Malaria is caused by infection with intracellular Plasmodium protozoan parasites, which are transmitted by the bite of a female Anopheles spp mosquito.
- P vivax and P ovale, two Plasmodium species, develop dormant parasite forms called hypnozoites that can remain in the liver for months or years after primary infection causing relapse and recurrent symptomatic disease.
- Fever is a distinguishing symptom that is caused by erythrocyte rupture and parasite release every 2 to 3 days, depending on the Plasmodium species.
- Malaria can be fatal due to high parasite burdens, which cause hemolysis and severe anemia, or to end-organ damage caused by vascular adherence of infected erythrocytes and microocclusion.
- P. vivax is the most important causative agent of human malaria in Nepal.
About 90-95% of malaria cases are due to P. vivax and rest due to P.
falciparum.
History and Examination
- Children younger than 18 develop symptoms earlier and are more likely to develop severe malaria.
- Risk Factors: Children living in or traveling to endemic areas
- Travel Hisotry: Patient present within 7 days to 3 months following an infected mosquito bite; suspect malaria in any afebrile traveler.
- Classic cyclical fever patterns described for malaria may not be present in travelers and young children
- Travelers are more likely to present with severe malaria, compared with the semi-immune residents of endemic areas
- Uncomplicated malaria typically manifests as a nonspecific febrile illness, similar in presentation to influenza and other common viral infections.
- Chronic asymptomatic bloodstream infection may result from P malariae infection, which can also cause a nephrotic syndrome from immune complex deposition in the kidney
Uncomplicated Malaria Clinical features
| Symptoms | Signs |
| -Fever with chills and rigors -Headaches -Lethargy -Myalgias and cough -Gastrointestinal symptoms (Nausea, Vomiting, Diarrhea, and Abdominal pain) |
-Pallor, tachycardia, hepatosplenomegaly, jaundice, and increased respiratory rate -Cerebral malaria (Altered mental status) |
Severe Malaria Manifestation
Severe malaria is most commonly caused by P falciparum infection, which can reach higher parasite levels than other species.
| Cerebral malaria | –Impaired consciousness (including unarousable coma): A Glasgow Coma Score <11 in adults or a Blantyre Coma Score <3 in children. –Prostration: Generalized weakness so that the patient is unable to sit, stand or walk without assistance –Multiple convulsions: More than two episodes within 24h. |
| Blackwater fever |
-Intravascular hemolysis causes acute renal failure and hemoglobinuria. -Acute kidney injury/Renal Impairment |
| Severe anemia and Shock |
-A low hemoglobin level of less than 7 g/dL caused by a high parasite burden and hemolysis of infected erythrocytes. |
| Acute respiratory distress syndrome |
-Deep breathing and respiratory distress (acidotic breathing). – Oxygen saturation < 92% on room air with a respiratory rate > 30/min, often with chest indrawing and crepitations on auscultations. |
| Hyperparasitemia | Malaria parasite infection of more than 5% of circulating red blood cells is commonly defined. |
| Metabolic complications | Severe metabolic acidosis and life-threatening hypoglycemia |
Laboratory finding in Severe Malaria
- Hypoglycaemia (< 2.2mmol/l or < 40mg/dl)
- Metabolic acidosis (plasma bicarbonate < 15mmol/l)
- Severe normocytic anaemia (haemoglobin < 5g/dl, packed cell volume
< 15% in children; <7g/dl, packed cell volume < 20% in adults) - Haemoglobinuria
- Hyperlactataemia (lactate > 5mmol/l)
- Renal impairment: serum creatinine > 265μmol/l (3mg/dl) or Blood
urea > 20mmol - Pulmonary oedema (radiological).
- Hyperparasitaemia: P. falciparum parasitaemia > 10%
Differential Diagnosis (D/D) & Complications
D/D
- Dengue
- Scrub typhus
- Typhoid fever
- Septicemia
Complications
- Coma
- Convulsion
- Acute pulmonary edema
- ARDS
- Acute Renal Failure
- Severe Bleeding
- Metabolic Acidosis
- Spontaneous Bleeding and Coagulopathy
Investigation
Microscopy
- Microscopic examination of peripheral smear (both thick and thin films) is gold standard.
- Thick flim for diagnosis and thin flim for species identification
- Done in all suspected cases before administration of antimalarials.
Rapid Diagnostic Test
- RDTs detect different Plasmodium-specific antigens such as
histidine-rich protein 2 of Plasmodium falciparum (PfHRP2), a pan malarial parasitespecific lactate dehydrogenase (pLDH), and Plasmodium aldolase (PMA) - PfHRP2 can persist in the blood for 28 days, so RDTs detecting PfHRP2 can remain positive even after clinical cure.
- RDT cannot distinguish new infection from recent and effectively treated infection.
- None of the RDTs are useful in monitoring response to treatment.
- Has high sensitivity and specificity for P falciparum and P vivax infection, with reduced sensitivity for P ovale and P malariae.
- Useful for screening purpose only.
