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.
- 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.
- 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.