This document discusses infections in immunocompromised patients. It begins by describing the various microbes that can cause infection, including bacteria, parasites, fungi and viruses. It then discusses the different types of underlying immune defects that determine infection risk, such as humoral versus cell-mediated defects. The document outlines various factors that influence the risk of infection, including the level of immunosuppression, transplant organ, graft-versus-host disease, exposures, and immune-modulating medications. It presents several case examples of infections in immunocompromised patients.
Chronic Granulomatous Disease (CGD) is an inherited primary immunodeficiency disease (PIDD) which increases the body’s susceptibility to infections caused by certain bacteria and fungi.
Granulomas are masses of immune cells that form at sites of infection or inflammation. People with CGD are unable to fight off common germs and get very sick from infections that would be mild in healthy people.
This is because the presence of CGD makes it difficult for cells called neutrophils to produce hydrogen peroxide. The immune system requires hydrogen peroxide to fight specific kinds of bacteria and fungi.
These severe infections can include skin or bone infections and abscesses in internal organs (such as the lungs, liver or brain).
Aside from the defective neutrophil function in CGD, the rest of the immune system is normal. People with CGD can be generally healthy until they become infected with one of these germs. The severity of this infection can lead to prolonged hospitalizations for treatment.
Children with CGD are often healthy at birth, but develop severe infections in infancy or early childhood.
The most common form of CGD is genetically inherited in an X-linked manner, meaning it only affects boys. There are also autosomal recessive forms of CGD that affect both sexes.
Chronic Granulomatous Disease (CGD) is an inherited primary immunodeficiency disease (PIDD) which increases the body’s susceptibility to infections caused by certain bacteria and fungi.
Granulomas are masses of immune cells that form at sites of infection or inflammation. People with CGD are unable to fight off common germs and get very sick from infections that would be mild in healthy people.
This is because the presence of CGD makes it difficult for cells called neutrophils to produce hydrogen peroxide. The immune system requires hydrogen peroxide to fight specific kinds of bacteria and fungi.
These severe infections can include skin or bone infections and abscesses in internal organs (such as the lungs, liver or brain).
Aside from the defective neutrophil function in CGD, the rest of the immune system is normal. People with CGD can be generally healthy until they become infected with one of these germs. The severity of this infection can lead to prolonged hospitalizations for treatment.
Children with CGD are often healthy at birth, but develop severe infections in infancy or early childhood.
The most common form of CGD is genetically inherited in an X-linked manner, meaning it only affects boys. There are also autosomal recessive forms of CGD that affect both sexes.
HEALTH IS THE SINGLE MOST IMPORTANT ISSUE IN THE HUMAN RACE TODAY.TB IS A MAJOR PROBLEM FACING MANKIND AND SO THIS NEW W.H.O TEST IS A MAJOR BOOST TOWARDS THE FIGHT AGAINST TB
This presentation describes the key performance indicators to assess the quality of work in microbiology department. The KPIs in common use are mentioned and other indicators are summarized.
Diagnosis & Mangement of Community-Acquired Pneumonia, Hospital Acquired Pneu...Riaz Rahman
Clinical overview of Community Acquired Pneumonia, Hospital Acquired Pneumonia, Aspiration Pneumonia. Covers pathophysiology, clinical management, prevention, risk stratification (pneumonia severity index), prognostic factors, complications. Includes case studies, comprehension questions. Given at Jackson Park Medical Center on 12/1/2013. Includes references.
HEALTH IS THE SINGLE MOST IMPORTANT ISSUE IN THE HUMAN RACE TODAY.TB IS A MAJOR PROBLEM FACING MANKIND AND SO THIS NEW W.H.O TEST IS A MAJOR BOOST TOWARDS THE FIGHT AGAINST TB
This presentation describes the key performance indicators to assess the quality of work in microbiology department. The KPIs in common use are mentioned and other indicators are summarized.
