Malaria Flashcards
(40 cards)
Malaria: An Introduction
tropical parasitic disease - distributed in tropical and subtropical zones and imported into the UK
caused by protozoan parasites which infect red blood cells
often transmitted by the bite of an infected Anopheles mosquito
causes much morbidity and mortality around the world
Malaria modes of transmission
Mosquito bites (most cases)
Via the placenta
Blood transfusions
Transplantation
Contaminated equipment
Via routes associated with air travel
Species of malaria parasites that infect humans
Plasmodium falciparum
Plasmodium vivax
Plasmodium ovale
Plasmodium malariae
Plasmodium knowlesi
What makes malaria a global problem
more prevalent in some areas of the world than others due to obvious reasons such as climate and abundance of mosquitoes
Other factors include availability of funding and the degree of cooperation of governments with charities and organisations such as WHO
Education and preventative measures taken (e.g. supply of insecticide treated nets, indoor insecticide sprays, covering of bare skin)
Access and adherence to preventative measures
Accurate diagnosis
Access to treatment
Malaria Vaccines
- The first malaria vaccine, RTS,S, was recommended by WHO to prevent malaria in children in October 2021.
- December 2023 the R21/Matrix-MTM malaria vaccine developed by the University of Oxford and the Serum Institute of India, leveraging Novavax’s adjuvant technology, has been awarded prequalification status by the World Health Organization (WHO).
Malaria Cycles
The malaria parasite life cycle involves two hosts. During a blood meal, a malaria-infected femaleAnophelesmosquito
1 inoculates sporozoites into the human host
2 Sporozoites infect liver cells
3 mature into schizonts ,
4 which rupture and release merozoites (Of note, inP. vivaxandP. ovalea dormant stage [hypnozoites] can persist in the liver (if untreated) and cause relapses by invading the bloodstream weeks, or even years later.) After this initial replication in the liver (exo-erythrocytic schizogony(A) ), the parasites undergo asexual multiplication in the erythrocytes (erythrocytic schizogony (B)).
5. Merozoites infect red blood cells.
6. The ring stage trophozoites mature into schizonts, which rupture releasing merozoites
7. Some parasites differentiate into sexual erythrocytic stages (gametocytes)
8. Blood stage parasites are responsible for the clinical manifestations of the disease. The gametocytes, male (microgametocytes) and female (macrogametocytes), are ingested by anAnophelesmosquito during a blood meal
Schematic model of steps on Pf meozotie invasion
1-Merozoite in bloodstream attaches to receptor on RBC surface.
2-Merozoite re-orientates so that the apical pole is directed towards the RBC surface ( Merozoite attachment to receptor on RBC surface.)
3-Tight junction forms between merozoite and RBC surface accompanied by initial deformation of RBC membrane
4-Entry of merozoite coinciding with formation of parasitophorous vacuole.
5-Closure of RBC and parasitophorous vacuole membranes.
6-Junction between RBC membrane and parasitophorousvacuole severed releasing merozoite into the cell where it transforms into a young trophozoite.
P. falciparum binds to glycophorins A, B, and C.
* P. vivax and P. knowlesi bind to the Duffy antigen.
* The receptors for P. malariae and P. ovale are unknown.
7- Some parasites differentiate into sexual erythrocytic stages (gametocytes)
8- Blood stage parasites are responsible for the clinical manifestations of the disease. The gametocytes, male (microgametocytes) and female (macrogametocytes), are ingested by anAnophelesmosquito during a blood meal
9- The parasites’ multiplication in the mosquito is known as the sporogonic cycle(C). While in the mosquito’s stomach, the microgametes penetrate the macrogametes generating zygotes.
10- The zygotes in turn become motile and elongated (ookinetes)
11- which invade the midgut wall of the mosquito where they develop into oocysts
12- The oocysts grow, rupture, and release sporozoites ,which make their way to the mosquito’s salivary glands. Inoculation of the sporozoites
1- into a new human host perpetuates the malaria life cycle. Source CDC
Malaria in the UK - Common groups presenting with malaria
New entrant
Foreign student studying in the UK
Foreign visitor ill whilst in the UK
British citizen who has been working abroad
Armed services
Business travellers
ratio of malaria in UK residents visiting friends and relatives compared with malaria cases acquired in holiday travellers is around 10:1
Malaria in the UK - Considerations
Access to medical guidance before travel
Adherence to medical guidance
Awareness of risk
Familiarity with destination
Targeting this group along with their healthcare providers should be considered a priority
what determines individual risk?
