*(XV) Parasite (2)*Malaria Flashcards
ART (artemisinin) is generally used for […]
Chloroquine is generally used for […]
ART (artemisinin) is generally used for P. falciparum
Chloroquine is generally used for P.vivax & P.ovale
General rule of thumb to help with MCQs!!
Carriers of malaria: […]
Carriers of malaria: Anopheles mosquitos and humans
Chill card: Brief pathophysiology of malaria
- Injection of […] by infected anopheles mosquito
- 10-100 sporozoites injected
- within an hour sporozoites enter liver (NOTE that only […] form can infect! The only way to get infected is DIRECTLY FROM MOSQUITOS)
- undergo […]sexual replication (20000-50000 folds, aka EXPONENTIAL wth thats damn alot) (these ones cannot re-infect liver cuz they change target to RBC alr ~)
Chill card: Brief pathophysiology of malaria
- Injection of sporozoites by infected anopheles mosquito
- 10-100 sporozoites injected
- within an hour sporozoites enter liver (NOTE that only sporozoites form can infect! The only way to get infected is DIRECTLY FROM MOSQUITOS)
- undergo asexual replication (20000-50000 folds, aka EXPONENTIAL wth thats damn alot) (these ones cannot re-infect liver cuz they change target to RBC alr ~)
Clinical manifestation and pathophysiology of malaria
Anemia, Jaundice –> […]
Chills, Rigors, Fever, Perspiration –> […]
Thrombosis and inflammation (also results in renal impairment and metabolic acidosis) - TNF-a and IFNλ release when infected RBCs adheres to endothelial wall.
Clinical manifestation and pathophysiology of malaria
Anemia, Jaundice –> when RBCs burst (and when splenic macrophage engulfs RBCs)
Chills, Rigors, Fever, Perspiration –> macrophage release cytokines (in cycles, each time RBCs burst, releasing merozoites)
Thrombosis and inflammation (also results in renal impairment and metabolic acidosis) - TNF-a and IFNλ release when infected RBCs adheres to endothelial wall.
https://www.youtube.com/watch?v=oQmL6XqCKSU - watch for more info
“Merozoites infect red blood cells . The ring stage trophozoites mature into schizonts, which rupture releasing merozoites “
Compared to a mosquito bite, a malaria related needlestick transmission is urgent because it […]
Compared to a mosquito bite, a malaria related needlestick transmission is urgent because it bypasses the 2 weeks liver stage (so you only have a few days to save the patient)
Dictionary for forms of plasmodium yey
Sporozoites = […] form
- Cells infected with sporozoites –> trophozoites –> eventually burst, releasing […] into the bloodstream
- Sporozoites are motile and they move by gliding.
Hypnozoites = […] form
- only in p.[…] and p.[…]
Merozoites = […] form
- result of merogony (asexual repro) that takes place within a host cell. - - In coccidiosis, merozoites form the first phase of the internal life cycle of coccidian.
- In the case of Plasmodium, merozoites infect […] and then rapidly reproduce asexually (can’t reinfect liver)
Trophozoites = Active feeding stage, ring stage
Schizont = mature form of trophozoites
- ruptures RBC to infect other RBCs (each time this happens, clinical manifestation of fever, chills)
Gamatocytes = the precursors of male and female gametes formed in the human host through the developmental switch from asexual replication in erythrocytes
TLDR, Sporozoites –> hypnozoite (Pv/Po) –> Merozoites –> trophozoite (2 fates)
- First fate (exponential asexual reproduction ): –> schizont –> Merozoites –> repeat
- Second fate: –> gamatocyte –> pass to mosquitos –> sexual repro in mosquitos –> sporozoites –> pass to another human
Dictionary for forms of plasmodium yey
Sporozoites = Liver Infective form
- Cells infected with sporozoites –> trophozoites –> eventually burst, releasing merozoites into the bloodstream
- Sporozoites are motile and they move by gliding.
Hypnozoites = dormant form
- only in p.vivax and p.ovale
Merozoites = RBC Infective form
- result of merogony (asexual repro) that takes place within a host cell. - - In coccidiosis, merozoites form the first phase of the internal life cycle of coccidian.
