Pediatric Case Management
By
Dr. Rachel Gast MD
&
Dr. Apryle Funderburk MD
March 2nd 2010
January Cases

BR

TD

KT
3 mo FT baby found face down, not
breathing in crib, after 1.5 weeks of nasal
congestion, presented to ER, RSV +,CXR
wnl
died
Teenager with Wrist laceration, tendon
exposure-transferred to Union Memorial
for Hand surgery
4yo presented to ER with facial, LE
swelling & abd distension x 1 week, Hpt,
Blood and pr in urine –transferred to JHU
for acute Hpt in face of AGN.
HPI
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15 year old male
Headache x 2 days
Pain in middle of back on morning of
admission radiating to chest
Progressive weakness in L.E. bilaterally
Patient First → St. Joseph’s E.D.
Past History
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PMH
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Meds
Allergy
Vacc
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Fam Hx
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Social:
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ADHD, exercised-induced asthma,
depression, migraines
Atomoxetine, Trazadone
Shellfish, wheat, soybeans, peanuts
UTD, received H1N1 (I.M.) one
month prior
Mother-COPD, arthritis, Father Hepatitis B & cysts in brain,
“misalignment” in spine, healthy
siblings
Attends 10th grade, lives with mom &
step-dad and cats, mom smokes
Physical Exam – St. Joseph
E.D.
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Pulse = 58, B.P. = 160/100
General: unable to walk, nausea with emesis x 1
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Moving legs per ED physician; absent reflex in right LE
and diminished in RE
Weak grasp
↑ tone in upper extremities with intact reflexes
WBC = 8.6
Hgb = 14.8/Hematocrit = 43.8
Platelets = 275
Electrolytes and coags normal
Toxicology screen = normal
CXR/Head CT/ECG = normal
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Solu-medrol 125 mg, IV
Labetolol
Zofran
Transferred to Sinai PICU
Case #2
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7 yr. old male with juvenile-onset D.M. type 2, in usual
state of health
Flu-like symptoms week prior to presentation
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Day prior to presentation – at school – left leg
weakness, limping, gradual loss of motor function
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“Bronchitis” – prednisone, clarithromycin, albuterol
No tingling, numbness nor loss of sensation
No incontinence
ED – progression of weakness, loss of function,
areflexia; symptoms starting in opposite leg
Admitted to PICU for further work-up
P.E./Labs
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P.E. – Flaccid left LE, strength 0/5, intact sensation and
vibratory sense, ↓ tone in right LE, motor 0-1/5,
able to dorsi-/plantar flex right foot, absent DTRs,
negative Babinski
Labs –
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CBC WBC 13.7 ( N 51 L 36, M 9.2, E 2.2, B 0.2)
CSF WBC 168 (N 38, L50,M12 RBC = 59, Glu 95, Pr59
CSF (-)GS/Cx
Stool Cx (+) for heavy Candida albicans
EBV IgM 2.3 , VCA Ab IgG positive, EBNA Ab IgG positive
Anticardiolipin Ab IgM positive
Objectives
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To discuss updates on current influenza
activity
To discuss neuronal injury from
influenza / influenza vaccine
To discuss adverse events from H1N1
2009 influenza strain vs. those from
H1N1 vaccine
To discuss current CDC statement
concerning H1N1 vaccine
www.cdc.gov
Pediatric Deaths from Influenza
2009-10
www.cdc.gov
Influenza Vaccine

Seasonal Flu – trivalent inactivated, live
attenuated – 3 virus strains

A
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B
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H1N1
H3N2
For the 2009--10 influenza season, the influenza B vaccine
virus strain was changed to B/Brisbane/60/2008, a
representative of the B/Victoria lineage, compared with the
2008--09 season. The influenza A, H1N1 and H3N2 vaccine
virus strains were not changed
“Swine” Flu –

