Flashcards in Plasmodium and Malaria Deck (31)
How prevalent/important is Malaria? Deaths? 00:30
- Most important tropical disease; affecting 207 million worldwide
- 3 billion at risk worldwide
- > 600,000 people die from malaria every year; mainly children U5 years old; one death a minute.
>>> Preventable and curable
Who should be assessed for possible malaria infection?
- Any patient w/recent history of travel to an endemic country (luggage can be vector too) or been in an international airport presenting WITH FEVER should be assessed
- Malaria can present up to a year after travel to an endemic area
Who is at risk of contracting malaria?
- Any person; regardless of age, gender, ethnicity or country of birth
What is the UK stance on malaria?
Notifiable disease (Health Protection Regulation 2010)
What are the main causative agents of human malaria, and the respective strain they cause?
- Plasmodium falciparum (malaria subtertiana)
- Plasmodium ovale (malaria tertiana)
- Plasmodium vivax (malaria tertiana)
- Plasmodium malariae (malaria quartana)
- Plasmodium knowlesi; still considered zoonotic though (malaria quotidiana)
>>> This one not diagnosed by RDT, difficult by microscopic tests (from monkeys in SE Asia)
What is the vector malaria is spread by, and what is their typical habitat?
- Plasmodium spread by Anopheles (genus) mosquito; the vector
- Anopheles deposits eggs in stagnating waters e.g. rice paddies, swamps, marshes for egg maturation
What is the life cycle of the Anopheles spp. mosquito?
- Adult female mosquito takes a blood meal, then lays eggs; 50-200 at a time (only females transmit malaria)
- The eggs are laid onto still water, developing into aquatic larvae (close to the surface; have breathing tubes)
- Over 8-10 days; the larvae go through 4 stages of development called instars.
- During the last larval instar, the larvae develop into pupae
- After 1-2 days, the adult mosquito emerges from the water.
>>> Development time is 10-14 days (depending on species and ambient temperature; greater temperature = shorter time, but too low a temperature and Plasmodium do not develop)
Why do countries like Norway/Siberia/North Africa have the malaria vector Anopheles spp., but no incidence of malaria?
- Non-tropical/sub-tropical areas
- Plasmodium does not develop in lower temperatures
Some sub-species of Anopheles spp. mosquito are zoophilic; what does that mean?
- Some sub-species of Anopheles spp. in (primarily in) Europe are primarily zoophilic; preferring to feed on animals such as cattle or birds
- But most species are not exclusively anthropophilic or zoophilic; thus will feed on humans if needs be etc.
>>> Climate change may bring malaria back to Europe
What is the lifecycle for the malaria parasite?
1) During a blood meal (essential before laying eggs), a malaria-infected female Anopheles injects anti-coagulant (its saliva) into the human first, so it can get the blood - the saliva contains the Plasmodium, inoculating sporozoites into the human host)
2) Kuppfer cells of the liver take up Plasmodium (sporozoites) into the hepatocytes (liver cell), which divide and replicate...
3) Maturing into schizonts, which rupture...
4) Releasing merozoites (1000s); killing the hepatocyte cell.
(responsible for clinical manifestations of disease)
5) These merozoites then infect RBCs (hiding from immune system in RBCs)
6) Ring-stage (immature) trophozoites then mature into schizonts, which then rupture, releasing more merozoites (starting Erythrocytic Cycle again, 5)
7) Some parasites differentiate into sexual erythrocytic stages; gametocytes.
8) The male and female (micro/macro-) gametocytes are ingested by an Anopheles spp. during a blood meal
- The parasite (malaria) multiplies in the mosquito, gametocytes > zygotes > ookinetes > oocysts > sporozoites; which make their way to mosquito's salivary glands.
>>> 1) Inoculation of the sporozoites into a new human host kicks off the malaria life cycle again.
What are sporozoites thin and slender in shape?
To fit in the salivary glands of the Anopheles spp. mosquito.
What are the symptoms associated with malaria infection?
- No symptoms associated with liver stage (exo-erythrocytic)
- Symptoms occur when RBC stages (erythrocytic cycle) rupture cells and release malaria 'toxins' and pyrogens (which in turn induce fever)
- Fever (can be w/o)
- Anaemia (loss of RBCs)
- Splenomegaly (dead RBCs trapped in spleen; becomes enlarged)
- Jaundice (sub-optimal liver function)
- Diarrhoea (non-specific)
- Vomiting (non-specific)
What is unique WRT malaria tertiana (P. vivax/P. ovale) life cycle?
- They have an extra step in the Exo-erythrocytic cycle (liver stage)
- Hypnozoites (a dormant stage) can persist in the liver and cause relapses by invading the bloodstream weeks/years later
What is malarial fever caused by?
