Protozoans

Protozoa

• Free living single eukaryotic cells

• Injest food through a cytosome

• reproduce asexually or sexually.

• When exposed to new temps of environmental changes, they secrete a protective coat to create a cyst

  • This is the form that is infective when injested

  • once injested, converts back into the motile trophozoite form

Cyst

A dormant, protective form of protozoa that can survive harsh environmental conditions and is infective when ingested.

Trophozoite

The active, motile feeding stage of protozoa that reproduces and carries out metabolic processes.

2 stages of plasmodium life cycle

1. sexual repoductive stage in mosquito hosts

2. asexual reproductive stage in human hosts with 2 cycles:

   1. one in RBCs (erythrocytic cycle)

   2. one in Liver (exo-erythrocytic cycle)

Primaquine

Drug that is active against the quiescent hypozonites of P. vivax and P. ovale

eg, can kill the hyphozoites hiding in the liver

This drug MUST be added to malaria regimens for P vivax and P ovale

Plasmodium Species

• Transmitted via the bite of a female Anopheles mosquito generally in resource-limited settings

• Africa accounts for 94% of cases globally

• 4% for the rest of the Americas

• U.S.: Travelers with 2000/cases a year
  • 85% from Africa with the majority from West Africa

Plasmodium species incubation periods

1. Bitten by mosquito: 2 hours later migrate to liver and stay there

2. Asymptomatic for 12-35 days after infection

3. Symptoms begin b/c parasite enters erythrocytic stage → red blood cells to rupture and release merozoites, which cause fever and other symptoms

What is unique about P vivax and P ovales incubation periods?

They can remain dormant in the liver as hypnozoites, leading to relapses after initial infection. Relapses may occur within 2-3 years

P Falciparium and P Malariae

DO NOT RELAPSE

Clinical Presentation of uncomplicated plasmodium

• Fever at intervals

• Anemia

• Palpable spleen

• mild jaundice

• Dx: blood smears and rapid tests

Fever interval for P vivax and P ovale

Every other day

Fever interval for P malariae

Every third day

P Falciparium differentiating characteritstics

• Banana shaped gametocyte

• more than one organism in a RBC

• more than one organism seen in a blood smear

• Has HIGH infectivity and a HIGH parasite load

Duffy blood group factor

Required by P vivax to invade RBCs

Sickle Cells

Protects you from getting P falciparium

Partial immunity

displayed by those living in endemic areas of malaria; however, if they move away and return years later, they will get malaria again

P Falciparium is commonly resistant to

chloroquine

Nephrotic syndrome

Can be caused by P malarie due to a mixed immunoglobin IgM and IgG basement membrane immune complex neuropathy

G6PD patients

Primaquine CANNOT be used in these individuals (causes hemolysis)

Main causes of malaria in the US

• Not taking prophalylaxis

• Stopping prophalylaxis too soon

Babesia Microti

• Nantucket island, Massachusetts, Northeast, Uppermidwest

• Tick bite

  • coinfection with lyme

• Asymptomatic infection is common

• May see haptosplenomagaly

• Sever disease seen in immunocomp or older:

  • splenic infarcts and rupture

Maltese cross

Babesia Microti

Toxoplasma gondii

• Cats are the only animal where they can complete their reproductive cycle

• Humans inject oocytes, organisms invade to intestinal epithelium and disseminate throughout the body

  • can encyst in ANY nucleated cell and lie dormant in host

• Increased risk of injesting oocytes: owning 3 or more kittens!

• Vertical transmission from mother to baby: TORCH

• Pregnant woman CANNOT clean out litter boxes

Toxoplasma Gondii clinic presentations

• Most asymptomatic

• If ill, bilateral, symmetrical, nontender cervical adenopathy

• Dx: ELISA, PCR, serology

• Tx: symptomatic

Toxoplasma Gondii TORCH

• Transplacental transmission is HIGHEST in 3rd trimester

• HOWEVER! The earlier the infection the more likely severe issues will occur

• Severe manifestations at birth: Microcephaly, cerebral calcifications, seizures, psychomotor retardation

• Others appear normal but develop symptoms months or years later

  • Chorioretinitis

Chorioretinitis

• due to Toxoplasma Gondii ToRCH infection

• Presents during teens or 20s. (Thought to be reactivation latent tissue cysts)

• Accounts for 25% of all granulomatous uveitis in the U.S

Cryptosporidium

• Life cycle can be completed in humans!

