Exam Notes on Malaria and Other Protozoan Diseases

Malaria

• Ancient disease, around as long as humans have existed.
• First writings: 4th century BCE, Greeks noted a disease in swamp workers.
• 17th century: Italians named it "mal air" (bad air).
• 1902: Determined mosquitoes were involved in the spread.
• Insect vector: Female Anopheles mosquito.
• Greatest causes of death throughout history.
• Each year: 300-500 million new cases diagnosed.
• Each year: 1.5-3 million deaths.
• Contracted only where Anopheles mosquitoes live.
• Female mosquito injects pathogen via proboscis (two chambers).
• One chamber injects saliva creating pressure; the other draws blood.
• Mosquitoes don't suck blood; they inject and create pressure for flow.
• No Anopheles mosquitoes in the US currently (Culex and Aedes present).
• Historically, Anopheles mosquitoes were in the Deep South but died out during extremely cold winters.
• Concern about reintroduction due to climate change (via ships in bilge water or cargo).
• US malaria cases are from travelers.
• Five causative agents (genus Plasmodium):
  • Plasmodium knowlesi
  • Plasmodium vivax
  • Plasmodium falciparum
  • Plasmodium ovale
  • Plasmodium malariae
• Numbers in parentheses indicate cycle length (24, 48, or 72 hours).
• Cycle length corresponds to symptom duration and asexual reproduction time.
• Plasmodium falciparum is the most deadly.
• Plasmodium vivax is also significant.
• Initially, Plasmodium knowlesi was thought to be an animal pathogen.
• Plasmodium malariae cycles every 72 hours.
• Infected female Anopheles mosquito bites introduce Plasmodium.
• Mosquitoes are not born infected; they acquire it through blood meals.

Symptoms of Malaria

• Itchy bump from mosquito bite is not a malaria symptom.
• Symptoms begin ~2 weeks later.
• Generic flu-like symptoms: fever, headache, joint/muscle pain, fatigue, nausea.
• Last 2-3 weeks, progressing into three phases of malaria.
• Each set of three phases is considered a bout of malaria.
• Phases:
  • Cold phase: mild fever (below 101°F), feeling of being immersed in ice water.
  • Hot phase: dangerously high fever, problematic in children (brain development complete around age 8), potentially causing brain damage.
  • Wet phase: fever breaks, soaking perspiration occurs.
• Followed by fatigue and recovery.
• Cycle duration depends on the Plasmodium strain (24, 48, or 72 hours).
• Some individuals experience only one cycle before dormancy.
• Dormancy can last weeks, months, or even years.
• Severe cases: anemia develops (caused by Plasmodium invading and rupturing red blood cells).
• Throughout cold and hot phases: vomiting, diarrhea (possibly bloody), muscle/joint pain, convulsions, seizures, delirium.
• Death usually occurs in a hospital due to high fever causing brain damage.

Life Cycle of Plasmodium

• Two parts: inside the insect and inside the animal host.
• Other mammals (primates) and birds can also get malaria.
• Female mosquito takes a blood meal containing gametocytes if the host is infected.
• Gametocytes (young, immature Plasmodium) undergo sexual reproduction in the mosquito's midgut if two mating types (+/-) are present.
• Oocyst is produced.
• The mosquito digestive system has 3 chambers that includes the foregut, midgut and hindgut.
• In the foregut, the red blood cells will be degraded and contents of red blood cells are released.
• If two mating types are present, sexual reproduction occurs in the midgut to produce an oocyst. Oocyst then moves into the hindgut.
• Oocyst ruptures to release sporozoites.
• Sporozoites migrate to the salivary gland.
• Next blood meal injects Plasmodium into the host.
• In the host (e.g., human), sporozoites are injected into bloodstream, travel to the liver, and mature into schizonts.
• Schizonts rupture, releasing merozoites.
• Merozoites invade red blood cells.
• Red blood cell is altered to prevent further merozoite entry.
• Merozoites develop into trophozoites (early, late stages) and then schizonts, filling the red blood cell.
• Red blood cell ruptures, releasing merozoites, repeating the cycle.
• Cycle length (24, 48, 72 hours) is how long this process takes in the host.
• Symptoms correlate with the life cycle stages:
  • Merozoites leaving the liver trigger low-grade fever (cold phase).
  • Asexual reproduction inside red blood cells leads to cells filled with schizonts and trophozoites which ruptures at the same time causing the hot phase.
  • Immune system raises temperature during the burst effect.
  • Merozoites race to enter other red blood cells.
  • Immune system senses absence of free merozoites, fever breaks (wet phase).
• Symptoms reoccur with each new burst.

Microscopic Observations

• Pink cells: red blood cells.
• Purple bodies inside pink cells: red blood cells infected with Plasmodium (various stages).
• Anopheles mosquito injects sporozoites into the host via saliva.
• Sporozoites travel to liver cells and mature into schizonts.
• Schizonts rupture, release merozoites into the bloodstream.
• One merozoite enters each red blood cell, modifying it.
• Red blood cell fills with Plasmodium; ruptures, releasing merozoites.
• Occasionally, early trophozoites develop into gametocytes (taken up during the next mosquito blood meal).
• Malaria is a leading cause of death globally.

