Overview
Malaria is an infectious disease caused by Plasmodium spp. It is one of the leading causes of morbidity and mortality, particularly in children < 5yo in Kenya. Plasmodium falciparum is the MCC of malaria. A parasitological dx of malaria is recommended for all patients with suspected malaria. However, treatment should NEVER be delayed or denied due to inability to test for malaria.
- Signs and Symptoms of malaria (non-severe)
- Fever
- Chills
- Profuse sweating
- Muscle pains
- Joint pains
- Abdominal pain
- Diarrhoea
- Nausea
- Vomiting
- Irritability
- Signs and symptoms of severe malaria ***Severe malaria can occur in the absence of fever
- Prostration: Inability to sit upright, stand or walk without support in a child normally able to do so, OR Inability to drink in children too young to sit
- Altered level of consciousness: Ranges from drowsiness to deep coma
- Cerebral malaria: Unrousable coma not attributed to any other cause in a patient with Falciparum malaria
- Respiratory distress: Manifests as Acidotic breathing
- Multiple generalized convulsions: 2 or more episodes within a 24 hour period
- Shock: Circulatory collapse (low BP, tachycardia) and/or Septicemia (High fever in the setting of low BP, tachycardia etc.)
- Pulmonary oedema
- Abnormal bleeding: due to Disseminated intravascular coagulation
- Jaundice
- Hemoglobinuria (Black water fever)
- Acute renal failure: Presents as oliguria or anuria
- Severe anemia: Hb < 5g/dL OR, Hct < 15%
- Hypoglycemia: Blood glucose < 2.2 mmol/L
- Hyperlactatemia
- Splenic rupture
- Investigations
- CBC: anemia, leukocytosis, platelet count (DIC)
- U/E/Cs: assess kidney function
- Blood Smear for Malaria Parasites: at least 3 consecutive blood slides taken 8 hours apart
- Thick film: parasite detection and quantification, and to monitor response to Tx
- Thin film: species identification
- Rapid diagnostic test (RDTs):
- Histidine-rich protein 2 (HRP2): specific for P. falciparum
- parasite Lactate dehydrogenase (pLDH) or aldolase: to differentiate between P. falciparum and non P. falciparum malaria (vivax, malariae, and ovale)
- Why are RDTs NOT recommended for follow-up testing
- Most tests remain positive between 2 to 3 weeks following effective antimalarial treatment and clearance of parasites
- Cannot be used to determine parasite density
Malaria Distribution in Kenya
Endemic zones: Transmission is high and intense throughout the year**; Lake Victoria, Western Region, Coast Region** (29% of the Kenyans, prevalence 20-40%)
Epidemic-prone zones: Transmission is seasonal, influenced by temperature and rainfall variation; Western highlands (20% of Kenyans, prevalence 1 – 5%)
Seasonal transmission zones: Transmission happens in short periods during rainfall seasons. Norther and Southeastern Kenya (21% of Kenyans, <5% prevalence)
Low-risk zones: Little to no disease; Central highlands (30% of Kenyans)
Life-cycle
Pathophysiology
Cytoadherence → Sequestration in various organs (heart, lung, brain, liver, kidneys, intestines, placenta, SC tissue) → rosetting → ischemia
- Hypoglycemia
- Plasmodium derives energy from anerobic glycolysis (contributes to hypoglycemia, as well as lactic acidosis)
- Diminished hepatic gluconeogenesis
- Depletion of liver glycogen stores
- Increased glucose consumption by the host
- Quinine-induced hyperinsulinemia
- Acidosis
- Anerobic glycosis in host tissues (sequestered parasites interfere with microcirculatory flow)
- Plasmodium produces lactate
- Hypovolemia
- Insufficient hepatic and renal clearance
- Jaundice
- Haemolysis
- Hepatocellular injury
- Cholestasis
- Anemia
- Hemolysis
- Accelerated splenic clearance
- TNF production suppresses hemopoiesis
- Renal failure
- Mechanical obstruction of RBD
- Immune mediated
- Fluid loss due to alterations in renal microvasculature
- Fever
- Cytokines
Management
Supportive Treatment
- Treatment of fever and pain
- Antipyretics (Paracetamol)
- Tepid sponging
- Fanning
- Exposure
- Treatment of seizures
- Maintain airway
- Prompt IV/Rectal Diazepam
- Check Blood glucose
- Treatment of pulmonary edema
- Prop patient at 45 degrees
- Give oxygen
- Give diuretic
- Stop IV fluids
- Intubate and add PEEP/CPAP in life-threateningn hypoxia
- Treatment of anemia
- If Hb < 5 g/dl
- 10 mls/kg pRBC over 4 hours
- 20 mls/kg whole blood over 4 hours
- If Hb < 5 g/dl
- Treatment of hypoglycemia
- 5 mls/kg 10% dextose
- Oral /NG glucose or feeds ASAP
- Other supportive treatments
- Ensure good nutrition and hydration, CT breastfeeding
- Input output monitoring
- Monitor vitals
- Follow up notes
- Monitor for complications and manage accordingly
