Malaria is a parasitic infection caused by a protozoan of the genus Plasmodium, transmitted to humans by the bite of a mosquito (Anopheles). Transmission is also possible by transfusion of infected blood, and in the fetus via the placenta.
Most infections are caused by four species of Plasmodium: P. falciparum, P. vivax, P. ovale and P. malariae. The 4 species can cause an uncomplicated malaria; severe malaria (defined by the presence of complications) is almost always due to P. falciparum.
Clinical suspicion of malaria should be confirmed whenever possible by parasitological diagnosis. However, no possibility of confirmation, treatment of a suspect case should not be delayed: uncomplicated malaria can quickly become severe and untreated severe malaria can be fatal within hours.
Clinical signs :
In case of fever (or history of fever in the last 48 hours) in a patient or resident returning from an endemic area, systematically evoke malaria.
Fever is often associated with chills, sweats, headache, myalgia, malaise, anorexia and nausea. In children, it can be associated with abdominal pain, diarrhea and vomiting. Anemia is common in children and pregnant women.
In addition to these symptoms, presence of one or more of the following complications:
– Altered consciousness, delirium or coma
– Generalized convulsions or focal (eg, abnormal eye movements..)
– Prostration: extreme weakness; in children, failure to eat / drink / suck
– Respiratory distress: rapid and difficult breathing or slow, deep breathing
– Circulatory collapse (shock): cold extremities, weak or absent pulse, slow capillary refill time (> 3 seconds), cyanosis
– Jaundice (to look at the oral mucosa, conjunctiva, palms)
– Hemoglobinuria: dark red urine
– Bleeding: skin (petechiae), conjunctival, nasal, gingival; blood in stool
– Acute renal failure: urine output <12 ml / kg / day in children and <400 ml / day in adults, despite adequate hydration
Patients with at least one of these complications or severe anemia should be hospitalized immediately.
The blood smear and thick blood can detect the parasite, to identify the species, quantify and monitor parasitaemia.
Attention examination may be negative in a genuine severe malaria by sequestration of parasitized erythrocytes in peripheral capillaries, and in the vessels of the placenta in pregnant women.
– Rapid Diagnostic Tests (RDTs) 1
Rapid tests detect parasite antigens. They give a qualitative result only (ie of positive or negative.) And may remain positive several days or weeks after effective treatment.
Note: exclude other causes of fever, even if the diagnosis is positive.
– Hemoglobin (Hb) to systematically measure in cases of clinical anemia and severe malaria.
– Blood glucose: to systematically measure to detect hypoglycemia (<3 mmol / l or <54 mg / dl) for severe malaria or malnutrition associated.
Treatment of P. vivax malaria 2, P. ovale, P. malariae Chloroquine (CQ)PO:
Children and adults: 10 mg base / kg / once daily on D1, D2
5 mg base / kg once daily on D3 P. vivax and P. oval can cause relapses due to reactivation of dormant parasites in the liver. To eliminate them, treatment with primaquine 3 can be administered after initial treatment with CQ. However, this treatment is reserved for patients with little risk of being re-infected, ie d. those living in non-endemic area or low transmission.
Treatment of uncomplicated falciparum malaria:
The treatment is a combination therapy artemisinin (ACT) 4 orally for 3 days. The choice of ACT first line depends on its effectiveness in the area concerned. The co-formulations (2 antimalarials combined in one tablet) are preferable to co-blisters (2 distinct antimalarials presented in the same blister).
The artemisinin derivatives should not be used alone apart from exceptional circumstances:
1) in young children below the age required to take an ACT: artesunate PO is given alone at a dose of 4 mg / kg once daily on Days 1 and 2 mg / kg / day in
taking J2 to J7;
2) when repeated vomiting prevent oral treatment to follow. In this case, treatment is started rectally (see artesunate suppository, or IM, until the patient tolerates a complete oral treatment for 3 days with an ACT.
1 * Most rapid tests look for the following antigens or a combination of these antigens specific HRP2 protein of P.falciparum; a specific enzyme of P. falciparum (Pf pLDH); an enzyme common to the 4 Plasmodium species (pan pLDH). HRP2 protein may remain detectable for 2 to 3 weeks or more after removal of the parasite; pLDH the enzyme remains detectable for several days (up to 2 weeks) after the elimination of parasites.
2 * P. vivax generally remains sensitive to CQ but there are resistances in Papua New Guinea, Solomon Islands,Burma, India, Indonesia, East Timor. In these regions follow national recommendations.
