Sepsis and Microbial Infections Part 2

Question 1

what are the two categories of parasites and examples?

Answer 1

• Protozoa: single celled eukaryotes like rhizopods, ciliates, flagellates, sporozoa
• Metazoa: multi celled eukaryotes (heminthes) flatworms and roundworms

Question 2

what are blood sporozoa?

Answer 2

parasites that causes Malaria and babesiosis

Question 3

how do sporozoa reproduce?

Answer 3

asexually and sexually

Question 4

what is Malaria?

Answer 4

mosquito transmitted disease caused by protozoan parasites, plasmodium

Question 5

what are the two most important species that cause Malaria?

Answer 5

plasmodium falciparum (worldwide) and plasmodium vivax (asia)

Question 6

how is Malaria spread?

Answer 6

insect vector Anopheles mosquito (sexual) and blood transfusion

Question 7

what are the two organs infected by Plasmodium in humans?

Answer 7

liver and RBC

Question 8

how is Malaria transmitted?

Answer 8

female mosquito probes for a blood meal, deposits parasites through their salivary glands where they transverse the capillary wall, enter the blood stream and migrate to the liver

Question 9

what occurs once Malaria parasites have traveled to the liver?

Answer 9

asexual reproduction begins once the parasites invade the hepatocytes to multiply/increase in number and then release thousands of parasites to infect RBC

Question 10

what happens once the Malaria parasites invade RBCs?

Answer 10

• multiply using amino acids obtained from digesting hemoglobin
• remodels the RBC surface making them more sticky and permeable
• RBCs burst and invade new RBC

Question 11

what happens once a mosquito ingests infected RBCs from a human blood meal?

Answer 11

the parasite differentiate into transmissible male and female gametocytes that fuse to form a zygote that develops into a parasite filled oocyst that bursts and moves to salivary glands of mosquito to infect a new host

Question 12

what is cytoadherence?

Answer 12

parasitized red blood cells (pRBCs) stick to other cells instead of circulating freely causing disruption of blood supply to organs, lysis of RBCs and tissue hypoxia

Question 13

what is the differences between rosetting and endothelial cytoadherence?

Answer 13

• rosetting is when infected red blood cells stick to uninfected red blood cells
• endothelial is when infected RBCs adhere directly to endothelial cells lining blood vessels

Question 14

what are the clinical presentations of Malaria?

Answer 14

• signs and symptoms occur within a few weeks of infection varying from person to person
• most symptoms are mild
• can lie dormant
• severe cases can be incapacitating and fatal

Question 15

what are the symptoms of malaria?

Answer 15

shaking cills, high fever, profuse sweating and body temperature falls in a cyclic pattern; oral conditions as well

Question 16

how is fever generated in Malaria?

Answer 16

the innate immune system’s response to the synchronized rupture of red blood cells (RBCs) infected by Plasmodium parasites releasing cytokines and interacting with he hypothalamus

Question 17

What causes severe malarial anemia (SMA), and what is “blackwater fever”?

Answer 17

SMA is caused by chronic and repeated RBC destruction due to malaria. “Blackwater fever” refers to hemoglobinuria from massive hemolysis

Question 18

How does malaria lead to renal insufficiency and metabolic acidosis?

Answer 18

Lysis of RBCs (~5%) releases contents that lower blood pH, causing acidosis and potential kidney damage

Question 19

What is acute respiratory distress syndrome (ARDS) in malaria?

Answer 19

ARDS is caused by inflammation and fluid accumulation in the lungs, which impairs oxygen exchange and causes difficulty breathing

Question 20

How does malaria cause organ failure?

Answer 20

Low blood pressure can lead to multi-organ failure, including kidney, liver, cardiovascular collapse, or splenic rupture

Question 21

What is cerebral malaria, and why is it dangerous in children?

Answer 21

In children under 5, infected RBCs autoagglutinate and form rosettes that obstruct brain microvasculature, causing inflammation, blood-brain barrier disruption, and brain swelling

Question 22

How does the malaria parasite suppress the host immune response?

Answer 22

decreasing HLA-DR expression on dendritic cells, reducing antigen presentation and innate immune activation

Question 23

How does the sickle cell trait protect against malaria?

Answer 23

Individuals heterozygous for HbS have abnormal hemoglobin that creates a hostile environment for Plasmodium inside RBCs, reducing parasite survival and replication

Question 24

Why are people with Duffy-negative blood type resistant to Plasmodium vivax?

Answer 24

P. vivax requires the Duffy antigen to enter red blood cells. Individuals who are Duffy-negative lack this receptor, making them resistant to infection

Question 25

How does Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency protect against malaria?

Answer 25

causes increased oxidative stress inside red blood cells, which damages Plasmodium parasites and makes the host cells less hospitable for parasite survival, providing protection against malaria

Question 26

how is Malaria diagnosed?

Answer 26

- macroscopic exam of blood (banana shaped gametocytes and ring shaped trophozoites) - PCR

Question 27

what are the treatments for Malaria?

Answer 27

- chloroquine (not anymore due to resistance) and artemisinin (main)

Question 28

what are the preventions for Malaria?

Answer 28

vector control - outdoor fogging or area spraying (weak effectiveness) - indoor residual spraying or insecticidal nets

Question 29

What are the key features of the WHO-approved R21 malaria vaccine?

Answer 29

- Approved in 2023 to protect babies for up to 18 months - Consists of virus-like particles with the circumsporozoite protein fused to hepatitis B surface antigen (HBsAg) and uses Matrix-M adjuvant to enhance the immune response

Question 30

who is at the highest risk of becoming infected with Malaria?

