Sickle Cell Disease and - PowerPoint Presentation

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Sickle Cell Disease and Infection

Sherrill Brown, M.D.

Assistant Clinical Professor

Division of Infectious Diseases

UC Davis Medical Center

9/8/18

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Disclosures

None

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Goals for Discussion

Discuss the mechanisms that make Sickle Cell patients more susceptible to infections.

Review Common Infectious Complications in Sickle Cell Anemia

Diagnostic and Management Guidance for these Infections

Discuss Preventative Strategies

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Infection is a major cause of morbidity and mortality for sickle cell patients. Worldwide, infections are the leading cause of death in sickle cell patients.

In developed nations, such as the US, measures to prevent and effectively treat sickle cell disease and infection have led to a longer and better quality of life for our patients.

Sickling of cells can be precipitated by many factors including dehydration, hypoxia, cold, dehydration as well as adhesion molecules and cytokines associated with infections.

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Why are sickle cell patients more susceptible to infection?

Sickle Gene

causing abnormal red blood cells causes

an increased susceptibility to infection

Splenic Dysfunction

Acute and Chronic Inflammation and Ischemia Causing Organ Damage

Higher Risk for Healthcare

R

elated Infections

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Normal Splenic Function

Functions as a filter for damaged cells and micro-organisms in the blood.

Produces antibodies to fight infection.

Participates

in complement activation.

Encapsulated bacteria are poorly opsonized by complement proteins and can only be effectively cleared by the spleen.

Streptococcus pneumoniae,

Haemophilus

influenzae, Neisseria meningitidis and Salmonella species

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Splenic Dysfunction- 6mo to 3 yrs of age

The sluggish circulation through the spleen, high rates of O2 extraction and local acidosis promotes sickling which leads to blockage and diversion of blood through shunts.

Bypassing the normal filtering mechanisms.

Macrophages responsible for engulfing abnormal cells and microorganisms get blocked with sickled cells and cannot function properly.

Repeated episodes of this over time, leads to infarcts/death of spleen tissue.

 Auto-splenectomy

Lack of IgM memory B cells

Cannot mount a rapid response to encapsulated organisms.

Overwhelming sepsis can develop quickly, especially in younger individuals.

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Chronic end organ damage.Bone marrow is expanded to create more RBCs, high O2 demand and blood flow is sluggish.

Sickling

Vaso-occlusion

and Infarction of

BoneDamaged

bone at high risk of

infectionOsteomyelitis

Patchy ischemia and infarction in bowel can lead to chronic intermittent translocation of gut bacteria.

Chronic microvascular disease is associated with increased risk for severe respiratory infection>Acute Chest Syndrome

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Healthcare Associated Infections

Frequent transfusions with unsafe blood products in less regulated countries leads to increased risk of blood borne infection.

HIV,

Hep

B,

Hep

C, CMV, Parvovirus B19

Frequent use of prolonged central catheters leads to increased risk of Central Line Associated Bloodstream Infection

Increased pain medication requirements

respiratory depression and inactivitypneumonia, bed sores and ulcers, decreased cardiac stamina

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Infections may also precipitate Vaso-occlusion.

Increased neutrophil counts correlate with the severity of SCD.

Patients with severe SCD have increased expression of leukocyte adhesion molecules suggesting a role for leukocytes in the

vaso

-occlusive process.

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Encapsulated BacteriaStreptococcus pneumoniae

Haemophilus

influenzae

Neisseria

meningitidis

Salmonella species

Dysfunctions in splenic sequestration of these bacteria lead to severe infections

Meningitis, Bacteremia, Pneumonia, Osteomyelitis

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OsteomyelitisNecrotic and damaged bone is at risk of infection especially from Salmonella species.

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Encapsulated Bacteria Diagnosis/TreatmentDiagnosis

Blood culture prior to antimicrobials

CSF studies and culture if suspicious for meningitis

Strep pneumoniae urine antigen

MRI and Bone biopsy with path and culture if evidence of osteomyelitis

Prompt Anti-

bacterials

directed at common pathogens

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Encapsulated Bacteria Prevention

Routine childhood immunizations including additional scheduled Streptococcus pneumoniae, Neisseria

meningitidis

vaccines

Annual Flu shot

Oral Penicillin prophylaxis twice daily for children 3months-5yrs

Frequent handwashing

Washing fruits/vegetables including lettuce thoroughly, avoid cross contamination of meats with food especially chicken and eggs.

Cook meats thoroughly.

