Lecture 4 - Malaria Flashcards
Which are the two plasmodium species that cause the most cases of malaria?
P. falciparum
P. vivax
Discuss transmission by female Anopheles mosquitos during the year.
It’s stable/year-round transmission or seasonal/unstable with epidemics.
Name characteristics of two Anopheles species: An. gambiae and An. arabiensis.
Breeding sites, day or night biters, indoor or outdoor biters, and anthrophilic level.
Breeding sites: unpolluted pools, puddles, marshes, rice paddies, etc.
Night biters
Endophilic
Highly anthrophilic
What are four factors that determine vectoral capacity?
- No. of vectors per human
- No. of human blood meals/day/vector
- Daily survival rate
- Extrinsic incubation period of parasite
Where are the majority of parasites killed in anopheles mosquitoes?
In the midgut epithelium cells by innate immune effector genes such as TEP1.
Explain the difference between recrudescences and relapses in human malaria.
Recrudescence = erythrocytic infection falls to subclinical or subpatent levels but is not eliminated, then re-appears. Is frequently associated with P. malariae.
Relapse = erythrocytic infection is eliminated. If chemotherapy to eliminate dormant hypnozoites in the liver is not performed then these can re-activate and generate new erythrocytic infection.
Relapses in human malaria can only occur in a few plasmodium species. Which ones and why do these relapses occur?
This happens in P. vivax and P. ovale species.
Erythrocytic infection can only be eliminated via chemotherapy (natural immunity is unlikely to eliminate infection). If the dormant hypnozoites in the liver are not eliminated a new erythrocytic infection can occur, because these hypnozoites can be re-activated.
There are no symptoms associated with the liver stages - symptoms begin with onset of blood stage infection (typically 7-30 days after bite).
Clinical features: describe the stages that accompany the classic symptom fever.
- Cold stage
- Hot stage
- Sweating stage
- Cold stage - patient shivers, then temperature rises rapidly.
- Hot stage - peripheral vasodilation (flushed appearance), rapid pulse and high temperature.
- Sweating stage - copious sweating leading to a fall in temperature.
Other common systems include anaemia, splenomegaly, and jaundice.
Can patients develop immunity against malaria?
Yes and no. P. falciparum can be fatal, but if the patient survives they will develop some immunity BUT repeated re-infections are required for clinical immunity.
Other species tend to cause morbidity rather than mortality.
Cerebral malaris is a serious complication of P. falciparum infection resulting in coma. How does the brain get infected?
Cytoadhering of infected red cells in the brain:
Binding of PfEMP1 (encoded by var genes) to endothelia or other erytrhocytes (throughout the body).
What is the method of choice to diagnose malaria?
Microscopy –> parasites shown in erythrocytes (headphones).
Treatment of malaria consists of two components: supportive and specific.
Explain these components.
Supportive: manage the symptoms - reducing temperature, rehydration, blood transfusions, preventing convulsions.
Specific: eliminate the parasite - via chemotherapy, which depends on the parasite and geographical origin of infection.
Why can a good non-toxic antimalarial like chloroquine not be used as much anymore?
What other antimalarial can be used in its place?
Resistance is now widespread.
Quinine is main drug used to treat severe p. falciparum in areas of chloroquine resistance.
Which antimalarial is used mainly in combination therapies to prevent drug resistance?
Artemisinin. Derived from Artemisia annua (Chinese herbal remedy).
Evolution of Plasmodium spp. and impact on human populations:
When and why did plasmodium spp. expand into human populations? What is the impact of this?
About 10’000 years ago. Emergence as major human pathogen coincides with the development of agriculture and resident human communities.
Impact: malaria is the strongest known selective presure in the recent history of the human genome. Different human populations have developed independent evolutionary responses to malaria: HbAS for example.
Why is there an unusually high prevalence of HbAS in malaria endemic regions, even though the homozygous state can be lethal?
The heterozygous state of sickle cell gives protection against malaria. Sickled cells are more likely to be degraded by the spleen, so if malaria parasites reside in these cells they will be more likely to die.
Malaria control happens via vector control and therapeutic drugs (e.g. chloroquine).
Name 2 ways of vector control.
- Indoor residual spraying (e.g. DDT).
- Insecticide treated nets (e.g. pyrethroids on bednets).
The WHO came up with a solution to eradicate female anopheles mosquitoes: insecticide treated walls.
Why did they think this was the solution?
What were problems of this solution?
Development of malaria cycle takes about 12 days, during which there are about 4-6 additional feeds - this increases chance of mortality of it rests on insecticide treated walls.
Problems: vectors developed resistance to insecticides; parasites developed resistance to drugs.
What was the main reason that eradication of malaria did not happen in sub-saharan africa?
Technical challenges of executing the strategy:
- Eradication was not sustainable (too expensive)
- Vertical programme (disease-specific)
- No eradication –> donors withdrew their money
What are some factors that helped the spread of chloroquine resistance?
- Exposure of parasites to sub-therapeutic dose of drug
- Incomplete compliance because of sharing the drugs
- Parasites not killed gave them an opportunity to become resistant
What is ‘Roll Back Malaria’?
What are 4 of its aims?
Global partnership of national governments, NGOs, academia, etc. with aims:
- Access to effective treatment
- Promotion of ITNs and improved vector control
- Prevention and management of malaria in pregnancy
- Improving the prevention of and response to epidemics and malaria in complex emergencies
What is the ‘Global Malaria Programme’ responsible for?
- Malaria … and … formulation
- … support & capacity …
- Coordination of … to fight malaria
- Convenes experts to …, set global …
- Focus on providing … solutions to the various … and operational challenges
- Malaria policy and strategy formulation
- Operations support & capacity development
- Coordination of WHO’s global efforts to fight malaria
- Convenes experts to review evidence, set global policies
- Focus on providing integrated solutions to the various epidemiological and operational challenges
There no vaccine against malaria. Name the three main challenges why there isn’t.
- Choosing the right antigens (> 5000 genes)
- Generating strong enough immune responses
- Avoiding immune escape mechanisms
Name three things that would make the ideal anti-malaria vaccine.
- Effective against all life cycle stages & against disease - contains multiple antigens
- Generate appropriate immune responses - antibody and cell-mediated
- Tailored for both host AND parasite genotypes
