Download - INFECTIONS AFTER TRANSPLANTATION
![Page 1: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/1.jpg)
INFECTIONS AFTER TRANSPLANTATION
Lora Thomas MD, MPH
September 28, 2012
![Page 2: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/2.jpg)
Topics To Be Discussed
How are we doing in transplantation?
Review basic precepts of transplant infections
Discuss some classic transplant pathogens: CMV, EBV, fungal diseases, pneumocystis, TB
Emerging transplant problems: polyomaviruses, RSV, respiratory viruses, arenaviruses
Avoidance of infection
![Page 3: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/3.jpg)
Graft and Patient Survival After Transplantation by Organ
Graft Survival (%) Patient Survival (%)
Type 1 year 3 year 1 year 3 yearRenal-LD 96 90 99 95Renal-Cad 91 80 96 89Pancreas 76 60 98 92Heart 88 81 88 82Liver 84 74 88 79Lung 82 64 83 66Heart-Lung 81 62 81 62
Data from SRTR 2009 Annual Report
![Page 4: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/4.jpg)
Decreasing Infectious Mortality in Subsequent Cardiac Transplant Cohorts
1980-1990
PPID, chapter 304, 2000
![Page 5: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/5.jpg)
Lack of Change in Infectious Mortalityafter Cardiac Transplantation: 1990-2000
![Page 6: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/6.jpg)
Infection Related Mortality in Lung Transplant Recipients
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
1998 1999 2000 2001 2002 2003 2004 2005 2006
Other
Cancer
BO/Graft Dys
Infection
Proportion of All Deaths Related
to Cause
VUMC Data
![Page 7: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/7.jpg)
Basic Precepts of Transplant Infections
Infections occur on a time scale
Type and frequency of infection vary with transplant type: lung>liver>heart>kidney
More surgery more infection
More immunosuppression more infection
Beware of donor as a source of infection especially early post-transplant
Transplantation does not protect from infections “normal” people get
![Page 8: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/8.jpg)
Time Scale of Infection after Transplantation
Types of Infections vary depending on time post-transplant:
0-30 days: mostly ”surgical” infections, common bacteria, Candida, HSV
1-6 months: opportunistic pathogens, CMV, Pneumocystis, Nocardia, Aspergillus
6 months onward: common community infections,
occasional opportunists, endemic fungi (histo, crypto)
![Page 9: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/9.jpg)
![Page 10: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/10.jpg)
Frequency and Severity of Infections by Organ
Type N Inf /Pt. CMV Bacteremia Fungal Inf. Death
Renal 64 0.98 8% 5% 0% 0%
Heart 119 1.36 16% 13% 8% 15%
Liver 101 1.86 22% 16% 16% 23%
H-Lung 31 3.19 39% 19% 23% 45%
Dummer JS, PPID, 2000, Churchill Livingstone, based on data from early 1980’s in Pittsburgh
![Page 11: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/11.jpg)
Partial List of Organisms Transmitted by Transplantation Viruses: CMV and other herpesviruses, HIV, hepatitis A, B C
& D, HTLV-1, WNV, Rabies, LCMV
Fungi: Histoplasma, Coccidioides, Cryptococcus
Protozoa: Toxoplasma, malaria, T. cruzii
Bacteria: TB, nosocomial pneumonia agents (lung), urinary bacteria (kidney), bacteremic donor
Prions: Creutzfield-Jakob disease (cornea)
Gottesdiener, Ann Int Med 1989;110:1001; Dummer JS, PPID, 2004
![Page 12: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/12.jpg)
Infectious Episodes Related to Total Time Spent in the Operating Room
Total operative time in hours
![Page 13: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/13.jpg)
Immunosuppression and Infection- A Summary
No good marker is available for state of immunosuppression (unlike CD4 in HIV)
“Net state of immunosuppression” must be estimated based on clinical status, doses or levels of drugs, and recent treatment of rejection
Treatment of rejection increases clinical infection rates
Patients are treated with a cocktail of oral drugs with different modes of action; some IV drugs are also used either for treatment of rejection or induction early post-transplant
Dummer JS, PPID, 2000; Halloran PF NEJM 2004;351:2715
![Page 14: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/14.jpg)
Immunosuppression and Infection
Infections increase with increased intensity of immunosuppression
Two major immunosuppressive drugs introduced since 1980, cyclosporine and tacrolimus, have similar infectious risk but are associated with less infection than the earlier regimen of azathioprine/steroids
Two cell cycle inhibiting agents, azathioprine and mycophenylate mofetil, have similar infectious risk
Risk of post transplant malignancy and CMV may be reduced with rapamycin
Dummer JS, PPID, 2000
![Page 15: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/15.jpg)
Antibody Therapy and Infection
Antithymocyte Globulin Rabbit Equine
Increased risk of CMV, PTLD
Anti-CD25 (IL-2 receptor) antibodies Basiliximab (Simulect®)
Infection risk not significantly increased
Anti-CD20 antibody
Rituximab (Rituxan®)HBV reactivation
Anti-CD52 antibody Alemtuzumab (Campath®)
