What is malaria?

Malaria is caused by a protozoan parasitic infection of red blood cells.  It is transmitted to humans via the bite of an infected female Anopheles mosquito. Which typically bite between dusk and dawn.  These protozoans are all of the genus Plasmodium.

The four main species are:

  • Plasmodium Falciparum
  • Plasmodium Vivax
  • Plasmodium Ovale
  • Plasmodium Malariae

 

    N.B.:

    1. P. Falciparum and P. Vivax are the most common, whilst Falciparum can be the most dangerous.

    2. In addition to the above Plasmodium Knowlesi, previously only seen in monkeys, has also been identified in humans in South East Asia.

    Epidemiology

    • Around 500 million people affected each year
    • Results in almost 1 million deaths each year
    • 3.3billion are at risk of infection
    • Accounts for 20% of childhood mortality in sub-Saharan Africa
    • 25,000 international travellers are infected.
    • On average there are 1600 cases each year in the UK, in people returning from malaria-endemic regions
    • Cases of malaria have fallen 25% globally since 2000, and 33% in the WHO African region.

     

    Map highlighting areas at risk of Malaria

    Aetiology

    • Transmission is usally from mosquito bite (female anopheline mosquito)
    • Common in tropic areas along the equator (90% of mortality occurs within Africa); but also suspect Americas; Indian Subcontinent; China; Thailand and Indonesia.

    The longer life-span and stronger human biting habits of the African vector species is the suggested reason why 90% of malaria death's occur in Africa. Varying weather patterns also mean following heavy rainful, the risk of infection rises.

      Alongside mosquitos being a vector, there are other modes of transmission:

      • Contaminated blood transfusions
      • Contaminated hospital equipment(s)
      • IV drug users sharing needles

      Patients at greater risk of complications following infection are: 

      • Without a spleen 
      • HIV/AIDs positive patients
      • Pregnant women (induced miscarriage)
      • Children (lack of immunity)
      • International travellers/ Immigrants (lack of immunity)

       

      Certain Individuals are protected such as those with:

      • Sickle Cell trait 
      • G6DP Deficiency
      • lack of duffy antigen
      • Iron Deficiency Anemia, etc.

          Pathophysiology

          Pre Erythrocyte

          1. A Mosquito takes in infected blood with malaria gametocytes, which develop for 7-20 days in the gut to form sporozoites, which are stored in the salivary glands
          2. The Infected mosquito injects a human with Plamodium sporozoites
          3. Sporozoites migrate directly to liver and infect hepatocytes; these grow and develop into merozoites
          4. Hepatocytes burst from excess growth, releasing merozoites which enter the blood stream; some remain dormant as hypnozoites in liver and may reactivate months or years later (in P.ovale/ P. vivax)

           

            Erythrocyte stage

            1. Merozoites are rapidly taken up by erythrocytes
            2. Merozoites mature into trophozoites, and then finally schizonts
            3. In P. Falciparum, the infected RBC adhere to the capillary linings in brain, kidney, liver and other organs, leading to mechanical obstruction and subsequent toxin release and further infection
            4. Red blood cells burst, and schizonts burst releasing merozoites and infecting more red blood cells - this accounts for the periodic fever and causes haemolytic anemia.

             

              Sexual Stage

              1. Sexual forms called gametocytes are produced; if bitten again by a mosquito then these may be ingested, thus infecting the mosquito and repeating the cycle

              Signs and symptoms



              Fever Paroxysms

              1) Shivering for 1 hr

              2) Hot stage (pyrexia temp=41c) for 2-6h

              3) Sweating for 2 h as temp falls. 

              The incubation period of malaria is usually 10-21 days and fever and headache may very well be the first symptom!