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https://www.cdc.gov/vaccines/schedules

/

Haemophilus

influenzae

Pneumococcal conjugate and polysaccharide

Meningococcal ACWY, B Vaccine

Important to protect from encapsulated bacteria.

Additional vaccine doses recommended for Pneumococcal and Meningococcal vaccines.

Vaccines

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PROPS Trial 1986

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Parvovirus B19Infectious Prior to Rash and usually transmitted through Respiratory Droplet route.

Usually mild and self-limiting infection.

Erythema

infectiosum

“Fifth disease”, “slapped cheeks”

Non-specific viral illness

Post infectious

arthropathy

More severe infections.

Infects erythroid progenitor cells->temporary cessation of erythropoiesis->Pure red cell aplasiaIn pregnancy, novel infection hydrops

fetalis

, stillbirth, and spontaneous abortion.

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Parvovirus B19 and Sickle CellSickle patients with chronic anemia due to decreased RBC lifespan depending on increased erythropoiesis to maintain baseline Hemoglobin.

Infection leads to cessation of erythropoiesis for 7-10 days

Leads to aplastic crisis, severe anemia and vascular collapse in severe infection

.

Requires prompt identification, droplet isolation, blood transfusion until erythropoiesis can resume again.

Transient aplastic crisis in 65-80% of infections in Sickle cell disease.

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Parvovirus Diagnosis/TreatmentDiagnosis: Parvovirus B19 IgM or Parvovirus PCR with clinical correlation

Treatment: supportive care, blood transfusions in Aplastic crisis

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Parvovirus PreventionNo vaccine at this time.

Infection leads to lifelong protection, and infection uncommon after age 15.

Isolate infected or exposed individuals from other at risk populations (immune compromised, sickle cell patients) DROPLET precautions

Wash hands frequently and avoid people with respiratory illnesses or rash

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Acute Chest Syndrome (ACS)Chest pain, SOB, fever, pulmonary infiltrates on CXR

Looks like a pneumonia

Precipitants include: pulmonary infection, fat embolism from bone infarcts, decreased respiration.

Sickling and

vaso

-occlusion in the lung lead to local ischemia and infarction.

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ACS Diagnosis/TreatmentAttempt to identify underlying cause

Chest CT with contrast to

eval

for fat embolism

Respiratory viral panel, Flu testing, Streptococcus pneumoniae antigen, sputum culture if productive cough, MRSA nares screening

Supportive care and antimicrobials directed at possible infectious etiology

De-escalate antimicrobial therapy if alternative cause is identified.

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ACS PreventionOptimize sickle cell treatment to avoid sickling episodes and end organ damage.

Decrease respiratory depressant medications and encourage deep breathing with incentive spirometry.

Get good ventilation and avoid sick contacts.

Wash hands frequently.

Get all routine vaccinations including annual flu shot, Strep pneumonia vaccines,

Hemophilus

influenzae

vaccine.

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Yersinia enterocolitica

Gram negative coccobacilli

Transmitted by Fecal Oral route through contaminated hands, food, water

Causes diarrhea and can cause abdominal lymph node swelling and blood stream infection.

“pseudo-appendicitis”, RLQ abdominal pain, rectal bleeding,

ileal

perforation.

Can also cause pharyngitis and erythema

nodosum

. Disease more common in iron overload syndromes such as in Sickle Cell Disease. HLA-B27 a risk factor for reactive arthritis

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Y. enterocolitica Diagnosis/Treatment

Blood Culture

Stool Culture

Pharyngeal Culture

Lymph node biopsy

Treatment indicated in those that are severely ill.

Ciprofloxacin, TMP/SMX, or Doxycycline for about 5 days

Ceftriaxone +

Genamicin

in severe sepsis

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Y. enterocolitica Prevention

Eat food that has been prepared using hygienic precautions.

Avoid raw or undercooked meat and seafood (tripe, chitterlings)

Wash fruits and vegetables carefully.

Drink purified water.

Wash hands with soap and water.

Screen blood bank donors for acute symptoms of infection.

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Healthcare Associated Infections (HAIs)Hospital Acquired Pneumonia

Central Line Associated Blood Stream Infections

Catheter Associated Urinary Tract Infections

Clostridium difficile Colitis

Antibiotic Resistant Bacterial Infections

Spread of Infections from Healthcare Workers or Patients to other Patients.

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Hospital Acquired PneumoniaPneumonia acquired and diagnosed 2 or more days after admission to a hospital.

Higher risk of antibiotic resistant organisms as cause including MRSA or Pseudomonas.

Necessitates broader spectrum

antibiotics to start.