3 * Primaquine PO for 14 days: 0.25 to 0.5 mg / kg / once daily in children> 4 years; 15 mg / once daily in adults.Primaquine is against-indicated in patients with G6PD deficiency. The decision to prescribe primaquine must take into account the prevalence of G6PD deficiency in the population.
4 * ACT (or CTA): artemisinin combination or one of its derivatives (eg artesunate, artemether..) With antimalarialbelonging to a different class.
In case of failure of a well conducted treatment with ACT for first line use another ACT or quinine PO.
PO quinine D1 to D7
Children and adults ² 50 kg: 30 mg / kg / day in 3 divided dosing interval 8 hours
Adult> 50 kg: 1800 mg / day in 3 divided dosing interval 8 hours
A reduced sensitivity to quinine has been observed in Southeast Asia and in the Amazon region. In these areas, quinine is combined with doxycycline or clindamycin: doxycycline PO D1 to D7
Children over 8 years and adults: 200 mg / once daily or in children younger than 8 years:
clindamycin PO D1 to D7 of 20 mg / kg / day in 2 divided doses
Note: P. falciparum is resistant to chloroquine (CQ) in Africa, Latin America,
Southeast Asia and Oceania but appears to remain sensitive to CQ in Haiti and the Dominican Republic. In these regions, CQ remains the first-line treatment (equal treatment for non-falciparum malaria).
Symptomatic treatment :
– Fever: paracetamol PO.
Treatment of severe malaria:
Hospitalize the patient.
At the clinic:
Before transferring the patient, administer the first dose of either artemether IM (loading dose, see below) or a dose of rectal artesunate:
To the hospital :
The treatment of choice is the IM artemether or artesunate IV or IM:
artemether IM (anterolateral thigh):
loading dose of 3.2 mg / kg by IM injection on day 1 followed by 1.6 mg / kg / once daily until the patient can tolerate oral treatment (patient able to eat and drink).
Use a 1 ml syringe calibrated in 100th to doses below 1 ml.
artesunate IV (or if the IV is not possible, IM in the anterolateral
thigh): 2.4 mg / kg injected on admission and 12 hours and 24 hours after admission and then once a day until the patient can tolerate oral medication.
For preparing injection, follow the manufacturer’s instructions.
In relay artemether or artesunate, administer a 3-day treatment with ACT5 (see uncomplicated falciparum malaria).
Only in young children below the age required to take the ACT, continue with artesunate PO to complete 7 days of treatment.
IV quinine is an alternative. The dosage is expressed in terms of quinine salt:
– Loading dose: 20 mg / kg administered over 4 hours, followed by glucose infusion 5% keep the vein for 4 hours; then
– Maintenance dose: 8 hours after the start of the loading dose, 10 mg / kg every 8 hours (alternate quinine 4 hours and 4 hours of 5% glucose).
For an adult, each dose of quinine in 250 ml of glucose; for a child under 20 kg, administer each dose of quinine in a volume of 10 ml / kg.
Do not administer the loading dose if the patient received oral quinine, mefloquine or halofantrine within the previous 24 hours: start with the maintenance dose.
As soon as the patient can tolerate oral treatment, the relay processing can be either a 3-day treatment with ACT 5 is treatment with quinine PO (± doxycycline or clindamycin if required) to complete 7 days of treatment.
If the AS-MQ is used in relay IV quinine, observe a 12-hour interval between the last dose of quinine and administration of MQ.
5 * Do not use artesunate-mefloquine (AS-MQ) if the patient developed neurological signs during the acute phase.
The derivatives of artemisinin IM may not be well absorbed in patients in shock, use artesunate IV or IV quinine.
Note: on the outskirts, it is absolutely impossible to transfer the patient to a center that can administer these treatments, artesunate suppositories are to be administered once / day, until the patient can tolerate full treatment 3 days with ACT.
Symptomatic treatment and management of complications:
Maintain adequate hydration. Indication, volume to be administered orally or IV:
Adapt these volumes according to the clinical condition to avoid dehydration or otherwise fluid overload (risk of acute pulmonary edema).
If hydration IV, rotate Ringer Lactate (or sodium chloride 0.9%) and 5% glucose. The volumes used to administer medications are included in the total volume to be administered every 24 hours.
Correct dehydration if present.
– A transfusion is indicated:
• In children if Hb is <4 g / dl (or between 4 and 6 g / dl in the presence of signs of decompensation 6).
• In pregnant if Hb is <7 g / dl (before 36 weeks) or <8 g / dl (from 36 weeks).
– In the other patients whose Hb is <7 g / dl, monitor clinical status and Hb and transfusion decide case by case.
