Malaria in Children

Pooja Dewan
Director-Professor
Department of Pediatrics
UCMS & GTB Hospital
 Introduction
• Malaria comes from Italian words
“mal” and “aria” meaning bad air.
• Mostly in developing country
• Deaths occur mostly in infant and
children
Charles Louis Alphonse Laveran Sir Ronald Ross
French physician who won the Nobel A Scottish-born doctor in the
Prize in Physiology or Medicine in Indian Medical Service, Sir
1907 for his discoveries of parasitic Ronald proved in 1897 the long-
protozoans as causative agents of suspected link between anopheles
infectious diseases such as malaria and mosquitoes and malaria. Awarded
trypanosomiasis the Nobel Prize for Medicine in
1902.
 Etiology
• Vector-borne febrile illness
• Five species of malarial parasite Plasmodium
infect humans:
– Plasmodium falciparum
– Plasmodium vivax
– Plasmodium ovale: Odisha
– Plasmodium malariae
– Plasmodium knowlesi
 Etiology
• Vector: Transmitted by the infective bite of female
Anopheles mosquito
• Anopheles stephensi: Urban areas
• Anopheles culicifacies: Rural areas

• Disease not above 2000 m

• Temp: 20-30 C
 Epidemiology
• World malaria report - 263 million cases of malaria in 2023 with
597000 deaths
• Top five countries carrying the heaviest estimated burden of
malaria cases in 2023 were Nigeria (26%), the Democratic
Republic of the Congo (13%), Uganda (5%), Ethiopia (4%) and
Mozambique (4%): >90% of deaths in sub-Saharan Africa.
• India is one of the HBHI (High burden high impact) countries for
malaria accounting for maximum burden of cases and deaths
• Almost all malaria deaths are caused by Plasmodium
falciparum.
• Most of these deaths occur in children younger than 5 years.
• India’s global share: 0.8% cases (2023); 0.6% deaths (2023)
• P. falciparum & P. vivax: Nearly all cases; P. falciparum
contributes to 46% of cases
 Epidemiological indicators of malaria

• Annual Parasite Incidence (API)

• Annual Blood Examination Rate (ABER)

• Slide Positivity Rate (SPR)

• Slide Falciparum Rate (SFR)

 Annual Parasite Incidence (API)
 API : Confirmed cases during one year X 1000
population under surveillance

 <1 per 1,000 population: Low transmission.

 1 and 10 per 1,000 population: Moderate transmission
 >10 per 1,000 population: High transmission.

 API data is typically derived from public health records, which

include reported parasitologically confirmed symptomatic malaria
infections (cases)
 potentially underestimating the true burden of malaria, as
asymptomatic infections and cases treated in private clinics are not
always recorded.
 Distribution in India

India has sustained an API of less than one since 2012

Malaria-Mukt Bastar (Chhatisgarh: 7 districts in 2021)
Annual Blood Examination Rate (ABER)
• ABER: Number of slides examined X 100
population
• NVBDCP: Should be at least 10% on the
presumption that 10% of the population in a year will
have fever at one point in time
 Slide Positivity Rate (SPR)
• SPR: % of slide +ve for malarial parasite irrespective
of species per 100 slides examined in suspected
cases
SPR = Total positive x 100 / Total slides
examined
SPR under 2.9% is considered the absence
of indigenous transmission
• Slide Falciparum Rate (SFR): % of slide +ve for
falciparum
• Slide Vivax Rate (SVR): % of slide +ve for vivax
 PATHOGENESIS
LIFE CYCLE OF PLASMODIUM

• Asexual life cycle in human (intermediate host)

Exoerythrocytic and erythrocytic

• Sexual life cycle in female anopheles (definitive host)

 COMPONENTS OF THE MALARIA
Sporogoni
LIFE CYCLE
c
cycle

Infectiv
e
Period Mosquito
bites
uninfected Mosquito
person Vector
Parasites
Mosquito visible Human
bites Prepate Host
gametocytem nt Symptom
ic Period onset
person Recover
y
Incubation
Period
Clinical
Illness
 P vivax P falciparum
• Tendency to invade young • No preference, in uncomplicated
RBCs (13% red cell malaria, 40% RBCs involved: Prone
to severe anemia
population)
• Erythrocytic schizogony occurs in
• Erythrocytic schizogony capillaries of internal organs with
completed in peripheral only early ring forms in peripheral
circulation circulation
• RBCs containing mature forms of P
• Hypnozoites: Relapse falciparum become sticky and
common adhere to capillary walls
(cytoadherence) and adhere to
non-infected RBCs (rosetting):
Microcirculation blockage: Prone
to lactic acidosis, shock, algid
malaria, hemoglobinuria, hypoxia
• Hypnozoites absent: NO RELAPSE
• Recrudescence: Due to persistent
erythrocytic forms
DIFFERENT STAGES OF PLASMODIUM
KNOBS:
Cytoadherence,
applique forms
 FOUR IMPORTANT PATHOLOGIC PROCESS

• Fever (erythrocytic rupture and release of merozoites )

• Anemia (hemolysis, sequestration of RBC in spleen,
bone marrow suppression )
• Immunopathologic event (release of pro-inflammatory
mediators e.g. TNF )
• Tissue anoxia (cytoadherence )
DIAGNOSIS
 MALARIA DIAGNOSIS
1. Clinical Diagnosis

