infection in immunocompromised F and medicine

Infectious department of the medical report study

1. Level 4 Semester 8

2. INFECTIONS IN IMMUNOCOMPROMISED PATIENTS By Raghda El-Sayed Farag Prof. Of Endemic Medicine Mansoura University

3. Name: Raghda ElSayed Farag Department: Endemic Medicine Official e-mail: [email protected] Mobile or WhatsApp number (optional): 01154796766 Office hours: Day: Sunday Available time: Sunday : 9:00-2:00 PM Office number and place: INSTRUCTOR INFORMATION

4. Mission and Vision of Faculty رسالة الكلية: تلتزم كلیة الطب البشري – جامعة الدلتا للعلوم والتكنولوجیا بتقدیم برنامج تعلیمي تكاملي متمیز یقوم على المھـارة والمعرفـة ویھـدف الى تخریج أطبـاء قـادرین على الوفـاء بواجبـاتھم المھنیـة والأخلاقیـة، والتعلیم الطبي المستمر والمشاركة الفعالة في البحث العلمي وخدمة المجتمع. رؤية الكلية : تسعى كلیة الطب البشري - جامعة الدلتا للعلوم والتكنولوجیا من خلال تطبیق برنامج التعلم القائم على اكتســاب الجدارات أن تكون في مقدمة المؤسسات الطبیة التعلیمیة المتمیزة على المستوى المحلي والقومى والعالمي .

5. Learning Outcomes By the end of the lecture, the students will be able to: Review the immune system defense mechanisms Define opportunistic infections Know Types of Immunodeficiencies Discuss Common infections in Immunocompromised person

6. Case scenario Sara is a 45-year-old woman who has been feeling tired , low grade fever, pallor and weakness for several weeks. She has also noticed that she bruises easily and has frequent nosebleeds. She decides to visit her primary care physician to see what's going on. At the appointment,  Sara also reports having a fever and experiencing frequent infections such as respiratory tract infections and urinary tract infections. Sara's physician notes that she has pale skin and an enlarged spleen What is further investigation?.

7. Sara's blood cell counts reveal that

8. Immune systeme & Defense Against Disease If these barriers are penetrated, the body responds with If the innate immune response is insufficient, the body responds with Adaptive(specific) Immune Response cell-mediated immunity, humoral immunity Nonspecific External Barriers skin, mucous membranes Innate Immune Response phagocytic and natural killer cells, inflammation, fever

9. Major players The major players in the specific immune response include: Macrophage T cells (helper, cytotoxic, memory) B cells (plasma, memory) Antibodies Complement system

10. Clonal Selection

11. DEFINITION: Immunocompromised person: Denoting an individual with deficient immunologic mechanisms either because of an immunodeficiency disorder by immunosuppressive agents. Opportunistic infection An infection by a microorganism that normally does not cause disease but becomes pathogenic when the body's immune system is impaired and unable to fight off infection, as in AIDS.

12. When one Suspect Immunodeficiency Disorders: Chronic or recurrent infections. Infection caused by opportunistic or unusual pathogens. Failure to respond as expected to standard treatment for infectious process. Unusual complications to a usual infection. Family history of primary immunodeficiency.

13. Types of immunodeficiency 1- Primary immunodeficiency (congenital) Susceptibility to infections begins from childhood onward. Many of these disorders are hereditary and are autosomal recessive or X-linked. They are generally grouped by the part of the immune system affected such as lymphocytes, granulocytes, complement,T cells and B cells. The treatment of primary immunodeficiency depends on the nature of the defect, and may involve: - antibody infusions - long-term antibiotics - stem cell transplantation

14. Example of Primary immunodeficiency (congenital) HEMOGLOBINOPATHY genetic  defect that results in abnormal structure of one of the globin chains of the  haemoglobin  molecule - Common infectious agents are encapsulated organisms , particularly  Streptococcus pneumoniae .   PHAGOCYTE DEFICIENCY   Granulocyte deficiency including: - decreased numbers (granulocytopenia or agranulocytosis) - decreased function such as in chronic granulomatous disease. S. aureus,  streptococci, candida, Aspergillus Recurrent absceses (soft tissues and lung)