Increased risk of CMV, Pneumocystis jirovecii pneumonia, invasive fungal infections, immunosuppression effects can last up to 12 months
![Page 16: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/16.jpg)
Herpesvirus Infections after Transplantation
Up to 35% of patients develop oral or genital herpes simplex infection in the first 2-3 weeks after transplantation; rare invasive or primary infections may be fatal
Herpes zoster or shingles occurs in up to 1/3 of transplant recipients. Chicken pox can be fatal
Epstein-Barr virus is associated with lymphoma after transplantation. Risk is 0.3-4%, may be 10 times higher with primary infection
Human herpes virus 8 associated with Kaposi’s sarcoma after transplantation
Cytomegalovirus has been the single most important pathogen in transplant recipients
![Page 17: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/17.jpg)
Labial Herpes
![Page 18: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/18.jpg)
Intraoral Herpes Simplex
![Page 19: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/19.jpg)
Herpes Simplex Esophagitis
![Page 20: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/20.jpg)
Herpes Simplex: Donor Transmitted Disease
![Page 21: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/21.jpg)
Cytomegalovirus and Transplantation
At one time CMV was the most important serious infection after transplantation
Now largely controlled by antivirals Usually occurs 30-90 days after transplantation Manifestations: Fever most common, but sometimes invasive
infection in bowel, liver, lung or retina Risk factors for disease are primary infection (usually donor
derived), level of immunosuppression, organ transplanted (lung) Diagnosis used to be by viral culture, now most often by blood
antigenemia or quant. PCR Treatment: ganciclovir, foscarnet
![Page 22: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/22.jpg)
Infection and Morbidity due to CMV in Different Transplant Groups*
Data collected in Pittsburgh before the use of antiviral medications
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Kidney Liver Heart Heart-lung
Asymptomatic infection Symptomatic infection Pneumonia
![Page 23: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/23.jpg)
![Page 24: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/24.jpg)
Manifestations of CMV Disease Following Cardiac Transplantation
Manifestation No. of Patients % of Patients
Fever > 38º 17 100%Atypical Lymphs > 3% 15 88%Interstitial Changes (CXR) 8 47%WBC < 4,000 8 47%Platelets < 100,000 7 41%SGPT > 40 IU 7 41%Abdominal Pain 7 41%Myalgia 2 12%Arthralgia 2 12%
Data from Dummer, JID, 1985
![Page 25: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/25.jpg)
Vogel et al.Br J Radiol 2006 (epub)
CMV Pneumonitis
![Page 26: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/26.jpg)
Horger et al.AJR Am J Roentgenol 2006;187:W636
CMV Pneumonitis
![Page 27: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/27.jpg)
Cytomegalovirus Pneumonitis: Pathology
![Page 28: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/28.jpg)
Microabscess Caused by CMV in the Liver
![Page 29: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/29.jpg)
CMV Colitis
jmedicalcasereports.com
![Page 30: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/30.jpg)
CMV Retinitis - Early
![Page 31: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/31.jpg)
Management of CMV Infection
Most patients receive preventive regimens, either post-transplant prophylaxis for 3 or more months or viral monitoring with preemptive therapy
Valganciclovir is the preferred prophylaxis in the USA; some oral ganciclovir is also used. High dose valacyclovir is also used but more outside than inside the USA
Advantage of prophylaxis is simplicity. Some data supports better long term outcomes with prophylaxis
Costs of pre-emptive therapy are potentially lower and late CMV disease is less likely with pre-emptive therapy
Treatment of CMV disease is usually with IV ganciclovir or oral valganciclovir
![Page 32: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/32.jpg)
Epstein-Barr Virus (EBV) and Transplantation
Epstein-Barr virus can cause lympho-proliferative disease after transplantation
Some cases are polyclonal proliferations that respond to reduction of immunosuppression; others are true lymphomas
Risk varies by transplant group - lowest in renal transplants (~0.3%) and highest in lung transplants and pediatric transplants (~4%)
As with CMV primary infection and level of immunosuppression are the main risks
![Page 33: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/33.jpg)
Transplant Lymphoma - Case
A 41 year old woman received a heart-lung transplant for cystic fibrosis in 1993 in North Carolina. She was EBV seronegative at the time of transplantation. She converted to EBV after transplantation possible from the donorShe maintained excellent lung function post-transplant. 13 years later she presented with a month of headache, low-grade fevers and malaise. Exam showed only left sided ptosis. An MRI scan of the head showed numerous enhancing lesions in the brain.