  • Injest oocytes → excystation in small intestine → release of sporozoites that infect intestinal epithelial cells.

• 3 main scenario we see this organism

  • Sporadic, water-related outbreaks of self-limited diarrhea in
    immunocompetent hosts

  • Chronic, life-threatening illness in immunocompromised (HIV)

  • Diarrhea and malnutrition in young children in resource poor countries

• Source of infection: contaminated water

  • SWIMMING POOL OUTBREAKS! PONDS/LAKES. “Occasionally in tap water!”

Clinical Manifestations of Cryptosporidium

• Secretory diarrhea and can be very minimal or up to 25L/day of watery stool

  • Resolves without therapy in usually 10-14 days in immunocompetent

• AIDS: longer course and extraintestinal disease

  • Biliary involement in 10-30%

• Dx: PCR

  • oocytes in stool are acid-fast positive

• Tx: immunocomp need Nitazoxanide or Paromomycin

Cyclospora

• Initial U.S outbreak (TEXAS) were raspberries from Guatemala

  • Lettuce, basil, snap peas, cilantro and prepackaged salads from
    Guatemala and Mexico

• Usually asymptomatic, but if symptoms watery diarrhea and low grade fever

• Dx: Acid-fast stain of stool! 8-10 microns (Cryptosporidium is smaller)

• TX: Trimethoprim/sulfamethazine (important to distinguish from Cryptosporidium because of this!)

Cystoisopora belli (formerly isopora belli)

In contrast to all the other protozoan diarrheal illnesses
(Cryptosporidium, Cyclospora) this organism causes EOSINOPHILIA

Balamuthia

A free-living amoeba that causes weeks to months of chronic neurologic disease with skin lesions

Naegleria Fowleri

• Thermophilic ameboflagellate protozoan parasite in water and soil

• Risks:

  • Swimming in a Texas Cow pond

  • TAP WATER

  • NETI POTS Be sure to use DISTILLED WATER!!!

• Primary amebic meningoencephalitis

• Dx: Motile trophozoites on exam of centrifuged CSF wet mount

Primary amebic meningoencephalitis

• Caused by Naegleria Fowleri

• 99% mortality rate

• Mean incubation period is 5 days

• High fever, H/A, photophobia

• Rapid deterioration with severe cranial hypertension leading to herniation and death in a few days

Acanthamoeba

• Most common ameba found in nature

• Found humidifiers and contact lens!!

• Transmission has been by inhalation of cysts carried by wind through respiratory tract or direct skin contact with subsequent hematogenous spread

• Can occur simultaneously with Legionella, Listeria, and Mycobacterium

• Causes opportunistic infection in immunocompromised hosts (except for eye disease in immunocompetent contact lens wearers)

Keratitis

• Caused by Acanthamoeba

• Contact lens wearers
  • Using non-sterile tap water to put contact lens in the eye
  • COMMERCIAL contact lens solutions (SCARY!!)
  • Showering while wearing contact lens!
  • Symptoms: Conjunctival hyperemia, tearing, pain, photophobia

• Dx: See organisms via staining corneal scrapings with florescent dye calcofluor

Entamoeba hisolytica

• Can cause intestinal AND extraintestinal disease

• Worldwide (seen in US immigrants)

• 2 forms

  • cyst stage (infective)

  • trophozoite stage (causes invasive disease)

• Infection from ingesting cysts from contaminated food or water or sexual contact through fecal-oral contact

• 1 single cyst can cause disease

Entamoeba histolytica disease process

• Ingest a cyst, the cyst passes into the small intestine and it excysts to form a trophozoite

• Trophozoite penetrates the colon → tissue destruction and increased intestinal secretions resulting in bloody diarrhea

• The trophozoite can kill epithelial cells AND inflammatory cells!

