Parasites

Introduction

• Plasmodium species!
• Areas with significant malaria:
  • Africa, Middle East, India, Southeast Asia, South America, Central America, parts of Caribbean.
• Transmitted to humans via anophiline female mosquito.  (requires blood to lay eggs)
• Prevent by:
  • Bed nets
  • Insect repellant (DEET)
  • Adherence to chemoprophylaxis
• Life cycles:
  • Humans: Intermediate Host
  • Mosquitoes: Definitive Host
  • Sporozoite enters human via mosquito bite.  Migrates to liver --> invate hepatocytes (via receptor) --> within hepatocyte, sporozoites mature to merozites (some dormant as hypnozoite - 6-11mo to activate) --> hepatic cell lysis --> merozites invade single RBC--> asexually replicate 5 times in 48-72hrs --> RBC lysis --> invasion of additional RBC

• Protective genetic factors that interfere with Plasmodium invasion:
  • Surface Proteins
    • Absence of "Duffy" group protein on surface --> resistant to P. vivax
    • Reduced CR-1 expression --> less rosetting in P. falciparum (less cerebral involement)
  • Cytoskeleton (interfere with entry and release of parasite)
    • Hereditary ovalocytosis
    • Hereditary elliptocytosis
    • Hereditary spherocytosis
  • Hemoglobin
    • Sickle cell disease or trait (HbS) --> resistance to P. falciparum (slows growth with abnormal hemoglobin)
      • When P. falciparum forms "knobs" to aggregate RBC's --> traps RBCs in small vessels --> decrease O2 tension --> HbS polymerizes --> kills P. falciparum
      • People with Sickle cell are resistant to SEVERE P. falciparum infection
      • Other types of malaria P. vivax/ovale/malariae do not form knobs --> HbS has no effect.
    • Other hemoglobinopathies (Hb C, Hb E, a-thalassemia, and (lesser extent) B-thalassemia) reduce severity of P. falciparum infection.
    • Neonatal hemoglobin Hb F --> interferes with P. falciparum growth, neonates are protected form severe malaria.
• Highest risk:
  • Tourists with no previous malaria exposure
  • Pregnant women + fetuses.  (P. falciparum binds chondroitin sulfate A in intervillous space of placenta causing hemolytic anemia --> low birth weight infants).

Symptoms

• FEVER, FEVER, FEVER!!!! (the only reliable symptom)
  • Characteristic paroxysms of fever every 48-72hrs.
  • Others: headache, myalgia, nausea, vomiting, abdo pain, diarrhea.
  • Fever often fluctuating, but three stages:
    • 1. "Cold stage" feeling code + chills for 15-60min.
    • 2. "Hot stage" body temp rises 39-41°.  Lassitude, loss of appetite, vague pains in bones/joints.  Influenza-like.  (many other sx: diarrhea, unwell, back pain, nausea etc....)
    • 3. "Sweating stage": diaphoresis, and resolution of fever at 2-6hrs.  --> then fatigue and desire to sleep.

  • Fever in a patient returning from an endemic country is MALARIA UNTIL PROVEN OTHERWISE! (Also look out for Jaundice or Confusion/Obtundation)

• Hemolysis markers
  • Unconjugated bilirubin
  • Hemoglobinuria (dark coke-colored urine)
  • Jaundice  (jaundice + hemoglobuinuria --> blackwater fever).
• CNS confusion
  • P. falciparum --> RBCs form knobs --> aggregate in small vessels --> hypoxic damage.

falciparum: 9-14d very rarely >6mo

P.vivax (10-30 days) 

ovale 12-18d

P vivax up to 6-12mo

P. malariae 18-40d

P knowlesi 9 days to 4 weeks (limited data)

Diagnosis/Workup

• Three Questions:
  • 1. Is there malaria?
  • 2. MUST differentiate falciparum vs. non-falciparum.
  • 3. Is there chloroquine resistance?
  • 4. Where is parasitemia?

