Pediatric Malaria Treatment & Management

Oral paracetamol (acetaminophen) is safe and effective for fever and should be used in doses of 10 mg/kg. This dose can be repeated 3-6 times a day, as required. If the child has hyperpyrexia, tepid sponging can rapidly bring the temperature down.

Many children with malaria develop anemia. Because the onset is gradual, children withstand a low level of hemoglobin quite well and blood transfusions are rarely needed. Standard hematinic therapy is effective.

Vomiting is common in malaria. An antiemetic such as domperidone can be used, and antimalarials should be continued. Vomiting stops when the malaria is cured. If repeated vomiting has led to dehydration, the child needs appropriate parenteral fluids to correct it. Glucose-containing fluids help to counter the hypoglycemia that sometimes accompanies severe malaria.

Indications for immediate hospitalization include the following:

• Intractable vomiting

• Dehydration

• Seizures

• Altered consciousness or coma

• Repeated convulsions

• Difficulty in breathing or acidotic breathing

• Severe pallor (indicating severe anemia)

• Hypoglycemia (blood glucose < 2.5 mmol/L, or 3 mmol/L in malnourished children)

• Oliguria or anuria, signifying renal affliction

• Shock

• Hyperparasitemia

• Bleeding diathesis

In a child with malaria, impaired consciousness, respiratory distress, hypoglycemia, and jaundice are risk factors for death. Such a child should be treated as an emergency. On the other hand, children with malaria who are fully conscious, who have low to moderate fever, and who are maintaining their nutrition and hydration orally can be treated on an outpatient basis.

Malaria can be severe in pregnancy. This is a major problem because many antimalarial drugs are considered unsafe during pregnancy.

Severe malaria is known to be associated with bacteremia and may be the cause of a sudden deterioration. The coexisting bacterial infection is difficult to diagnose clinically, especially in children, as the clinical features overlap to a significant extent. The World Health Organization (WHO) recommends a low threshold for starting antibiotic treatment in children with severe malaria. Salmonella species are commonly encountered, but other organisms are also frequently isolated; initial empiric therapy should be broad spectrum. ^[6]

No restrictions are needed in the diet for patients well enough for outpatient management. Indeed, the appetite and activity level are remarkably well preserved for the degree of fever. Advise increased fluid intake. Children should be allowed to decide their own activity levels. If the fever is intermittent, many children feel quite well between paroxysms of fever and come to no harm through activity.

Consult an infectious diseases specialist for patients with malaria. With regard to patient transfer, if appropriate drugs and experience in treating malaria are not available, the patient may need urgent transfer to a referral hospital.

Malaria can be life threatening, and intensive care may be required. Indications for admission to the intensive care unit (ICU) include the following:

• Suspicion of cerebral malaria (ie, seizures, prolonged postictal coma, repeated seizures)

• Complications of malaria (eg, bleeding, renal failure, pulmonary edema)

Admit patients from nonmalarious areas to the ICU if more than 2% of erythrocytes have malaria parasites. Patients from an endemic area can tolerate higher levels, but patients should be admitted to the ICU if more than 5% of erythrocytes are parasitized.

Blood smears should be repeated after 24-48 hours to ensure that the drug is effective. This is especially important with P falciparum. If parasites are not cleared in 48 hours, a change in drug is required.

An exchange transfusion is valuable in a very sick child. It reduces parasite load rapidly, corrects any bleeding diatheses, and corrects anemia. Erythrocytapheresis, the use of cell separation techniques to remove only the erythrocytes, has been used successfully in adults. It removes the parasites and has the added advantage of hemodynamic stability.

Radical cure implies the destruction of the dormant forms in the liver. Primaquine is the only drug active against the hypnozoites in the hepatocytes.

Measures to prevent mosquito bites are very important for people living in or traveling through a malarious area.

Chemoprophylaxis is undermined by poor adherence and parasite resistance to almost all drugs, and is not fully dependable on its own. Therapy should be started a week before entering a malarious area and continued for 4 weeks after leaving it.

Chloroquine is the most commonly used drug, at a dose of 5 mg/kg once a week; however, significant resistance to it is now present. Mefloquine (5 mg/kg once a week) is recommended in areas where chloroquine resistance is common. Mefloquine may cause adverse neuropsychiatric reactions and should not be prescribed for prophylaxis in patients with active or recent history of depression, generalized anxiety disorder, psychosis, or schizophrenia or other major psychiatric disorders. ^[7] The CDC provides country-specific advice on malaria chemoprophylaxis. Infants younger than 6 weeks should not be administered chemoprophylaxis.

In July 2018, the FDA approved tafenoquine, an antiplasmodial 8-aminoquinoline derivative indicated for the radical cure (prevention of relapse) of P vivax malaria in patients aged 16 years or older who are receiving appropriate antimalarial therapy for acute P vivax infection. The drug is active against all stages of the P vivax life cycle. Tafenoquine is administered as a single oral dose on the first or second day of appropriate antimalarial therapy (eg, chloroquine) for acute P vivax malaria. Approval was based on an international programme of over 4000 participants.

In 1 of the clinical trials, 329 patients were randomly assigned to a treatment group (chloroquine plus tafenoquine 50 mg [n=55], 100 mg [n=57], 300 mg [n=57], 600 mg [n=56]; or to chloroquine plus primaquine [n=50]; or chloroquine alone [n=54]). Relapse-free efficacy at 6 months was 89.2% with tafenoquine 300 mg and 91.9% with tafenoquine 600 mg compared with chloroquine alone (37.5%). The results showed a significantly improved treatment difference compared with chloroquine alone of 51.7% (p < 0.0001) with tafenoquine 300 mg and 54.5% (p < 0.0001) with tafenoquine 600 mg. ^[8]

Because tafenoquine increases risk of hemolytic anemia in patients with G6PD deficiency, patients must be tested before initiating the drug. The drug is contraindicated in patients with G6PD deficiency (or unknown status), during breastfeeding of an infant with G6PD deficiency (or unknown status), and those with known hypersensitivity. ^[9]

Prevention of mosquito bites is the most effective means of individual malaria protection. Cover the body while outdoors. Wear full-length sleeves and trousers. Clothes can also be treated with an insecticide, such as permethrin, which is safe for this purpose. Diethyl-m-toluamide (DEET) is an effective mosquito repellent when applied to the skin.

Increased precautions are needed during the night, because Anopheles species are nocturnal in habit. Sleeping under insecticide-treated (permethrin 0.2 g/m² of material every 6 mo) mosquito nets is perhaps the most beneficial antimalarial measure available. Bedrooms should be sprayed with an aerosol insecticide at dusk.

Malaria vaccines

Vaccines against various malarial antigens have been tried for many years, all around the world. In one study, the use of the RTS,S/AS02D vaccine had a promising safety profile and reduced malaria infections. ^[10] Other vaccines have been tried and abandoned, and several are currently under evaluation. Unfortunately, the immunity provided by candidate malaria vaccines is inadequate and short lived. A safe, effective vaccine that provides reliable, long-lasting protection against malaria has proven elusive and will probably not be available for some years yet.

Interim phase 3 trial results have been reported for the malaria vaccine RTS,S/AS01. The results included 6000 African children aged 5-17 months who received the malaria vaccine or a comparator vaccine and were followed for 12 months. The incidence of malaria was 0.44 case per person-year in the RTS,S/AS01 group, compared with 0.83 case per person-year in the comparator vaccine group. The vaccine efficacy rate was calculated to be 55.8%. ^{[11, 12]}