- In the case of Plasmodium, merozoites infect red blood cells and then rapidly reproduce asexually (can’t reinfect liver)
Trophozoites = Active feeding stage, ring stage
Schizont = mature form of trophozoites
- ruptures RBC to infect other RBCs (each time this happens, clinical manifestation of fever, chills)
Gamatocytes = the precursors of male and female gametes formed in the human host through the developmental switch from asexual replication in erythrocytes
TLDR, Sporozoites –> hypnozoite (Pv/Po) –> Merozoites –> trophozoite (2 fates)
- First fate (exponential asexual reproduction ): –> schizont –> Merozoites –> repeat
- Second fate: –> gamatocyte –> pass to mosquitos –> sexual repro in mosquitos –> sporozoites –> pass to another human
NGL it is damn confusing but no worries it takes time!!! :)
A merozoite (G. meros, part [of a series] +zōon, animal) is the result of merogony that takes place within a host cell. In coccidiosis, merozoites form the first phase of the internal life cycle of coccidian. In the case of Plasmodium, merozoites infect red blood cells and then rapidly reproduce asexually. The red blood cell host is destroyed by this process, which releases many new merozoites that go on to find new blood-borne hosts. Merozoites are non-motile. Before schizogony, the merozoite is also known as the schizozoite.
In the following species of plasmodium, the sporozoites may enter the dormant phase, known as hypnozoites. They can reactivate later in life.
[…]
In the following species of plasmodium, the sporozoites may enter the dormant phase, known as hypnozoites. They can reactivate later in life.
Plasmodium Vivax & Plasmodium Ovale
(and Plasmodium cynomolgi)
Treat with primaquin
Malaria are caused by eukaryotic organelles known as […] which belong to a family of organisms known as […]
Malaria are caused by eukaryotic organelles known as plasmodium which belong to a family of organisms known as apicomplexa
The Apicomplexa are a diverse group that includes organisms such as the coccidia, gregarines, piroplasms, haemogregarines, and plasmodia. Diseases caused by Apicomplexa include:
Babesiosis (Babesia)
Malaria (Plasmodium)
Cryptosporidiosis (Cryptosporidium parvum)
Cyclosporiasis (Cyclospora cayetanensis)
Isosporiasis (Isospora belli)
Toxoplasmosis (Toxoplasma gondii)
Malaria infection, you remain latent for about…
[…] after the infective mosquito bite
Then you’ll get […] which may be mild and difficult to recognise as malaria
then….
[…]
PERIODIC FEVER bc of life cycle of plasmodium
If not treated within 24 hours, Plasmodium falciparum malaria can progress to severe illness, often leading to death
Malaria infection, you remain latent for about…
in 7 days (10 15 days) after the infective mosquito bite
Then you’ll get : flu like symptoms, tiredness which may be mild and difficult to recognise as malaria
then….
high fever, shaking chills, headaches, myalgia, tiredness, nausea, vomiting and diarrhea, anemia and jaundice
PERIODIC FEVER bc of life cycle of plasmodium
If not treated within 24 hours, Plasmodium falciparum malaria can progress to severe illness, often leading to death
In some case….
Malaria is transmitted mainly by […], but also by […]
Malaria is transmitted mainly by Anopheles mosquito, but also by transfusion, congenital (rare) and needlestick injuries
The latter 3 more urgent because bypass liver stage!!!