Prolongs hospitalizations and increases risk of needing additional procedures.

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Central Line Associated Bloodstream Infections

Central lines often needed due to poor venous access, exchange transfusions,

and long

term IV therapy in sickle cell patients.

Central lines include: ports, tunneled catheters, dialysis catheters and PICC lines

The longer a central line is in

place, the higher

the

risk

of bloodstream infection developing.Can lead to repeat line procedures, endocarditis and seeding infection to additional organs in the body (brain, lungs, kidneys, bones)

Requires initiation of broad spectrum antibiotics to treat.

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Catheter Associated Urinary Tract InfectionUrinary Tract Infection in the setting of Indwelling

Urinary catheter

The longer

the catheter

is used, the higher the risk of developing infection.

May be caused by drug resistant bacteria.

Can lead to pyelonephritis, blood stream

infections

and more severe illness.

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Clostridium difficile ColitisInfectious Diarrhea infecting the colon caused by Clostridium difficile

Usually acquired after antibiotics use and spread from person to person on hands and surfaces.

Sickle cell patients at higher risk given increased risk for admission and antibiotics use.

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Prevention of Infection at Home

Avoid

sick

contacts

.

Clean and prepare food carefully to avoid contamination.

Cook meats fully.

Stay hydrated with water and low sugar low caffeine beverages.

Get plenty of rest, avoid stress and eat healthy nutritious meals.

Caretakers, families and patients must wash their hands frequently with soap and water.Take all prescribed medications regularly. Seek care quickly if patients develop fever >38.5 or respiratory symptoms.

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Prevention of Infection in the Clinic

Optimize Sickle Cell therapy to avoid pain crisis requiring

hospitalization.

Get recommended vaccines to avoid infection leading to hospitalization

.

Annual flu shot

Prescribe and take Penicillin

prophylaxis to avoid Invasive Pneumococcal Disease

.

Consider vitamin including Zinc supplementation. Counsel patients on compliance with prevention strategies.Healthcare workers wash hands

frequently

with soap and water or alcohol solution.

Patients and families wash hands frequently while at clinic.

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Prevention of Infection at the Hospital

Avoid

the use of central lines and indwelling Foley catheters to avoid infection.

Minimize broad spectrum antibiotics use to avoid development of resistance.

Healthcare

workers, caretakers

and patients wash hands frequently.

Frequently utilize incentive spirometry to expand lungs and limit hypoventilation.

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Barriers to Prevention of Infection

Decreased understanding from families, caretakers, patients and healthcare providers about the importance of prevention including:

Hand hygiene

Meticulous preparation of foods

Avoiding sick contacts

Compliance with taking prescribed medications and vaccinations.

Many families with sickle cell disease are from socioeconomic groups with decreased access to resources such as stable housing, nutritious food, and appropriate medical care including prescriptions.

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Future directions in infection prevention, diagnosis and treatment.

Further research for prevention strategies in developing countries that are cost effective and directed at endemic pathogens. (ex. malaria, parasitic infections)

Validate biomarkers that can help determine if a bacterial infection is complicating an ACS picture or febrile syndrome. (ex.

Procalcitonin

)

Curative treatments that eliminate the damage from sickle cell in the beginning.

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References

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A, Sabharwal V,

Fonebi

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Haematol

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: 10.1111/bjh.13526.

Epub 2015 May 27. Review. PubMed PMID: 26018640.Milunsky A. Sickle Cell Disease. N

Engl

J Med. 2017 Jul 20;377(3):304-5.

doi

: 10.1056/NEJMc1706325. PubMed PMID: 28727408.

Servey

JT,

Reamy

BV, Hodge J. Clinical presentations of parvovirus B19 infection. Am Fam Physician. 2007 Feb 1;75(3):373-6. Review. PubMed PMID: 17304869.

Booth C,

Inusa

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Obaro

SK. Infection in sickle cell disease: a review.

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doi

: 10.1016/j.ijid.2009.03.010.

Epub

2009 Jun 3. Review. PubMed PMID: 19497774.

Gaston MH,

Verter

JI, Woods G,

Pegelow

C, Kelleher J,

Presbury

G,

Zarkowsky

H,

Vichinsky

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Iyer

R,

Lobel

JS, et al. Prophylaxis with oral penicillin in children with sickle cell anemia. A randomized trial. N

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J Med. 1986 Jun 19;314(25):1593-9. PubMed PMID:

3086721

https://

ghr.nlm.nih.gov/condition/sickle-cell-disease

https://www.cdc.gov/vaccines/schedules/