Diagnosis & Mangement of Community-Acquired Pneumonia, Hospital Acquired Pneu...Riaz Rahman
Clinical overview of Community Acquired Pneumonia, Hospital Acquired Pneumonia, Aspiration Pneumonia. Covers pathophysiology, clinical management, prevention, risk stratification (pneumonia severity index), prognostic factors, complications. Includes case studies, comprehension questions. Given at Jackson Park Medical Center on 12/1/2013. Includes references.
Infections and salivary gland disease in pediatric age: how to manage - Slide...WAidid
The slideset by Professor Susanna Esposito aims at explaining how to manage the salivary gland infections in pediatric age, from pathogenesis, to transmission, treatments and vaccination coverage, that should be urgently increased in Italy as well as in EU Countries.
Intro to TB
epidemiology of TB
Structure of Mycobacterium TB
pathogenesis of TB
Immunosuppression by Mycobacterium TB
types of TB
Clinical manifestation
Diagnosis
Treatment
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Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
3. Infections in the
Immunocompromised
Immune Deficit?
Meds, GVHD, s/p splenectomy, s/p
transplant,
hypogammaglobulinemic, T cell
deficiencies?
Exposure
community vs. nosocomial
Prophylaxis: yes/no
5. Levels of Immunosuppression &
Risk of Infections
High level
• Primary combined
immunodeficiency
• Receiving cancer chemotherapy
• Within 2 months after solid
organ transplantation
• HIV with CD4 <200
• Daily corticosteroid therapy with
dose ≥20mg or prednisone or
equivalent for ≥ 14 days
• Receiving certain biologic
immune modulators- tumor
necrosis factor-alpha (TNF-α)
blocker or rituximab
Low level
• Asymptomatic HIV with CD4 ≥200
• Lower daily dose of systemic
corticosteroids
• Methotrexate ≤0.4mg/kg/week;
azathioprine ≤3mg/kg/day, or 6-
mercaptopurine ≤1.5mg/kg/day
Rubin et al, CID 2013: 1-57.
7. Risk of Infection According to
Biologic Agent
INCREASED RISK (meta-analysis, RCT)
Adalimumab, Infliximab, Certolizumab, Etanernept, Abatacept,
Anakinra, Rilonacept, Efalizumab, Alemtuzumab, Y-ibritumomab,
Rituximab, I-tositumomab, Gemtuzumab, Bevacizumab, Cetuximab,
Panitumumab, Trastuzumab, Natalizumab
PROBABLE RISK (post hoc phase III RCT)
Alefacept, Basiliximab, Daclizumab,
Muromonab
POSSIBLE RISK (case reports)
Abciximab
Omalizumab,
Palivizumab
Salvana. Clin Micro Rev. 2009,22(2):274
8. Risk of Infection and
Transplanted Organ
Bacteremias Deep fungal infections
Liver
Lung,
Heart-lung
Kidney
Lung, Heart-lung
Liver
Kidney
Mortality rate from
infections
Lung, Heart-lung
Liver
Kidney
9. Graft-versus host disease and
risk of infections
Mucositis
GVHD
Functional
hyposplenism
Prophylactic
immuno-suppressants
Treatment with
high-dose
steroids or
immuno-suppressants
Altered
humoral/cellular
immunity
GVHD is the most
important cause
of mortality after
HCT
17. Case #1: What is your
diagnosis?
• A) Pneumococcal meningitis
• B) TB meningitis
• C) Histoplasma meningoencephalitis
• D) Nocardia pulmonary disease with brain
abscess
18. Risk of TB Activation According to Level of
Immune Compromise
Risk of
activation
per year
Normal host 0.1%
Hemodialysis 1-2%
Solid organ
5-6%
transplant
HIV/AIDS 10%
Positive TST in HIV = > 5mm
19. TUBERCULIN SKIN TEST RESULTS
INTERPRETATION
≥ 5mm ≥ 10mm ≥ 15mm
HIV infection
Close contact
Abnormal CXR
Immunosuppressed:
TNF-alpha inhibitors,
chemotherapy,
organ transplant,
glucocorticoid
treatment
Risk factors for reactivation:
silicosis, HD, DM, malignancies
(leukemia, lymphoma,
head/neck/lung cancer),
underweight, jejunoileal bypass,
IVDA
Children < 4
Foreign born from high-risk
countries
Residents/employees in high-risk
settings: prisons, jails, healthcare
facilities, mycobacteriology labs,
homeless shelters
Healthy persons
with low likelihood
of true TB infection
22. Corticosteroids and TB
≥15mg prednisone ≥1 month are at increased risk
for TB reactivation (but exact risk unknown)
Am J Respir Crit Care Med. 2000;161(4 Pt 2):S221
• Arthritis Rheum. 2006;55(1):19
Arthritis Rheum. 2006;55(1):19
23. IFX or ADA Associated with Increased Risk of TB
compared to ETN
Study Country Results demonstrating risk of active TB
Brassard. CID. 2006 Canada ETN <<<< IFX (by 1.3x)
Gomez-Reino. Arthritis
Rheum. 2006
Spain No diff btw the 3 groups risk active TB, but
ETN <<<< IFX (by 2x)
Tubach. Arthritis Rheum.
