For health professionals: Malaria

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What health professionals need to know about malaria

Malaria is an infection by a parasite of the genus Plasmodium. 5 of the different species of parasites within this genus are infectious in humans. They are:

  1. Plasmodium falciparum
  2. Plasmodium vivax
  3. Plasmodium malariae
  4. Plasmodium ovale
  5. Plasmodium knowlesi

P. falciparum and P. vivax are the 2 species that pose the greatest threat. P. falciparum is the most prevalent malaria parasite on the African continent. It is responsible for most malaria-related deaths globally. P. vivax has a wider distribution than P. falciparum, and predominates in many countries outside of Africa.

The infection is initiated when Plasmodium sporozoites are injected by the bite of a female mosquito of the Anopheles genus.

Transmission can occur rarely by:

  • blood transfusion
  • sharing needles
  • from mother to fetus (congenital malaria)

The majority of deaths due to malaria are preventable with early diagnosis and treatment.

Nationally notifiable disease

Malaria is a nationally notifiable disease in all provinces and territories.

Cases are reported to:

Clinical manifestations

The first clinical symptoms are non-specific.

After being bitten by an infected mosquito, malaria symptoms can appear as early as 7 days or more.

Symptoms usually present in 10 to 15 days after infection. The classical malaria paroxysm is rare, and has symptoms occurring at regular intervals, such as:

  • headache
  • fever spikes
  • chills and rigours

Many clinical abnormalities have been described in acute malaria. Most uncomplicated infections have few abnormal findings other than:

  • mild anemia
  • a palpable spleen (in some cases)

Symptoms commonly wax and wane.

It is possible to contract more than 1 strain of malaria without the signs and symptoms being distinguishable for individual strains.

The literature suggests that:

  • infection with Plasmodium falciparum is potentially fatal
  • for the other infections, certain persons could experience serious consequences from:
    • fever
    • anemia
    • risk of spontaneous splenic rupture

For all malaria cases, clinical assessment should be carried out daily until the fever ends.

Diagnosis

A stained blood test for malaria with thick and thin smears should be obtained.

Table 1: Criteria for severe Falciparum malaria.
Clinical manifestation Laboratory results
Prostration or impaired consciousness Severe anemia in children less than 12 years of age: Hb less than or equal to 5 g/dl or hematocrit of less than or equal to 15%
In adults: Hb less than 7 g/dL and hematocrit less than 20%
Respiratory distress Hypoglycemia (blood glucose less than 2.2 mmol/L)
Multiple convulsions Acidosis (arterial pH less than 7.25 or bicarbonate less than 15 mmol/L)
Circulatory collapse Renal impairment (creatinine greater than 265 umol/L)
Pulmonary edema (radiological) Hyperlactatemia
Abnormal bleeding Hyperparasitemia (greater than 10%)
Jaundice Total bilirubin greater than 50 ┬Ámol/L
Hemoglobinuria Macroscopic

Patients are classified as suffering from severe malaria if they have both of these conditions:

  • Plasmodium falciparum asexual parasitemia and no other obvious cause of symptoms
  • the presence of 1 or more of the clinical or laboratory features in the above table

A timely (within 2 hours) parasitology laboratory result is essential for the effective management of malaria.

If symptoms recur in Plasmodium falciparum cases, carry out repeat malaria smears at day 7 and 28 to ensure sustained clearance.

The diagnosis of malaria (resolved) could be considered if:

  • the condition is no longer present
  • the patient has a history of malaria

Treatment

The initial management of the patient depends on many factors, including the:

  • patient's age
  • severity of infection
  • infecting species of malaria
  • safety, availability and cost of antimalarial drugs
  • pattern of drug resistance in the area of acquisition

Timely (within 1 to 2 hours) availability of an appropriate anti-malarial drug is essential for the effective management of malaria.

Treatment varies according to the species of malaria. Severe or complicated malaria:

  • usually requires parenteral therapy
  • sometimes requires an exchange transfusion

Parenteral quinine is preferable for those who do not have severe malaria and cannot tolerate oral medication. Otherwise the use of parenteral artesunate is preferable to parenteral quinine:

  • for the treatment of severe malaria
  • when there is a quinine:
    • failure
    • intolerance
    • contraindication

A patient who deteriorates suddenly should be:

  • assessed and treated immediately
  • suspected of hypoglycemia or other complications of severe malaria
    • hypoglycemia can occur with severe malaria and could potentially be exacerbated by quinine therapy, which stimulates insulin release

Seizures should be treated promptly with benzodiazepines.

Treatment of severe malaria

Health care providers treating a case of severe malaria should contact the Canadian Malaria Network for assistance and to obtain parenteral therapy.

