Malaria

Malaria - Acute
Rahul Soman, M. Pharm

 

Definition  

A blood-borne infection with protozoan parasites of the genus Plasmodium, transmitted by the bite of infected Anopheles mosquitoes

 

Medical History  

* Mosquito bite

* Transfusion of blood product

* Solid organ transplant

* Shares needles

* Travel

 

Findings  

* Coma

* Focal neurological signs

* Impaired cognition

* Nuchal rigidity

* Respiratory distress

* Retina finding

* Seizure - Acute

* Splenomegaly

* Delirium - Acute

* Edema - Acute

* Extreme exhaustion

* Headache

* Increased heart rate

* Jaundice

* Nausea and vomiting - Acute

* Pallor

* Tachypnea

* Abdominal pain - Acute

* Hepatomegaly - Acute

* Retinal hemorrhage

* Cool skin

* Cough

* Diaphoresis

* Fever

* Myalgia

* Orthostatic hypotension - Acute

* Shivering or rigors

* Urticaria - Acute

* Warm skin

 

Tests  

 

Suspected malaria and monitoring therapeutic response to known malaria  

* Peripheral blood smear examination, light microscopy: The presence of parasites in the stained peripheral blood is diagnostic of malaria .

 

Suspected malaria  

* Complete blood count with white cell differential, manual: Atypical lymphocytes are universally present, and relative or absolute monocytosis occurs frequently.

 

Malaria  

* Hematocrit determination: Decreased hematocrit is common with malaria and the cause is multifactorial . The most severe anemia occurs with falciparum infections .

 

Suspected malaria  

* Plasma random glucose measurement: Hypoglycemia with glucose <40 mg/dL indicates poor prognosis in severe malaria. Falciparum malaria with hypoglycemia may mimic cerebral malaria .

 

Suspected cerebral malaria  

* Cerebrospinal fluid examination: Cerebrospinal fluid findings suggestive of cerebral malaria include elevated pressure, elevated protein levels, and lymphocytic pleocytosis .

 

Suspected malaria  

* Platelet count: Thrombocytopenia is a common finding in malaria , but it is rapidly reversible with appropriate antimalarial therapy.

 

Suspected and known malaria  

* Serum C reactive protein level: C-reactive protein levels correlates well with the severity of P falciparum malaria and the response to therapy .

 

Differential Diagnosis  

* Vivax malaria

* Falciparum malaria

* Quartan malaria

* Ovale malaria

* Congenital malaria

* Relapsing fever

* Visceral leishmaniasis

* Typhoid fever

* Influenza

* Encephalitis

* Meningitis

* Pneumonia

* Gastroenteritis - Acute

* Appendicitis - Acute

* Septicemia

* Hepatitis

* Thrombotic thrombocytopenic purpura - Acute

* Subacute bacterial endocarditis

 

Treatment  

 

Drug Therapy  

 

Uncomplicated, chloroquine-resistant vivax malaria  

 

QUININE

Adults: Quinine sulfate 542 mg base (=650 mg salt) orally three times daily for 3-7 days AND primaquine phosphate 30 mg base orally once daily for 14 days AND tetracycline 250 mg orally four times daily for 7 days

Pediatrics: Quinine sulfate 8.3 mg base/kg (=10 mg salt/kg) orally three times daily for 3-7 days AND primaquine phosphate 0.5 mg base/kg orally once daily for 14 days AND tetracycline 25 mg/kg/day orally divided four times daily for 7 days

 

QUININE

Adults: Quinine sulfate 542 mg base (=650 mg salt) orally three times daily for 3-7 days AND doxycycline 100 mg orally twice daily for 7 days AND primaquine phosphate 30 mg base orally once daily for 14 days

Pediatrics (over age 8): Quinine sulfate 8.3 mg base/kg (=10 mg salt/kg) orally three times daily for 3-7 days AND doxycycline 4 mg/kg/day orally in two divided doses daily for 7 days AND primaquine 0.5 mg base/kg orally daily for 14 days

