Malaria in more depth

Question 1

outline the basic characteristics of malaira

Answer 1

• belong to the sporozoa, Apicomplexa with the key feature being the cluster of special organelles in the apical complex
• not caused by a single parasite but several different species from the genus plasmodium
• vector borne disease transmitted by female, grandmother mosquitos
• found in 106 countries and territories known as endemic areas

Question 2

what are the five species of plasmodium which can infect humans

Answer 2

1) plasmodium falciparum = most severe aka cerebral malaria
2) plasmodium vivax = second greatest threat
3) plasmodium malariae
4) plasmodium ovale
5) plasmodium knowlesi = quite rare and only in certain parts of SE Asia

Question 3

outline some basic characteristics of the Anopheles mosquito (the vector)

Answer 3

historically associated with swamps as their larvae are aquatic - derived from Italian translating to ‘bad air’
- around 460 species of Anopheles mosquitos globally
- around 41 of these species can vector malaria in nature

Question 4

what are some of the most important species of anopheles mosquitos

Answer 4

1) Anopheles gambiae
2) Anopheles funestus ( sub-saharan africa)
3) Anopheles stephensi (India and Asia countires

Question 5

outline the global burden of malaria

Answer 5

3.3 billion lives at risk
229 million cases globally in 2019
94% of cases in African regions
409,000 deaths in 2019 of which 67% under 5 yrs

Question 6

outline the three key features of the plasmodium lifecycle which are common to all the species

Answer 6

1) BITE- female mosquito bites injecting 100-200 parasites with infective saliva
2) LIVER- the eco-erythrocytic stage, schizont formation and merozoite release
3)RED BLOOD CELL-erythrocytic stage, merozoites infect by endocytosis and divide into 12-16 new merozoites in red blood cells feeding on haemoglobin before bursting out cell and repeats

• duration of the erythrocytic stage depends on parasite species

Question 7

what stage of the plasmodium life cycle makes individuals feel sick

Answer 7

during the red blood stage aka erythrocytic stage
- liver stage are asymptomatic aka the pre-patent period, this can last as few as 9 days or up to a month
- begin to feel sick when ruptured RBC (HAEMOLYSIS) occur releasing parasite, waste, metabolites and host cell debris (PYOGENIC MATERIALS) leading to illness, fever, anaemia and other problems

Question 8

how can taking travel prophylaxis alter the length of the pre patent stage in the liver

Answer 8

they are anti-malarial drugs which try to prevent infection but they don’t always work resulting in delayed appearance of malaria symptoms by weeks

Question 9

what are the specific signs and symptoms of malaria from a clinical perspective

Answer 9

PAROXISMS= chills, fever (around 41 degrees) and sweats
chills/shaking (rigors)
fevers begin very abruptly and are chaotic to begin with but after a week or two haemolysis becomes synchronised (depending on species) therefore so do fevers

SIGNS= can bee seen or detected by physician e.g. high blood pressure
SYMPTOMS= felt by patient but cant be seen e.g. pain

Question 10

outline non-specific signs and symptoms which may be looked for from a clinical perspective

Answer 10

flu- like symptoms; muscle pain, headache abdominal discomfort, fatigue, cough, enlarged spleen/liver
- in endemic regions a fever will be treated as malaria until proven otherwise

Question 11

when looking at clinical presentation of malaria when is it considered uncomplicated (when the life of patient is not in danger)

Answer 11

fever and rigor, abdominal pain, headache, cough, enlarged spleen/liver

Question 12

when looking at clinical presentation of malaria when is it considered severe (when the life of patient is in danger)

Answer 12

many of all the uncomplicates symptoms in addition with
- decreased consciousness ( more than two convulsions in 24hours)
- difficulty breathing
- liver impairment/jaundice
- impaired kidneys
- inability to stand up
- low blood sugar

Question 13

what is a virulence factor and how does it make plasmodium falciparum more deadly than other species

Answer 13

VF= cellular structures, molecules and regulatory systems which enable microbial pathogens to successfully exploit a niche

P.falciparum has a VF called PfEMP1 which forms knobs on the surface of infected RBC allowing infected cells to stick to blood vessel walls (CYTO-ADHERENCE) impeding blood flow leading to blockages –> hypoxia–> death of brain tissue

