DIAGNOSIS AND MANAGEMENT OF

MALARIA

Guided by, Dr. R.B.Patil

Microscopic diagnosis

• Light microscopy of well stained thick and thin films by a skilled microscopist has remained the "gold standard" for malaria diagnosis.

• Thick films are nearly 10 times more sensitive for diagnosis of malaria as larger amount of blood are there in a given area as compared to thin films.

• Species identification is better with thin films as morphology of the parasite and RBC are well preserved.

Collection of blood Sample

• As soon as malaria is suspected.• Any time irrespective of fever and not necessarily

only at the height of fever.• Before administration of antimalarials.• Smears should be prepared soon after collection

which enables better adherence of films to the slide and cause minimal distortion of parasites and red cells.

Examination of blood film

• Smear should be examined with 100X oil immersion objective.

• A minimum of 100 fields should be examined before concluding the slide to be negative.

• Once negative, samples may be examined for at least three consecutive days where clinical suspicion of malaria persists.

Advantage of microscopy

• Species identification along with characterization of the stage of parasite is possible thereby helping in adequate treatment and prognostication.

• Determining the parasite density. The parasite load is utilized to determine the severity of malaria along with prognosis and assessing the response to treatment.

Rapid diagnostic tests (RDTs)• These are

immunochromatographic test (ICT) to detect plasmodium specific antigens in blood sample. Test employ monoclonal antibodies directed against targeted parasite antigens.

• Histidine rich protein II (HRP-II) is actively secreted by asexual stages and young gametocytes of P. falciparum but not by mature gametocytes.

• A metabolic enzyme Parasite lactate dehydrogenase (pLDH)(13) is produced by all four species of plasmodia, both asexual and sexual (gametocytes) stages provided they are viable.

• Commercially available kit can detect falciparum, vivax and other malaria but cannot differentiate ovale and malarie malaria

• HRP-II tests can remain positive for 7-14 days following successful malaria treatment even when blood doesn't show parasitemia by microscopy.

• On the other hand as pLDH is produced by only viable parasite so the tests detecting this antigen becomes negative within 3-5 days of treatment.

Advantages of RDTs in comparison to Microscopy

• They are simple, straight forward and less time consuming requiring no special equipment or skill/training. Test result vary little between individual performance.

• They can detect P. falciparum infection even when the parasite is sequestered in the deep vascular compartment.

• This test can exclude mixed falciparum and vivax malaria where the former may not be evident microscopically.

Quantitative Buffy Coat (QBC) test• The new method of identifying malarial parasite in the

peripheral blood.• It involves staining of the centrifuged & compressed

red cell layer with acridine orange & its

Examination under UV light source.

• It is fast, easy and more sensitive than traditional thick smear examination.

Polymerase chain reaction PCR

• Highly sensitive and specific for detecting all species of malaria.

• Not commercially available and hence limited practical utility.

Tests for disease management and assessing severity

• Blood counts and culture,• PT, PTT, Blood glucose, electrolytes, pH,

bicarbonate, chloride and lactate.• Chest X-ray for respiratory distress syndrome,• Serum bilirubin, transaminases and creatinine.• Urine Hb,• Lumbar puncture.

Management of uncomplicated malaria in children

• Presumptive-A case of fever treated for malaria without parasitological diagnosis with an aim to prevent mortality and morbidity due to delay in treatment.

• Curative-Treatment given after diagnosis but without 8 aminoquinolines because of contraindication.

• Radical-Therapy after parasitological confirmation to eliminate all the forms of parasite from all possible host tissues

Basis of Antimalarial treatment

• Malaria in children has some unique features. Young children below 5 years whose passive immunity wanes and as yet to develop sufficient immunity of their own are most vulnerable.

• Falciparum malaria can be rapidly progressive and can develop rapid clinical deterioration hence this group needs constant monitoring.

• Children can tolerate antimalarial drugs better than adults and their symptoms resolve more quickly following successful treatment.

