Malaria in Children

Jeanne Rini Poespoprodjo

Mimika District Hospital – Timika, Papua

Uncomplicated Malaria
Diagnosis of Malaria Outpatient
Anamnesis: •  Non specific symptoms:
Fever, chills, headache, –  Fever
diarrhea
–  Cough-runny nose
Living in malaria endemic
area –  Diarrhea
History of visiting endemic –  Pale
area 1-4 weeks before

•  Malaria smear for

Physical Examination:
Temp > 37.5 0C children with fever
Malaria smear positive
Hepato + splenomegaly
Pale, Icteric
Severe signs

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 Treatment Protocol Treatment
Kemenkes, 2013
•  Uncomplicated P. falciparum and P. vivax malaria: Before 2013…
–  First line: DHP (DHA 40 mg and PPQ 320 mg) for 3 days •  DHP is given to children weighing > 5 kgs upon laboratory diagnosis
•  DHA 2-4 mg/kgBB/dose confirmation for 3 days
•  Seven day Quinine* and Clindamycin** is given to infants weighing < 5 kgs
•  PPQ 16-32 mg/kgBB/dose
•  Primaquine is given as per treatment protocol and not given to infant < 1 y.o
–  Second line: Q7C7 (< 8 years old); Q7Dox7 (> 8 years old)
–  Primaquine:
•  Pf single dose 0.75 mg base/kgBB Weight Age Dosage
•  Pv dan PO 0.25 mg base/kgBB for 14 days < 1 mo 2-11 mo 1-4 years 5-9 years DHA Pip mg/kg
mg/kg
•  Bayi < 5 kgs: = 5 kg 0.25 2 16
–  Q7C7
–  Primaquine is not given to infants < 1 year old 6-10 kg 0.5 2-4 16-32

11-17 kg 1 2.4-2.6 19-29

•  Severe Malaria:
–  Artesunate (60 mg artesunate per vial) iv 2.4 mg/kgBB on 0, 12 18-30 kg 1.5 2-3.3 16-27
and 24 hours and then every 24 hours until patient can tolerate
oral antimalarial drug (intravenous therapy should be minimal 24
hours) *Quinine 10 mg/kgBW 3x/day
–  Continues with DHP/AAQ for 3 days
**Clindamycin 10 mg/kgBW 2x/day

An#malarial  Drug     WHO 2010 and WHO 2015

in  Children   Kemenkes 2013:
Uncomplicated P. falciparum
Uncomplicated P. falciparum
and P. vivax malaria: and P. vivax malaria:
•  Slow  drug  absorp/on  and  low  plasma  drug  
concentra/on:  risks  of  “under  dosed”   DHP (DHA 40 mg and PPQ 320
mg) for 3 days
DHP (DHA 40 mg and PPQ 320
mg) for 3 days
•  Efficacy  studies:  Includes  children  >  1  year  old   •  DHA 2-4 mg/kgBB/dose •  Children < 25 kg BW: minimum
•  PPQ 16-32 mg/kgBB/dose DHA 2.5 mg/kg BW and PPQ
•  Limited  efficacy  data  in  infants  <  6  mo   20 mg/kg BW per day
•  Infant  and  young  children:  vulnerable  to   Infants < 5 kgs: Infants < 5 kgs:
severe  malaria  and  death   –  Q7C7 –  DHP = 5 kgs infant’s
–  Primaquine is not given to dosing
•  WHO  recommends  ACT  use  in  infants  with   infants < 1 year old –  Primaquine is not given to
malaria:  Early  detec/on  and  effec/ve   infants < 6 months old
(unless G6PD status is
treatment   known)

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WHO 2010 and WHO 2015 WHO 2010 and WHO 2015
Kemenkes 2013 Kemenkes 2013
Primaquine:
Primaquine: •  Pf single dose 0.25 mg base/ Severe Malaria: Severe Malaria:
kgBB
•  Pf single dose 0.75 mg base/
kgBB •  Pv dan PO 0.25 mg base/kgBB
for 14 days •  Artesunate (60 mg artesunate Children weight < 20 kgs:
•  Pv dan PO 0.25 mg base/kgBB per vial) iv 2.4 mg/kgBB on 0, •  Artesunate 3 mg/kg BW per
for 14 days Except for: 12 and 24 hours and then dose on 0, 12 and 24 hours
every 24 hours until patient and then every 24 hours until
Except for: Pregnant women, Infants aged < can tolerate oral antimalarial
6 months old, Women patient can tolerate oral
Pregnant women, Infants aged < drug (intravenous therapy antimalarial drug (intravenous
breastfeeding infants, G6PD should be minimal 24 hours)
1 year old, Women breastfeeding deficient therapy should be minimal 24
infants’ G6PD deficient patient hours)
•  Continues with DHP/AAQ for 3
G6PD deficient: days •  Continues with DHP/AAQ for 3
•  Consider primaquine 0.75 mg/ days
kg BW once a week for 8
weeks
•  Close medical supervision for
potential induced hemolysis

