Treatment (Refer to box diagram below)

Two types of drugs are used to treat malaria. Blood

schizonticides, which attack parasites in red blood cells, are used in acute infection to prevent or terminate the clinical attack. Tissue schizonticides are medications that act on the exoerythrocytic parasite stages (forming merozoites and hypnozoites)

in liver cells to prevent relapse. Treatment with tissue schizonticides, known as "radical" cure, is required for infections of P. vivax and P. ovale. During treatment, patients must be monitored for response to therapy and complications from the infection

or treatment. Repeated clinical assessment is important in cases of severe malaria, where early detection of complications and immediate intervention may be lifesaving.

Treatment approach for complicated malaria is listed below:

• Start treatment as soon as diagnosis is suspected.

• Calculate dosage according to patient weight.

• Give medication intravenously.

• Give loading dose of medication (not indicated if patient has received quinine, quinidine, or mefloquine in the last 24 hours). Switch to oral medication as soon as patient can tolerate tablets, and response to treatment is confirmed. Observe patients carefully for drug toxicity and complications.

• Loading doses have been shown to decrease the duration of fever, parasitemia, and coma, and should be given if the patient has not received quinine, quinidine, or mefloquine in the last 24 hours.

Loading doses of quinine or quinidine should be given followed by continuous infusion. Baseline blood pressure and ECG should be obtained before initiating therapy, and periodically throughout treatment. Therapy should be discontinued if systolic blood pressure persists below 80 mm Hg, if either the QRS interval widens greater than 50%, or the QT interval is greater than 50% of the preceding R-R interval; or if a cardiac arrhythmia arises. Overdose of quinine, particularly if too rapidly infused, can cause convulsions, hypotension, cardiovascular collapse, heart block, and ventricular fibrillation. The maintenance dose should be reduced to one-third to one-half after 48 hours to prevent accumulation and toxicity, unless the patient has improved and can tolerate oral medication. Therapeutic doses of quinine can cause hypoglycemia through stimulation of insulin release. Blood glucose should be monitored periodically during treatment.

Alternate treatments include intravenous chloroquine, intramuscular FansidarR, mefloquine or halofantrine tablets crushed and mixed with water given via nasogastric tube, or artemisinin derivatives. Intravenous chloroquine is less toxic than quinine or quinidine, but resistance to it is so prevalent that it is not used for treatment of severe malaria cases. If oral therapy with mefloquine is chosen to complete the recommended 7 days of therapy, delay the initial dose for 12 hours after the last dose of quinidine or quinine.

Halofantrine should not be used inpatients who developed P. falciparum infections while on mefloquine prophylaxis because parasite resistance to both drugs is similar. In addition, fatalities have occurred when halofantrine has been used for treatment in patients who received mefloquine prophylaxis.

Intramuscular FansidarR (a combination drug containing sulfadoxine and pyrimethamine) has been shown to clear parasitemias quickly as chloroquine, but hypersensitivity reactions to sulfonamides are common and cause complications.

Antimalarial chemotherapy in adults or children with uncomplicated malaria who can swallow tablets

Chloroquine-resistant P.Falciparum or species Chloroquine-sensitive P.falciparum or or origin unknown P.vivax, P.ovale, P.malariae

1. Quinine 1. Chloroquine

Adults : 650 mg of the salt 3 times each Adults: 600 mg of the base on the 1st and day for 7 days and, if quinine resistance is 2nd days, 300 mg on the 3rd day. known or suspected, followed by either Children: 10 mg base/kg, followed by fansidar 3 tablets (sulfadoxine 500 mg per 5 mg base /kg after 6 hours, tablet, pyrimethamine 25 mg tablet)^d or 24 & 48 hours.. tetracycline 250 mg 4 times each day for 7 days when renal function has returned to normal^. Children: Approximately 10 mg of the salt/kg 3 times each day for 7 days and, if quinine resistance is known or suspected, followed by Fansidar (dose see 3 below)

