1. INFECTIONS IN HEMOPOEITIC STEM CELL TRANSPLANT RECIPIENTS DR E.O SHOBOWALE CLINICAL MICROBIOLOGIST PATHCARE NIGERIA

2. OUTLINE Introduction Infectious agents Diagnosis Prophylactic agents PathCare’s role Conclusion

3. INTRODUCTION The transplantation of haematopoietic stem cells from bone marrow results in a transient state of immunologic incompetence. Shortly after transplantation phagocytes, T and B cells are rapidly depleted and the host is extremely susceptible to various infections.

4. Infectious Agents Bacterial Fungal Parasitic Viral

5. Infectious agents Site of Infection< 28 days1 to 4 months> 6 months DisseminatedS aureus, CONS Nocardia, Candida, Aspergillus spp H influenzae, S pneumoniae, N meningitides Skin and Mucous Membranes HSVHHV 6VZV LungsCandida, Aspergillus spp, Klebsiella spp CMV, Toxoplasma, P jiroveci P jiroveci GITCMV KidneyBK Virus, Adenovirus BK Virus BrainHHV 6HHV 6, Toxoplasma Toxoplasma, JC Virus Bone MarrowHHV 6

6. Bacterial Usually seen in the first 28 days after HSCT. Marked granulocytopenia is observed Neutropenia usually lasts for 1 to 3 weeks. However bacterial infections are more common in the first 7 days Organisms are usually from the Skin or Intravenous catheters of recipients

7. Bacterial Staphylococcus aureus, Coagulase Negative Staphylococci are acquired from the skin and catheters. Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa are acquired from the bowel. Nocardia asteroides which is partially acid fast occurs after the first week of transplantation.

8. Bacterial Encapsulated bacteria such as Streptococcus pneumoniae cause infections in the late post transplantation period i.e. >6 months. Chemotherapy and the use of broad spectrum antimicrobial agents place recipients at risk of Clostridium difficile associated diarrhea.

9. Fungi Fungal infections tend to occur after the first week post transplantation. Seen after chemotherapy, steroid and broad spectrum antibiotic administration. Granulocytopenia predisposes towards Candida infections. The increased use of Fluconazole has also helped to select out Molds such as Aspergillus spp, Penicillium marfennei and Scedosporium spp

10. Fungi The following drugs predispose to fungal infections particularly Candida and Aspergillus spp infections in HSCT patients Prednisolone Cyclosporine Tacrolimus Mycophenolate Rapamycin Alemtuzumab

11. Fungi The above mentioned drugs may also cause reactivation of infections due to Histoplasma capsulatum Coccidioides imitis Blastomyces dermatidis.

12. Fungi The prolonged use of intravenous lipid formulations for TPN may predispose to Malassaezia furfur infections HSCT patients are at increased risk of interstitial pneumonia due to Pneumocystis jiroveci.

13. Parasites Reactivation of Toxoplasmosis occurs in transplant recipients and may cause CNS lesions.

14. Viruses Occurs within 14 days post transplantation Causes Mucositis, esophagitis and anogenital disease. HSV Reactivation of herpes zoster may occur in the first month especially with pre-transplant immunosuppression Reactivation rates are more with allogeneic transplantation VZV Seen 30 -90 days post transplantation with low granulocyte counts. Encountered in GVHD. Causes interstitial pneumonia, colitis, BM suppression and graft failure. CMV

15. Viruses HHV 6 reactivates in 30% of children post HSCT Reactivation is common in those receiving steroids HHV6 Reactivation is secondary to marrow ablation Lymphoproliferative disease occurs EBV Fatal pneumonias can occur Hemorrhagic cystitis Influenza, RSV, Adenoviruses

16. Clinical Syndromes Hemorrhagic Cystitis Elevated loads of BK Virus, Polyoma Virus, Adenovirus Also HSV, CMV and HHV 6 Hepatitis HBV, HCV, VZV, Adenovirus Others include HSC and CMV Pneumonia Syndromes S pneumoniae, RSV, P jiroveci H influenzae, Adenovirus

17. Clinical Syndromes Diarrhea – 15% are due to infectious agentsSkin eruptions – due to VZV or fungiOsteomyelitis – following marrow aspiration and usually due to S aureus

18. THE ROLE OF PATHCARE PathCare can reliably and accurately diagnose infectious syndromes pre and post transplantation. We have world class diagnostic equipments in all the 4 branches of Pathology – Microbiology, Clinical Chemistry, Hematology and Histopathology. PathCare has over 13 Pathologists on board who verify and help interpret laboratory reports Our pathologists are also available for consultation in the patient management

19. THE ROLE OF PATHCARE We are located in the following areas Lagos – Victoria Island, LUTH, FESTAC and Ikeja Benin Abuja Portharcourt Enugu Warri Kaduna Gwagwalada Ibadan Illorin – opening in August

20. THE ROLE OF PATHCARE PathCare was established in Nigeria in October 2004 due to demand for accurate and reliable tests It was started by consortium of health care practitioners including pathologists, haematologists, gynaecologists amongst others who required precision and a wider range of testing to ensure more favourable outcomes for their patients Sought reputable Partners: PathCare South Africa (foremost pathology service in South Africa). **First to achieve ISO Accreditation in South Africa with an unparalleled reputation for quality and service. PathCare has since enjoyed a meteoric rise (3 Laboratories and 9 Depots and still growing) in demand for its tests because of the trust clinicians have in the brand

21. THE ROLE OF PATHCARE Our Consultant Pathologists Prof. Ibironke Akinsete Consultant Haematologist and Chairman Board of Directors Dr. Tunji Soriyan Consultant Chemical Pathologist Dr. Abiola Ogbenna Consultant Haematologist Prof. Folasade Ogunsola Consultant Microbiologist Dr. Jaf Momoh Consultant Chemical Pathologist Dr. Adediran Consultant Haematologist Dr. Tamuno Wakama Consultant Haematologist Dr Olushola Shobowale Consultant Microbiologist Dr Tolulope Adewole Consultant Chemical Pathologist Over 70 Specialist Pathologists available in SA for referrals and second opinions

22. THE ROLE OF PATHCARE We are currently the first and only ISO 15189 accredited laboratory in West Africa. This means that our test methodologies and results meet international standards and are acceptable outside Nigeria.

23. THE ROLE OF PATHCARE Accurate and reliable results Highly specialised testing Timely results (Fast Turn around time) Excellent service Nationwide Access

24. THE ROLE OF PATHCARE TECHNOLOGY – New Methodology – New Processes … – Wider range of tests TRAINING  New Skills, Attitudes & Techniques COMPUTERIZATION – Improved efficiency & accuracy – Reduction of Errors due to human intervention TOTAL QUALITY MANAGEMENT

25. THE END PLEASE USE PATHCARE THANKS FOR LISTENING