Patients with severe or complicated malaria infections (usually due to Plasmodium falciparum) require:

  • immediate hospitalization
  • urgent, intensive medical management, ideally in an intensive care unit

They should receive initial treatment in an observation unit to:

  • ensure that treatment can be tolerated
  • confirm decreasing parasitemia with treatment

Severe or complicated disease or the inability to tolerate oral therapy requires:

  • parenteral therapy
  • close clinical monitoring, preferably in an intensive care unit

Important considerations when choosing treatment regimens include:

  • drug tolerability
  • adverse effect profile
  • speed of therapeutic response

There are 2 classes of drugs that are effective for the parenteral treatment of severe malaria:

  1. cinchona alkaloids, which are:
    • quinine
    • quinidine
  2. artemesinin derivatives, which are:
    • artemotil
    • artesunate
    • artemether

A diagnosis of severe malaria requires parenteral therapy. This therapy requires one of the following parenteral drugs within an hour of the diagnosis:

  • quinine
  • quinidine
  • artesunate

If none of these 3 drugs are available within an hour, start oral quinine while awaiting parenteral therapy. If the patient cannot tolerate oral therapy, then give oral quinine:

  • by nasogastric tube
  • after a dose of an anti-emetic to decrease the risk of vomiting or

Seizures should be treated promptly with benzodiazepines.

Blood transfusions

There have been some cases of complicated Plasmodium falciparum infection with high parasitemia (under 10%).

Exchange blood transfusion has been used on an experimental basis as a potentially life-saving procedure.

The rationale for the use of exchange blood transfusion includes the:

  • removal of infected red blood cells (RBCs) from the circulation
    • this thereby reduces the parasite load
  • rapid reduction of the antigen load and burden of parasite-derived:
    • toxins
    • metabolites
  • removal of host-derived toxic mediators
  • replacement of rigid unparasitized RBCs with normal functioning cells
    • this thereby reduces microcirculatory obstruction

Exchange blood transfusion requires:

  • intensive nursing
  • a safe blood supply
  • multiple units of packed RBCs

There is no consensus on the indications or volume of blood to be exchanged. However, a volume of 5 to 10 packed RBC units should be anticipated.

Uncomplicated Plasmodium falciparum

Infections acquired in a chloroquine-sensitive zone may be treated with chloroquine alone.

Most cases of Plasmodium falciparum malaria seen in Canada are infections possibly or definitely acquired in drug-resistant regions. These cases should be treated with:

  • atovaquone-proguanil (if not used as prophylaxis)
  • quinine and a second drug (preferably doxycycline)

If the patient can tolerate quinine orally, administer both:

  • quinine
  • doxycycline (or clindamycin for those in whom doxycycline is contraindicated)

The drugs should be administered simultaneously or sequentially (start quinine first).

If the patient cannot tolerate oral medication, administer 1 of the following:

  1. quinine
  2. parenteral artesunate

Non-falciparum malaria

Chloroquine remains the treatment of choice for non-falciparum malaria outside of New Guinea, which includes:

  • Papua New Guinea
  • Papua (Irian Jaya)

A recurrence of asexual parasitemia:

  • less than 30 days after treatment suggests chloroquine-resistant Plasmodium vivax
  • after 30 days suggests primaquine-resistant Plasmodium vivax

A 7-day course of quinine is often required to cure Plasmodium vivax infection from New Guinea.

Mefloquine and halofantrine have been shown to be efficacious in small clinical trials. However, each is limited by safety issues associated with therapeutic doses.

To reduce the risk of relapse following treatment of symptomatic Plasmodium vivax or Plasmodium ovale infection, primaquine is indicated. This medication will provide radical cure.

Primaquine is:

  • not routinely recommended for preventing relapsing malaria in asymptomatic returning travellers (terminal prophylaxis)
  • generally indicated for people with prolonged exposure in malaria-endemic areas where Plasmodium vivax or Plasmodium ovale malaria occurs

For terminal prophylaxis, primaquine is administered after the traveller has departed from a malaria-endemic area. This is usually during or after the last 2 weeks of chemoprophylaxis.

The recommended dosage of primaquine to prevent relapse is 30 mg (0.5 mg/kg) base daily for 14 days.

In patients with known or suspected G6PD deficiency, expert medical advice should be sought. This is because primaquine may cause hemolysis in such patients.

During pregnancy:

  • primaquine use is contraindicated
  • use standard doses of chloroquine to treat:
    • Plasmodium vivax infections
    • Plasmodium ovale infections

Relapses can be prevented by weekly chemoprophylaxis with chloroquine until after delivery.

After delivery, primaquine can be safely used for mothers with normal G6PD levels.

It is suggested that patients from Southeast Asia be diagnosed as Plasmodium knowlesi if they have these 2 conditions:

  • parasite levels greater than 1%
  • a parasite morphology resembling that of Plasmodium malariae

Treatment with chloroquine is reportedly effective. However, systemic symptoms and complications similar to hyperparasitemic Plasmodium falciparum infections require:

  • careful management
  • very close monitoring

Expert advice from an infectious or tropical disease specialist should be sought for the management of drug-resistant infections.

Clinical monitoring

For severe malaria cases, clinical observations should be made as frequently as possible and should include:

  • coma score
  • urine output
  • vital signs monitoring
  • accurate assessment of respiratory rate and pattern

Blood glucose should be monitored every 4 hours using rapid stick tests, especially in unconscious patients.

Surveillance

Health professionals in Canada play a critical role in identifying and reporting cases of malaria. See the surveillance of malaria section for more information on surveillance in Canada.

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