OR For radical cure of vivax/ovale add 2. Mefloquine 2. Primaquine

Adults : 15-25 mg of the base/kg (maxi- Adults (except pregnant and lactating mum 100 mg) given as doses 6-8 h apart. women and G6PD-deficient patients): Children :15- 25 mg of the base/kg given as 15 mg base/day on days 4-17 or 45 mg/ single dose. week for 8 weeks^a

OR

3. Sulfadoxine (500 mg per tablet) (Fansidas) Children: 1-3 years 2.5 mg/kg plus pyrimethamine (25 mg) 4-6 5 mg/kg

Adults : 3 tablets as a single dose. 7-10 7.5 mg/kg

Children: 6-11 months ¹/4 tablet for 5-7 days

1-3 years ^1/2 tablet (0.3 mg/kg up to 15 mg)

4-8 years 1 tablet

9-14 years 2 tablets

> 14 years 3 tablets

Antimalarial chemotherapy in adults or children with severe malaria or in those who cannot swallow tablets

Chloroquine-resistant P.falciparum or origin Chloroquine-sensitive P.falciparum or un-known P.vivax, P.ovale, P. malariae

1. Quinine 1. Chloroquine

Adults: 20 mg of the salt/kg (loading dose) 10 mg base/kg (maximum 600 mg) diluted diluted in 10 ml/kg isotonic fluid by i.v. infu- in isotonic fluid by continuous i.v. infusion sion over 4 h. 8-12 hourly until patietns can over 8 h. followed by 15 mg base/kg swallow. (maximum 900 mg) by continuous i.v. Children: 15 mg of the salt/kg (loading dose) infusion over 24 h diluted in 10 ml/kg isotonic fluid by i.v.

OR

infusion over 2 h, then 10 mg/kg over 2 h.

12-hourly until patients can swallow. 2. Quinine

The 7-day course should be completed with (see above left-hand column) quinine tablets approximately 10 mg salt/kg 8-hourly.

OR

2. Quinine (in intensive care unit)

7 mg of the salt/kg (loading dose) i.v. by infusion pump over 30 min followed immediately by 10 mg/kg (maintenance dose) diluted in 10 ml/kg isotonic fluid by i.v. infusion over 4 h repeated 8-12 hourly until patient can swallow etc.

OR

3. Artemether or Artesunate 3.2 mg/kg I.M. followed by 1.6 mg/kg IM every 12-24 hrs until patient wakes up.

If it is not possible to give drugs by intravenous infusion

1. Quinine 1. Chloroquinine

20 mg of the salt/kg (loading dose) diluted to Total dose 25 mg base/kg given either 60 mg/ml. by deep i.m. injection (half dose (a) i.m. or s.c. 2.5 mg/kg 4-hourly; into each anterior thigh) with strict sterile pre- or (b) i.m. or s.c. 3.5 mg/kg 6-hourly cautions, then 10 ml/kg 8-12 hourly until

OR

patient can swallow etc.

2. Artemether, Artesunate, or Artemisinin 2. Quinine by i.m. injection or suppository i.m. (see above, left-hand column)

Artemisinin, a compound known as qinghaosu in China, has been used with great success there and in trials in Thailand. It is available as heterogeneous compounds in suppository, intravenous, and tablet forms. "Radical" Cure: To prevent relapse, P. vivax and P. ovale infections need to be treated to eradicate tissue schizonts (persistent liver cell stages known as hypnozoites). This is known as "radical" cure, and currently the only available effective drug is primaquine. It is a potent oxidant, and can cause severe hemolytic anemia in G-6-PD deficient patients.

Parameters to monitor while on treatment include:

• Vital signs (temperature, pulse, blood pressure, respiration)

• Parasite concentration.

• Urinary output.

• Serum electrolytes.

• Blood glucose.

• Hematocrit/hemoglobin.

• ECG (required for quinidine treatment).

Response to therapy is monitored by serial blood smears. Fewer parasites will be seen equivalent setting, and rapid access to surgical consultation.