Experiences in Using DHP in

Core Principles
Children Underfive
1.  Early diagnosis and prompt effective
treatment: •  In general, children can tolerate very well:
–  Access to early diagnosis and treatment –  Low vomiting rate
within 24-48 hours after the onset of malaria –  Mild diarrhea that quickly resolves
symptoms
•  Improve compliance
2.  Rational use of antimalarial agents
•  DDR negative on day 7 on clinical follow
3.  Combination therapy
up
4.  Appropriate weight-based dosing
•  Second line treatment is rarely used

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 Severe Malaria

•  P.falciparum infection with severe

Severe Malaria in Children manifestation according to WHO criteria
•  Some P.vivax infections is associated with
signs of severe malaria

WHO Criteria of Severe Malaria

1 month, P. falciparum malaria
PFRF 182/1000 RBC, PFG 4/200 WBC, PFsch
2/200 WBC; Hb 7 g/dl; Bilirubin total: 30.8 mg/
dl (direk: 14.4,indirek: 16.4) 1 month, P. vivax malaria
PVT 7/1000 RBC; HB 4 g/dl
Parasitemia (geometric mean):
Pf : 6,186 µL [2,441-14,765]
Pv : 5,378 µL [3,641-7,332], p=0.72
1.  Impaired consciousness (including unrousable
coma)
2.  Prostration: unable to sit, stand and walk without
assistance
3.  Multiple convulsions: >2 episodes in 24 hours
4.  Deep breathing and respiratory distress
5.  Acute pulmonary edema and acute respiratory
distress syndrome
6.  Circulatory collapse or shock
7.  Acute Kidney Injury
8.  Clinical jaundice plus other vital organ dysfunction
9.  Abnormal bleeding
WHO, 2012

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 Severe Signs - Timika
1.  GCS < 11/15 or Blantyre<2 / 5,
Malaria
2.  Hb<5g/dl or Hct<15% in children; Hb<7 g/dl or
Hct<20% in adults Respiratory insufficiency (74)
7%
3.  Cr>3mg/dl +/- Urine Output <400ml day-1 (41)
3.7% 75% (4)
4.  Plasma Glucose < 40mg/dl (28)

5.  Asexual Parasitaemia > 10%. 55%

(9) Impaired consciousness (18)
2%
6.  Systolic BP <80mmHg and <50mmHg in children and (364)
cool peripheries
40% (6)
7.  Hemoglobinuria/Black urine
8.  Acidosis HCO3<15 mmol/L Severe anaemia (399) 100% (1)
Other severe signs: 16% (25)
9.  Hyperlactataemia (lactate>5 mmol/L 84% (399/474) of severe
malaria

Percentage is mortality, figures in brackets are number of cases

Problems in the Management of

Severe Malaria in Children
•  Diagnosis difficulties:
–  Meningitis/encephalitis and cerebral malaria
–  Pneumonia and respiratory distress/acidosis
in malaria
•  Child’s condition can quickly worsened
•  All children with symptom and sign of sepsis,
meningitis or pneumonia must be screened for
malaria
•  If positive malaria, give intravenous antimalarial
apart from antibiotics

•  More prone to hypoglycemia, febrile

•  Similar treatment applies to severely ill children
convulsion, dehydration and acidemia (shock, severe dehydration, etc)
•  Asymptomatic malaria is rather high

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 Severe Malaria Classification
in Children
•  Group 1:
–  General prostration (unable to sit/drink-eat) :
lethargic, decrease of consciousness and
coma
–  Respiratory Distress:
•  Mild: nose flare and /or intercostal retraction
•  Severe: chest retraction or acidotic breathing
Management
•  Secure airway, oxygenation and
circulation status
•  Maintain hydration status
•  Treat the convulsion, if any
•  Immediate intravenous antimalarial drug
•  Hypoglycemia correction, if any
•  Group 2:
Absence of group 1 symptoms, but
requires close monitoring:
•  Children with Hb < 5 g/dl or Hct < 15%
•  Children with convulsion >2 times within 24 hours
•  Group 3:
–  Children requiring parenteral therapy due to
inability to take oral medication (persistent
vomiting)
–  Absence of symptoms from Group 1 and 2
Antimalarials for severe malaria
•  Death in severe malaria : within 48 hours
of presentation (one asexual cycle of
blood stage infection)
•  IMPORTANT: prevention of the
development from less pathogenic ring
stages (0-16 hours) to more pathogenic
sequestered stages Rapid acting
antimalarials: artesunate
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 Treatment Laboratory Examination
First Line
–  Artesunate IV : 2.4 mg/kgBW IV at 0, 12 and •  Malaria smear
24 hours and then every 24 hours and •  Hb
followed with oral DHP (if patient able to take •  Random blood glucose
oral medication) - Children < 20 kgs: artesunate 3
mg/kgBW