Prevention & Treatment

• Prevention: Avoid mosquito bites.
  • Protective clothing, insect repellent, eliminate standing water, mosquito netting.
• Treatment: Antiprotozoal drugs (relatively inexpensive; < $2 to manufacture).
• Problems with treatment:
  • Drugs made in developed countries, profit-driven.
  • Getting treatment to where it's needed is difficult due to access.
  • No lifelong immunity after cure; reinfection possible.
  • Short-term memory (up to 6 months) after treatment before susceptibility returns.

Historical Context: WHO Programs (1955)

• Smallpox eradication: vaccination for herd immunity (high percentage of immune population).
  • Herd immunity: reduces likelihood of pathogen finding vulnerable hosts.
• Mosquito eradication: eliminate all mosquitoes.
  • Failed.
• DDT (insecticide): initially effective but mosquitoes developed resistance.
• DDT found to be a human and animal carcinogen, endocrine disruptor.
• US banned DDT.
• Mosquito eradication program quietly ended in the mid-1970s.
• Malaria still exists today.

Toxoplasmosis

• Causative agent: Toxoplasma gondii.
• Primary reservoir: cats.
• Transmission: fecal-oral route or undercooked meat ingestion.
• Pregnant women advised to avoid cleaning cat boxes.
• Being around the cat is not at risk.
• Three affected groups:

Immunocompetent Individuals

• Usually asymptomatic (10-20% develop symptoms).
• Symptoms: sore throat, enlarged lymph nodes/spleen, fever.
• Self-limiting; rarely progresses to heart or CNS involvement.

Developing Fetus

• Responsible for ~50% of maternal infections during pregnancy.
• First trimester infection: most severe effects; miscarriage/spontaneous abortion likely.
• If fetus survives: severe birth defects (small/enlarged head, lung/liver damage, mental impairment, seizures); short lifespan.
• Third trimester infection: more common (2/3 of maternal cases); less severe effects.
• Babies appear normal at birth but may develop retinitis later in life (light sensitivity, blurred vision), typically affecting one eye.
• Retinitis can be permanent despite treatment.
• Rarely leads to mental impairment or seizure disorder.

Immunodeficient Individuals

• Examples: AIDS patients, chemotherapy patients.
• Typically leads to encephalitis (brain infection) in ~50% of cases; confusion, weakness, impaired coordination, seizures, stiff neck, paralysis, coma.
• Brain, heart, and other organs can be involved; often fatal.
• Treatment with antiprotozoal drugs, but harder to treat in the CNS.

Cryptosporidiosis

• Infectious agent: Cryptosporidium parvum.
• Transmission: fecal-oral route.
• Ingestion of < 30 cysts can cause the disease.
• Cysts are very small and can pass through standard water purification filters.
• Produces diarrheal disease 4-12 days after ingestion.
• Symptoms: fever, loss of appetite, crampy abdominal pain, profuse watery diarrhea (10-14 days).
• Self-limiting for most people.
• Higher incidence in immunodeficient patients (AIDS).

Balantidiasis

• Phylum Ciliophora: ciliates move by waving cilia.
• Balantidium coli: only known ciliate to cause human disease.
• Spread by fecal-oral route.
• Swine is the main reservoir; waste contains cysts.
• Produces ulcers in the large intestine (not like Helicobacter pylori in stomach).
• Ulcers can bleed, causing bloody stool.
• Diarrheal disease.
• Rare in US due to water quality and waste treatment standards.

Pneumocystis Carinii (Pneumocystis jirovecii)

• Produces cysts with 2-8 sporozoites, and trophozoites.
• Complex life cycle, treated with antiprotozoal drugs.
• Originally thought to be a protozoan based on looks, disease, and treatment.
• Resistant to antifungal agents.
• Genetic testing showed it is fungi and bridges two different tree of life.
• Causes pneumocystic pneumonia (fluid accumulation in lungs).
• Symptoms: difficulty breathing, poor blood oxygenation, wet nonproductive cough, discolored skin patches (poor oxygenation).
• Problematic in immunodeficient individuals.
• Fungi and not Protozoan

Viruses

• Every level of life has viruses.
• Responsible for most diseases, especially in developed countries.
• Not considered alive because they don't meet all criteria for living things.
• Cannot metabolize, grow, replicate independently, or respond to the environment.
• Recruit host cell's metabolic pathways for replication.
• No cytoplasmic membrane, cytoplasm, cytosol, or organelles usually.
• Extracellular (virion) and intracellular state.

Virion

• Composed of a protein coat (capsid) covering nucleic acid.
• Nucleic acid + capsid = nucleocapsid.
• Some have a phospholipid envelope (host cell membrane).
• Outermost layer provides protection and recognition sites for host cells.
• Capsid: made of protein subunits (capsomeres).