– In one patient can swallow: 50 ml 10% glucose or 40 ml of water + 10 ml 50% glucose or 50 ml of water + 5 g (1 tsp) caster sugar or 50 ml of milk.
– In an unconscious patient:
10% glucose 5 ml / kg IV infusion or slow (5 minutes) or 50% glucose 1 ml / kg IV slowly (5 minutes). The 10% glucose is preferred in children (less viscous and irritating than 50% glucose 7).
– Check blood sugar after 30 minutes. If left <3 mmol / l or <54 mg / dl, the dose or give glucose orally, according to the patient’s condition.
The hypoglycaemia may recur: maintain a steady supply of sugar (5% glucose, milk, as applicable) and continue monitoring hours.
6 * The clinical signs of decompensation may include: shock, impaired consciousness, respiratory distress (acidosis).
7 * In children, to reduce the viscosity of 50% glucose, the dose may be diluted in an equivalent volume of infusion solution before being administered by slow IV.
– In an unconscious patient or prostrate, emergency or absence / pending venous access, use powdered sugar sublingually for the hypoglycaemia: slip under the tongue a teaspoon of sugar wet with a few drops of water. Place patients in the lateral position. Repeat after 15 minutes if the patient has not regained consciousness. As with other methods, then maintain regular sugar intake and monitor.
– The risk of hypoglycaemia is increased in patients treated with quinine IV, particularly among pregnant women.
Check / ensure the airway, measure blood glucose and evaluate the depth of coma (Glasgow Coma Scale or Blantyre).
In hypoglycaemia or if blood glucose can not be measured, give glucose.
If the patient does not respond to the administration of glucose or absence of hypoglycemia:
– Exclude meningitis (lumbar puncture) or set initially antibiotic treatment.
– Ask a urinary catheter, place the patient in the lateral position.
– Change the position of the patient every two hours; care of eyes and mouth, etc.
– Monitor constant, blood glucose, consciousness, urine output every hour until stabilization then every 4 hours.
– Monitor inputs and outputs.
Correct any causes (eg hypoglycemia.. Fever in children).
– Rapid and difficult breathing:
Think of a PAO, which can be linked or not to fluid overload: slow infusion if the patient is infused, semi-sitting position, oxygen, IV furosemide 1 mg / kg in children, 40 mg in adults . Repeat after one or two hours if necessary.
Think also to an associated pneumonia.
– Deep and slow breathing (acidosis):
Check for dehydration and correct it if necessary; decompensated anemia and transfuse appropriate.
Oliguria and acute renal failure:
Search first dehydration, especially in case of inadequate hydration or water loss (high fever, vomiting, diarrhea).Correct dehydration if present. Remember the risk of fluid overload and acute pulmonary edema. Check the resumption of diuresis.
Acute renal failure is found almost exclusively in adults and is more common in Asia than in Africa. It should be suspected if urine output remains <400 ml / day or <20 ml / hour (<12 ml / kg / day in children) despite adequate rehydration.
Ask a urinary catheter, measure urine output. Limit fluid intake to 1 liter / day (30 ml / kg / day in children), plus the volume of urine produced. Renal dialysis is often necessary.
Antimalarial treatment in pregnant women:
– Malaria P. vivax, P. ovale, P. malariae Chloroquine OP as for other patients.
Primaquine (radical cure of P. vivax and P. ovale) is against inappropriate.
– Uncomplicated P. falciparum
During the first quarter, it is recommended to use the PO quinine (± clindamycin).
The safety of artemisinin derivatives has not been formally established. However, given the risks associated with malaria, an ACT can be used if it is the only effective treatment available.
During the 2nd and 3rd quarter, the treatment of choice is an ACT; quinine (± clindamycin) is an alternative.
– Severe Malaria
During the first quarter, it is recommended to use quinine IV (± clindamycin).
However, a derivative of artemisinin injection can be used if it is the only effective treatment available.
During the 2nd and 3rd quarter, the initial treatment of choice is a derivative of artemisinin injection; followed by a full 3-day treatment with ACT; quinine (± clindamycin) is an alternative.
– In pregnant women, in areas with high risk of infection with P. falciparum sensitive to sulfadoxine / pyrimethamine intermittent preventive treatment (IPT) can be administered at regular intervals (refer to guide Obstetrics, MSF).
– All inpatient services, including nutrition centers or treatment of HIV, must be equipped with mosquito nets impregnated with long-lasting insecticide (LLINs) in endemic countries and areas at risk of malaria epidemics.
8 * For other anti-vector measures and prevention of malaria in travelers, refer to the literature.