              The fevers timing usually correlates with the species and the rate at which they replicate within the RBC:

              P. Falciparum; P Ovale; P Vivax- 48 hours

              P Ovale; P Vivax; P Malariae-72 hours

              Plasmodium Falciparum

              Plasmodium falciparum

              • Incubation period: 7-10 days.  Usually presents within 2 months.
              • Pyrexia, headache, myalgia, anorexia and fever paroxysms. 
              • Responsible for vast majority of malaria deaths. Cerebral malaria has mortality of 20%
              • No dormant parasites hence no relapses
              • High mortality is marked by parasitemia (>1% RBC infected with parasite)
              • Cerebral Malaria can lead to confusion, convulsions and leading to coma and death.
              • Black Water Fever: Characterised by hemoglobinuria (dark urine). represents widespread hemolysis affected both affacted and unaffected RBCs.
              • Metabolic Acidosis is common- characterised by kussmaul breathing
              • Pulmonary oedema may develop leading to ARDS and death. 
              WHO Classification of Severe Malaria, 2010

              Other species

              Plasmodium Malariae:

              • Incubation 18-40 days. 
              • usually mild illness, but runs chronic course. Rarely fatal.
              • May last for several years
              • Is associated with Glomerulonephritis and Nephrotic syndrome

              Plasmodium Vivax and Plasmodium Ovale

              • Incubation period: P.vivax and P.ovale 10 - 17 days. May present weeks or over 1 year later
              • Usually presents with anemia, hepatosplenomegaly.
              • Very low mortality rate- spontaneous recovery 2-6 weeks.
              • Relapses may occur if dormant parasites not eradicated (P.ovale and P.vivax)- due to hypnozoites within the liver.

              Diagnosis

              Malaria should be the differential diagnosis of anyone who has recently left a malarious area or presents with a fever. Falciparum unlikely >3 months of leaving malarious area. Vivax may present >1 year.

              Several Giesma stained thick and thin blood films are needed, ideally 3 at various intervals - don't rule malaria out after one negative test!  If P. falciparum is diagnosed, the percentage of infected red blood cells will be reported; >5% is hyperparasitaemia and can be an emergency. Thick stains are harder to interpret and are difficult to speciate, however are higher yield.

              Rapid diagnostic tests may be used in areas where there are limited resources or limited expertise in blood film diagnosis. They are quick on-the-spot tests, but are more expensive and less sensitive than blood films. (eg. Rapid Antigen detection; Quantative Buffy Coat analysis)

              Also request:

              • FBC - anaemia, thrombocytopaenia
              • Clotting- DIC
              • ABG/ Lactate- Lactic Acidosis
              • Glucose- hypoglycemia
              • U&E, creatinine - renal failure
              • Urinalysis- haemoglobinuria, proteinuria, casts
              • Blood Culture- rules out septicemia

              A lumbar puncture may be suitable to rule out bacterial infection, eg. Meningitis. 

                Differential Diagnosis

                Due to the usually non specific presenting symptoms, it is important to consider other diagnosis as well. Such as:

                • Hepatitis
                • HIV
                • Dengue Fever
                • Typhoid
                • Meningitis

                However, pyrexia within a returning traveller is malaria till proven otherwise and must be investigated for first due to the dangers of late diagnosis. 

                Management

                1. If severe falciparum is suspected don't delay antimalarial treatment!
                2. Otherwise await lab diagnosis before commencing treatment- The WHO recommends suspected cases of Malaria be confirmed by parasite based diagnostic testing 
                3. Liver hypnozites need to be eradicated in P.ovale and P.vivax so as to prevent later relapses.
                4. If patient has been given prophylaxis eg. chloroquine, use a different medication for treatment.
                5. Malaria is a notifiable disease, so the public health authority must be notified, and the case should be discussed with the local infectious disease team.
                6. The severity of the disease and the strain of Plasmodium, degree of resistance are all factors which should shape up treatment and management.

                Treatment



                Severe P. Falciparum Management

                • Without treatment mortality is 100%, with treatment 20%. 

