Table of contents
- 1. General Principles
- 2. Malaria
- 2.1. Introduction
- 2.2. Symptoms
- 2.3. Diagnosis/Workup
- 2.4. Treatment
- 3. Babesia
- 4. Echinococcosis
- 4.1. Lifecycle:
- 4.2. Clinical Presentation
- 4.3. Investigations
- 4.4. Treatment
- 5. Other
- 5.1. Leishmaniasis
- 5.2. Trypanosoma Cruzi
.
General Principles
- Definitive Host: The host in which sexual reproduction takes place.
- Intermediate Host: The host in which asexual reproduction takes place
- Divided into:
- Blood Protozoa
- Malaria (Plasmodium)
- Babesiosis (Babesia)
- Tissue Protozoa
- Leishmaniasis (Leishmania)
- Trypanosoma cruzi
- Intestinal Helminths
- Intestinal Nematodes (Roundworms)
- Acquired by Ingestion
- Trichuris trichiura (Whip Worm)
- Ascaris
- Enterobius (Pinworm)
- Acquired by Skin Penetration
- Strongyloides
- Hookworm
- Acquired by Ingestion
- Intestinal Nematodes (Roundworms)
- Tissue and Blood Helminths
- Trichinella
- Echinococcosis
- Cysticercosis
- Schistosomiasis
- Filariasis (Wuchereria Bancrofti and Brugia Malayi)
- Dirofilariasis (Dog Heartworm)
- Onchocerciasis
- Loiasis
- Blood Protozoa
Malaria
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
Species (red-bold kill) | Type of cell | Risk of Parasitemia (Disease severity) | Dormant Phase? | Features |
---|---|---|---|---|
P. falciparum (Inc: 8-25d) | Hepatocytes RBC any age | HIGH | None! | - Most common, most dangerous. - Can invade RBC of any age! - RBC membrane forms knobs that adhere to vascular endothelium knobs bind CR-1 receptor on other RBC causes clumping "Rosetting". These clumps block flow-->hypoxic damage to brain + kidneys. - Results in hemolysis, renal failure, CNS damage, pulmonary edema - VERY HIGH Chloroquine resistance |
P. vivax (Inc: 10-30d) | Hepatocytes Young RBC (mostly retics) | LOW | Dormant In Liver | - 2nd most common - Can remain dormant in liver (relapse after tx) - Low level parasitemia - Some chloroquine resistance |
P. ovale (Inc: 10-20d) West-African SE Asia | Hepatocytes Young RBC (mostly retics) | LOW | Dormant In Liver | - VERY RARE - Can remain dormant in liver (relapse after tx) - Low level parasitemia. - NO chloroquine resistance described |
P. malariae (Inc: 15-35d)
| Hepatocytes ? RBC | LOW | - Uncommon - No dormant phase, but can persist low-level for 30yrs. - Very low level parasitemia - RARE chloroquine resistance | |
P. knowlesi (Inc: unknown) S/SE Asia | Hepatocytes ? RBC | HIGH | - Isolated only in Malaysia - Known to infect only monkeys, now infects humans. - Looks like P. malariae, but kills like P. falciparum - No relapse reported - NO chloroquine resistance |
- 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.
- Sickle cell disease or trait (HbS) --> resistance to P. falciparum (slows growth with abnormal hemoglobin)
- Surface Proteins
- 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.
- 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)
- If areas of resistance:
- No vaccine! Immune response is poorly understood.. makes vaccine development difficult.
- Chloroquine susceptible areas: chloroquine. (weekly)
- 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.
- Refer to websites
Drug | Advantage | Disadvantage |
Chloroquine | Short Course | Limited efficacy (resistance) |
Atovaquone/prog. | Short Course | Vomiting |
Mefloquine | Short Course | Neuropsych |
Quinine + doxy | Long Course | Cinchonism |
Quinine + clinda | Long Course | Cinch + C. diff. |
Artemisinin | Short Course | Availability |
Babesia
- Disease of cattle and wild animals, but can infect humans.
- Similar to malaria --> blood protozoan, but no hepatic phase. (lifecycle similar to Plasmodium)
- Transmitted by deer tick Ixodes scapularis.
- Babesia does not infect deer (curiously).
- White-footed deer moouse is primarily infected.
- Nymph (tick) can leave mouse and attach to human.
- Replicates by binary fission inside RBC. (Hemolysis never massive).
- Symptoms:
- Presents with intermittent fever "summer flu" 1-3 weeks post-exposure.
- Often hiking hx in tick infested areas.
- Often no hx of tick bite. Ixodes scapularis nymph too small - mistaken for small freckle.
- Often resolves, but serious in splenectomized patients and elderly.
- Pts with babesiosis can have Lyme disease b/c same tick transmits both.
Echinococcosis
- Two species:
- Echinococcus multilocularis:
- usually symptomatic, and progresses to symptoms.
- Found: Northern Europe, Asia, Northern US, and Arctic
- Echinococcus granulosus:
- usually asymptomatic (90%), rarely progressive.
- Found worldwide (incl. Africa, Middle East, Southern Europe, Latin America, southwestern US)
- Echinococcus multilocularis:
- Member of the cestode (tapeworm) family.
- Humans --> Intermediate host
- Transmission: Food infected with parasite eggs.
- Carried in: feces of sheep, goats, camels, horses, and domestic dogs that live around lifestock.
- Eggs resistant to drying - viable for many weeks (can contaminate food indirectly)
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.
Other
Leishmaniasis
TODO
Trypanosoma Cruzi
TODO
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