A/California/07/2009
Mechanism of neuronal Injury
•
•
Vaccinations may induce autoimmune process
 Influenza vaccines made in chicken eggs which are
endemically infected with Campylobactor
 Antibodies cross-react against peripheral-nerve
antigen
However, the immunologic process that leads to GBS
or other neuronal injury is largely unknown
Vaccine Adverse Event
Reporting System
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National reporting system jointly administered by CDC
Immunization Safety Office and FDA
 reports submitted voluntarily by people who believe
an adverse event occurred after vaccination
May be submitted healthcare providers, patients, or
family members
VAERS staff follow-up on all serious and other selected
adverse event reports
Data does not infer causality
Addressing parents’ concerns: do vaccines
contain harmful preservatives, adjuvants,
additives or residuals?
Offit, Paul A., Jew, Rita K. Pediatrics, 2003
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Preservatives
Adjuvants
Additives
Residuals
Antibiotics
Cellular residuals
www.cdc.gov
Pediatric hospitalizations associated with 2009 pandemic influenza a
(H1N1) in Argentina.
Libster, R., et al. N. Engl J Med 2010
Vaccine 27 (2009) 2114-2120
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1990-2005
Adults > 18 years of age
747.1 million doses of TIV
Event reporting rate to VAERS of 24.4
per million TIV
18,245 (14%) were classified as serious
events
VAERS
Vellozzi, C., et al. Safety of trivalent inactivated influenza vaccines in adults:
Vaccine 27 (2009) 2114-2120
Lancet 2010; 375: 49-55
• Pandemic vaccine – Fluval P – monovalent vaccine with 6 υg
haemagglutinin per 0.5 ml content and aluminum phosphate gel
adjuvent (n = 178)
•Seasonal vaccine – Fluval AB - trivalent inactivated whole-virion
(n = 177)
Vajo, Z., et al. Safety and immunogenicity of a 2009 pandemic influenza A,
H1N1 vaccine , Lancet 2010; 375: 49-55
VAERS
GBS and H1N1 vaccination
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
October 1997 – the Advisory Committee on
Immunization Practices of the U.S. Public Health Service
recommendations noted:
“ Among persons who received the swine influenza
vaccine in 1976, the rate of Gullain-Barre syndrome that
exceeded the background rate was slightly less than 10
cases per million vaccinated. Even if Guillain-Barre
syndrome were a true side effect in subsequent years,
the estimated risk for Guillain-Barre syndrome of 1-2
cases per million persons vaccinated is substantially less
than that for severe influenza…”
CDC Statement
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
As of November 24, VAERS had received 10
reports of Guillain-Barré syndrome, and two
additional reports of possible Guillain-Barré
syndrome were identified by medical officers
reviewing other reports to VAERS describing
neurologic events
After chart review, four of these 12 reports
met Brighton Collaboration criteria for
Guillain-Barré syndrome, four did not meet
the criteria, and four are under review
References
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Libster, R., et al. Pediatric hospitalizations associated with 2009 pandemic
influenza a (h1n1) in argentina. N Engl J Med 2010; 362: 45-55
Vellozzi, C., et al. Safety of trivalent inactivated influenza vaccines in adults:
background for pandemic influenza vaccine safety monitoring. Vaccine 27
(2009) 2114-2120
Kerr, Douglas A., Ayetey, Harold. Immunopathogenesis of acute transverse
myelitis. Current Opinion in Neurology 2002, 15: 330-347
Mossad, Sherif B. The resurgence of swine-origin influenza a (h1n1).
Cleveland Clinic Journal of Medicine Volume 76 Number 6 June 2009
Haber, P., et al. Guillain-barre syndrome following influenza vaccination.
JAMA, November 24, 2004—Vol 292, No. 20
Scheibner, Viera. Adverse effects of adjuvents in vaccines. Nexus Dec 2000
(Vol 8, No1) & Feb 2001 (Vol 8, Number 2)
Vajo, Z., et al. Safety and immunogenicity of a 2009 pandemic influenza a
h1n1 vaccine when administered alone or simultaneously with the seasonal
influenza vaccine for the 2009-10 influenza season: a multicentre,
randomised controlled trial. Lancet 2010; 375: 49-55.
MMWR. “Update on Influenza A (H1N1) 2009 Monovalent Vaccines.”
October 9th, 2009.
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5839a3.htm