2009
France ETN SIR 1.8<<<IFX SIR 18.6<<< ADA SIR 29.3
(SIR = standardized incidence ratio)
Fonseca. Acta Reumatol
Port. 2006
Portugal ETN <<<< IFN or ADA (3-4x)
Dixon. Ann Rheum Dis. 2010 UK ETN<<<<IFN or ADA (3-4x)
24. TB Risk Factors in Patients on TNF
Antagonists
Tubach et al. Arthritis & Rheum. 2009
25. TNF is Needed to Create
Granulomas
A)TNF from macrophage
co-stimulates T cells
B)TNF from T cells primes
macrophages for
mycobactericidal
activity
C)Macrophage and T cell
TNF recruit monocytes
and promote
granuloma formation
D)Anti-TNF results in
granuloma breakdown
an dissemination of TB
Solovic et al. Eur Resp J. 2010
26. When to Screen for TB?
• Prior to initiation of any immune suppressant:
• Steroids > 10mg po q day
• Methotrexate
• Cyclosporine
• Azathioprine
• Leflunomide
• Cyclophosphamide
• Plus prior to initiation of any TNF antagonist
• Yearly while on TNF antagonist in high TB endemic areas
• Every 3 months while on TNF antagonist therapy for those
who have completed treatment for TB (BTSSCC. Thorax. 2005)
Fonseca et al. Acta Reumatol Port. 2006
27. When Is It Safe to Resume
Biologics?
Guidelines Latent TB Active TB
France > 3 weeks of prophylaxis > 2 months after completion of TB treatment,
but recommend prophylaxis while on TNF
antagonists after completion of therapy
Germany >1-2 months of prophylaxis
Ireland As long as possible after starting
prophylaxis
On completion of TB treatment
Portugal >1 month of prophylaxis > 2 months on TB treatment
Spain 1 month, but may consider days after
starting prophy
Switzerland 1 month after completion of prophylaxis
UK Abnl CXR after completion of
prophylaxis
Nl CXR start concurrently
> 2 months on TB treatment
USA Preferably complete prophylaxis Preferably complete TB treatment
TBNET > 4 weeks after initiation of prophylaxis Preferably complete TB treatment
Solovic. Eur Resp J. 2010, Doherty. J Am Acad Derm. 2008,
29. Case #2:
• 56 yo WM Veterinarian with fevers to 102-105, nightsweats,
fatigue, 10lb weight loss x 2 months
• No other localizing symptoms
• Labs:
• 14.6
3.4>--------<69 (N 72%) ferritin 766
34. Case #2: What is your
diagnosis?
• A) Disseminated candidiasis
• B) Blastomycosis
• C) Mycobacterium avium intracellulare
• D) Disseminated Histoplasmosis
35. Histoplasmosis capsulatum var.
capsulatum
www.mycology.adelaide.edu.au
pathmicro.med.sc.edu/mycology
Courtesy Francesca Lee
36. Histoplasma and
Immunocompromised
• Histoplasma –
• Most commonly
reported- “classic
intracellular pathogen”-
contained primarily by
cell-mediated immunity
• No data re prophylaxis
or routine screening
• Avoid high risk
activities-construction,
spelunking
• Incidence of
histoplasmosis
• 18.78 per 100,000
persons for infliximab
• 2.65 per 100,000
persons for etanercept
Drugs 2009 Jul 30;69(11):1403-15.
