an association between at least one rejection episode and PCP. There were seven discordant pairs, and in each of these pairs, the case had experienced one or more rejection episodes whereas the matched control had not. A matched odds ratio could not be calculated due to the absence of control exposed discordant pairs. However, upon testing with McNemar's significance test corrected for small samples, a P-value of 0.02333 was calculated. Risk factors where no association was found included lymphocyte count, donor type (cadaveric vs live) and type of underlying renal disease. Although no significant association was found between PCP infection and CMV, there appeared to be an uneven distribution of cases with CMV PCR positivity post transplant.
      Table IIRisk factor analysis
      VariableDiscordant pairs case exposedDiscordant pairs control exposedMatched odds ratio (exact CI)Corrected McNemar’s P-value
      Sex – male422.00 (0.29–22.11)0.68
      CMV – yes616.00 (0.73–275.99)0.13
      Transplant – cadaveric111 (0.01–78.50)1.00
      Comorbidity – 4+420.5 (0.04–3.49)0.68
      Prophylaxis – yes02-0.48
      Rejection – at least one episode70-0.0233
      Lymphocyte count – 0–12450.8 (0.16–3.72)1.00
      CMV, cytomegalovirus; CI, confidence interval.

      Discussion

      Outbreaks of PCP in renal units have been described but remain rare. A systematic review performed in 2011 identified 16 outbreaks published in the English literature.
      • de Boer M.G.
      • de Fijter J.W.
      • Kroon F.P.
      Outbreaks and clustering of Pneumocystis pneumonia in kidney transplant recipients: a systematic review.
      Earlier PCP outbreaks supported transmission between HIV-infected patients and kidney transplant recipients. Furthermore, introduction of cyclosporin and an increasingly susceptible population were deemed to be significant risk factors.
      • de Boer M.G.
      • de Fijter J.W.
      • Kroon F.P.
      Outbreaks and clustering of Pneumocystis pneumonia in kidney transplant recipients: a systematic review.
      In the majority of early reported PCP outbreaks, chemoprophylaxis had not been administered.
      • Hauser P.M.
      • Francioli P.
      • Bille J.
      • Telenti A.
      • Blanc D.S.
      Typing of Pneumocystis carinii f. sp. hominis by single-strand conformation polymorphism of four genomic regions.
      Whilst early studies suggested re-activation of PCP, more recently, molecular tools such as genotyping have provided evidence for cross-transmission by airborne droplets between patients in hospital wards, outpatient clinics or social settings. The use of genotyping in outbreak settings has demonstrated single circulating genotypes against a background of known strain diversity, making it unlikely that re-activation has occurred.
      • Sassi M.
      • Ripamonti C.
      • Mueller N.J.
      • et al.
      Outbreaks of pneumocystis pneumonia in 2 renal transplant centers linked to a single strain of pneumocystis: implications for transmission and virulence.
      Data from Northern Ireland found a diverse population with 15 different strain types circulating from samples from eight hospitals.
      • Curran T.
      • McCaughey C.
      • Coyle P.V.
      Pneumocystis jirovecii multilocus genotyping profiles in Northern Ireland.
      Environmental sources are also a possibility, but air sampling has proved inconclusive in previous outbreak reports.
      • de Boer M.G.
      • de Fijter J.W.
      • Kroon F.P.
      Outbreaks and clustering of Pneumocystis pneumonia in kidney transplant recipients: a systematic review.
      This study identified two different PCP genotypes in the outbreaks belonging to alleles A3 and B. Outbreaks with multiple genotypes have been reported. Rostved et al. reported an outbreak in Copenhagen between 2007 and 2010 involving 29 renal and liver transplant recipients caused by three distinct strains of PCP.
      • Rostved A.A.
      • Sassi M.
      • Kurtzhals J.A.
      • et al.
      Outbreak of pneumocystis pneumonia in renal and liver transplant patients caused by genotypically distinct strains of Pneumocystis jirovecii.
      In Sydney, Australia, colleagues reported an initial outbreak with a dominant strain, with subsequent identification of closely related strains.
      • Chapman J.R.
      • Marriott D.J.
      • Chen S.C.
      • MacDonald P.S.
      Post-transplant Pneumocystis jirovecii pneumonia – a re-emerged public health problem?.
      Given the relatively small numbers and a significant number of untypeable strains in most outbreaks, it is impossible to draw firm conclusions regarding whether single genotypes predominate, although such outbreaks have been reported.
      • Chapman J.R.
      • Marriott D.J.
      • Chen S.C.
      • MacDonald P.S.
      Post-transplant Pneumocystis jirovecii pneumonia – a re-emerged public health problem?.
