Malaria

Malaria is a protozoan parasite widespread in the tropics and subtropics. Each year 500 million people are affected, with a mortality rate of 0.2%. In endemic areas mortality is principally in infants, and those who survive to adulthood acquire significant immunity. In hyperendemic areas an exaggerated immune response to repeated malarial infections leads to massive splenomegaly, anaemia, and elevated IgM levels (hyperreactive malarial splenomegaly, the tropical splenomegaly syndrome). Malaria parasites are scanty or absent in this syndrome and the disease responds to prolonged antimalarial treatment.


Aetiology

• Malaria is transmitted by the bites of infected female anopheline mosquitoes.
• Occasionally it is transmitted in contaminated blood (transfusions, contaminated equipment, injecting drug users sharing needles).
• Rarely the parasite transmitted by importation of infected mosquitoes by air (airport malaria).
• Four malaria parasites infect humans; by far the most hazardous is plasmodium falciparum, and the symptoms of infection with this virus can rapidly progress from an acute fever with rigors to severe multiorgan failure, coma and death
• Once successfully treated this form does not relapse
• The other malaria parasites are P.vivax, P.ovale and P.malariae
• These may relapse though

Pathogenesis

• The infective form of the parasite (sporozoites) passes through the skin and via the bloodstream to the liver.
• Here they multiply inside hepatocytes as merozoites.
• After a few days the infected hepatocytes rupture, releasing merozoites into the blood where they are taken up by erythrocytes and pass through further stages of development, which terminate with the rupture of the red cell
• Rupture of red blood cells contributes to anaemia and releases pyrogens, causing fever
• Red blood cells infected with P.falciparum adhere to the endothelium of small vessels and the consequent vascular occlusion causes severe organ damage, chiefly in the gut, kidney, liver and brain
• P.ovale and P.vivax remain latent in the liver, and this is responsible for the relapses that may occur

Clinical features

• The incubation period varies:
• 10 to 14 days in P.vivax, P.ovale and P.falciparum infection
• 18 days to 6 weeks in P.malariae infection

• The onset of new symptoms may be delayed up to three months and 1 year in vivax malaria in the partially immune or after prophylaxis
• There is an abrupt onset of fever (>40 degrees celcius), tachycardia and rigors, followed by profuse sweating some hours later. This may be accompanied by anaemia and hepatosplenomegaly
• P.falciparum infection is a medical emergency because patients may deteriorate rapidly. The following clinical forms are recognised and are more likely to occur when more than 1% of the red blood cells (RBCs) are parasitized:
• Cerebral malaria - diminished consciousness, confusion, convulsions, coma and eventually death. Hypoglycaemia, a complication of severe malaria, may present in a similar way and must be excluded
• Blackwater fever - dark brown-black urine (haemoglobinuria) resulting from severe intravascular haemolysis

Investigations

• The conventional method for diagnosing malaria is light microscopy of a Giemsa-stained thick and thin blood smear. Thick smears are most useful for diagnosis of malaria and thin smears are quantification of the percentage of parasitized red cells and for species identification
• Three smears should be taken over 48 hours before the diagnosis of malaria is ruled out. Rapid antigen tests are available for near-patient use
• Full blood count, serum urea and electrolytes, liver biochemistry and blood glucose are checked in falciparum malaria to detect complications

Management

• Parasitological testing and confirmation of the diagnosis should be performed before antimalarial treatment is started except in remote rural areas
• Treatment of uncomplicated malaria
• Symptomatic malaria without signs of severity or evidence (clinical or laboratory) of vital organ dysfunction and parasite count <2%
• Artemisinin-based combination therapies (ACT) are the recommended treatments for uncomplicated P.falciparum malaria and for the treatment of P.vivax from chloroquine-resistant areas (Indonesia, Papua New Guinea, Timor Leste and other parts of Oceania)
• Fixed-dose combinations are preferred to the loose individual medicines co-dispensed
• Antipyretics such as aspirin and paracetamol are given as necessary, and intravenous fluids may be required to combat dehydration and shock

• Severe falciparum malaria
• Is a medical emergency
• Optimal management may require admission to the intensive care unit (ITU). Expert advice should be sought from a malaria reference centre.
• Parenteral artesunate 2.4 mg/kg body weight i.v. or i.m given at diagnosis and then at 12 hours and 24 hours, then once a day until patient able to tolerate oral medication and complete treatment by a course of an ACT
• Quinine if artesunate is unavailable. Quinine 20mg/kg loading dose in 5% dextrose intravenously over 4 hours, then 10mg/kg over 4 hours every 8 hours plus oral doxycycline 200 mg daily for 7 days.
• Omit loading dose if patient taking quinine or mefloquine already as prophylaxis
• Treatment can be switched to oral quinine when patient is stable and responding to treatment
• Rectal artesunate is given in remote rural areas of some countries (Africa and Asia) to patients with suspected severe malaria before referral to a health facility for definitive treatment. Intramuscular artesunate or quinine are also used in this setting

• Intravenous glucose is given for hypoglycaemia and benzodiazepines for seizures. Early dialysis for acute kidney injury should be commenced and positive-pressure ventilation for non-cardiogenic pulmonary oedema

Prevention and control

• Effective prevention of malaria includes the following elements (ABC):
• AWARENESS OF RISK
• BITE AVOIDANCE - using mosquito repellants, covering up with permethrin-impregnated clothing, sleeping under impregnated bednets
• Chemoprophylaxis

• As a result of changing patterns of resistance, advice about chemoprophylaxis should be sought before leaving for a malaria-endemic area
• Prophylaxis does NOT afford full protection
• Drug regimens must start for at least 1 week before departure and continued without interruption for 4 weeks after return 
• The rationale for this advice is to ensure therapeutic drug levels before travelling and to enable unwanted effects to be dealt with before departure
• THe continued use of drugs after returning home will deal with infection contracted on the last day of exposure. With the now widespread geographical prevalence of chloroquine resistant P.falciparum, mefloquine (250mg weekly) is for many travellers the mainstay of malarial chemoprophylaxis
• Malarone (proguanil/atovaquone) or doxycycline are alternatives to mefloquine