FYI: the two species are A. sundaicus (coastal brackish waters) and A.maculatus (clear water, streams, hilly areas)
Obstruction of blood flow in malaria infections are due to […] and increased levels of parasitemia
- Cytoadherance
- Rosetting
- Autoagglutination
- iRBC deformability
Obstruction of blood flow in malaria infections are due to RUPTURE of the RBC and increased levels of parasitemia
- Cytoadherance
- Rosetting
- Autoagglutination
- iRBC deformability
Of the 5 species of plasmodium, the 2 most important are
- […] - contributes to mortality
- […] - contributes to mortality
Less impt:
- P. malariae
- P. ovale
- P. knowlesi (monkeys)
Of the 5 species of plasmodium, the 2 most important are
- P. falciparum - contributes to mortality
-* P. vivax* - contributes to mortality
Less impt:
- P. malariae
- P. ovale
- P. knowlesi (monkeys)
Plasmodium falciparum invades […] while plasmodium vivax invades […]
Plasmodium falciparum invades erythrocytes while plasmodium vivax invades reticulocytes
Therefore scientists have trouble culturaing vivax. not enough reticulocytes
Rapid diagnostic test (preliminary testing) for malaria uses tests by identifying:
- […]
- only for […], is sensitive
- limitations: there are some HRP-2 negative strains, can persist after parasite clearance, not produced by gamatocytes - […]
- Pan specific (chim term for all species lol), indicates VIABLE parasites
- limitation: may be less sensitive (esp for Po/Pm)
These are immunochromatographics/dipsticks/card format, so they are
- easy to perform and intepret (~10mins)
- BUT EXPENSIVE compared to microscopy blood test (US $3-5 per test)
Rapid diagnostic test (preliminary testing) for malaria uses tests by identifying:
-
Histidine-rich protein-2 (HRP- 2)
- only for P. Falciparum, is sensitive
- limitations: there are some HRP-2 negative strains, can persist after parasite clearance, not produced by gamatocytes -
Parasite lactate dehydrogenase (pLDH)
- Pan specific (chim term for all species lol), indicates VIABLE parasites
- limitation: may be less sensitive (esp for Po/Pm)
These are immunochromatographics/dipsticks/card format, so they are
- easy to perform and intepret (~10mins)
- BUT EXPENSIVE compared to microscopy blood test (US $3-5 per test)
How it works:
3 lines –> means falciparum (It can only be sure of falciparum)
top and btm line –> means other species (vivax, etc, cannot be sure)
Symptoms of malarial infection
- nonspecific and may manifest as
- flulike illness with […]
- headache
- malaise
- fatigue
- muscle aches.
CAN LEAD TO DEATH esp p.falciparum and p.vivax
recurrent fever due to life cycle of plasmodium
- Schizont (mature form of trophozoites) ruptures RBC to infect other RBCs
- each time this happens, clinical manifestation of fever, chills
Symptoms of malarial infection
- nonspecific and may manifest as
- flulike illness with fever
- headache
- malaise
- fatigue
- muscle aches.
CAN LEAD TO DEATH esp p.falciparum and p.vivax
recurrent fever due to life cycle of plasmodium
- Schizont (mature form of trophozoites) ruptures RBC to infect other RBCs
- each time this happens, clinical manifestation of fever, chills
Some patients with malaria present with diarrhea and other gastrointestinal (GI) symptoms. Immune individuals may be completely asymptomatic or may present with mild anemia.
The key differentiating factor of various species of plasmodium on a THIN blood film (not thick. thick not to see species!!) (IMPT)
Plasmodium Falciparum
- […] infection in single RBC
- infected cell is […] as uninfected cell
- […] gametocytes (can be found if lucky)
- […] form (pushed to the side)
Plasmodium Vivax
- infected cell is […] uninfected cell
- […]
Plasmodium malariae
- band-like
- EASILY CONFUSED WITH P.KNOWLESI - monkey malaria
The key differentiating factor of various species of plasmodium on a THIN blood film (not thick. thick not to see species!!) (IMPT)
Plasmodium Falciparum
- multiple infection in single RBC
- infected cell is SAME SIZE as uninfected cell
- crescentic gametocytes (can be found if lucky)
- Accole form (pushed to the side)
Plasmodium Vivax
- infected cell is BIGGER THAN uninfected cell
- Schuffner’s dots
Plasmodium malariae
- band-like
- EASILY CONFUSED WITH P.KNOWLESI - monkey malaria
Note that we only see early stages for falciparum bc only later stages sequester (hide) in the tissues.
But for the other species, all stages can be seem.