Recommended Treatment in Chloroquine Sensitive Malaria.

Drug sensitivityP. vivax and chloroquine sensitive P. falciparum

Recommended treatment• Chloroquine 10 mg base/kg stat followed by 5 mg/kg at 6, 24

and 48 hours OR• Chloroquine 10 mg base/kg stat followed by 10 mg/kg at 24

hours and 5 mg/kg at 48 hours. (Total dose 25 mg base/kg)• In case of vivax malaria to prevent relapse primaquine should

be given in a dose of 0.25 mg/kg/day for 14 days. • In case of falciparum malaria a single dose of primaquine (0.75

mg/kg) is given for gametocytocidal action.

• Chloroquine should not be given in empty stomach and in high fever. Bring down the temperature first. If vomiting occurs within 45 minutes of a dose of chloroquine that particular dose is to be repeated after taking care of vomiting by using Domperidone/Ondansetron.

• As primaquine can cause hemolytic anemia in children with G6PD deficiency they should be preferably screened for the same prior to starting treatment.

• As infants are relatively G6PD deficient it is not recommended in this age group and children with 14 days regime should be under close supervision to detect any complication.

• In cases of borderline G6PD deficiency once weekly dose of primaquine 0.6 - 0.8 mg/kg is given for 6 weeks.

Recommended Treatment in Chloroquine Resistant P. falciparum

Drug sensitivityChloroquine resistant P. falciparum

Recommended treatment• Artesunate 4 mg/kg of body weight once daily for 7 days

followed the next day by sulfadoxine/pyrimethamine (SP) as 25 mg/kg of sulfadoxine and 1.25 mg/kg of pyrimethamine as a single dose OR

• Mefloquin 25 mg divided in two(15 + 10) doses at 4- 6hrs interval.

• A single dose of Primaquine (0.75 mg/kg) is given for gametocytocidal action.

Recommended Treatment of Multidrug Resistant P falciparum (Both to CQ and SP)

Drug sensitivityMultidrug resistant P. falciparum i.e., both to CQ and SP

Recommended treatment• Quinine, 10 mg salt/kg/dose3 times daily for 7-10 days. • In case of cinchonism, • Quinine, 10 mg salt/kg/dose 3 times daily for 3-5 days

+ • Tetracycline (if age >8 yrs) 4 mg/kg/dose 4 times daily for 7-10 days

OR • Doxycycline (if age >8 yrs) 3 mg/kg/day 2 times daily for 7-10 days OR• Clindamycin 20mg/kg/day divided 3 times daily for 7-10 days.• A single dose of primaquine above 1 year age (0.75mg/kg) is given

for gametocytocidal action.

Monitoring of uncomplicated malaria

• WHO developed a new system of monitoring with follow up for 14 days where both clinical and parasitological assessment was done.

• Parasitological assessment should include detection of malaria parasite, species determination and parasite density measurement.

• Patient should also be assessed clinically with examination of body temperature.

• Microscopy should be done at day 0, before initiation of treatment, on day 3, 7 and 14 if not indicated more frequently. Parasite count on day 0 is taken 100% for that particular child.

Early treatment failure

• Development of danger sign or severe malaria during the first three days (day 1-3) in presence of parasitemia.

• Axillary temperature >37.5ºC on day 2 with parasite count greater than that of day 0.

• Axillary temperature >37.5ºC on day 3 in presence of parasitemia.

• On day 3 irrespective of axillary temperature parasite count is >25% of that of day 0

Late treatment failure:

• Development of danger sign or severe malaria on any day between day 4 and day 14 in presence of parasitemia.

• Axillary temperature >37.5ºC in presence of parasitemia on any day from day 4 to day 14.

General Danger signs of malaria

• Not able to drink or breast feed• Vomiting everything.• Recent history of convulsion• Lethargic or unconscious state• Unable to sit or stand up

The parent/guardian should be instructed to bring the child to the doctor if the patient develops any of the danger signs during the follow up.