Second Line •  Monitoring: malaria smear every 24 hours

–  Quinine drips: loading 20 mg/kgBB for 4 hours
continue with 10 mg/kgBB for 4 hours every 8
hours , switch to oral quinine and
clindamycine for 7 days

Monitoring: Very Important !!! Inpatient Management

(Timika)
Every 2-4 hours: •  Malaria screening to all children with severe
manifestations (WHO criteria)
–  General Condition
•  Malaria laboratory diagnosis should be obtained
–  Axillary temperature in less than 1 hour
–  Heart rate •  Treat Immediately administer:
–  Respiratory rate –  Intravenous Artesunate followed with oral DHP
–  Urine output •  Treat possible bacterial infection
–  Total fluid input
–  Blood glucose (as indicated)

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 Supportive Treatment
•  Clear airway and monitor respiration •  Median duration of stay: 3 days (range: 1
•  Maintain hydration status to 55 days)
•  Treat convulsion •  The majority negative on day 3
•  Correct severe anaemia (aim at Hb of >5 g/dl): hospitalization and day 7 (outpatient)
–  Packed Red Cells 10cc/kgBW in 4 hours or
–  Fresh Whole Blood 20cc/kgBW in 4 hours

•  Correct hypoglycemia with Dextrose 10% 5cc/

kgbw iv bolus

Logistic and Skill Problems

•  If artesunate is not available or IV line
cannot be established:
Common Problems –  Artesunate IM 2.4 mg/kgBW at 0 – 12 – 24
hours
–  Artemether IM 3.2 mg/kgBW, then 1,6 mg/
kgBW/24 hours
–  Quinine IM 20mg/kgBW (diluted in NS to
60-100 mg salt/ml): 10 mg/kgBB in each thigh
8 hourly

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 Oral Antimalarial Drug Severe Malaria and Sepsis
•  If DHP not available: •  Difficult to differentiate
–  First choice: quinine and clindamycin •  No culture facilities
–  Arthemeter lumefantrine: only effective for P. •  Severe malaria increase the risks of bacterial
falciparum malaria (in Timika) infections

•  We give intravenous ampicillin and gentamisin

for possible bacterial infection, in cases:
–  Very severe with more than 1 severe signs
–  Young infants (< 3 months old)

Early  Detec#on  and  Effec#ve  Treatment  

•  All sick infants were screened for malaria
•  Treated with Artemisinin Combination
therapy: dihydroartemisnin-piperaquine
•  Artesunate iv: severe malaria

Malaria  falciparum  dan  RDS  

Malaria  vivax   Malaria  falciparum,   2  months,  cough  and  

Hb  2  g/dl   rapid  breathing    
3  months,  acute   6  months,  dyspnea,  pale  
diarrhea  

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 NEONATUS: Falciparum Malaria
IBU: G11P10A0; Malaria negative, no history of
fever during pregnancy

t
failure to conduct an ophthalmoscopic examination for

the presence of papilloedema and malarial retinopathy

t
misdiagnosis of severe P. knowlesi malaria. Mature stages

of P. knowlesi are indistinguishable from P. malariae, and
ring forms can resemble P. falciparum. For any patient from
a knowlesi-endemic area with a microscopic diagnosis of
P. malariae, treat with parenteral therapy if any features of
severe malaria or parasitaemia > 100 000/ul. If testing for
laboratory criteria for severe malaria is not readily available,
treat with parenteral therapy if parasitaemia >20 000/ul.
Table 1: Signs and symptoms of severe malaria
in adults and in childrena
ERRORS IN MANAGEMENT
Sign or symptom Adults Children
Duration of illness 5–7 days Shorter t
delay in starting antimalarial therapy this is the most
(1–2 days) serious error, as delays in starting treatment may be fatal.
Respiratory distress/ Common Common
deep breathing (acidosis)
t
inadequate nursing care
Convulsions Common (12%) Very common (30%)
Posturing Uncommon Common
(decorticate/decerebrate t
incorrectly calculated dosage of antimalarial medicines
and opisthotonic rigidity)
Prostration/obtundation Common Common t
inappropriate route of administration of antimalarial
Resolution of coma 2–4 days Faster (1–2 days) agents (see inside front cover flap)
Neurological sequelae Uncommon Common (5-30%)
after cerebral malaria (1%)
t
intramuscular injections into the buttock, particularly
Jaundice Common Uncommon
Hypoglycaemia Less common Common
of quinine, which can damage the sciatic nerve
Metabolic acidosis Common Common
Pulmonary oedema Uncommon Rare t
failure to switch patients from parenteral to oral therapy
Renal failure Common Rare after 24h, or as soon as they can take and tolerate oral
CSF opening pressure Usually normal Usually raised medication
Bleeding/clotting Up to 10% Rare
disturbances t
use of unproven and potentially dangerous ancillary
Invasive bacterial Uncommon Common (10%)
infection (co-infection) (<5%)
treatment
a
Derived from studies in south-east Asian adults
and children, and African children.6,7