 

Uncomplicated falciparum malaria or unidentified plasmodium species  

 

CHLOROQUINE PHOSPHATE  

Adults: 600 mg base (=1,000 mg salt) orally immediately, followed by 300 mg base (=500 mg salt) orally at 6, 24, and 48 hours (total dose 1,500 mg base [=2,500 mg salt])

Pediatrics: 10 mg base/kg orally immediately, followed by 5 mg base/kg orally at 6, 24, and 48 hours (total dose 25 mg base/kg)

 

 

Uncomplicated malariae malaria  

 

CHLOROQUINE PHOSPHATE  

Adults: 600 mg base (=1,000 mg salt) orally immediately, followed by 300 mg base (=500 mg salt) orally at 6, 24, and 48 hours (total dose 1,500 mg base [=2,500 mg salt])

Pediatrics: 10 mg of base/kg orally immediately, followed by 5 mg base/kg orally at 6, 24, and 48 hours (total dose 25 mg base/kg)

 

Uncomplicated vivax or ovale malaria  

 

CHLOROQUINE PHOSPHATE - PRIMAQUINE PHOSPHATE

Adults: Chloroquine phosphate 600 mg base (=1,000 mg salt) orally immediately, followed by 300 mg base (=500 mg salt) orally at 6, 24, and 48 hours (total dose 1,500 mg base [=2,500 mg salt]) AND primaquine phosphate 30 mg base orally once daily for 14 days

Pediatrics: Chloroquine phosphate 10 mg of base/kg orally immediately, followed by 5 mg base/kg orally at 6, 24, and 48 hours (total dose 25 mg base/kg) AND primaquine phosphate 0.5 mg base/kg orally once daily for 14 days

 

Uncomplicated, chloroquine-sensitive malariae or falciparum malaria in pregnancy  

 

CHLOROQUINE PHOSPHATE  

Adults: 600 mg base (=1,000 mg salt) orally immediately, followed by 300 mg base (=500 mg salt) orally at 6, 24, and 48 hours (total dose 1,500 mg base [=2,500 mg salt])

 

Uncomplicated, chloroquine-sensitive vivax or ovale malaria in pregnancy  

 

CHLOROQUINE PHOSPHATE  

Adults: 600 mg base (=1,000 mg salt) orally immediately, followed by 300 mg base (=500 mg salt) orally at 6, 24, and 48 hours (total dose 1,500 mg base [=2,500 mg salt]); then 300 mg base (=500 mg salt) orally once weekly throughout pregnancy

 

Uncomplicated falciparum malaria or unidentified Plasmodium species resistant to chloroquine or of unknown resistance  

 

QUININE

Adults: Quinine sulfate 542 mg base (=650 mg salt) orally three times daily for 3-7 days AND doxycycline 100 mg orally twice daily for 7 days

Pediatrics: Quinine sulfate 8.3 mg base/kg (=10 mg salt/kg) orally three times daily for 3-7 days AND doxycycline 4 mg/kg/day orally divided two times daily for 7 days

 

QUININE - TETRACYCLINE  

Adults: Quinine sulfate 542 mg base (=650 mg salt) orally three times daily for 3-7 days AND tetracycline 250 mg orally four times daily for 7 days

Pediatrics (>8 years): Quinine sulfate 8.3 mg base/kg (=10 mg salt/kg) orally three times daily for 3-7 days AND tetracycline 25 mg/kg/day orally divided four times daily for 7 days

 

Uncomplicated chloroquine-resistant falciparum malaria in pregnancy  

 

QUININE - CLINDAMYCIN HYDROCHLORIDE  

Adults: Quinine sulfate 542 mg base (=650 mg salt) orally three times daily for 3-7 days AND clindamycin 20 mg base/kg/day orally divided in three doses for 7 days