      Allele B, which was the dominant allele in this regional outbreak, has also been identified in German and Swiss hospitals.
      • Sassi M.
      • Ripamonti C.
      • Mueller N.J.
      • et al.
      Outbreaks of pneumocystis pneumonia in 2 renal transplant centers linked to a single strain of pneumocystis: implications for transmission and virulence.
      From the study data, it appears that allele B is the predominant strain type in the West of Scotland and, at least at University Hospital Crosshouse, there appeared to be a clustering of cases in the renal patients against a background of wider colonization of type B in non-renal patients. However, the overall numbers are relatively small to arrive at a firm conclusion.
      Few outbreaks have explored independent risk factors for development of PCP. In published outbreaks, immunosuppressive agents, concurrent CMV infection, increasing age and treatment for rejection have been identified as risk factors.
      • de Boer M.G.
      • de Fijter J.W.
      • Kroon F.P.
      Outbreaks and clustering of Pneumocystis pneumonia in kidney transplant recipients: a systematic review.
      In the outbreak at Western Infirmary, risk factor analysis identified one or more rejection episodes as a risk factor for PCP infection. Identification of this risk factor in the Western Infirmary cohort enabled a targeted approach to PCP prophylaxis.
      Owing to a lack of evidence, there is currently no consensus with respect to duration of PCP prophylaxis following renal transplant. The European Renal Association recommends a four-month duration,
      • EBPG Expert Group on Renal Transplantation
      European best practice guidelines for renal transplantation. Section IV: Long-term management of the transplant recipient. IV.7.1 Late infections. Pneumocystis carinii pneumonia.
      and the American Society of Transplantation recommends a longer duration of six to 12 months.
      • Wang E.H.Z.
      • Partvoi N.
      • Levy R.D.
      • et al.
      Pneumocystis pneumonia in solid organ transplant recipients; not yet an infection of the past.
      The patients in both outbreaks had their transplants performed at the Glasgow hospital, where the policy is to give three months of prophylaxis with co-trimoxazole. This is in keeping with guidance from the UK Renal Association, which recommends prophylaxis for three to six months post transplant.
      • Baker R.
      • Jardine A.
      • Andrews P.
      Postoperative care of the kidney transplant recipient..
      Some centres with a low incidence of PCP do not administer prophylaxis at all.
      • Wang E.H.Z.
      • Partvoi N.
      • Levy R.D.
      • et al.
      Pneumocystis pneumonia in solid organ transplant recipients; not yet an infection of the past.
      A low incidence of PCP in renal transplant patients previously in Glasgow led to the decision for three months of prophylaxis. The majority of published outbreaks have reported cessation of cases following introduction of PCP prophylaxis with TMP-SMX. The rationale for prophylaxis is to reduce PCP load and onward transmission. During an outbreak in Australia in 2010, all patients were commenced on prophylaxis for 1 year and until at least six months after the last case was diagnosed. Following this, PCP prophylaxis was restricted to those with CMV, chronic respiratory disease and late rejection, which were the risk factors identified in this patient population.
      • Chapman J.R.
      • Marriott D.J.
      • Chen S.C.
      • MacDonald P.S.
      Post-transplant Pneumocystis jirovecii pneumonia – a re-emerged public health problem?.
      In the two study hospitals, different approaches were taken to prophylaxis. At University Hospital Crosshouse, the outbreak team advised six months of PCP prophylaxis for approximately 150 patients (approximately 100 transplant patients and 50 patients with immunosuppression due to other reasons). The reasons for this decision were a faster outbreak with a high mortality rate and social contact between patients. Treatment cessation took place as patients were seen individually at routine clinic appointments. The approach at Western Infirmary was to reinstitute prophylaxis on the basis of identified risk factors (i.e. rejection) and to continue it for six months. In addition, due to the increased incidence of PCP in these patients, the decision was made to extend post-transplant prophylaxis for all patients transplanted in Glasgow to six months. The Glasgow outbreak occurred two years before the outbreak at University Hospital Crosshouse, and mass prophylaxis was not considered because of insufficient evidence for cross-transmission at the time. Furthermore, the same level of social contact did not exist between the patients in Glasgow.
