Malaria Flashcards
How has the incidence of malaria changed from 2000-2015?
Decreased by ~40%
What is the current mortality rate of malaria?
62%
Why is malaria spread restricted to specific areas of tropics, and describe the compass points of these tropics?
Tropics located 60 degrees north and 40 degrees south
Anopheles mosquitos can breed here
Can malaria spread in areas at high altitudes?
Doesn’t occur in areas higher than 2000m as anopheline mosquitoes can’t survive and breed
What are the 3 WHO regions where malaria incidence is highest, from highest to lowest?
Africa WHO region
South-East Asia WHO region
Eastern Mediterranean WHO region
What percentage of deaths in young children under 5 yrs old occurred due to malaria?
~75%
3/4 deaths
What is the genus of the parasite that causes malaria?
Plasmodium
In the plasmodium lifecycle, is the parasitic material carried by male or female anopheles mosquitos?
Female anopheles mosquitos are affected
What is are the 5 species of parasite that cause malaria?
Plasmodium falciparum
P. Ovale
P. Malariae
P. Vivax
P. Knowlesi
In the plasmodium lifecycle, when an infected female anopheles mosquito bites a human, what does it release into the bloodstream?
Bites human and releases saliva which contains plasmodium sporozoite into human bloodstream
In the plasmodium lifecycle, when is are plasmodium sporozoites first exposed to the human?
When the infected female anopheles mosquito bites the human and injects its sporozoite-containing saliva into human bloodstream
In the plasmodium lifecycle, which cells do plasmodium sporozoites enter after being injected into human bloodstream, and what structure do they mature into?
Plasmodium sporozoite enter liver parenchymal cells
take 2 weeks to mature into pre-erythrocytic schizonts
In the plasmodium lifecycle, how long does it take for sporozoites to mature into pre-erythrocytic schizonts, and in which cells does this take place?
Takes 2 weeks
Liver parenchymal cells
In the plasmodium lifecycle, what do pre-erythrocytic schizonts release, and where is this structure transported to?
Pre-erythrocytic schizonts erupt and each release 10,000-40,000 merozoites
Merozoites circulate in blood before entering RBCs
Which 2 plasmodium species don’t have all of their sporozoites changed into merozoites, and what structure do they form instead?
P. Vivax and P. Ovale
Some sporozoites mature into hypnozoites, in the liver parenchymal cells
In the plasmodium lifecycle of P. Vivax and P. Ovale, what happens to the hypnozoites that form?
Hypnozoites stay dormant in liver, cause relapse of malaria when activated
In the asexual blood stage of the plasmodium lifecycle, what 2 structures are produced from merozoites in RBCs?
Merozoites mature into trophozoites (ring form)
Trophozoites mature into schizonts
In the asexual blood stage of the plasmodium lifecycle, what do schizonts release, and where are these transported to?
Schizonts erupt and release daughter merozoites
Daughter merozoites are released back into circulation
In the plasmodium lifecycle, does the sexual blood stage need to happen immediately after one cycle of the asexual blood stage has been completed, if not what happens instead?
Cycle containing asexual blood stage can continue for months-years until sexual stage begins
Daughter merozoites that were released into circulation at end of previous asexual stage will enter RBCs, reproduce asexually, release more merozoites into circulation: this cycle continues
In the sexual stage of the plasmodium lifecycle, what structure is formed from merozoites and how are these structures given to an unaffected female anopheles mosquito?
Merozoites in RBCs mature into male and female gametocytes
which are ingested by anopheles mosquito during blood meal
In which stage of the plasmodium lifecycle does the female anopheles mosquito become infected?
Sexual stage, when mosquito ingests male and female plasmodium gametocytes during blood meal from human
In the plasmodium lifecycle, what happens to the male plasmodium gametocyte in the mosquito’s gut, and what other structure does this combine with?
Male gametocyte exflagellates to from male microgametocyte
Male microgametocyte fertilises female gametocyte to from zygote
In the plasmodium lifecycle, what happens to the plasmodium zygote once it invades the gut mucosa of the mosquito?
Zygote invades gut mucosa and becomes oocyst
In the plasmodium lifecycle, what happens to the oocyst in order to create sporozoite-containing saliva of the mosquito?
Oocyst develops into 1000s of sporozoites
Sporozoites released from gut mucosa and migrate to mosquito salivary glands
How many receptor-ligand interactions are needed for plasmodium to enter RBCs, in the plasmodium lifecycle?
2
Eg. duffy antigen is a RBC cell receptor
Why is P. Vivax unable to invade RBCs of most west Africans, and so they can’t get infected with malaria (malaria resistance)?
Most west Africans are duffy-negative, and duffy antigen is one of the RBC cell receptors that P. Vivax need to bind to to invade the RBC
Therefore P. Vivax can’t invade RBCs
How has P. Vivax evolved to now be able to infect duffy-negative individuals (thought to be malaria-resistant)?
P. vivax has evolved to invade RBCs in another way, as P. Vivax infection of duffy-negative individuals has now been confirmed.
Apart from being duffy-negative, give 3 other examples of genetic traits that contribute to malaria resistance?
haemoglobin S (sickle cell)
beta-thalassaemia
glucose-6-phosphate dehydrogenase (G6PD) deficiency
When an individual has malaria caused by Plasmodium falciparum, how long after initial infection does malaria become fatal and why?
Fatal in first 2 weeks after initial infection
Due to complications
In hyperendemic areas, which 2 types of individuals are commonly affected by malaria caused by Plasmodium falciparum?
Pregnant women
Children aged 6 months-5 years
In non-immune individuals, which age range is most commonly affected by malaria caused by Plasmodium falciparum?
All ages
Do P. Ovale and P. Malaraie malaria need treatment or are they self-limiting?