6 Artesunate vs. quinine in the treatment of severe falciparum malaria in African children
(AQUAMAT): an open-label randomized trial. Lancet 2010; 376: 1647–57 62
7 South-East Asian Quinine Artesunate Malaria Trial (SEAQUAMAT) group. Artesunate versus quinine
for treatment of severe falciparum malaria: a randomized Trial. Lancet, 2005, 366:717-725.

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 t
failure to review antimalarial treatment for a patient whose
condition is deteriorating

t
failure to re-check blood glucose concentration in a

patient who develops seizure or deepening coma

t
failure to recognize and treat minor (‘subtle’) convulsions

t
failure to recognize and manage pulmonary oedema Terimakasih

t
delay in starting renal replacement therapy

t
failure to give antibiotics to treat possible meningitis

presumptively if a decision is made to delay lumbar
puncture

t
fluid bolus resuscitation in children with severe malaria who

are not severely dehydrated
COMMON
ERRORS

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Cerebral Malaria Convulsion

•  Blantyre coma scale < 3 •  Febrile Convulsion:
–  Best Motor Response:
•  Localizes pain/stimulus 2
–  Regain consciousness < 1 hour post
•  Withdraws to pain/stimulus 1 convulsion
•  No response 0 –  Convulsion occurs within 24 hours after the
–  Verbal Response: onset of fever
•  Cries to pain 2
•  Irritable cries 1 –  Majority in children < 6 years old
•  No response 0
–  Eye movements: •  Cerebral Malaria:
•  Follow object movement 1
–  Not regain consciousness > 1 hour after
•  No response 0
convulsion
–  No age limit

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 Convulsion Management Respiratory Distress
•  Diazepam rectal 0.3-0.5 mg/kgBB •  Due to severe anaemia or dehydration
•  Can be repeated if seizure persists for 5 and 10 •  Respiratory Distress:
minutes –  0-2 months : rr >=60x/min
•  If seizure persists until 20 minutes, give –  2 mo -1 y.o : rr >=50x/min
intravenous Phenitoin loading dose 20 mg/kgBB –  1-5 y.o : rr >=40x/min
in NS (1:1) with rates 1ml/kg/min followed with
maintenance dose of 5-8 mg/kgBB:2 iv •  Chest retraction, nasal flare, rapid
breathing
•  Alternative: intravenous Phenobarbital
(dose=Phenitoin)

Severe Anaemia Anaemia Management

•  Hb<5 g/dl or Hct < 15%
•  Parasite count > 10.000/ µL
•  Compare child’s palmar colour with mother’s
•  In children often with respiratory distress
•  Respiratory distress in severe anaemia is mainly
caused by acidosis, not heart failure
•  Packed Red Cells transfusion 10cc/kgBB
for 4 hours
•  If PRC not available: use Fresh Whole
Blood 20 cc/kgBB for 4 hours
•  Formula:
–  λ HB X BB X 4cc (PRC) or 6cc (Whole blood)
–  Blood is given with interval of minimum 6
hours between transfusion

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 Rapid fluid loading is dangerous in
Hipoglycemia severe malaria!
•  Random blood glucose < 40 g/dL RCT in 6 centres in East Africa
•  Frequently found in children •  Increased mortality in 20-40 ml boluses of
NS or 5% Albumin group VS no boluses
Management group:
•  Dextrose 10% 5 cc/kgBB iv bolus –  48 hour mortality 10.6% in bolus group vs
•  Repeat RBG after 30 minutes 7.3% in no bolus group
–  RR: 1.45 (95%CI, 1.13-1.86), p=0.003

Maitland et al, 2011

•  Fluid Requirements:

Maintenance:
D5% 1/2Saline : 3-4 ml/kg/hour

Shock and Severe Dehydration (without hypotension)

NaCL 0.9% or D5% ½ Saline: 3-5 ml/kg/hour over 3-4 hours followed
with maintenance D5% ½ Saline of 2-3 ml/kg/hour

Ringer’s Lactate is NOT recommended.

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