37. Case #3
• 24 year old WM with B-ALL s/p FLAG-IDA with prolonged
neutropenia with neutropenic fevers and R sided pleuritic CP.
38. Case # 3: What is your
diagnosis?
• A) Nocardia
• B) Pulmonary aspergillosis
• C) Mycobacterium tuberculosis
• D) Legionella
41. Invasive Aspergillosis in AML
Patients
Prolonged neutropenia is
a risk factor for invasive
aspergillosis
No significant difference
amongst L-AmB, Caspo,
and Vori
Pagano. Haematologica. 2010
42. Improved Survival in Voriconazole-treated
Patients with Invasive Aspergillosis
Herbrecht et al. NEJM.2002
43. Case #4
• 45 year old HF with RA s/p MTX/Enbrel 2009, later diagnosed
with ALL s/p HyperCVA 1A-4B with relapse s/p re-induction
chemotherapy with prolonged neutropenia who has the
following physical exam:
Courtesy Miloni Shroff
45. Case # 4: What is your
diagnosis?
• Blood cultures + mold
• Skin biopsy + narrow-branching fungal elements within vessel
walls
• A) Aspergillus
• B) Mucormycosis
• C) Fusarium
• D) Nocardia
46. Case #4: Skin lesions during
treatment
Courtesy Miloni Shroff
47. Case #4: Skin lesions weeks
into treatment
Courtesy Miloni Shroff
48. Case #5
• 36 year old HM with ALL, s/p induction chemotherapy with
prolonged neutropenia (1 month) with L sided chest
pain/upper back pain. + weight loss, no fevers, no SOB.
Former construction worker in Florida (15-17 years prior to
diagnosis of ALL). Had been on prophylactic micafungin.
0.2>-----<11 ANC 100
20.1
50. Case #5: What is your
diagnosis?
• Endobronchial biopsy of lung nodule – “…numerous fungal
hyphae characterized by broad hyphal elements with thin
membranes, irregular branching, non-parallel walls…”, non-septated,
“…focal areas of vascular invasion
• What is your diagnosis?
• A) Aspergillus
• B) Cryptococcus
• C) Coccidioidomycosis
• D) Zygomycosis
51. Non-AspergillusMolds
• Zygomycetes (8%), Fusarium & Scedosporium (16%),
Acremonium, Paecilomyces
• Clinical:
• 6% survival with Fusarium, 28% with Mucormycosis
• Diagnosis: Fungal blood culture (Fusarium), tissue biopsy cultures
• RX:
• Aggressive surgical debridement
• Liposomal ambisome (5mg/kg/day 10mg/kg/day?)
• Combination with azole?
• Reduce immune suppression
• ? GCSF
• Control blood glucose Silveira. Med Mycol. 2007
Hosseini-Moghaddam. Sem Resp Crit Care Med. 2010
52. Breakthrough Zygomycetes on
Prophylactic Voriconazole in
HSCT
Trifilio. Bone Marrow Transplant. 2007
•71 allo HSCT
•Voriconazole 200mg po bid
•6 Candida, 4 Zygomyces (3 lung, 1 sinus)
54. Case #6
• 45 year old Vietnamese female with metastatic high grade
pontine glioma with metastasis to the spine with
leptomeningeal dissemination undergoing chemo/XRT, DM2,
on dexamethasone 4mg po tid since 1/2013 (now 11/2013)
admitted with acute hypoxemic respiratory failure.
• Exam: + moon facies, 85% O2 sat on RA, tachy 120s
• Lungs with coarse crackles B
• Labs:
12.2
1.4>---------<61 Fungitell > 500 LDH 579
57. Case # 6: What is your
diagnosis?