The species of malaria parasite that causes most death is
[…]
The species of malaria parasite that causes most death is
Plasmodium falciparum (90%)
^ Mainly in sub-saharan africa
The rest of the species not as life threatening.
Vivax is second most.
The three lab tests for malaria are:
1.. […]
- lateral flow immunochromatographic assay
- provide preliminary result to clinical team, inform them confirmatory tests will follow
- […] MOST IMPT
- Microscopic examination of blood films
- Thin and thick blood smear + staining
- GOLD STANDARD!!
- Advantages: simple, cheap, sensitive, specific, quantitative :)
- Disadvantages: time consuming, laborious, requires trained personnel, biosafety (pathogens such as hepB and HIV potentially found in blood) - […]
- Advantages: Real time PCR is rapid and can identify all 4 species
- Disadvantages: Expensive, inhibitory blood products
The three lab tests for malaria are:
1.. Rapid Diagnostic Test
- lateral flow immunochromatographic assay
- provide preliminary result to clinical team, inform them confirmatory tests will follow
-
Microscopy: Blood Test MOST IMPT
- Microscopic examination of blood films
- Thin and thick blood smear + staining
- GOLD STANDARD!!
- Advantages: simple, cheap, sensitive, specific, quantitative :)
- Disadvantages: time consuming, laborious, requires trained personnel, biosafety (pathogens such as hepB and HIV potentially found in blood) -
PCR
- Advantages: Real time PCR is rapid and can identify all 4 species
- Disadvantages: Expensive, inhibitory blood products
if bloodtest/PCR is negative –> repeat testing as indicated
if bloodtest is positive –> provides identification of infecting species –> calculate percentage parasitemia
if PCR is positive –> calculate percentage parasitemia
Thick blood smear vs Thin blood smear (IMPT)
Thick blood films - for […] of malaria parasite
- lyse the blood cells
- tiny dots on blood slides
- concentration method
- difficult to identify species
Thin blood films - for […] of malaria parasite
- can see the parasites IN the blood cell
- can identify specific species
The staining is called […] stain (which is used for Chlamydia as well)
Thick blood smear vs Thin blood smear (IMPT)
Thick blood films - for PRESENCE of malaria parasite
- lyse the blood cells
- tiny dots on blood slides
- concentration method
- difficult to identify species
Thin blood films - for SPECIES of malaria parasite
- can see the parasites IN the blood cell
- can identify specific species
The staining is called Giemsa stain (which is used for Chlamydia as well)
HH’s ez dab understanding:
Thick = dense + rbc kaboom = can see presence easily
Thin = spread out + rbc intact = can identify species individual malaria parasites
To kill dormant form of malaria (eg. P. vivax, P. ovale), give […] (in combination with other drugs)
To kill dormant form of malaria (eg. P. vivax, P. ovale), give Primaquine (in combination with other drugs)
It’s the only drug that kills dormant malaria. Always comes out in MCQ!!!
DON’T DON’T DON’T DON’T DON’T Give it to someone with SEVERE G6PD deficiency
(or pregnant mummies bc babies might be G6PD deficient)
Treatment for uncomplicated malaria
[…] - rapidly and reliably effective
1. Artesunate-Mefloquine
2. Artemether-Lumefantrine
3. Dihydroartemisin-Piperaquine
Treatment for uncomplicated malaria
Artemisinin based combination therapy (ACTs) - rapidly and reliably effective
1. Artesunate-Mefloquine
2. Artemether-Lumefantrine
3. Dihydroartemisin-Piperaquine
MUST USE COMBINATION IF NOT GAIN RESISTANCE
The last 2 examples in the slides (out of 5) are known to be resisted alr. so don’t use.
Treatment of severe malaria
Medical emergency. IMMEDIATELY start with:
- […]
- Alternative: […]
Second-line
- Use the above WITH […]
Treatment of severe malaria
Medical emergency. IMMEDIATELY start with:
- Artesunate
- Alternative: Quinine (ORAL not IV)
Second-line
- Use the above WITH Doxycycline/Tetracyclin/Clindamycin