• Define level of parasitemia
  •  >1% ok,
  • >5% get nervous,
  • >10% very dangerous!!!
  • (NOTE: parasitized RBCs adhere to small blood vessels.)
• Associated with:
  • Alteration in mentation
  • Liver failure
  • DIC
  • Hemolysis
  • Metabolic acidosis
  • Renal Failure
  • Hypoglycemia
• Long-standing Infection:
  • Anemia
  • Splenomegaly

• Blood smear x 3  (primary dx method!)
  • Giemsa-stained blood
  • Best collected after fever spike (otherwise parasites clogged in peripheral capillaries and parasites not seen).
  • MUST take blood for 3-4 successive days before rule out malaria.
  • Thick films: Used for diagnosis (higher yield)
  • Thin film: 1000X with oil objective microscope. --> speciation
• Differentiate falciparum from non-falciparum
  • ELISA for histidine-rich P. falciparum antigen.
  • Immunoassay for lactate dehydrogenase enzyme
  • PCR for DNA or mRNA
• Other bloods:
  • Anemia
  • WBC (Decreased or Normal) [90%]
  • Platelets [60-83%]
  • LDH (high) [70-83%]
  • Liver Enzymes [50%]
  • Other:
    • Increased Retics
    • Elevated reatinine, proteinuria, hemoglobinuria. 

Treatment

• Aminoquinolones, chloroquine, quinine, mefloquine, primaquine, and halofantrine
  • 1. Inhibit proteolysis of hemoglobin in food vacuole
  • 2. Inhibit heme polymerase required for malaria pigment production.
  • --> kills organism.
• Pyrimethamine, fulfonamides, dapsone 
  • Folate antagonists
• Atovaquone
  • Inhibits mitochondrial transport
• Artemisinin
  • Binds iron --> produces free radicals --> damages proteins.
     
• All derivatives are faster acting than quinine.
• Africa, northern South America, India, Southeast Asia --> chloroquine resistant P. falciparum.
  • Energy depdent chloroquine efflux pump.
• Mefloquiine and halofantrine also found resistance (Southeast asia).
• Prophylaxis:
  • Chloroquine susceptible areas: chloroquine. (weekly)
    • If areas of resistance:
      •  Mefloquine 250mg PO /week.
      • Doxycycline 100mg PO /day
      • Primaquine 0.5 mg/kg/day
      • Atovaquone 250mg + Proguanil 100mg PO/day (called Malarone)
  • No vaccine! Immune response is poorly understood.. makes vaccine development difficult.
• Treatment:
  • Refer to websites
    • UK health protection agency
    • US CDC
    • WHO Malaria Programme.
  • General principles:
    • For chloroquine-sensitive strains: use chloroquine
    • For chloroquine-resistant strains: use qunine or equivalent. (Artemisinin very effective for severe disease, but manufacturing quality unreliable???).  If too ill use IV quinidine.

Lifecycle:

• Infected eggs hatch --> oncospheres --> penetrate bowel wall to bloodstream --> deposited in organs
  • Commonly: Lung, liver
  • Less common: Brain, heart, and bones.
• Re resulting Hydatid cysts consist of germinal membrane with multiple tapeworm heads --> buds to form daughter cysts within primary.
• Cysts survive in hosts for decades.
• 

Clinical Presentation

• Most asymptomatic, often detected incidentally on imaging.
• Can become asymptomatic when reaches large size >8-10cm compessing vital structures. and erode into biliary tract or bronchus (if in lung).
  • Cysts can become superinfected, resulting in bacterial abscess.
  • Cysts can rupture producing anaphylactic-type reaction (Fever, Hypotension)

Investigations

• U/S, CT, MRI:
  • Show hydatid cyst with distinct septated structure (daughter cysts).
  • Sometimes tapeworm heads can be visualized
  •  
• Laboratory:
  • ELISA - highly sensitive for liver cysts, less sensitive for extra-hepatic.

Treatment

• Surgical resection if symptomatic.
  • Must be removed INTACT, to avoid rupture that can spread infection.
  • Procedure involves removing fraction of contents, and injecting hypertonic saline (30% NaCl), iodophore, or 95% ethanol.  -> kills germinal layer and daughter cysts.
  • Instil solution 30min before surgery.
  • Peri-operative treatment 3-4 cycles of:
    • albendazole 400mg BID for 4 weeks followed by 2-week rest period.
  • (Some studies do 1 week pre-op and 1-3 months post-op).
• Medical treatment:
  • If small cyst and/or asymptomatic, can do medical treatment only:
  • Same as peri-operative treatment.
  • Can also percutaneously aspirate with needle to drain and instill of cidal agent (hypertonic saline or ethanol). Followed by re-aspiration in 15min to remove cidal agent. (Called PAIR treatment).
    • PAIR treatment is often curative, but no randomized trials comparing to surgery.

Leishmaniasis

TODO

Trypanosoma Cruzi

TODO