HPI
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C.A
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Day 1
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Day 2 -Taken to PMD
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Severe HA, b/L hip pain, low grade fever,
generalized malaise/ mylagias, H/o visit to Nigeria 3
weeks prior.
Congestion /T-103 with HA dx as acute sinusitis
Sent home on Bactrim
Day 3 - Taken to first OHS
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Symptoms worsen with persistent fevers
Chest-xray –negative/Rapid strep positive
Sent home with Pen VK (no h/o sore throat)
HPI
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Day 3
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Symptoms persisted plus onset of
abdominal pain/vomiting
Taken to 2nd OHS ER
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CT-negative for acute abdominal
process/patchy infiltrate of LLL- on chest x-ray
Thrombocytopenia/elevated
LFT’s/hyponatremia/ febrile
Patient admitted for w/u of poor clinical status
and abnormal labs
HPI
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Day 4-5
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HD 2-3
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Worsening thrombocytopenia, onset of anemia and
hyponatremia with elevated creatinine
Persistent fevers
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CMV neg, EBV positive, Hepatitis panel neg, Mono spot
neg, Urine cx / Blood cx neg
HD 2-Malaria Smear obtained
HD 3- Worsening labs/ Smear positive for
P.falciparum
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Obtained first dose of atovaquine-proguanil
Hypotensive to 80/50’s with heart rate 100’s/dizzy/
decreased UOP transferred to Sinai PICU
Physical Examination, Day 5
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Day 5, Transfer to Sinai PICU
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VS:
Wt-74.6kg, B.P-100/50, H.R-90’s,R.R-18 100% on 1LNC
General: Tired appearing but interactive
Skin:
No lesion or rashes
HEENT: No oropharyngeal erythema, PERRL, anicteric, no
nystagmus
Neck:
Normal ROM with some tenderness
CV:
RRR,S1S2 normal. No murmurs, rubs, gallops.
cap refill < 2sec
Lungs:
Occasional course BS with adequate/equal air entry
Abdomen: Tender diffusely, RUQ most tender, No guarding or
rebound, No HSM with normal BS
Neuro:
CN II-XII intact with motor/sensation intact throughout.
Alert/oriented X3
MS:
Pain on passive extension/flexion of hip. Negative hip
roll. No effusions or tenderness of joints. 3/5 strength of
b/l lower extremities ,5/5 strength of upper extremities
Labs
Remarkable for
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Creatinine of 1.13
T/D.bilirubin of 7.4/5.8, AST of 164, ALT of
140 and CBC with Hgb / Hct of 9.8/29.6 and
Platelets of 28
Slightly abnormal coagulapathy with INR of
1.2, D-dimer of 35.2, PT of 12.3,PTT of 38.7
Low haptoglobulin
Negative urine dip and normal VBG
Normal: Hgb electrophoresis, G-6PD study
PICU Course
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Day 5-8
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Continue on atovaquine-proguanil with improvement in fever
curve after 24 hours
Anemia persisted but all other labs improved
Blood smears collected every 12 hours,parasite density fell
from 13% to 4% in 24 hours and less than 1% prior to floor
transfer
Day 8-12
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On the floor improving symptoms except on Day of illness 11
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Double vision and headache reoccurred with dizziness
CT of head negative
Transfused with PRBCS for Hgb of 5.8 with resolution of
symptoms
D/C home after 3 negative smears, Course of 3 days of oral
anti-malarial and improved fever
Labs
Remarkable for
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Creatinine of 1.13
T/D.bilirubin of 7.4/5.8, AST of 164, ALT of
140 and CBC with Hgb / Hct of 9.8/29.6 and
Platelets of 28
Slightly abnormal coagulapathy with INR of
1.2, D-dimer of 35.2, PT of 12.3,PTT of 38.7
Low haptoglobulin
Negative urine dip and normal VBG
Normal: Hgb electrophoresis, G-6PD study
Blood Smear : Pre-treatment
Pre-treatment
Pre-treatment
Post treatment
Post Treatment
Objectives