![Page 34: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/34.jpg)
Initial MRI Scan of the
Brain
![Page 35: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/35.jpg)
Australas Radiol 2006;50:412
Lymphoproliferative Disease in the Abdomen related to EBV
![Page 36: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/36.jpg)
![Page 37: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/37.jpg)
Human Herpes Virus – 8 and Kaposi’s Sarcoma (KS) Most recently discovered Herpesvirus Endemic in Central Africa (50%); also
somewhat in Near East and around Mediterranean (10%); rare in USA
Strongly associated with KS in AIDS and transplantation
May respond to reduction of immunosuppression
![Page 38: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/38.jpg)
![Page 39: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/39.jpg)
Fungal Infection after Transplantation
Mucocutaneous Candida (Thrush and esophageal candidiasis) once common but are controlled by topical antifungals such as nystatin (“swish and swallow”)
Invasive Candida incidence varies with organ transplanted: bone marrow = liver>>lung=pancreas>heart=renal
Cryptococcal infection occurs in 0.5-2.0 % of organ recipients usually at least 6 months out and often quite late; rare in bone marrow recipient
Aspergillus: bone marrow>lung>liver>>heart=renal. Risk factors high dose steroids, GVHD, renal dysfunction, prolonged neutropenia
Endemic fungal infections occur sporadically
![Page 40: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/40.jpg)
Esophageal Candidiasis
![Page 41: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/41.jpg)
Candidiasis in Transplantation
![Page 42: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/42.jpg)
Cryptococcal Infection after Transplantation
Commonly presents either with pulmonary or central nervous system disease
Pulmonary: usually presents with lung nodule(s) on CXR with mild pulmonary or no symptoms
CNS disease presents as meningitis with gradual evolution of headache and neurological findings that are often subtle
Occasionally associated skin lesions
Diagnosis with invasive procedures (bronchoscopy, lumbar puncture and cryptococcal antigen)
Disease can usually be controlled but some patients stay on antifungals for prolonged durations, even lifelong
![Page 43: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/43.jpg)
Pulmonary Cryptococcosis
![Page 44: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/44.jpg)
Budding Cryptococcus neoformans
![Page 45: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/45.jpg)
Strongly Positive India Ink Smear
![Page 46: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/46.jpg)
Large Ulcer on Arm Caused by Cryptococcus
![Page 47: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/47.jpg)
Skin Lesions Due to Cryptococcus
![Page 48: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/48.jpg)
Mortality of InvasiveAspergillosis
Organ Transplanted % Incidence % Mortality (3 month)
Allo HSCT 12.8% 71%
Auto HSCT 1.1% 42%
Lung 2% 22%
Liver 1.9% 45%
Heart 1.3% <10%
Kidney 0.4% 25%
Trans Infect Dis 2010
![Page 49: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/49.jpg)
Pulmonary Infiltrates Caused by Aspergillus in a Neutropenic Host
![Page 50: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/50.jpg)
Hyphae of Aspergillus Invading Tissue
![Page 51: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/51.jpg)
Vascular Invasion by Aspergillus
![Page 52: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/52.jpg)
Pulmonary Nodule due to A. fumigatusin a Heart transplant Recipient
![Page 53: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/53.jpg)
Aspergillus: Halo Sign
http://radiology.rsna.org
![Page 54: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/54.jpg)
Cerebral Aspergillosis
![Page 55: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/55.jpg)
Transplant Histoplasmosis
Soil fungus seen mostly in south central USA. Occurs in about 0.5-1% in endemic areas
Transplant patients often have multisystem disease with fever, pneumonia, lymph node enlargement, low blood counts and liver and spleen enlargement
Diagnosis by culture (slow), urine or blood antigen (few days) and in sickest pts by blood smear
![Page 56: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/56.jpg)
H. Capsulatum
![Page 57: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/57.jpg)
Histoplasmosis: Miliary Pattern
Millet Seeds
![Page 58: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/58.jpg)
Pneumocystis Infection and Transplantation Pneumocystis pneumonia once occurred in 5-10% of transplant
patients, now controlled with prophylaxis
Typically presented with fever, hypoxemia and diffuse pneumonia 2-6 months after transplantation
Diagnosis usually required bronchoscopy with lavage of lung alveoli
Treatment with sulfa-trimethoprim or pentamadine was usually successful in clearing the organism but some patients died during period of hypoxemia
Two to three sulfa tablets a week prevent it
![Page 59: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/59.jpg)
Radiographic Picture of Pneumocystis Pneumonia
![Page 60: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/60.jpg)
Cysts of Pneumocystis in a Lung Biopsy