15. Result from exposure to v aroius immunosuppressive agents like: - malnutrition - aging - chronic diseases (CRF, LCF, DM) - medications ( chemotherapy, anti TNF, PPI) - immunosuppressive drugs after organ transplants - environmental toxins like mercury and heavy metals, pesticides. - Cancer that affect bone marrow and blood cells (leukemia, lymphoma). - Certain infections: HIV & acquired immunodeficiency syndrome (AIDS) 2- Secondary immunodeficiencies ( acquired immunodeficiencies)

16. Example of Secondary Immunodeficiency

17. MALNUTRITION Patients are more sucaptible to: Infectious diarrhea Pneumonia TB Measles Malaria Salmonellosis

18. LEUKEMIA OR LYMPHOMA Patients are susceptible to infection with - Staphylococci sp. - E coli - Candida - H influenzae - Herpes viruses.

19. Chronic Diseases Hepatic failure (LCF): - E coli - Streptococci - S . aureus. Metabolic complications (DM): - S aureus infection, - candidiasis Chronic Renal Failure (CRF): - S aureus - S pneumoniae - E coli

20. TREATMENTS AND MEDICATIONS - Drugs that decrease gastric acidity (e.g. prolonged use of PPI) : Patients are susceptible to infection with: - Salmonella sp. -V. cholerae - Inhibitors of TNF (infliximab adalimumab): TB, HSV, toxoplasmosis, CMV and activation of occult HBV or HCV . So, Patients should be screened for these infections before starting treatment with these drugs. - Corticosteroid therapy : S aureus, S pneumoniae . - Inhaled corticosteroid : oral candidiasis (thrush) community-acquired pneumonia (CAP )

21. ORGAN TRANSPLANT heart or heart-lung transplant : Toxoplasma  sp. renal transplant : Adenovirus stem cell transplantation : Aerobic gram-negative rods staphylococci sp. streptococci, C. difficile Candida, Aspergillus, Molds , T gondii Respiratory and enteric viruses

22. Asplenia In case of : - splenectomy - sickle cell anemia The main pathogens are: Polysaccharide encapsulated bacteria so annual vaccination is recommended

23. AIDS Acquired Immune Deficiency Syndrome - Caused by an infection by the HIV (Human immunodeficiency Virus), which attacks and destroys T-helper cells. - As the CD4 count declines (below 200 /dl, the immune function decreases and opportunistic infection will start.

24. EXAMPLES OF THE OPPORTUNISTIC INFECTIONS IN AIDS FUNGAL INFECTIONS Cryptococcosis Candidiasis Aspergillosis BACTERIAL INFECTIONS Tuberculosis Mycobacterium avium complex (MAC) infections Mycosis Legionnaire’s disease PARASITIC INFECTIONS Toxoplasmosis Cryptosporidiosis Strongyloides Stercolalis VIRAL INFECTIONS Herpes simplex virus infection (HSV) Cytomegalovirus virus CMV Varicella Zoster Virus Adenovirus

25. Oral candidiasis herpes simplex virus infection

26. Varicella zoster infection Mycosis : ulcers on leg

27. TOXOPLASMOSIS Toxoplasma gondii Transmission Ingestion of: Tissue cysts in raw or undercooked meat Oocyst in contaminated f ood or water Transplacental transmission from mother to fetus Blood transmission via: Organ transplantation from a seropositive donor C ontaminated blood transfusion N eedlestick injury

28. CLINICAL SYNDROMES Immuno-competent host Usually asymptomatic May be rash, fever, painless cervical lymphadenopathy, sweats Rarely: arthralgia, pericarditis Congenital toxoplasmosis Severe disease if acquired by mother early in pregnancy (~10% of infected foetuses): Spontaneous abortion/stillbirth Hydrocephalus Neurodevelopmental delay Choroidoretinitis (blindness)/micro-ophthalmia/cataract Rash/hepatitis/pneumonia/myocarditis