- Monitor Hb and give haematinics as appropriate
- Monitor and rehabilitate patients with neurological sequelae
Definitive Treatment
- Treatment of Uncomplicated Falciparum Malaria
- First line tx: Artemether-Lumefantrine (AL) given as a 6 dose regiment over 3 days (STAT, after 8 hours, BD at day 2 and 3)
- 20mg artemether and 120 mg Lumefantrine
- Given with food
- Malaria patients w/HIV/AIDS are treated with the same regimen above
- Malaria patients < 5kg (if appropriate W/A) tx is half a tablet of AL given in 6 doses
- Second line Tx: Dihydroartemisinin-piperaquine (DHA-PPQ) given OD for 3 days
- Adult tablets – 40 mg DHA and 320 mg PPQ
- Paediatric tablet – 20 mg DHA and 160mg PPG
- First line tx: Artemether-Lumefantrine (AL) given as a 6 dose regiment over 3 days (STAT, after 8 hours, BD at day 2 and 3)
- Treatment of Uncomplicated Vivax Malaria
- Artemether-Lumefantrine (AL) + Primaquine 0.25-0.5 mg/kg/day OD for 14 days
- Primaquine is added since vivax has both blood and liver stages
- Primaquine is taken with food, and can cause hemolysis in patients with G6PD deficiency
- Artemether-Lumefantrine (AL) + Primaquine 0.25-0.5 mg/kg/day OD for 14 days
- Treatment of severe malaria
- IV/IM Quinine
- IV/IM Artemisinins
- Artesunate at 0, 12, and 24h then OD for Max 7 days
- Slow IV over 3- 5 minutes
- ≤ 20kg: 3 mg/kg/dose
- ≥ 20kg: 2.4 mg/kg/dose
- Artemether
- Artesunate at 0, 12, and 24h then OD for Max 7 days
- Once can take orally put on ACT for 3 days
- When can we change to a full course of artemisinin combination therapy (ACT) when Tx severe malaria
- 8 – 12 hours after the last dose of artesunate after third injection of artesunate AND child can eat/drink
- What to do if there is Treatment failure in malaria (confirmed by parasitology)
- Consider other causes of illness
- If a child develops signs of severe malaria → change to Artesunate (or Quinine if not available)
- If a child on first-line treatment has fever and positive blood slide after 3 days → check compliance and if Tx failure proceed to second-line
Artemether (20mg) + Lumefantrine (120mg) dosing STATE then at 8h then BD on day 2 and 3
| Weight | Age | Tablets | Dose |
|---|---|---|---|
| <5 kg | – | 1/2 tablet | 10 mg artemether and 60 mg Lumefantrine |
| 5 – 15 kg | 3 – 35 mos | 1 tablet | 20mg artemether and 120 mg Lumefantrine |
| 15 – 24 kg | 3 – 7 yrs | 2 tablets | 40 mg artemether and 240 mg Lumefantrine |
| 25 – 34 kg | 9 – 11 yrs | 3 tablets | 60mg artemether and 360 mg Lumefantrine |
| ≥ 35 kg | ≥ 12 years | 4 tablets | 80mg artemether and 480 mg Lumefantrine |
Dihydroartemisinin Piperaquine dosing OD for 3 days
| Age | Dose |
|---|---|
| 3 – 35 mos | 1 paed tabs |
| 3 – 5 years | 2 paed tabs |
| 6 – 11 years | 1 adult tab |
Prevention
- Interventions to control malaria
- Provision of prompt and effective treatment of malaria cases
- Vector control
- Long lasting insecticidal nets (for all persons living in malaria endemic areas)
- Indoor residual spraying (in endemic and epidemic prone areas)
- Larviciding (in focal breeding sites)
- Screening of house inlets with wire mesh to reduce entry of mosquitoes
- Environmental management for source reducton of vector density eg. draining breeding sites
- Biological control measures where feasible (lavivorous fish, growth regulators, BTI – Bacillus thurigiensis var israeliensis)
- Repellents and fumigants
- DEET – protects for at least 4 hours, safe for infants and children > 2 mos
- Picaridin – protects up to 8 hours
- Prevention and treatment of malaria in pregnancy
- Epidemic preparedness and response
- Malaria vaccine (RTS,S /ASO1) given at 6 months, 7 months, 9 months, and 24 months in high-risk counties
- Chemoprophylaxis
- What does the RTS, S vaccine contain
- P. falciparum circumsporozoite protein (from pre-erythrocytic stage)
- Portion of Hepatitis B virus
- A chemical adjuvant
Chemoprophylaxis
| Drug | Frequency | Initiation (time before 1st exposure) | Discontinuation (Time after last exposure) | Mechanism |
|---|---|---|---|---|
| Atovaquone-Proguanil (Malarone) | OD | 1 – 2 days | 7 days | Hepatic and Blood schizonticide |
| Mefloquine | q1W | 3 weeks preferable (1-2 weeks acceptable) | 4 weeks | Blood schizonticide |
| Doxycycline | OD | 1 – 2 days | 4 weeks | Blood Schizonicide |
Vaccination schedule for malaria (RTS, S)
| Vaccine | Time | Dose | Administration |
|---|---|---|---|
| Malaria 1 | 6 months | 0.5 mL | IM left deltoid |
| Malaria 2 | 7 monhs | 0.5 mL | IM left deltod |
| Malaria 3 | 9 months | 0.5 mL | IM left deltoid |
| Malaria 4 | 24 months | 0.5 mL | IM left deltod |