                The most important things to assess on a daily basis alongside normal blood serology:

                1) Parasite count

                2) Plasma Bicarbonate + Creatinine 

                Whilst with clinical assessment it is important to remain vigilant for:

                1) Shock

                2) Metabolic Acidosis

                3) Hypoglycemia

                4) Renal Failure

                5) ARDS

                 

                It is important to start antimalarias on full dosage stat! 

                eg. IV Artesunate or Quinine Sulphate 20mg salt/kg IVI over 4 hours.  

                Then after 8 hours, give 10mg/kg over 4 hours every 8 hours. Aim to administer orally. 

                 

                Furthermore:

                1) Mechanical Ventilation/ Dialysis may be indicated

                2) Anemia may preciptate trasfusion, or heavy infections may indicate exchange transfusions

                3) Hypoglycemia may be caused by malaria/ quinines.

                4) Antibiotics may be needed for sumperimposed bacterial infection

                 

                Cerebral Malaria

                1) Hemofiltration indicated in renal failure/ pulmonary oedema

                2) Exchange transfusion may be indicated

                3) Monitor blood lactate/HCO3-

                 

                Prophylaxis

                Primary preventive measures to reduce the amount of mosquito bites should be taken, including:

                • Using insect repellent with DEET
                • Wearing long sleeves and trousers at night
                • Sleeping under mosquito nets

                 

                  Antimalarials should be started before entering a malaria-endemic area.  Antimalarial recommendations differ around the world due to resistance in certain areas so up-to-date advice should be sought before travelling.  None are 100% effective so should be combined with the above measures.

                   

                  • Atovaquone-proguanil  (Malarone) 

                  +Well tolerated

                  +Started 1 day before arrival in malarious region

                  +Effective against drug resistant P.falciparum

                  -Expensive

                   

                  • Doxycycline

                  +Cheap

                  +Usually well tolerated

                  +Commence 1 week before departure

                  -May increase photosensitivity 

                  -Risk of thrush for females

                  -Dyspepsia

                   

                  • Mefloquine (Lariam) 

                  +Taken weekly

                  +Fairly inexpensive 

                  -Take 3 weeks before departure

                  -Nausea and vivid dreams common

                  -Can cause neuropsychiatric event

                   

                  • Chloroquine and proguanil

                  -Many strains are now resistant 

                   

                   

                  Summary

                  • Malaria is a life threatening parasitic infection, typically spread by mosquitos.
                  • This is a notifiable disease so local health authorities must be notified.
                  • The infection can lead to haemolysis; with symptoms of fever, headache, shivers, join pain and signs such as jaundice, hepatospenomegaly and/or red urine.
                  • Malaria is diagnosed on blood films or by antigen based detection tests.
                  • It can be treated by artermisinin or quinine; or artesunate if in severe cases. No doubt treatments do vary by the strain of malaria; and requires co-ordination with the appropriate infectious disease control authorities.
                  • The transmission of such disease can be reduced by the use of mosquito nets, insect repellent and good prophylaxis.

                  References

                  1) EDDLESTON,M. ; 2008; OXFORD HANDBOOK OF TROPICAL MEDICINE; 3RD EDITION; OUP OXFORD

                  2) KUMAR, P. CLARK, M.; 2012; KUMAR AND CLARK'S CLINICAL MEDICINE; 8TH EDITION; SAUNDERS LTD

                  3) WORLD HEALTH ORGANISATION; 2013;MALARIA;AVAILABLE AT: http://www.who.int/mediacentre/factsheets/fs094/en/index.html [ACCESSED 28/9/2013]

                  4) PUBLIC HEALTH ENGLAND; 2013; MALARIA; AVAILABLE AT http://www.hpa.org.uk/Topics/InfectiousDiseases/InfectionsAZ/Malaria/ [ACCESSED 28/9/2013]

                  5) NHS; 2013; MALARIA; AVAILABLE AT http://www.nhs.uk/Conditions/Malaria/Pages/Treatment.aspx [ACCESSED 28/9/2013]

                   

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