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Discuss Malaria and its Presentation
Review Differential Diagnosis of Febrile
Traveler
Study CDC Guidelines for
chemoprophylaxis of malaria
Present CDC Treatment Guidelines
Investigate recent studies on Treatment
of Severe Anemia caused by malaria
Definition
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Parasitic infection with Plasmodium
protozoa
Transmitted by vector female Anopheles
mosquito
4 species to cause infection in humans
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P. falciparum
P.vivax
P.ovale
P.malariae
Plasmodium knowlesis recently identified
to cause human infection
Epidemiology
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350-500 million cases worldwide
Predominates in tropical areas
Over 1 million people die
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Most young children in Sub-Saharan Africa
Account 20% of childhood deaths in Africa
Every 30 seconds a child dies from malaria
1200 malaria cases reported annually
Epidemiology
Sources of Infection in U.S
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Imported
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Airport Malaria
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Mosquitoes fly from endemic to non-endemic area
and infect local residents
Locally transmitted
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Majority of cases
h/o of outbreaks in Southeast
Congenital
Blood Transfusions
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One case every 2 years
1 case per 4 million units of blood
Sources of Infection in U.S
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1997 to 2006-10, 745 cases of malaria reported in
the U.S
 59.3% -sub-Saharan Africa
 13.9% -Asia
 13.3%-Caribbean and Central/South America
 0.03% -Oceania
 54 fatal cases reported in the U.S
 85.2% caused by P.falciparum
 71.1% from sub-Saharan Africa
Life Cycle
Clinical Presentation
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Symptoms present as early as 7-14 days or as late
as several months or longer after exposure
Uncomplicated
 Fever, Anemia, influenza-like symptoms, jaundice,
transient HA, myalgias
Severe
 >5% parasite load
 Mental confusion, seizures, kidney failure, acute
respiratory distress syndrome, coma, death
Differential To Consider
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Typhoid Fever
Dengue
Filarians
Leishmanians
Onchoncerciasis
African trypanosomiasis
Diagnosis
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Smear Microscopy gold standard
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Rapid Diagnostic Test (RDT)
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Thick: Identify presence of parasite
Thin: Determine speciation/Parasite level
FDA approved for hospital use
Results in 2-15 minutes
PCR
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Not FDA approved
More sensitive than microscopy/delay in
results
Confirm species of parasite
CDC Chemoprophylaxis
Guidelines
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Areas with Limited Malaria Transmission
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Mosquito avoidance/dusk to dawn
DEET repellant
Insecticide covered Bed Tents
Areas with Mainly P.vivax Malaria
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Primaquine
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Areas with Chloroquine-Sensitive Malaria
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If Pts not G-6PD-deficient
Chloroquine
Areas with Chloroquine-Resistant Malaria
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Atovaquone/proguanil
Doxycycline
Mefloquine
CDC Chemoprophylaxis
Guidelines
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Areas with Mefloquine-Resistant Malaria
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Atovaquone/proguanil
Doxycyline
Infants, Children and Adolescents
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Chloroquine/mefloquine
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Doxycycline
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All weights/all ages
8 years or older
Atovaquone/proguanil
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Not in infants less than 5kg
Off-label less than 11kg
CDC Chemoprophylaxis
Guidelines