Answer 30

- immigrants living in non-endemic countries - pregnant people

Question 31

What is Babesiosis and how is it transmitted?

Answer 31

seasonal tick-borne protozoal infection of red blood cells, primarily caused by Babesia microti in the northeast and upper midwest US in warm months

Question 32

Where does sexual reproduction of Babesia microti occur, and through which vector?

Answer 32

occurs in the gut of the Ixodes scapularis tick (blacklegged tick), the same vector that transmits Lyme disease where the parasite completes sporogony and fertilization inside the tick

Question 33

Where does asexual reproduction of Babesia microti occur in its natural life cycle?

Answer 33

occurs in the red blood cells of the white-footed mouse, where the parasite multiplies and forms merozoites and gametes

Question 34

How do humans become accidental hosts in the Babesia microti life cycle?

Answer 34

when bitten by an infected tick, the parasite enters red blood cells, undergoes asexual/sexual replication, and may produce gametes that get ingested by another tick

Question 35

how can human-human transmission occur with Babesia microti?

Answer 35

blood transfusions

Question 36

what is the clinical presentation for Babesia microti?

Answer 36

an incubation period of 1-4 weeks that presents with non-specific flu symptoms that can last several weeks

Question 37

what individuals can develop the severe life threatening form of Babesia microti?

Answer 37

- those who do not have a spleen - have weakened immune system - elderly

Question 38

what is the diagnosis for Babesia microti?

Answer 38

- microscopic examination of blood smear showing maltese cross-shaped blood cells

Question 39

what is sepsis?

Answer 39

life threatening medical emergency that occurs when the bodies immune system overreacts to an infection in the bloodstream * 3rd leading cause of death

Question 40

what are the common causes of sepsis?

Answer 40

bacteremia (most common), candidemia, parasitemia and viraemia

Question 41

what does a sepsis infection trigger?

Answer 41

extensive inflammation throughout the body that damage organ systems leading to tissue damage, organ failure or death

Question 42

what are the general symptoms of sepsis?

Answer 42

fever, difficulty breathing, low blood pressure, fast heart rate and mental confusion

Question 43

Who is most at risk for developing sepsis, and how can it start?

Answer 43

- can affect anyone, but high-risk individuals are more prone to infection - often begins when bacteria in wounds (e.g., from bedsores, trauma, appendicitis, or surgery) enter the bloodstream

Question 44

How can a dental infection lead to sepsis?

Answer 44

Heavily infected teeth, especially in hospitalized patients, may harbor Gram-negative flora that allow bacteria to enter the bloodstream, particularly in those with weakened immunity or poor oral hygiene

Question 45

what are the stages of sepsis?

Answer 45

1. SIRs 2. Sepsis 3. Severe Sepsis 4. Septic Shock

Question 46

What are the clinical criteria for Systemic Inflammatory Response Syndrome (SIRS)?

Answer 46

diagnosed when two or more of the following are present: - Temperature >38°C or <36°C (Hypothermia/Fever) - Heart rate >90 bpm (Tachycardia) - Respiratory rate >20/min or PaCO₂ <32 mm Hg (Tachypnea) - WBC count >12,000/mm³ or <4,000/mm³ or >10% bands

Question 47

What defines Sepsis in relation to SIRS?

Answer 47

Sepsis occurs when SIRS is caused by a confirmed microbial infection

Question 48

What is Severe Sepsis?

Answer 48

sepsis that results in acute organ dysfunction or mental confusion

Question 49

What characterizes Septic Shock, and why is it dangerous?

Answer 49

involves persistent, extreme hypotension that requires vasopressors (like norepinephrine) to maintain blood pressure - has a hospital mortality rate >40%

Question 50

What triggers the innate immune response in sepsis?

Answer 50

Recognition of PAMPs (Pathogen-Associated Molecular Patterns) by pattern recognition receptors (PRRs) on immune cells, leading to systemic inflammation

Question 51

What is the key PAMP on gram-positive bacteria?

Answer 51

Peptidoglycan, found in the cell wall, is a major PAMP recognized by the immune system

Question 52

What is the key PAMP on gram-negative bacteria and what does it do?

Answer 52

Lipopolysaccharide (LPS) is found on the outer membrane of gram-negative bacteria which acts as an endotoxin, triggering strong immune responses and systemic inflammation

Question 53

What happens when TLRs (Toll-like receptors) are triggered by microbial antigens?

Answer 53

They activate a signal transduction pathway that stimulates NF-κB (nuclear factor-kappa B), a transcription factor critical in the immune response

Question 54

What is the role of NF-κB in sepsis?

Answer 54

binds to DNA and promotes the transcription of pro-inflammatory cytokines, such as TNF-α, IL-1, IL-6, which drive the inflammatory response

Question 55

How does a cytokine storm develop in sepsis?

Answer 55

A bloodstream infection creates an auto-amplifying loop of immune activation, releasing large amounts of cytokines and nitric oxide, leading to vasodilation, circulatory collapse, and multi-organ failure

Question 56

What are the key steps in the treatment and management of sepsis?

Answer 56

- Act quickly — early intervention is critical - Ensure hemodynamic stability using 30 mL/kg of isotonic crystalloids for fluid resuscitation - Perform primary source control (e.g., drain abscesses, treat infections surgically) - Collect cultures before antibiotics if possible - Administer broad-spectrum antibiotics ASAP - Use glucocorticoids if needed to manage inflammation - Maintain tight blood glucose control