• A) Streptococcal pneumonia
• B) Legionella pneumonia
• C) Pneumocystis pneumonia
• D) Mycobacterium tuberculosis
59. Pneumocystis Diagnostic Tests
Indirect tests
• High A-a gradient
• Decreased DLCO (< 70%)
• Elevated LDH (90%)
• Elevated fungitell
(13)-β-D-glucan
• Sensitivity 90-100%
• Specificity 88-96%
Direct tests
Sens Spec
Bronch with
BAL
90-98%
Induced
sputum DFA
100% 55-92%
Endotracheal
aspirate
92%
PCR 81-100% 86-100%
Note: decreased sensitivity BAL
(62%) in patients s/p aerosolized
pentamidine
60. Beta-D-glucan and Diagnosis of
Pneumocystis
Sax. Clin Infect Dis. 2011
Positive: Candida, Aspergillus, Pneumocystis, NOT
Zygomycetes or Cryptococcus
False positive: augmentin, zosyn, S. pneumo,
Pseudomonas, IVIG, albumin, HD, mucositis
61. Prophylaxis for PJP in
immunocompromised patients
• Cochrane review 2007 of 11
RCTs evaluating prophylaxis
with TMP/SMX vs. placebo or
other antibiotics with no PCP
activity:
• Adults with acute leukemia or
solid organ transplant; children
with acute leukemia
• No increased rate of adverse
events
• Number needed to treat to
prevent one episode of PCP = 15
• ATS 2010 Fungal Infections
Guideline
• Prednisone dose ≥
20mg/day >1 month,
especially if patient has T
cell defects, or has other
cytotoxic drugs or TNF-a
inhibitors
Green. Cochrane Database Syst Rev. 2007 Jul 18;(3):CD005590
Am J Respir Crit Care Med Vol 183. pp 96–128, 2011
Rahier et al, Journal of Crohn's and Colitis (2009), p1-46
Courtesy Francesca Lee
63. TMP-SMX vs. Aerosolized
Pentamidine vs. Dapsone
TMP-SMX
Dapsone,
atovaquone
Aerosolized
pentamidine
> >
Best tolerated
No toxo coverage
Screen for tb
•Most effective
•Covers toxo, salmonella,
listeria, nocardia, strep,
staph
Less toxo coverage
Check G6PD
64. Aerosolized pentamidine
Upper lobe infiltrates 38%
pentamidine vs.. 7% no
pentamidine
Jules-Elysee. Ann Int Med. 1990
Levine et al. Am Rev Respir Dis. 1991
65. Case #7
• 60 year old HM with DM, s/p DDKT 2007, admitted with
abdominal pain, found to have skin nodules:
Courtesy Suresh Kachhdiya
67. Case #7
• Biopsy of skin nodule shows suppurative granulomatous
inflammation with yeast forms + by PAS/GMS stain, mostly
with narrow bases.
• Crypto Antigen 1:64 Creatinine 2.5
• What would you do next?
A) Start Ambisome + flucytosine
B) Start Fluconazole + flucytosine
C) Start Posaconazole
D) Start Itraconazole
68. • Risk factor: T cell defect (i.e. AIDS, SOT)
• Calcineurin inhibitors
• Alemtuzumab, antithymocyte
• Clinical: asymptomatic, acute
respiratory distress, pneumonia, 53-
72% with disseminated disease in SOT
• Radiography: nodules, lobar infiltrates,
pleural effusions,
• Diagnosis: culture, crypto antigen in
blood positive in 56-70%
• Treatment:
• Amphotericin and 5-FC for severe
cases
• Fluconazole for mild cases and for
long term maintenance
• Watch out for immune
reconstitution inflammatory
syndrome (5-11%)
• Mortality in SOT 14%
Singh. Am J Transplant. 2009
69. Case #7…but wait…
• He had abdominal pain and difficulty swallowing…
• s/p EGD esophagitis and gastric ulcer & duodenal stricture
• Path: + duodenitis with + H. pylori and cells with viral
inclusions CMV duodenitis (CMV PCR detectable only)
• Eventually also diagnosed with:
• Enterobacter bacteremia
• Candida glabrata endocarditis
• EBV + in CSF
70. Case #8
• 53 year old WF with ileocolonic Crohn’s disease s/p small
bowel resection on imuran x 10 years and prednisone 20mg
daily admitted with fevers, chills, and abdominal pain, bloody
diarrhea, shortness of breath.