Pregnancy and Breastfeeding

Chloroquine/Hydroxychloroquine
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Mefloquine
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Limited data in 1st trimester/safe in 2nd and 3rd
Chloroquine resistent areas
Atovaquone/proguanil
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Not been shown to have harmful effects
Insufficient data
Primaquine
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Never use in pregnancy
CDC Chemoprophylaxis
Guidelines
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Atovaquone/Proguanil
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Chloroquine and Hydroxychloroquine
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1-2 days PTT, Same time daily in area, 4wks daily post
Mefloquine
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“Aralen”/“Plaquenil”
1-2 wks PTT, Same day weekly, 4wks post
Doxycycline
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“Malarone”
1-2 days PTT, Same day daily in area, 7 days post
1-2 wks PTT, Same day weekly, 4wks post
Primaquine
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Primary: 1-2 days PTT, Same time daily in area, 7 days post
Anti-relapse : 14 days post
Tips for Primary Doctor
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Don’t hesitate to refer patient to local travel clinics prior
to travel
Preventative Measures depend on variety of factors

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Destination of country, Season of year, age of
patient/underlying health conditions, itinerary of traveler
Travel to malaria-endemic areas should be a part of
patients chart
Highest risk of infection are 1st/2nd generation of nonendemic visiting friends/family in endemic country
Highest risk of severe infection are non-exposed
individuals, infants/children, pregnant women
CDC Treatment Guidelines
Clinical Diagnosis
Region of
Infection
Adult drug
Pediatric Drug
Uncomplicated
P.falciparum
Chloroquineresistant or
unknown
resistance
Atovaquoneproguanil
Atovaquoneproguanil
Artemetherlumefantrine
Artemetherlumefantrine
Quinine sulfate+
Clindamycine,
Doxycycline or
Tetracylcine
Quinine sulfate
+Clindamycin,
Doxycycline or
Tetracycline
Mefloquine
Mefloquine
CDC Treatment Guidelines
Clinical Diagnosis
Region of Infection
Adult Drug
Pediatric Drug
P.Falciparum or
unidentified
Chloroquine-sensitive
Choloroquine or
Hydroxychloroquine
Choloroquine or
Hydroxychloroquine
P.Malariae or
P.knowlesi
All regions
Choloroquine or
Hydroxychloroquine
Choloroquine or
Hydroxychloroquine
P.Vivax or P.ovale
All regions
Choloroquine or
Hydroxychloroquine
+ Primaquine
Uncomlicated
malariae for
pregnant women
Chloroquine-sensitve
Chloroquine or
Hydroxychloroquine
N/A
Chloroquine –
resistant Falciprum
Quinine
sulfate+Clindamycin
N/A
Chloroquine-resistant
P. Vivax
Quinine sulfate
primaquine s/p birth
N/A
CDC Treatment Guidelines
Clinical
Diagnosis
Region of
Infection
Adult drug
Pediatric Drug
P.vivax
Chloroquineresistant
Quinine+Doxyclin
e or Tetracycline
+Primaquine
Quinine+Doxyclin
e or Tetracycline
+Primaquine
Atovaquineproguanil
+Primaquine
Atovaquineproguanil
+Primaquine
Mefloquine+
Primaquine
Mefloquine+
Primaquine
Severe Malaria Treatment
Quinine/Quinidine
Artesunate/Artemisinins
EBM

Artesunate versus quinine for treating
severe malaria


Cochrane Database Syst Rev. 2007
Six trials enrolling 1938 participants

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1664 adults and 274 children
Compared IV artesnuate vs. IV quinine for
treatment of severe malaria
Treatment with artesunate significantly
reduced risk of death, reduced parasite
clearance and incidence of hypoglycemia
References
•
•
•
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•
www.cdc.gov/malaria/about/biology/index.html
http://wwwnc.cdc.gov/travel/yellowbook/2010/chapter2/malaria.aspx
Rosenthal P.J. Artesunate for the Treatment of Severe
Falciprum Malaria. NEJM 2008:358:1829-36.
Clinical Review:Evidence behind the WHO Guidelines:
Hospital Care for Children:Efficacy and Safety of
Artemisinin Derivatives in Children with Malaria. Journal of
Tropical Pediatrics 2006.52:1-2.
Malaria. The Red Book 2009. 1:438.
Griffith et al. Treatment of Malaria in the United States: A
systematic Review. JAMA 2007.297:20.