Nathaniel Atkin

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MALARIA

• Nathaniel Atkin

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Background

• NO NOTES PLEASE
• Case-based presentation
• Introduction to the format, youll see lots of
  these
• Introduction to the clinical problem solving
  approach
• AGAIN, NO NOTES PLEASE

3
Outline

• Very brief background
• Clinical case presentation
• History of present illness
• Past medical history
• Physical exam
• Differential diagnosis
• The workup
• Labs
• Micro
• Treatment plan
• Followup

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EPIDEMIOLOGY DEMOGRAPHICS

• Global
• 400900 million cases/yr  
•   1-3 million deaths/yr  
• 41 of the world's population lives in endemic
  area
• United States  
• 1500-1800 cases/ 5 yrs  
• 567 P. falciparum  cases
• FAHC 10-12 cases/ yr

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• Plasmodia Life Cycle
• Mosquito phase
• Female anopheline mosquito inoculates sporozoites
  (120/bite) into bloodstream  
• Liver phase
• Sporozoites mature to tissue schizont or become
  dormant hypnozoites  
• Schizont asexually divide ? merozoites (10,000 -
  30,000)   
• Blood phase 
• Intraerythrocytic parasites develop into
  gametocytes ? ingested by female anopheline
  during blood meal ? fertilize in the mosquito gut
  ? sporozoites migrate to salivary gland

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History of Present Illness

• 25 year old female
• Recent travel to Egypt, Ghana and Kenya working
  at refuge camps
• Group of friends stopped malarial prophylaxis in
  last month to months of the trip
• Felt generally ill last few weeks of the trip
• 1 week after return developed defuse copious
  diarrhea x 1-2 weeks. 6-12 x per day.
• Progressivly weaker and fatigued
• Acutely awoken with fever, headache
• Presented to FAHC ED the following morning

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Past Medical History

• Healthy 25 year old

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Physical Exam

• Vital signs
• General appearance
• ENT
• Pulmonary
• Cardiovascular
• Abdominal

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Physical Exam

• Vital signs
• Temp 38.7 ºC (37)
• Heart rate 120 beats/min (60-100)
• Respiratory Rate 16 respirations/min
• Blood Pressure 92/58
• Oxygen Saturation 97 on room air
• Positive Orthostatics

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Physical Exam

• General appearance
• Lying comfortably on the ED bed
• Pleasant demeanor
• Tired and weak appearing
• Yellowish coloration of her face

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Physical Exam

• ENT
• Dry mucus membranes
• Yellowish discoloration of the sclera

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Physical Exam

• Pulmonary
• Decreased air movement diffusely
• Lungs were clear
• No crackles, wheezes or pleural rubs

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Physical Exam

• Cardiovascular
• Regular Rhythm
• Tachycardic
• Appreciable first and second heart sounds
• No murmurs, friction rubs or gallops
• Weak radial, posterior tibial and dorsalis pedis
  (1 plus)

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Physical Exam

• Abdominal
• Soft
• Non distended
• Increased bowel sounds
• Right upper quadrant tenderness with palpation

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Physical Exam Summary

• Ill appearing 25 year old
• Fever
• Clinical signs of dehydration
• Heart rate is increased
• Jaundiced
• Right upper quadrant tenderness

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DIFFERENTIAL DIAGNOSIS

• Malaria
• Typhoid fever
• Dengue fever
• Yellow fever 
• Leishmaniasis 
• Trypanosomiasis  
• Rickettsial diseases  

• Leptospirosis
• Viral Hepatitis  
• Brucellosis 
• UTI  
• Influenza 

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The Workup
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The Workup

• Laboratory
• Thick and thin blood films
• Ring forms
• Banana-shaped gametocytes

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The Workup
What process could cause her LDH be high?
Bonus Question Why is the D-Dimer
Elevated? Hint think back to the structure and
function of fibrin.

• Additional Labs
• Hemoglobin Very Low
• Platelets Very Very Low
• Lactate Dehydrogenase (LDH) High
• Liver Function Tests (ALT, AST) High
• Fibrinogen split products (D-Dimer) High
• Bilirubin High
• Na, K, Mg, Cl abnormalities

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Fibrinogen activated by Thrombin and then
crosslinked by XIIIa
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Plasmin cleaves fibrin to leave D-Dimers in
solution
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Treatment Plan

• TREATMENT
• Malarone once a day x 3 days
• Combination pill
• Atovaquone poisons parasite mitochondrial
  electron transport
• Proguanil acts as a mitochondrial sensitiser
  and synergizes with atovaquone
• Follow parasite count daily
• Supportive Care
• Blood, Fluids, Clotting Factors, Electrolyte
  replacement

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How does that happen?
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The Followup Story

• Parasite count fell
• Hemoglobin, platelets continued to fall
• Acute episode of Pulmonary Edema
• Bright red blood GI bleed
• Received clotting factors, platelets, blood
  transfusion
• Responded well, continued to improve
• Discharged home with her family

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Summary

• The history is where the money is
• Understanding the basic sciences makes the
  clinical findings seem cooler
• Clinical decision making drives the Tests and not
  the other way round

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References

• Pasvol et al. Management of Severe Malaria
  Interventions and Controversies. Infect Dis Clin
  N Am. 2005 pp 211-240.
• CDC
• UpToDate
• Harrisons
• Wikepedia
• Some slides taken from Dr. Josephine Amalia
  Taverna