Case 18- Malaria Flashcards
Malaria transmission
Has a two stage/host lifecycle. Malaria is transmitted by female mosquitos of the Anopheles complex. There are more then 70 species. Anopheles gambiae is closely associated with the transmission of malaria.
Alternative transmission routes for malaria
- Transfusion transmitted (TT) malaria- blood infusion, inadequate screening of blood
- Mother to foetus (Congenital malaria)- actual number hard to estimate, difference between endemic and non-endemic area
- Needle stick injury- health care professionals, IV drug use and needle share
Plasmodium lifecycle- whats infected first
- Mosquito takes blood meal from human and injects parasite into blood
- Liver infected initially, replication and amplification of parasite
- RBC’s subsequently infected
- Infected blood taken up upon second mosquito bite
Symptoms of Malaria
Blackwater fever= results from massive intravascular haemolysis (blood in urine), malaria is primary an intra-erythrocytic parasite. Within a few days of onset you get chills, with rigor, high fever, jaundice and vomiting. Cycles of chills and fevers. Rapidly progressive anaemia, dark red or black urine. Kidney damage likely.
Malaria species
5 main species of malaria which infect humans:
- Plasmodium falciparum (accounts for 75% of infections)
- Plasmodium vivax (accounts for 20% of infections)
- Plasmodium knowlesi
- Plasmodium malariae
- Plasmodium ovale
Plasmodium parasite
Eukaryotic, unicellular organism with the phylum Apicomplexa. Characterised by having an organelle called the ‘apicoplast,’ which is essential for infecting target cells. The Apicoplast has its own genome (plastid) which encodes enzymes for FA synthesis.
Uncomplicated Malaria
- Classical early symptoms (rare to observe) lasts 6-10 hours. A cold stage (sensation of cold, shivering). A hot stage (fever, headaches, vomiting, seizures in young children) and finally a sweating stage (sweats, return to normal, temperature, tiredness)
- Attacks occur every 2 days (tertian malaria) or every 3 days (quartan malaria).
- Symptoms- headache, fever, fatigue, muscular/back pain, chills, sweating, dry cough, spleen enlargement, nausea and vomiting
Malaria- what causes Paroxyms of fever
The parasite infects liver cells which rupture. The parasite can then infect RBCs, The RBCs lyse and cause the release TNFalpha and other inflammatory factors leading to fever. There is periodic waves of infection, replication and reinfection.
Malaria- how often is the fever
- Tertian fever (every 48 hours)- Plasmodium vivax or Plasmodium ovale
- Quartan fever (every 72 hours)- Plasmodium malariae
- Plasmodium falciparum- can be 24 or 48 hours
Recurrent malaria
- Caused by P.vivax and P.ovale infections. P.falciparum due to re-infection
- Patients having recovered from the first episode of illness may suffer several additional attacks (relapses) after months or even years without symptoms
- Reactivation is due to dormant liver stage parasite (hypnozoites) that may reactivate
P.falciparum
Time of onset- 6 days
Severity- severe
Relapse- no
P.vivax
Time to onset- 8 days
Severity- mild/severe
Relapse-yes
P.ovale
Time to onset- 9 days
Severity- mild
Relapse- yes
P.malariae
Time to onset- 14 days
Severity- mild
Relapse- no
Malaria symptoms
Fever, pain, convulsions -> coma -> death
Complicated (severe) Malaria
Defined by WHO as a patient presenting with any of the following complications:
- Decreased consciousness
- Significant weakness
- Inability to feed
- Two or more convulsions
- Low blood pressure
- Breathing problems
- Circulatory shock
- Kidney failure
- Haemoglobin in the urine
- Bleeding problems, or haemoglobin ≤ 50 g/L (5 g/dL)
- Pulmonary oedema
- Blood glucose ≤ 2.2 mmol/L (40 mg/dL)
- Acidosis or lactate levels ≥ 5 mmol/L
- Parasitemia ≥ 105/µL (ca. 5%) in low-intensity transmission areas, or 2.5 x 105/µL in high-intensity transmission areas
Problems with severe malaria
It is a medical emergency and should be treated urgently and aggressively
Why does P.falciparum cause moe severe disease
Infected RBCs develop knobs which contain histidine rich proteins. These can adhere to endothelial cells to the receptors ICAM-1, thrombopodin, CD36 which can cause exacerbation of microvascular pathology. Sequestration of RBSs in the blood vessels lead to tissue damage and Cerebral malaria (high mortality). The knobs cause the RBCs to become more sticky and adhere to blood vessels
Malaria epidemiology
Partial immunity can be gained in areas when malaria is endemic but this is incomplete protection. Genetic traits affecting RBCs are more prevailent in malaria endemic areas which can cause protection. Sickle cell trait (heterozygous) gives some protection against P.falciparum.
Diagnosis of malaria
Use a blood smear. Thick smear for quick determination of parasitaemia (% infected RBCs). The Giesma stain is used the most and has to be done in a few hours.
Treatment for Malaria
For P.falciparum the first line is Artemisinin. There is resistance to Chloroquine and mefloquine. Resistance to artemisin is on the rise and should not be used by itself. Artemisin Combined Therapy (ACT)- Artemisin + i.e. chloroquine.
Prevention of Malaria
- Vaccination- RTS, S/AS01- trade name Mosquirix, prevents infection of the liver. Has a poor efficacy and protective effect goes after 4 years
- Insecticide can be put on mosquito nets
- Removal of standing water
- Release of sterile male mosquito’s
- Release of fungally infected mosquito’s