  • It secretes proteinases

  • Kills human cells by apoptosis

  • Forms amebapores

• Changes intestinal permeability via disruption of tight-junction proteins

Clinical Presentations of Entamoeba histolytica

• Asymptomatic 90%

• Clinical acute

  • Mild diarrhea to severe dysentery

• Extraintestinal disease

  • Amebic liver abscess

    • 4th leading cause of death by parasite worldwide

• Dx: Stool antigen or PCR

• Tx: EVERYONE is treated

  • asym: paromycin to prevent future issue

  • sym: Metronidazole (systemic therapy) followed by paromomycin (to complete intraluminal killing)

Amebic Liver Abscess

• Caused by Entamoeba histolytica infection

• 4th leading cause of death by parasite worldwide

• Reach the liver by ascending the portal venous system

• 7-10x more likely in adult men between 30-50 years of age

• Clinical Manifestations

  • Median 12 weeks (8-20 weeks) presentation with 1-2 weeks of Right upper
    quadrant (RUQ) pain and fever. Pain can be referred to right shoulder.
    • Diarrhea is NOT present
    • PE: Hepatomegaly and point tenderness over the liver

• Rupture of the liver abscess can occur and can go into the chest (most likely)! Or peritoneal cavity

• Dx: Stool is NOT helpful here!!! KNOW THIS! (unless has diarrhea [rare])

  • BLOOD serologic test and radiologic imaging of the liver

  • U/S, CT or MRI

“Anchovy paste liver”

Tx for extraintestinal Entamoeba histolytica

• Systemic agent: Metronidazole or tinidazole

• Luminal agent: Paromomycin

Other extraintestinal sites of Entamoeba histolytica ASIDE from liver abscess

• Pleuropulmonary (occurs in 20-35% of those with liver abscess

  • Risk factor: Chronic alcoholism, Atrial septal defect (ASD) with a left-to-right shunt

  • Pain, cough, hemoptysis, dyspnea

    • Cough can be nonproductive or “LARGE AMOUNTS OF AMEBIC PUS”

• Dx: BLOOD serology

• Tx: Aspirate pleural effusions if present and same antibiotics

• Can affect the heart, brain, and skin more rarely

Flagellates general characteritics

• widespread in nature

• binary fission

• Originates from an intracellular focus known as a kinetosome (basal body)

Kinetosome

• It extends to the cell wall as a filamentous axoneme composed of microtubules arranged in the typical 9 pairs and 2 central microtubular pattern and continues extracellularly as a free flagellum

• A pair of dynein arms extends from each outer microtubule of a pair to an adjacent
  microtubular pair and is responsible for flagellar beating through ATP hydrolysis.

• The whole flagellar unit and its associated organelles are called a mastigont system

Trichomonas vaginalis

• most common nonviral STI

• infects squamous epithelium

• It is pear- or round-shaped with 4 anterior flagella and an undulating membrane that causes characteristic motility seen on wet-mount slide of vaginal sections

Trichomonas vaginalis clinical presentation

• Purulent, malodorous, thin vaginal discharge with burning, itching, dysuria, frequency, lower abdominal pain and/or dyspareunia (painful intercourse)

• Exam: Erythema of the vulva and vaginal mucosa

• Dx: PCR or microscopy

• We do test of cure in women (only); return in 3 weeks to
  3 months and get retested to make sure it’s cured.

Giardia duodenalis

• Sting-ray shaped flagellate with 2 life forms

  • Cysts

    • infectious form

    • excreted in stool

    • following infection, excytation in the duodenum and jejunum

  • Trophozoites

    • live in duodenum and jejunum

    • Does NOT invade mucosal epithelium

• Secretory immunoglobulin A antibodies appear to be important for humoral immunity

Giardia Duodenalis risk factors

• international travel

• Drinking water from a river, lake, stream, etc

  • “Phenotypic Patient We see in Colorado”
    • Caused by Coors Beer, but not due to consumption!

  • Contact with children in diapers (daycare!)

Giardia Duodenalis clinical manifestations

• Acute Infection
  • Incubation period of 7-14 days (less than this is likely NOT giardia)
  • Diarrhea, malaise, “stinkiest stools you will ever smell,” flatulence,abdominal cramps and bloating
  • “Sulfuric belching”

• Chronic Infection
  • 50% of acute if not treated will go on to develop chronic infection
  • Loose stools but not diarrhea, profound weight loss (10-20% body weight!), malabsorption, depression, abdominal cramping
  • Borborygmi

  • Deficiencies of Vitamin A, B12, and folate
  • 40% will get acquired lactose intolerance!