Being unaware of malaria risk areas
Amount of malaria in the area to be visited
Time of year
Type of parasite(s) present in the area
Preventative measures taken
Immunity or lack of immunity
Appropriate travel advice is very important
Immunity in Malaria -
Most pronounced in P.falciparum disease
In areas of high transmission, if a child survives to 5-6 years he or she is likely to have a high degree of immunity
Immunity wanes over a few years without regular exposure
Immunity also wanes during pregnancy
Pregnant women and young children are most at risk
Malaria Symptoms
Fever
Chills
Headache
Flu-like symptoms
Muscle aches
Fatigue
Anaemia
Diarrhoea
Vomiting
Cough
Symptoms of cerebral malaria in P. falciparum
Lab Diagnosis Tests for Malaria
Full blood count (FBC): non specific and non diagnostic:
Rapid diagnostic tests- Immunochromatography for detection of malarial antigens
Thin and thick blood films
Quantitative buffy coat
Polymerase chain reaction (usually only used in reference laboratories)
Malaria: Haematological changes observed from FBC results
- Abnormalities observed from FBC results are non-specific and not diagnostic
- Anaemia seen due to red cell rupture (haemolytic anaemia) and impaired haemopoiesis as well as the removal of parasitized cells via the RE system
- Thrombocytopenia (due to platelet pooling/clearance in the spleen and reduced platelet lifespan due to immune responses)
- WBC count is often normal but may be raised in severe disease: Abnormalities may be observed on the white cell scattergram
- Further tests are needed to confirm that malaria is present.
Lateral-flow immunochromatographic techniques
- Variety of formats e.g. dipsticks, strips, cards, wells, and cassettes All the same basic principle.
- Antibodies used that target proteins specific for P. falciparum, such as HRP-2 (PfHRP-2), or Panmalaria proteins present in all species, such as Plasmodium aldolase or Plasmodium lactate dehydrogenase (pLDH), which are enzymes in the glycolytic pathway of Plasmodium species. - P. falciparum LDH (PfLDH)-specific antibodies are also available.
- Blood added to a buffered solution containing a haemolysing agent and one or more antibodies against malaria antigens that are labelled with a marker which can be visualized by the naked eye, such as colloidal gold.
- Antibodies complex with their target antigens if present, then migrate by capillary action along the test strip until they encounter separate immobilized capture antibodies directed against each target antigen in specific sections of the strip.
- Further antibody directed against the labelled antibody, which is the final antibody in the sequence, acting as a control to indicate that the procedure itself has worked. The strip is washed with buffer to remove haemoglobin.
NOW malaria kit (BinaxNOW) (rapid diagnostic?
- Rapid immunodiagnostic assay
- Uses two antibodies immobilised on a test strip
- One antibody is specific for histidine-rich protein II of P.falciparum
- Oher is specific for an antigen common to all forms of malaria that infect man (pLDH)
- Colour formation immobilised area after sample and a reagent is added to test strip helps scientist to get an idea of a parasite that may be present
- Control band included
- Only takes about 15 minutes
Optimal- IT test ( rapid diagnostic?
- Monoclonal antibodies against metabolic enzyme, parasite lactate dehydrogenase are used to detect presence of malaria
- One antibody specific for P. falciparum
- Other is a pan-specific antibody
- PLDH reacts with specific antibodies against plasmodium falciparum and/or plasmodium spp. inthe presence of plasmodium spp.
Rapid malaria diagnostic kits advantages:
Cheap & Quick result
Easy to perform (this helps inexperienced staff make an accurate diagnosis)
Can be used in settings away from the laboratory
Rapid malaria diagnostic kits disadvantages:
False positives
False negatives
cross-reacting antibodies such as rheumatoid factor;
pfHRP-2 can cross-react with non-falciparum malaria;
PfHRP-2 can persist after parasites have been cleared from the blood;
the occurance of persistent viable asexual-stage parasitaemia undetectable by light microscopy.
genetic heterogeneity of PfHRP-2 expression;
HRP-2 gene deletions;
antibodies that block immune-complex formation;
prozone effect;
Unknown
prozone effect: Concentration of antibody or antigen is so high that the optimal concentration for maximal reaction with antigen is exceeded and binding is reduced or does not occur.;
Quantitative Buffy Coat
Capillary blood is taken into a glass haematocrit tube containing acridine orange (to stain parasite DNA) and potassium oxalate (an anticoaglulant)
A cylindrical float inserted into the tube which is then centrifuged to separate cells according to their densities
Discrete bands are formed which are made larger by the presence of the float
The tube is then placed on a holder and examined under a light microscope with a UV adapter
Parasites can be observed as they fluoresce under the microscope
Quantitative Buffy Coat Limitations
almost impossible to differentiate between species, quantification is not possible, false positives can be reported by inexperienced staff due to artefact
Polymerase Chain Reaction
- Involves DNA amplification in vitro and is highly sensitive and specific technique
PCR advantages
Can detect and differentiate malarial parasites
Technique is tenfold more sensitive than microscopy
More reliable in identifying the species of malaria present
PCR disadvantage
Time consuming
Expensive
Requires some degree of experience/expertise