 

Uncomplicated chloroquine-resistant vivax malaria in pregnancy  

 

QUININE

Adults: 650 mg salt orally three times daily for 7 days

 

 

Severe falciparum malaria  

 

QUINIDINE GLUCONATE - DOXYCYCLINE  

Adults: Quinidine gluconate [6.25 mg base/kg (=10 mg salt/kg) loading dose IV over 1-2 hours, then 0.0125 mg base/kg/minute (=0.02 mg salt/kg/minute) continuous IV infusion for at least 24 hours OR 15 mg base/kg (=24 mg salt/kg) loading dose IV infused over 4 hours, followed by 7.5 mg base/kg (=12 mg salt/kg) IV infused over 4 hours every 8 hours, starting 8 hours after the loading dose] AND doxycycline 100 mg IV every 12 hours, switch to 100 mg orally twice daily when patient is able to take oral medication; total treatment course of 7 days

Pediatrics (< 45 kg): Quinidine gluconate [6.25 mg base/kg (=10 mg salt/kg) loading dose IV over 1-2 hours, then 0.0125 mg base/kg/minute (=0.02 mg salt/kg/minute) continuous IV infusion for at least 24 hours OR 15 mg base/kg (=24 mg salt/kg) loading dose IV infused over 4 hours, followed by 7.5 mg base/kg (=12 mg salt/kg) infused over 4 hours every 8 hours, starting 8 hours after the loading dose] AND doxycycline 4 mg/kg IV every 12 hours, switch to 4 mg/kg/day orally divided two times daily when patient is able to take oral medication; total treatment course of 7 days

Pediatrics (? 45 kg): Quinidine gluconate [6.25 mg base/kg (=10 mg salt/kg) loading dose IV over 1-2 hours, then 0.0125 mg base/kg/minute (=0.02 mg salt/kg/minute) continuous IV infusion for at least 24 hours OR 15 mg base/kg (=24 mg salt/kg) loading dose IV infused over 4 hours, followed by 7.5 mg base/kg (=12 mg salt/kg) IV infused over 4 hours every 8 hours, starting 8 hours after the loading dose] AND doxycycline 100 mg IV every 12 hours, switch to 100 mg orally twice daily when patient is able to take oral medication; total treatment course of 7 days

 

QUINIDINE GLUCONATE - TETRACYCLINE  

Adults: Quinidine gluconate [6.25 mg base/kg (=10 mg salt/kg) loading dose IV over 1-2 hours, then 0.0125 mg base/kg/minute (=0.02 mg salt/kg/minute) continuous IV infusion for at least 24 hours OR 15 mg base/kg (=24 mg salt/kg) loading dose IV infused over 4 hours, followed by 7.5 mg base/kg (=12 mg salt/kg) IV infused over 4 hours every 8 hours, starting 8 hours after the loading dose] AND tetracycline 250 mg orally four times daily for 7 days

Pediatrics: Quinidine gluconate [6.25 mg base/kg (=10 mg salt/kg) loading dose IV over 1-2 hours, then 0.0125 mg base/kg/minute (=0.02 mg salt/kg/minute) continuous IV infusion for at least 24 hours OR 15 mg base/kg (=24 mg salt/kg) loading dose IV infused over 4 hours, followed by 7.5 mg base/kg (=12 mg salt/kg) IV infused over 4 hours every 8 hours, starting 8 hours after the loading dose] AND tetracycline 25 mg/kg/day orally divided four times daily for 7 days

 

QUINIDINE GLUCONATE - Clindamycin  

Adults: Quinidine gluconate [6.25 mg base/kg (=10 mg salt/kg) loading dose IV over 1-2 hours, then 0.0125 mg base/kg/minute (=0.02 mg salt/kg/minute) continuous IV infusion for at least 24 hours OR 15 mg base/kg (=24 mg salt/kg) loading dose IV infused over 4 hours, followed by 7.5 mg base/kg (=12 mg salt/kg) IV infused over 4 hours every 8 hours, starting 8 hours after the loading dose] AND clindamycin 10 mg base/kg loading dose IV followed by 5 mg base/kg IV every 8 hours, switch to 20 mg base/kg/day orally divided three times daily when patient is able to take oral medication; total treatment course of 7 days