• Dx: PCR

Leishmaniasis

• Blood and Tissue Flagellates

• complex of vector-borne diseases caused by the genus

• Species determines the diease process

  • cutaneousm→ may or may not heal

  • visceral → highly lethal

• Transmitted by sandflies

• complement mediates macrophage attachment

• BUT sandfly salivary peptides inhibit macrophage killing

Cutaneous Leishmaniasis

• Incubation period of weeks to months and even years (asymptomatic infection in about 10%)

• Wide spectrum of disease

Localized Cutaneous Leishmaniasis

• Lesions on exposed skin bc sand fly mouthparts cannot
  penetrate through clothing

• Starts as painless pink papule → a large nodule → painless ulceration with an indurated border

• Gradual healing over months/years

• Reactivation can develop during the subsequent year or later for mucosal leishmania (which is very destructive of nasal and other cartilage!)

• Dx: Skin histology, culture or PCR (usually all 3)

• Tx: Azoles, pentavalent antimony, etc

Visceral Leishmaniasis

• Known as Kala-azar (black fever)

• invade and replicate within host macrophages

  • Infection persists after clinical cure of primary infection

  • Many keep the infection “in check” and are asymptomatic and have the infection for life without any symptoms

• 2-6 month incubation (range weeks to years)

• Insidious or subacute onset with slow progression of fever, weight loss and splenomegaly over weeks to months

• May complain of abdominal discomfort and fullness of LUQ

• Dx: smears showing Leishman-Donovan
  bodies (amastigotes seen in mononuclear phagocytes on blood smear)

Human African Trypanosoma

• Sleeping sickness

• Transmitted by tsetse flies

• Acute form: East and Southern Africa

  • rhodesiense HAT

    • FAST

    • incubation is less than 3 weeks

    • rapidly progressive

• Chronic form: West and Central Africa

  • gambiense HAT

    • SLOW

    • incubation is months

    • slowly progressive

Stages of Trypanosomiasis

• First stage

  • penetration of skin

  • chancre at site ot tsetse bite

  • Rhodesiense: Lymphadenopathy less commonly and submandibular, axillary, inguinal regions

  • Gambiense: Posterior cervical node lymphadenopathy

• Second stage

  • Profound fatigue, changes in behavior, Sleep cycle reversed—awake night/sleep day, anxiety, delirum

  • CNS involvement

Dx: lymph node aspirate

American Trypanosoma (T. Cruzi)

• Chagas Disease

• Leading cause of chronic heart disease and accounts for 25% of all deaths in 25-44 year olds

• 3 cm large insect hides and comes out at night to feed on its sleeping hosts (reduviid, “Kissing bug”)

• ~300,000 in the U.S. who immigrated here are infected and do not know it

How is American trypanosomi different from African trypanosomi?

The bloodstream trypomastigotes do not replicate. Replication resumes only when the parasites enter another cell or are
ingested by another vector

Clinical Presentation of Chagas disease

• The patients has 8-12 weeks of circulating trypomastigotes that only cause mild symptoms (fever, malaise) or are asymptomatic

  • Rarely at the site of inoculation inflammation/swelling occur called a chagoma

    • Usually on the face or extremities

    • If on the conjunctiva (OUCH!), it leads to a painless swelling of upper and lower eyelid known
      as Romaña's sign.

  • < 1% will have severe acute disease with acute myocarditis, meningoencephalitis

• Dx: Microscopy of fresh blood or “buffy coat”= you spin down a vial of blood and between the red blood cells and the plasma is a thin layer of just white blood cells, AKA the buffy coat

• Tx: Benznidazole and nifurtimox

  
  

Chronic Chagas Cardiomyopathy

• • Asymptomatic or have dyspnea on exertion, palpitations

• Present with ventricular arrhythmias, abnormalities of the
  conduction system

• Cardiac exam findings:
  • Mitral and or tricuspid regurgitation murmurs
  • Wide splitting of the 2nd heart sound due to right bundle branch block

• CXR will show cardiomegaly

Chronic Chagas Cardiomyopathy 4 major types of disorders

1. Heart failure

2. Arrythmias

3. Thromboembolism

4. Chest pain syndrome

Chronic Chagas Gastrointestinal Disease

• Occurs between ages 20-40 years

• Can be any part of GI tract

  • A big dilated poorly functioning esophagus develops with difficulty and pain
    with swallowing.

  • Regurgitation of food is likely

• A dilated colon (Megacolon) result in constipation and abdominal pain

  • Weeks may occur before they have a bowel movement