Capsid Removal

• Inside the host cell, the capsid is removed, and DNA or RNA is released.
• Nucleic acid causes disease.
• Viruses take over host cell ribosomes to make viral protein.
• Either DNA or RNA (not both).
• Classified as either DNA or RNA viruses.
• Can be double-stranded or single-stranded.
• Linear, circular, or segmented.
• Relatively small genome with not many genes.

Host Specificity

• Viruses must attach to an appropriate host cell.
• Attachment fibers (spikes) on virus fit perfectly into receptor sites on host cells.
• Receptor sites must allow attachment.
• If no appropriate cell/attachment, no infection.

Viral Shapes

• Capsomere arrangement determines shape.
• Icosahedral: arrange to form triangular faces.
• Helical: capsomere arrange in a tube to form a capsid.
• Bacteriophages: shown here.
• Enveloped viruses: Surrounded by host cell membrane. Naked viruses are not enveloped viruses are more at risk of being dried out as its outside of a host.

Viral Replication: Lytic Cycle

• Lytic Cycle of Replication includes the Attachment, inject/Insert/Entry/ Insertion, Integration +-, Synthesis. Assembly Release.
• In this cycle the genetic material from the virus is incorporated into the host.
• Attachment: virus attaches to a host cell and has it's receptor fit perfectly to host cell.
• Injection/Entry : Is brought into the host cell.
• Insertion +-: The genetic material of the virus is escorted to the nucleus where its incorporated in the host genome. Every-time host cell replications it will be copying the DNA.
• Synthesis: Production of components of virus in the host cells.
• Assembly: Assembles all components of the virus.
• Release: Virus is being released in 2 ways a Naked virus meaning that it breaks out of the host or release from a host cell, viruses buds out one at a time.
• B cells produce antibodies, covering parts of the virus called attachment fibers and prevents them from attaching to a host cell.
• Naked virus gets detected much earlier and enveloped viruses are very likely to protect from immunity.

Viral Replication: Lysogenic Cycle

• LYSOGENIC involves being the opposite. Starts and is still a cycle of reproduction.
• Insertion, integration. Then there is the period of dormancy. This period doesn't show symptoms.
• Evolutionary reasons why a virus has dormancy is that it can remain dormant until weakening of the host occurs. There are chemical changes that cause it . Sunlight to get it out of dormancy.
• Following from that it's the same step.
• Infection- If no appropriate cell/attachment, no infection.

Transformative Viruses

• Not only do they take over a whole cell and make them do something new, but they can also, in some cases, be a neoplastic virus or a neo can result in neoplasia.
• Cause cancer by transforming host cells and is benign and is in some long term and cause harm
• Transformation results in the old host cells job is nothing and it just replicates as viruses
• HPV, all tend to be HPV.

Methods of studying Virus

• Tissue test.
• Can't be grown in dishes has to be grown in tissue and the injection virus is injected in chicken and cultivated.

Immune Function

• Viruses need to break the immune system to cause diseases this can be broken down into 2 part specific and non specific.
• Non specific immunity which is the innate immunity that doesnt target any pathogen however this doesn't have memory.
• More important probably specific immunity or adaptive immunity is respond to particular antigen or anything foreign. This will generate memory.
• Non specific includes all the Flora or Microbes, lymph system chemical barrier, reflexes hormones inflammation. However it doesnt generates memory.. How Interferon works.

Interferon

• Interfoon is a nonanti body protein that activate antiviral protectants and viruses and isnt species specific . However its labile. Not produce in the first trimester of pregnancy. This makes the infant suseptical..

Specific Immunity

• Put into 2 types of cells. Tcells and B CELLS.
• Bcells produce antibodies and detect all things foreign.
• B cells cant operate without order and relies on other Tcells that can direct them where to go and what to do.
• Tcells directs all Bcells.
• Acrired immunodeficiency acquired Immunodificiency Symdrom. HIV.
• Tcells are infected by something which causes the host to die and thats HIV which also is only 9 genes.
• Then our Tcells goes to destroy and tries to triger Apoptosis which it can cause a cell to die if behaving abnormally.
• Tcells is very sneaky as tcells stay alive but don't act causing T cells to stay aive we are seeing the number of cells.
• Cubic Millimeter = number of cells in a bloods
• 200 or below that in our blood we are seeing that.
• So the overall theme is not one Disease or many other and have a tendency to be infected one.
• Transmited through sexual content or other Fluids can be transmited.
• While we dont have a cure and it helps to keep us treated.

Papillomavirus | HPV

• Naked and only 3 cells and tend to be epitheliel in reproductive area.
• HPV strain 6 or 11 cause about 90% of genital warts that become removed. However
• HPV strain 16& and 18 moster cause sercivel cancer and 90% caused from papllovirus.
• Garsaile is used as vaccine that begins between and old age. However dont like the idea. Parents give permission.