According to IAP recommendations,• If by day 3 of the treatment, there is no clinical

improvement, a blood smear is to be repeated. • In case it is positive and the level of asexual

parasitemia is more than or equal to 25% of the pretreatment value, revise treatment.

• If less than 25%, follow the patient till 28 days.• Continuation of fever till day 5 or reappearance

thereafter, but within 28 days, repeat blood smear. • If positive, irrespective of the percentage of

parasitemia, revise treatment.

Features of severe malaria(i) Cerebral malaria (Unrousable coma) (ii) Severe normocytic anemia (Hb <5 g/dL) (iii) Renal failure (Serum creatinine >3 mg/100 mL)(iv) Pulmonary edema(v) Hypoglycemia (<40 mg/100 mL) (vi) Circulatory collapse/Shock (Systolic blood pressure less than 50 mmHg in children

below 5 years) (vii) Spontaneous bleeding/Disseminated intravas- cular coagulopathy (viii) Repeated generalized convulsions (ix) Acidemia/Acidosis (x) Macroscopic hemoglobinuria. Other manifestations : (xi) Impaired consciousness but rousable (xii) Prostration, extreme weakness (inability to stand or sit) (xiii) Hyperparasitemia (>5% RBC infected) (xiv) Jaundice (total serum bilirubin >3 mg/dL) (v) Hyperpyrexia (axillary temperature

>39.5ºC)

Management of severe malaria in children

• Severe life threatening malaria is nearly always due to P. falciparum.

• All cases with severe manifestations are to be treated in the same line of complicated malaria with inject-able antimalarials irrespective of the species.

• High degree of suspicion of severe malaria is of utmost importance and any delay in initiation of treatment can be fatal.

• It should be treated as a medical emergency at highest level of medical facility available preferably in a intensive care setting. Confirmation of the diagnosis is preferable but one should not delay the treatment if it needs more than one hour.

• Further, in cases of strong clinical suspicion prompt antimalarial therapy is needed even if parasite are not found in the initial blood examination.

• Effective therapy in children with severe malaria includes antimalarial chemotherapy, supportive management and management of complications. All these three interventions are equally important and to be taken care of simultaneously.

Antimalarial chemotherapy of severe and complicated malaria

Given initially by intravenous infusion, which should be replaced by oral administration as soon as condition permits.

• Quinine salt20 mg salt/kg (loading dose) diluted in 10 ml of glucose containing isotonic fluid/ kg by infusion over 4 hours.

• Then 12 hours after the start of loading dose give a maintenance dose of 10 mg salt/kg over 2 hours.

• This maintenance dose should be repeated every 8 hours, calculated from beginning of previous infusion, until the patient can swallow, then quinine tablets, 10mg salt /kg 8 hourly to complete a 7 day course of treatment (including both parenteral and oral).

• If controlled IV infusion cannot be administered then quinine salt can be given in the same dosages by IM injection in the anterior thigh (not in buttock).

• The dose of quinine should be divided between two sites, half the dose in each anterior thigh.

• If possible IM quinine should be diluted in normal saline to a concentration of 60-100mg salt/ml. (Quinine is usually available as 300mg salt/ml)

(i) Loading dose of quinine should not be used if the patient has received quinine, quinidine or mefloquine within the preceding 12 hours.

(ii) Alternatively loading dose can be administered as 7mg salt/kg by IV infusion pump over 30 minutes, followed immediately by 10mg salt/kg diluted in 10 ml isotonic fluid/kg by IV infusion over 4 hours.

(iii) Quinine should not be given by bolus or push injection.(iv) If there is no clinical improvement after 48 hours of parenteral

therpy the maintenance dose of quinine should be reduced by one third to one half i.e. 5-7 mg salt/kg.

(v) Quinine should not be given subcutaneously as this may cause skin necrosis.