29. Ocular toxoplasmosis Periodic reactivation of infection established prenatally → disease in 2 nd to 3 rd decades → inflammatory episodes → necrotizing retinitis Toxoplasmosis in HIV Occurs when CD4 + T-cell count < 100/mm 3 Presentation: CNS: multiple ring-enhancing lesions Headache, fever ± Choroidoretinitis Cough, dyspnoea; may present like pneumocystis pneumonia (PCP) Dissemination: heart, liver, lungs Toxoplasmosis in transplant ( l ife-threatening complication )   1. Solid organ transplant (most commonly heart) Disease only if host has no prior exposure Donated organ must contain viable cysts Presentation: fever, confusion, respiratory failure Prophylaxis: co-trimoxazole for graft recipients 2. Bone marrow transplant due to reactivation of latent disease TOXOPLASMOSIS CLINICAL SYNDROMES continue

30. DIAGNOSIS of Toxoplasmosis Serology ( only reliable in immune-competent host) IgM May appear and decline more rapidly than IgG antibodies . limit ed use as sole marker of acute infection IgG Usually appear within 1 - 2 weeks, peak at 1-2 months, and persist for life. The most widely used tests are: ELISA, indirect fluorescent antibody (IFA) test Modified direct agglutination test (DAT) IgG avidity test Sabin-Feldman dye test (gold standard) IgA More sensitive than IgM in congenitally infected babies IgE Present for a shorter duration than IgM or IgA and may be useful for diagnosing recently acquired infection.

31. DIAGNOSIS of Toxoplasmosis in immunocompromised continue Only by Direct Isolation Isolation of T. gondii from blood, body fluids, placenta, or fetal tissues is diagnostic of acute and recent infection s . T issue culture (3-6 days) or mouse inoculation. PCR : D etection of T. gondii DNA in body fluids and tissues Sensitivity is 15-85% in blood and 11-77% in CSF

32. Immuno-competent adults Only in severe and persistent symptoms , visceral disease is overt , or infection is parenterally acquired. Immunodeficient patients Acute/primary therapy is recommended for 3-6 weeks with pyrimethamine /sulfadiazine , followed by lifelong maintenance therapy/secondary prophylaxis. Ocular toxoplasmosis Treatment is generally indicated for only lesions that threaten or cause visual loss. Toxoplasmosis in pregnancy Treatment with spiramycin reduces the risk of transmission to the fetus, but spiramycin does not cross the placenta. If fetal infection occurs, treatment should be changed to pyrimethamine (not in the first trimester) and sulfadiazine. Congenital toxoplasmosis Treatment is with pyrimethamine and sulfadiazine for up to 12 months. MANAGEMEN

33. Systemic Fungal Infections

34. C RYPTOCOCCOSIS ( Cryptococcus neoformans ) A potentially fatal  fungal infection   mainly affects the   lungs  ( pneumonia ), and  brain  ( meningitis ). It is caused by the  fungi   Cryptococcus neoformans .   It is acquired by inhalation the  spores  from the air. These fungi are found around the world in soil, decaying wood, pigeon droppings, and in the hollows of some species of trees. Typical host has defective T cell immunity like: AIDS Organ transplant Lymphoma High-dose steroids

35. CNS infection (meningitis, meningoencephalitis) Headache Memory loss Personality change Pulmonary infections ( pneumonia) Effusion Cavitation Infiltrates Mass lesions CIinical Presentations

36. TREATMENT of CNS Diseases Induction (2 weeks) Amphotericin + 5-fluorocytosine (5-FC) intravenously Daily lumbar puncture is safe Consolidation (6–10 wks ) Fluconazole 400 mg once daily Maintenance (minimum 12 months) Fluconazole 200 mg once daily Treatment in HIV-positive patients can be stopped when CD4 count >100, HIV RNA undetectable, and low Cr Ag titer