Question 14

how does the vivax and ovale species form relapsing malaria

Answer 14

the production of hyponozoites aka sleeping parasites which are a particular developmental stage which goes dormant in liver cells then reactivates, re-occuring at intervals from every few weeks to months for up to 5 years
- hard to do well in school or job
- challenging to treat as need to clear parasites from both liver and blood
- allowed spread into more temperature regions as they can now tolerate lower temps

Question 15

what are some malaria diagnostic tests and how do they help with staging

Answer 15

1) blood smear (gold standard)
- takes skilled technician about 30 mins a slide
- costly to maintain e.g. equipment
2) Rapid diagnostic test (RDT)
- narrow down the species or sub species
- cheaper and faster, no skilled technician
3) Nucleic acid amplification test (NAAT)
- tell us if drug resistant strain
answers questions for staging
1) how serve in infection
2) what is plasmodium species
3) is it drug resistant form

Question 16

what are the two types of blood smear used to diagnose malaria

Answer 16

1) thick smear = small drop of blood
- goof for initial conformation
2) thin smear = small drop which is then thinly smeared over the slide from edge to edge
- good for detail e.g. infection stage and species

slides are then fixed and stained
if slides are negative repeat after 12-24 hours and after another 24 hours

Question 17

outline of RDTs are carried out

Answer 17

dipstick format immuno-chromatography on blood samples
- detects malarial antigens using dye-labelled antibodies to bind them
- similar to covid diagnostic

Question 18

outline the advantages and disadvantages of using RDTs

Answer 18

+ can be used with limited training
+ can be rapidly available
+ modern RDTs are high quality
+ helps distingusih between malarial/nonmalrial fevers
- cant speciate
- impaired if stored at wrong temp
- not highly sensitive just produced negative or psotive result
- poses as selective pressure so malarial strains evoloved to lack hrp2 gene which needed to identify

Question 19

outline how NAAT tests work

Answer 19

DNA is amplified enzymatically
- by PCR
-by LAMP

allows parasite specific genes to be amplified to detectable levels and detection of specific mutations

Question 20

what can result if malaria is left untreated

Answer 20

becomes fatal
acquired immunity will eventually develop but takes years and doesn’t last a lifetime
asymptomatic carriers pose a risk to others

Question 21

what was used as an old treatment to malaria and how did it work

Answer 21

chloroquine
used as a monotherapy until plasmodium strains evolved resistance so the efficacy was compromised

targeted a process unique to the parasite so the drug had few side effects , the parasite splits Hb into two components, globin (food) and heam which is converted to a non-toxic crystal, the drug interferes with this process so parasite dies from build up of waste products

Question 22

what is Artemisinin combination therapy (ACT)

Answer 22

it is a modern malarial treatment for uncomplicated falciparium
it is always used in combination with a partner drug and works by quickly reducing most of the parasites whilst partner drugs clears remaining ones

• choice of partner drug is dependant on geographical region and local variation in drug resistance profiel

Question 23

what are the three main categories for malarial intervention

Answer 23

1) vector control
e.g. Insect treated nests, indoor residual spraying
2) chemoprophylaxis- antimalarial drugs
e.g. deployed in risk zones, travel prophylaxis taken several weeks before travel e.g. doxycycline, malarone or mefloquine
3) case management

Question 24

what factors influence the choice of mosquito control startegies

Answer 24

1) host preference e.g. humans or other animal s
2) feeding time
3) resting locations e.g. indoors or outdoors
4) ideal temp or humidity range
5) urban or rural

Question 25

outline the WHOs global technical strategy for malaria

Answer 25

by 2030
- reduce malaria by at least 90%
- reduce malaria mortality by 90%
- eliminate malaria in at least 35 countries
- prevent the return of malaria in all countries which are malaria free

Question 26

what are the 3 main threats to ending malaria

Answer 26

1) diagnosis = parasites evolving e.g. hrp2 gene deletions leading to false negatives
2) Mosquito = vector insecticide resistance
3) treatment= parasite drug resistance

Question 27

what are the vaccines which have been developed for malaria

Answer 27

just one has been developed = RTS,S/AS01 aka Mosquirix
- uses plasmodium surface molecules
- blocks falciparum from entering liver
39% efficacy so used in addiation with existing stratergies

4 injections
- 3 injections in first 60 days
- booster at 20 months
- aimed at young children

Question 28

outline the experimental vaccine being developed

Answer 28

transmission blocking vaccines
induced immunity to block plasmodium development in mosquito gut

• humans vaccinated generate antibodies so when bite and blood drunk contains antibodies