• Exam: febrile to 101.7, tachycardic
• Abdomen tender in upper epigastric region, + bowel sounds, no
rebound
• Labs:
10
• 1.1>-------<182 (ANC 800) AST 98 ALT 43
73. Case # 8: What is your
diagnosis?
• A) Legionella Pneumonia
• B) Mycobacterium tuberculosis
• C) CMV colitis and pneumonitis
• D) Adenovirus pneumonia and enteritis
74. Case #8: Results
• CMV PCR 413,000
• CMV + BAL and + lung biopsy
• CMV + immunostain on flex sig
• Initiated on ganciclovir and cytopenias resolved
and abdominal pain/diarrhea/hypoxia resolved.
• Also + C difficile
75. Cytomegalovirus-
“Big Bad Wolf of SOT”
• Risk: GVHD, lymphopenia, D+/R-
• Immunomodulatory
• Superinfections: PJP, Aspergillus, GNR, Listeria,
Candida
• Clinical:
• pneumonitis
• enteritis
• bone marrow suppression
• retinitis (rare)
• Diagnosis: CMV PCR
• NOTE GI disease often occurs WITHOUT CMV
viremia
• Prevention: CMV-safe transfusions
• Treatment: ganciclovir, valganciclovir, CMV
immune globulin
77. CMV and Solid Organ Transplant:
Serostatus and Risk of Reactivation
Rubin RH. TID. 2001 Courtesy J. Gillman
78. Case #9
• 69 year old WM s/p R lung transplant 2/2013 presents 4
months later with respiratory distress and UGIB.
79. Case #9:What is your diagnosis
• s/p EGD with this
found on biopsy and
in the BAL fluid.
1) Ascaris
2) Strongyloides
3) Schistosomiasis
4) Toxoplasmosis
81. Screening for Strongyloides?
• “Experts estimate that there are between 3-100 million infected
persons worldwide”
• US- 0-6.1% of persons sampled
• Immigrants to US- 0-46.1% of persons sampled
• Risk factors: contact with soil
• Walking with bare feet
• Contact with human waste or sewage
• Occupations that increase contact with contaminated soil, such as
farming and coal mining
http://www.cdc.gov/parasites/strongyloides/epi.html
• Consider screening with serologic testing in “at risk” patients
• Immigrants from Central and South America
• If positive, treat with ivermectin prior to immunosuppression
Curr Opin Infect Dis 2012, 25:458–463
82. Case #10
• 58 year old WM with AML
s/p allo SCT c/b GVHD,
admitted with SOB with
pleuritic CP, L buttock mass
x 6 weeks after scraping his
bottom on a yucca plant,
and R axillary nodule
• Exam: Afebrile, 95% on RA
• L buttock wound s/p I&D
with minimal erythema
• R axillary mobile soft, NT,
subcutaneous nodule
• R thigh with soft
erythematous nontender
nodule
85. Case #10: What is your
diagnosis?
• Culture from I&D of buttock abscess, R thigh and R
axillary nodules + gram positive branching filamentous
rods.
• A) Mycobacterium abscessus
• B) Stenotrophomonas maltophilia
• C) Scedosporium
• D) Nocardia
86. Case #10: What should you do if you
diagnose a patient with pulmonary
nocardia?
• A) Start oral bactrim prophylaxis
• B) Get MRI brain
• C) Order nocardia serum PCR assay
• D) Place in airborne isolation
89. Case # 11
• 35 year old white female with relapsed Hodgkin’s lymphoma
s/p auto SCT 2012 c/b GVHD of gut, skin, and lungs and h/o
CMV colitis who was admitted with pleuritic R sided CP with
shortness of breath
• Exam: afebrile, O2 sat 88% on 2LPM O2, tachypneic,
tachycardic
• Moon facies, dyspneic, decreased BS R> L, stable GVHD skin rash
• Labs:
• 17.4>-------<133 LDH 286 fungitell 210
• 36.2
• Resp PCR panel + rhinovirus/enterovirus