![Page 61: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/61.jpg)
Tuberculosis after Transplantation
Uncommon (< 1%) in developed world compared to developing world (2-10%)
2/3 of cases occur in first year; most thought to be due to reactivation but only 20% in pts with +PPD
½ of cases disseminated or extra-pulmonary; few patients have classic upper lobe cavitary changes
TB can be transmitted by donated organs but this accounts for <5% of all cases
Singh N, Patterson DL, CID, 1998;27:1266
![Page 62: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/62.jpg)
Polyomaviruses and Transplantation Two related small DNA viruses (JC & BK); serology shows 60-80%
of humans infected in childhood
JC causes progressive multifocal leukoencephalopathy (PML) in immunosuppressed patients
Polyomaviruses (esp. BK but also JC) found by culture in urine of 10-45% of renal and bone marrow transplant patients; occasionally in normal hosts
In 1980’s polyomaviruses shown to cause ureteral stenosis (renal TX) and hemorrhagic cystitis (BM Tx)
In recent years polyomavirus (mostly BK) shown to cause severe nephropathy in 2-4% of renal recipients
![Page 63: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/63.jpg)
BK Virus Nephropathy
![Page 64: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/64.jpg)
Polyomavirus Infection of the Transplanted Kidney: “Decoy” Cells in the Urine
![Page 65: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/65.jpg)
Risk Factors for Polyomavirus Nephropathy after Renal Transplantation
Generally strongest risk factor is detection of virus; in one study just finding BKV in urine had an odds ratio of 68 for nephropathy
Demographic risk factors are older age, male gender and caucasian ethnicity
Polyomavirus nephropathy is associated with level of immunosuppression, but findings are variable.
![Page 66: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/66.jpg)
Ramos et al. J Am Soc Nephrol 2002;13:2145-51
BK Virus Nephropathy: Graft Survival
![Page 67: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/67.jpg)
Respiratory Syncytial Virus (RSV) RNA virus
Seasonal: Fall-early Spring
>90% have had primary infection by age 2
Reinfection common throughout life
More severe disease seen in stem cell and lung transplant recipients
Rhinorrhea, sinus congestion, sore throat usually precede pneumonia
![Page 68: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/68.jpg)
RSV Pneumonia
![Page 69: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/69.jpg)
Respiratory Viral Infections
Influenza Parainfluenza Adenovirus Metapneumovirus Adenovirus Enterovirus Rhinovirus Coronavirus
Respiratory Viral Panels increasingly being used at centers
Nasopharyngeal swab, wash, BAL
Sensitivity 79% Specificity 99%
![Page 70: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/70.jpg)
Lymphocytic Choriomeningitis Virus (LCMV) Transmission by Organ Donation
Multiple cases reported of LCMV transmission through organ transplantation
Fevers in recipients began between 3 and 22 days after transplantation: other symptoms included peri-incisional rash, headache, abdominal pain, mental status changes
Most donors with no evidence of LCMV infection (one donor had exposure to pet hamster that tested positive)
Only one known survivor had reduction in immunosuppression and ribaviron treatment
NEJM 2006;354:2235
![Page 71: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/71.jpg)
LCMV In Transplant Patients
Kidney Skin
NEJM 2006;354:2235
![Page 72: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/72.jpg)
Prevention of Exposure to Infection
Hospital exposures: usually just standard infection control. Bone marrow units may HEPA filter air and restrict visitors with colds
Enteric pathogens: avoid raw eggs, unpasteurized milk and juices, certain soft cheeses, water from streams or lakes
Varicella: if seronegative avoid contact with chickenpox or shingles
Zoonoses: avoid cat litter, bird cages, avoid jobs with frequent animal contact
![Page 73: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/73.jpg)
Prevention of Exposure to Infection
Respiratory viruses: avoid persons with colds, public places during flu outbreaks, vaccinate family members
![Page 74: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/74.jpg)
Prevention of Exposure to Infection- Continued
Airborne molds: avoid barns, silos, chicken coops etc.
STD’s: Practice safer sex
Exotic infections: Before international travel outside Canada or W. Europe, confer with infectious disease expert
![Page 75: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/75.jpg)
Vaccination after Transplantation
No clear evidence connecting vaccination to rejection episodes
Inactivated vaccines safe to use starting 3 months after transplant if at baseline immunosuppression
Avoid live virus vaccines after transplant (minimum 4 weeks from live vaccine to transplantation)
Influenza: inactivated seasonal vaccine recommended, insufficient data to support use of high dose influenza vaccine, adjuvant, or booster dose
American Journal of Transplantation 2011; 11: 2020–
2030
![Page 76: INFECTIONS AFTER TRANSPLANTATION](https://reader035.vdocuments.us/reader035/viewer/2022062309/56815ad9550346895dc8a598/html5/thumbnails/76.jpg)
Questions
?