Self-limiting usually
Can P. Ovale and P. Malariae malaria relapse, if so what does a relapse commonly present with?
Yes, commonly presents with anaemia
What is the common initial presentation of malaria caused by P. Vivax, and what 2 later presentations cause it to have severe mortality?
Initial presentation is chronic fever
Late presentations are severe anaemia and respiratory distress
Is malaria caused by P. Knowlesi rare or common?
Rarely seen in clinical practice
What 3 factors affect the presentation of malaria?
Current blood stage of the plasmodium parasite
Plasmodium species
Travel history
Which stage of the plasmodium lifecycle causes fever to present in a patient with malaria?
Asexual blood stage, when erythrocytic schizonts erupt and release daughter merozoites
Do all plasmodium species cause the fever to present the same way in malaria cases?
Different plasmodium species cause periodicity (consequent fevers develop with no symptoms inbetween) and characteristic patterns
What is Hyper-reactive Malarial Splenomegaly Syndrome (HMSS), in the presentation of malaria?
Splenomegaly (spleen enlargement) occurs due to increased production of myeloid cells in spleen to remove infected RBCs
Give 3 conditions that occur due to malaria progression, that cause presentation of intra-abdominal pain?
Splenic rupture
Hepatitis
Acute renal failure
What is the most severe neurological complication of malaria, and which plasmodium species causes it?
Cerebral malaria
Plasmodium falciparum
What are the 2 initial and 1 late characteristic feature of cerebral malaria, which is caused by Plasmodium falciparum?
Initial features: seizures, impaired consciousness
Late feature: rapid progression to coma
Give 2 causes of severe anaemia,in the presentation of malaria?
RBC destruction
Dyserythropoiesis (defective development of RBCs) in bone marrow
Which Plasmodium species causes hypoglycaemia to be a feature of malaria presentation, and give 2 reasons why it occurs?
Plasmodium falciparum
Increased glucose use
Decreased glucose production due to gluconeogenesis inhibition
In malaria caused by Plasmodium falciparum, is hypoglycaemia an important contributor to mortality?
Yes
Is lactate acidosis an important contributor to mortality, in the presentation of malaria?
Yes
Give 2 causes of lactate acidosis, which occurs in the presentation of malaria?
increased lactate production from anaerobic glycolysis
lack of lactate clearance due to liver dysfunction
Which 2 Plasmodium species cause acute renal failure as a severe complication of malaria?
Plasmodium falciparum
P. knowlesi
In the investigation of malaria, what is the gold-standard method for confirming diagnosis?
Identifying parasitised RBCs in thin and thick blood films (layer of blood smeared on slide to be examined microscopically)
In the investigation of malaria, what 2 factors can be identified from thin and thick blood films?
Plasmodium species
Current stage of Plasmodium lifecycle
Why are multiple thin and thick blood films needed to exclude a malaria diagnosis?
Single negative blood film does not exclude malaria of any species
Eg. P. Falciparum infection, later (schizont) stages may be sequestered in deep tissues, so parasites may be deceptively scarce in, or even absent from, the peripheral blood.
How does lateral-flow immunoassay/dipstick diagnose malaria, and give 2 benefits of this method compared to obtaining thin and thick blood films?
Pre-coated antibodies on test lines will bind to malarial antigens
This is quicker to complete and doesn’t require lab
How does a malaria DNA/RNA assay diagnose malaria, and give 1 benefit and 2 disadvantages?
Measure of Plasmodium in the blood
Is highly-specific
Laborious as it has multiple processing steps, expensive as it has costly reagents
How does serology IgG antibody test indicate malaria?
Detects IgG antibodies against malaria that are present due to recent infection (positive test)
To treat malaria, what are 2 pieces of info you should have before administering a chemoprophylactic agent?
Prophylaxis was obtained from reputable UK source
Prophylactic agent is appropriate for the patient (eg. are they HIV positive) and their destination
What are the first-line and second-line drugs to treat severe malaria, and what are each of these drugs used in combination with?
First-line: IV artesunate
Second-line: IV quinine
Use first/second-line drug in combination with other anti-malarial drugs to prevent drug resistance?
To treat severe malaria, when would you use IV quinine (second-line) instead of IV artesunate (first-line)?
Quinine used when artesunate can’t be obtained without delay
What drug is used to treat uncomplicated falciparum malaria?
oral artemisinin combination therapy
Which drugs are used to treat uncomplicated vivax, ovale, malariae or knowlesi malaria?
oral artemisinin combination therapy
OR
oral chloroquine
What drug is used to treat complicated vivax, ovale, malariae or knowlesi malaria?
Oral artemisinin combination therapy
Which drug prevents relapses of vivax and ovale malaria, and describe the mechanism of action?
Primaquine
Kills hypnozoites of P. Vivax or P. Ovale in the liver, and thus prevent relapses of these infections
When is primaquine contraindicated for use in preventing relapses of vivax and ovale malaria?
Contraindicated in G6PD deficiency
Is preventative chemoprophylaxis alone effective in preventing malaria, if not then how is this improved?
Chemoprophylaxis and mosquito avoidance combined give significant protection (not 100% effective)
How can websites help prevent malaria?
Websites such as Fit For Travel, Government provide travel info about malaria
What makes bed nets effective in preventing malaria?
They are bed nets with insecticide so will kill mosquitos
What percentage of the household surface area should be sprayed with insecticide to effectively protect against malaria?
Over 80% of SA
What is the RTS,S vaccine, and what does WHO recommend about its implementation in Africa?
RTS,S vaccine: recombinant circumsporozoite protein based vaccine designed to combat invasive sporozoite stage either in the skin or as it invades the liver
WHO recommended large-scale implementation of vaccine in African children aged 5-9 months