Pediatrics: Quinidine gluconate [6.25 mg base/kg (=10 mg salt/kg) loading dose IV over 1-2 hours, then 0.0125 mg base/kg/minute (=0.02 mg salt/kg/minute) continuous IV infusion for at least 24 hours OR 15 mg base/kg (=24 mg salt/kg) loading dose IV infused over 4 hours, followed by 7.5 mg base/kg (=12 mg salt/kg) IV infused over 4 hours every 8 hours, starting 8 hours after the loading dose] AND clindamycin 10 mg base/kg loading dose IV followed by 5 mg base/kg IV every 8 hours, switch to 20 mg base/kg/day orally divided three times daily when patient is able to take to take oral medication, total treatment course of 7 days

 

Prophylaxis of falciparum malaria  

 

ATOVAQUONE/PROGUANIL HYDROCHLORIDE  

Adults: 1 adult tablet orally daily

Pediatrics (11-20 kg): 1 pediatric tablet orally daily

Pediatrics (21-30 kg): 2 pediatric tablets orally daily

Pediatrics (31-40 kg): 3 pediatric tablets orally daily

Pediatrics (>40 kg): 1 adult tablet orally daily

 

CHLOROQUINE

Adults: 500 mg (300 mg base) orally once weekly, starting 1-2 weeks before travel, during travel, and 4 weeks post-travel

Pediatrics: 8.3 mg/kg (5 mg/kg base) orally once weekly (maximum dose 300 mg base)

 

Prophylaxis of chloroquine-resistant falciparum malaria  

 

ATOVAQUONE/PROGUANIL HYDROCHLORIDE  

Adults: 1 adult tablet (atovaquone 250 mg/proguanil 100 mg) orally daily with food 1-2 days prior to, during, and 7 days after travel

Pediatrics (11-20 kg): Atovaquone 62.5 mg/proguanil 25 mg orally daily

Pediatrics (21-30 kg): Atovaquone 125 mg/proguanil 50 mg orally daily

Pediatrics (31-40 kg): Atovaquone 187.5 mg/proguanil 75 mg orally daily

Pediatrics (>40 kg): Atovaquone 250 mg/proguanil 100 mg orally daily

 

Alternative prophylaxis of chloroquine-resistant falciparum malaria for nonpregnant adults  

 

PRIMAQUINE PHOSPHATE

Adults: 30 mg base orally daily

 

Alternative prophylaxis of chloroquine-resistant falciparum malaria in pregnant adults  

 

MEFLOQUINE HYDROCHLORIDE  

Adults: 250 mg (228 mg base) orally once weekly, 1 week before, during, and 4 weeks after travel

 

 

Fever  

 

ACETAMINOPHEN

Adults: 650 to 1,000 mg orally every 4 to 6 hours as needed (maximum 4 g/day)

Pediatrics: 10 to 15 mg/kg orally or rectally every 4 to 6 hours as needed (maximum 5 doses or 4 g/day)

Neonates: 10 to 15 mg/kg orally or rectally every 6 to 8 hours as needed

 

Procedural Therapy  

 

Malaria  

    * Infectious disease notification

 

Dehydration  

* Intravenous fluid replacement: Intravenous fluid replacement is indicated for patients with dehydration when oral replacement cannot be accomplished .

 

Malaria  

* Transfusion of blood product: Malarial patients with severe anemia and parasitemia >10% or hypovolemic shock may require blood or packed red cells transfusion .

 

Non-Procedural Therapy  

 

Prophylaxis of malaria  

* Protective Measures