- Caused by host cytokines (IL-6) released in response tp released pyrogens from lysed RBC
What are the classical stages of malarial fever?
Do all malaria infection follow this pattern?
- Cold stage; patient shivers or shows rigor (15-60 min)
- Hot stage; patient becomes flushed, has rapid pulse and high temperature (41 degrees C) for hours (2-6 hrs)
- Sweating stage; patient sweats abundantly (as a result of high temp in Hot stage), temperature drops (2-4 hours, evaporation of sweat)
>>> Particularly w/P. vivax
>>> But there can serious cases of malaria infection w/o fever
What is rigor?
- Sudden feeling of cold with shivering, accompanied by a rise in temperature
- Often w/copious sweating (especially at fever onset)
What fever patterns are there for subtertiana, tertiana, and quartana?
- Subtertiana (P. falciparum); irregular, every 3rd day (48 hour cycle)
- Tertiana (P. vivax/ovale); regular, every 3rd day (48 hour cycle)
- Quartana (P. malariae); regular, every 4th day (72 hour cycle)
What are the effects of further development of malaria in the absence of a treatment?
Dependent on species:
> P. falciparum/P. malarie; small percentage will develop severe malaria, dying from complications
- But after a single infection, fever attacks may recur over the course of the next year, but then die out (no mortality)
> P. vivax/P. ovale; weaker symptoms w/less mortality, BUT hypnozoites survive in hepatocytes for years or decades; possibly recurring after that time.
What are the complications of P. falciparum infection?
- P. falciparum is most dangerous strain of malaria; can cause life-threatening complications
- Altered consciousness and coma; can be caused by hypoglycaemia, acidosis, seizures or very severe anaemia.
- Cerebral malaria; main cause of malarial death, large numbers of RBCs containing mature parasites found in capillaries and venules of brain and other organs.
What are the underlying mechanisms of hypoglycaemia in P. falciparum infection? Who is commonly affected?
- Cytokine-induced impairment of gluconeogenesis in the liver (liver stops producing glucose, parasite consumes more)
- Additional glucose consumption by millions of parasites
- Also occurs as complication of QUININE therapy; can induce insulin production.
>>> Untreated children/pregnant women
What are the underlying mechanisms of severe anemia in P. falciparum infection?
- Direct destruction of RBC when schizonts rupture; immune-mediated haemolysis also occurs
- Cytokines produced affects RBC formation (erythropoiesis); in the bone marrow (= dyserythropoiesis) (make less RBCs = even worse anaemia)
What are the underlying mechanisms of acidosis in P. falciparum infection?
- Tissue anoxia (O2 depletion in tissues due RBC depletion; severe anaemia) leads to anaerobic metabolism, and release of lactic acid, lowering pH
- Anoxia also caused by hypotension, hypovolemia (low blood volume) and sequestration of infected RBCs ('hostage; don't perform normal functions')
What are the dangers of malaria in pregnancy?
- Pregnant women particularly threatened by malaria
- All types of malaria can lead to abortion
- Can cause anaemia; making blood less during birth more problematic, as well as low birth weight (low O2 availible for foetal development)
- Parasites usually not transmitted from mothers to neonate in endemic areas (usually not across placenta); but possible in non-immune mothers.
>>> Not all drugs can be used in pregnancy; Primaquine should not be used.
What does recrudescence of malaria entail?
- When malaria is caused by a small number of parasites persisting in RBCs
- Treated but some left over; initially have no symptoms but then they return.
What is meant by malaria reinfection?
- Malaria attack caused by new inoculation of parasites from infected vector
What is meant by malaria relapse?
- Hypnozoites in the liver are reactivated, initiating a new cycle of RBC infection, even after elimination of all parasites from blood
- P. vivax and P. ovale only
>>> Hypnozoites not killed by anti-malarials (target blood stage only)
How is immunity acquired to malaria?
- Children who survive in areas of very high transmission develop a degree of immunity
- Can limit parasitaemia by producing parasite-specific IgG
- Protection (immunity) requires frequent re-exposure, lost (over a few years) when living in non-endemic areas.
How does HIV infection exacerbate malaria?
- HIV-infected individuals become more susceptible to malaria infection as CD4+ (T-cell) counts progressively decrease (less proficient at generating antibodies against malaria)
- Developing high parasitaemia than immunocompetent people if infected
What are some non-immune protective factors against malaria? How?
- Duffy Factor
Not being examined:
- Sickle cell anaemia
- Glucose-6-phosphate dehydrogenase deficiency
> Genetic mutations affect RBC physiology; associated with varying degrees of protection against malaria
> Frequent in malarial countries (Mediterranean/Africa)