Other Investigation
- CBC
- RFT, RBS
- Arterial Blood Gas Analysis
- URME
- Chest X-ray
- Blood Culture
- Lumbar Puncture in unconcious patient
Admission Criteria
All severe case of malria should be admitted for injectable Antimalarial drugs.
Management
Treatment of Uncomplicated Malaria
- Uncomplicated P. Vivax, P. ovale, P. malariae, or P. knowlesi Malaria
-Treat with Chloroquine (3 Days) and Primaquine (14 days) for P. vivax
and P. ovale.
-Treat with chloroquine (3 days) for P. malariae or P. knowlesi.
Note: Do not give Chloroquine in empty stomach or when there is high fever. You should control fever first. If patient vomit within 45 minutes, does should be repeated after antiemetic ( Ondansetron or domepridone).
Preventing relapse in P. vivax or P. ovale malaria
-14-day course of primaquine – (except pregnant women, infants aged
< 6 months, and women breastfeeding infants aged < 6 months).
– G6PD testing is encouraged prior to 14 days as Primaquine cause hemolysis. If test is not available closely supervised 14 days PQ therapy will be given.
-Do follow up on days 3, 7 and 14 to monitor for adverse effects and compliance with primaquine. Explain side its side effects to patient party.
– Primaquine is eliminated rapidly (3.5 -8 hours) so haemolysis is self-limiting once the drug is stopped.
Dosing
Day 1: chloroquine is given at an initial dose of 10 mg base/kg body weight.
Day 2: followed by 10 mg/kg body weight.
Day 3: 5 mg/kg body weight.
Primaquine: 0.25mg/kg/ Once daily for 14 days
In 6 months – 1 yr: 2.5 mg tablet of primaquine should be given, 1 tab daily for 14 days .
Second line treatment
The recommended 2nd line option in Nepal is dihydroartemisinin +
piperaquine (DHA/PPQ).
- Use when patient does not tolerate or has adverse reactions to the first
line medicine. - Recrudescence (treatment failure) – reappearance of symptoms and
parasites within 28 days following initial antimalarial treatment of
the 1st line drug - Suspected chloroquine resistant vivax infection
- Uncomplicated Plasmodium Falciparum Malaria
Aim: To cure the infection as rapidly as possible and to prevent progression to
severe disease. “Cure” is defined as elimination of the parasites from the
body
First Line of Treatment
-Artemether + Lumefantrine (AL) given over three days and a single dose primaquine.
– Primaquine single dose of 0.25 mg/kg bw (except in pregnant women, infants aged < 6 months and women,breastfeeding infants aged < 6 months). Testing for glucose-6- phosphate dehydrogenase (G6PD) is not required.
(Each tablet of AL contains 20mg/120mg artemether and lumefantrine respectively)
- Treatment of Mixed Infection Malaria
ACTs are effective against all malaria species and is the treatment of choice for blood stage mixed infection. In case of vivax or ovale mixed infection with P. falciparum, 14 days of primaquine should be given along with the 1st line ACT (AL) for 3 days.
Other mixed infections (P. malariae or P. knowlesi) should be treated like
uncomplicated P. falciparum infection.
- Treatment of Severe Malaria
The antimalarial medicine recommended for the treatment of severe malaria is an initial treatment with injectable (IV/IM) artesunate followed by a full course of AL as soon as the patient is stable enough and able to tolerate oral medication.
Artesunate
Recommended Dosage for injectable artesunate:
- Children less than 20kg – artesunate 3.0 mg/kg body weight
- Older children and adults – artesunate 2.4mg/kg body weight
Give 3 parenteral doses of injection artesunate in the first 24 hours
- First dose on admission (time zero),
- Second dose 8 hours after the first dose and
- Third dose at 24 hours after the first dose.
- Thereafter every 24 hours until patient is able to tolerate oral medication for P. falciparum.
Note: The parenteral antimalarial drugs should be given for a minimum of 24 h once started (irrespective of the patient’s ability to tolerate oral medication earlier) or until the patient can tolerate oral medication, before giving the oral follow-up treatment with single dose of primaquine .
Symptomatic Treatement
Advices
- Explain dangers sign and importance of adherence to drugs.
- Encourage to use mosquito net
Referral
Refere all case with severe malaria. The risk of death is highest in 24 hours so before referral, give Artesunate Intramuscular.
Recommended Dosage for injectable artesunate:
- Children less than 20kg, – artesunate 3.0 mg/kg bodyweight
- Older children and adults – artesunate 2.4mg/kg bodyweight
Follow up
| Definition | |
|---|---|
| Early-Treatment Failure | – Worsening of clinical condition or increase in parasitemia during days 1-3.<br> – Persistence of fever even after 72 hours.<br> – Inadequate decrease in parasitemia. |
| Late-Treatment Failure | – Late clinical failure (late worsening or incomplete resolution/recurrence of parasitemia and fever).<br> – Late parasitological failure (failure to clear parasitemia or presence of parasitemia on any day from day 7 to day 28). |
| Adequate Clinical and Parasitological Response | – Absence of parasitemia on day 28 (day 14 in intense transmission areas) irrespective of axillary temperature. |