Alternative Drugs Rather Than Quinine in Severe Malaria

• Artesunate2.4 mg/kg IV (loading dose), followed by 1.2 mg/kg at 12 and 24 hours, then 1.2 mg/kg daily for 6 days.

• If the patient is able to swallow, then the daily dose can be given orally. OR • Artemether 3.2 mg/kg (loading dose) IM, followed by 1.6 mg/kg daily for 6

days. • If the patient is able to swallow, then the daily dose can be given orally.• Artesunate, 60mg per ampoule is dissolved in 0.6ml of 5% sodium

bicarbonate diluted to 3-5 ml with 5% dextrose and given immediately by IV bolus (push injection).

• Artemether is dispensed in 1 ml ampoule containing 80mg of artemether in peanut oil.

• At the end of the therapy a single dose of SP as 25 mg/kg of sulfadoxine and 1.25 mg/kg of pyrimethamine OR Mefloquine 25 mg/kg (divided into 2 doses of 15 mg/kg and 10 mg/kg 4 to 6 hours apart ) is to be given.

• According to the National Anti Malaria Programme (NAMP), drug policy in all cases of severe malaria is either IV quinine or parentral artemisinin derivatives to be given irrespective of chloroquine resistance status.

• A single dose of primaquine (0.75 mg/kg) is to be given for gametocytocidal action irrespective of the drug given.

Management of complications of malaria

Cerebral malaria• Initial presentation is usually fever followed by inability

to eat or drink. • The progression to coma or convulsion is usually very

rapid within one or two days. • Convulsions may be very subtle with nystagmus,

salivation or twitching of an isolated part of the body. • Effort should be given to exclude other treatable causes

of coma (e.g., bacterial meningitis, hypoglycemia). • Patients should be given good nursing care, convulsions

should be treated with diazepam/midazolam and avoid harmful adjuvant treatment like corticosteroids, mannitol, adrenaline and phenobarbitone

Severe anemia• Children with hyperparasitemia due to acute

destruction of red cells may develop severe anemia. • Packed red cell transfusion should be given

cautiously when PCV is 12% or less, or hemoglobin is below 4g%.

• Transfusion should also be considered in patients with less severe anemia in the presence of respiratory distress (acidosis), impaired consciousness or hyperparasitemia (>20% of RBCs infected)

Lactic acidosis• Deep breathing with indrawing of lower

chest wall without any localizing chest signs suggest lactic acidosis. It usually accompanies cerebral malaria, anemia or dehydration.

• Correct hypovolemia, treat anemia and prevent seizures.

• Monitor acid base status, blood glucose and urea and electrolyte level

Hypoglycemia• It is common in children below 3 years specially with

hyperparasitemia or with convulsion. • It also occurs in patients treated with quinine.• Manifestations are similar to those of cerebral malaria so it

can be easily overlooked. • Monitor blood sugar every 4 to 6 hours. If facilities to

monitor blood glucose is not available assume hypoglycemia in symptomatic patient and treat accordingly.

• Correct hypoglycemia with IV dextrose (25% dextrose 2 to 4 mL/kg by bolus) and it should be followed by slow infusion of 5% dextrose containing fluid to prevent recurrence

Hyperpyrexia• High fever is common in children and may lead

to convulsion and altered consciousness. Paracetamol 15mg/kg, Tepid sponging and fanning should be given.

Hyperparasitemia• Specially seen in nonimmune children associated

with severe disease. • Consider exchange transfusion/cytapheresis if

greater than 20% of RBCs are parasitised.• Circulatory collapse (Algid malaria)• In case of circulatory collapse suspect gram negative

septicemia, send blood for culture before starting antibiotics.

• Resuscitate with judicious use of fluids.

Spontaneous bleeding and coagulopathy (DIC)

• Usually seen is nonimmune children which should be treated with vitamin K, blood or blood products as required.

Thank you,…