      In terms of potential exposures, the authors were unable to confidently determine the reason for the clustering of cases over a short period. The possibility of transmission in the common waiting areas at the outpatient clinics was explored, and whilst there was some degree of contact between patients, particulary in the Glasgow outbreak, this did not explain the majority of cases of PCP. In a PCP outbreak in France in 2010 involving nine renal transplant patients, each individual had been in contact with at least one other in the outpatient setting.
      • Brunot V.
      • Pernin V.
      • Chartier C.
      • et al.
      An epidemic of Pneumocystis jiroveci pneumonia in a renal transplantation center: role of T-cell lymphopenia.
      Furthermore Yazaki et al. found evidence of PCP DNA in consulting rooms during an outbreak in the outpatient setting involving 27 renal transplant patients.
      • Yazaki H.
      • Goto N.
      • Uchida K.
      • Kobayashi T.
      • Gatanaga H.
      • Oka S.
      Outbreak of Pneumocystis jiroveci pneumonia in renal transplant recipients: P. jiroveci is contagious to the susceptible host.
      In a study evaluating P. jirovecii air diffusion in patients with PCP, Choukri et al. found PCP in 79% of air samples collected at a distance of 1m from infected patients. In addition, PCP was detected in patient rooms and surrounding corridors, but not in locations where PCP patients were not present.
      • Choukri F.
      • Menotti J.
      • Sarfati C.
      • et al.
      Quantification and spread of Pneumocystis jirovecii in the surrounding air of patients with pneumocystis pneumonia.
      These findings support the isolation and use of single-room accommodation for patients with PCP, which was implemented as an infection control measure in both of the study outbreaks. The role of asymptomatic colonization in patients and/or healthcare workers is unclear.
      The study outbreaks took place in the West of Scotland region spread over a wide area incorporating two health boards. Regional outbreaks have been reported previously in the UK. An outbreak in the renal units in North-West England in Liverpool and Salford resulted in 27 cases from November 2008 to 2010. Following this outbreak, a nationwide survey revealed that one-quarter of UK renal units reported an increase in cases of PCP.
      • Thomas S.
      • Vivancos R.
      • Corless C.
      • Wood G.
      • Beeching N.J.
      • Beadsworth M.B.
      Increasing frequency of Pneumocystis jirovecii pneumonia in renal transplant recipients in the United Kingdom: clonal variability, clusters, and geographic location.
      Key control measures in both outbreaks included patient isolation and the institution of PCP prophylaxis to reduce the likelihood of future cases. In addition, a recent systematic review recommended surveillance for PCP and designation as an alert organism for infection control teams; the authors have subsequently implemented such surveillance.
      • Yiannakis E.P.
      • Boswell T.
      Systematic review of outbreaks of Pneumocystis jirovecii pneumonia: evidence that P. jirovecii is a transmissible organism and the implications for healthcare infection control.
      The authors also recommend assessing ventilation standards to ensure that ward and clinic areas achieve six air changes per hour, and the use of surgical masks if patients are transferring to other areas. Consideration of masks for patients attending outpatient clinics with respiratory symptoms is also suggested. This latter recommendation is supported as, in the Glasgow outbreak, the only link between patients was that several had attended the same outpatient clinic on the same day. Further studies are required to assess the role of the environment and asymptomatic carriers in PCP outbreaks. In both outbreaks, staff used surgical masks while caring for PCP-positive patients. This was due to previous reports of transient colonization in healthcare workers and concern that they might serve as a route for ongoing transmission.
      • Vargas S.L.
      • Ponce C.A.
      • Gigliotti F.
      • et al.
      Transmission of Pneumocystis carinii DNA from a patient with P. carinii pneumonia to immunocompetent contact healthcare workers.
      However, CDC guidance does not recommend the use of surgical masks for staff as a matter of routine due to insufficient evidence.
      • Centers for Disease Control and Prevention
      Guideline for isolation precautions: preventing transmission of infectious agents in healthcare settings.
      Infection control teams should be alert to cases of PCP in renal transplant patients, and outpatient clinics should be considered as potential high-risk areas for cross-transmission. Key control measures include patient isolation and chemoprophylaxis.

      Conflict of interest statement

      None declared.

      Funding sources

      None.

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