37. Pulmonary Diseases -Severe pneumonia / pneumonia with other disseminated disease : treat as for CNS disease Mension ? -Mild/moderate pulmonary disease: fluconazole (alone) for 6-12 months

38. M ore common in individuals with defect ive T-cell immunity, especially HIV   CLINICAL SYNDROMES Asymptomatic Majority of cases Acute self-limiting infection Flu-like illness ± pneumonia Possible skin involvement (erythema multiforme, erythema nodosum) Disseminated disease Widespread reticuloendothelial i nvolvement Mouth ulcers, skin nodules Renal, bone, CNS, liver lesions Adrenal involvement (hypoadrenalism) Uveitis, panophthalmitis HISTOPLASMOSIS Histoplasma capsulatum

39. DIAGNOSIS Histopathology Small oval yeast cells in macrophages/monocytes Culture Grows in 1–4 weeks Demonstrate dimorphism and characteristic macroconidia Antigen detection In serum/urine Antibodies False-negative: Immunocompromise PCR From culture/tissue specimens

40. High-dose amphotericin Itraconazole: - Prolonged course (4 months–2 years) and/or until immune reconstitution if immunocompromised -Long-term secondary prophylaxis with itraconazole if immunocompromised Surgery in case of erosion into high-risk structures TREATMENT

41.   Severe/disseminated fungal disease associated with immunocompromise person (organ transplant, diabetes, HIV) Coccidiomycosis

42. Acute or c hronic pneumonia Pulmonary nodules Thin-walled cavities ± Pulmonary fibrosis Disseminated disease Chronic skin disease Bone and joint involvement Meningeal disease ± hydrocephalus Other organ involvement: GI tract, GU tract, adrenals, thyroid, pericardium Clinical syndroms

43. DIAGNOSIS Same principles as for histoplasmosis Culture takes up to 4 weeks TREATMENT Amphotericin for severe disease (or high-dose fluconazole for meningitis) Prolonged itraconazole up to 1 year and/or until immune reconstitution if immunocompromised Long-term secondary prophylaxis with itraconazole if immunocompromised Surgery i n case of erosion into high-risk structures

44. INTESTINAL COCCIDIANS

45. Cryptosporidium parvum Cyclospora cayetanensis Cystoisospora belli diagnosis •Histopathological with special stain • PCR -Histopathological with special stain • PCR Histopathological with special stain • PCR Clinical syndromes 1.Childhood diarrhea 2.Travelers’ diarrhea 3.Diarrhea in immunocompromised (mostly HIV) 4. Outbreaks of diarrhea (food/waterborne) same same

46. INTESTINAL COCCIDIANS, continue Cryptosporidium parvum Cyclospora cayetanensis Cystoisospora belli Clinical presentation - Watery diarrhea, bloating, abdominal cramps, anorexia, weight loss, low-grade fever, malaise - Mostly self-limiting, but may be more severe and protracted in HIV same same Management Supportive management + nitazoxanide,or azithromycin Supportive management +co-trimoxazole) Supportive management + co-trimoxazole

47. Summary In immune deficiency diseases, most of patients died from infections rather than original disorder. Managing opportunistic infections is the MOST IMPORTANT part in the treatment of immuno-deficient patients. As a preventive measure, one must prevent these patients from getting exposed and getting the disease.

48. Discussion & Feedback Is there any point that was difficult to understand and would like to be further explained in the coming sessions?

49. Case Discussion & Management Back to our case Sara is advised to undergo chemotherapy and to take measures to prevent infection. Over the next few months, Sara undergoes several rounds of chemotherapy. She experiences some side effects, such as nausea, hair loss, and frequent episodes of fever but her blood cell counts begin to improve. She also receives supportive care, such as blood transfusions and antibiotics, to manage complications such as infection and anemia.

50. References & recommended readings Manson Tropical diseases . Edition 23 rd . Elsevier https://www.clinicalkey.com/student/institution-login