2. Microscopy

3. Antigen Detection

4. Malarial serology

5. Polymerase chain reaction

 CLINICAL MANIFESTATIONS

• Children are asymptomatic during initial phase-the

incubation period.
– P falciparum :9-14 days
– P vivax :12-17 days
– P ovale :16-17 days
– P malariae :18-40 days
 PRODROMAL SYMPTOMS

• Headache
• Fatigue
• Anorexia
• Myalgia
• Pain abdomen
• Vomiting/diarrhea
• Prone to severe bacterial sepsis: WBCs engulf
vacuolated RBCs with malarial parasite, very few
WBCs left to counter other bacteria; Heme
oxygenase liberated by parasite inhibits
neutrophilic oxidative burst
• Hypoglycemia: failure of hepatic gluconeogenesis,
increased use by febrile patient, drug induced
(quinine)
• Cytokine burst from ruptured RBCs
• Acidosis
• Intravascular hemolysis: Jaundice, hemoglobinuria
 SEVERE MALARIA
Clinical Criteria Laboratory Criteria
1. Impaired consciousness, unrousable 1. Hypoglycemia (Plasma glucose <40 mg/dl
coma; for children < 5 year and, < 54 mg/dl for
children > 5 year);
2. Prostration;
2. Metabolic acidosis (plasma bicarbonate <
3. Multiple convulsions: >2 episodes within 15mmol/l);
24h; 3. Severe normocytic anemia (Hb < 5g/dl);
4. Acidotic breathing; 4. Hemoglobinuria (BLACK WATER FEVER);
5. Acute pulmonary edema and acute 5. Hyperlactatemia (lactate > 5mmol/l);
respiratory distress syndrome; 6. Renal impairment (serum creatinine > 3
6. Circulatory collapse or shock, SBP < mg/dl);
50mm Hg in children (ALGID MALARIA); 7. Serum bilirubin > 3 mg/dL
8. Pulmonary edema (radiological)
7. Acute kidney injury (Urine output < 0.5
9. Hyperparasitemia (In high-transmission
ml/kg/h despite normal hydration);
area, if >5% RBCs are parasitized; in low-
8. Clinical jaundice plus evidence of other transmission areas, if >2% RBCs are
vital organ dysfunction; and parasitized)
9. Abnormal bleeding
 Common mimics
• Typhoid fever
• Typhus fever
• Septicemia
• Viral hemorrhagic fevers including Dengue
• Influenza
• Brucellosis
• Leptospirosis
• CNS infections
• Febrile seizures in under-five children
• Severe pneumonia
 Microscopy(peripheral smear)
gold standard

Parasite detection

Thick blood film

• Used for screening of parasites.

• 5-10 parasites/µL

Thin blood film

• Species & stages of parasites

• 200 parasites/µL

• Percentage of infected erythrocytes

 The Malaria Parasite
• Three developmental stages seen in blood films
 Microscopy
Disadvantages
Advantages
• Low direct costs • Accuracy depends on skilled staff

• High sensitivity • Delay in providing results to

• Differentiation between patient

plasmodium species
• Determination of parasite
densities
• Ability to monitor response to
therapy
 Microscopy
• Timing: As soon as suspected, Collect
irrespective of fever, not necessarily at height
of fever, Before giving antimalarials
• Make smears within 2h of collection of blood
• Examine under 100X
• Minimum 100 fields to be examined
• Atleast 3 consecutive days before saying
negative
QUANTITATIVE BUFFY COAT TEST
(QBC)
• Involve staining of centrifuged and compressed red cell

layer with acridine orange and examination under UV

light source.

• Fast, easy, more sensitive

• Need special equipment, costly, more false positivity

d/t staining artifacts, not able to differentiate the

parasite

• Malarial parasite DNA stains green and RNA stains

orange under blue-violet light in the Paraviewer

QBC
 RAPID DIAGNOSTIC TESTS

• Immunochromatographic tests that detect parasite

specific antigen in a finger prick blood sample

⮚ Based on
1. Histidine-Rich Protein 2 (HRP2)
2. Parasite specific lactate dehydrogenase (pLDH)
3. Aldolase
Antibody Antigen detected Species recognized

Anti Pv-pLDH pLDH P. vivax

P. vivax, P. ovale, P.
Anti Pvom-LDH pLDH
malariae

All Plasmodium speci

Anti Aldolase Aldolase
es

All Plasmodium speci

Anti pan pLDH pLDH
es

Anti Pf-pLDH pLDH P. falciparum

Anti HRP2 HRP2 P. falciparum

 Advantages- RDT
• Quick to perform (in practice, about 20 minutes)

• Sensitive in detecting P. falciparum, which causes severe

malaria: Microscopy may not pick up Pf in sequestered RBCs

• Does not require skilled laboratory technicians and can be

used by health workers and non-health personnel after a few
hours of training

• Does not require electricity or laboratory equipment

• Can complement microscopy

 Advantages- RDT
FALSE NEGATIVE RESULT FALSE POSITIVE RESULT
• Insufficient parasites to register a • Dead parasite
positive result: esp for PV
• Persistence of malaria gametocytes
• RDT kit damaged
• Individuals with high immunity
• Illness by another species of
malaria parasite which RDT is not
designed to detect
• Pfhrp2 gene deletion
 RAPID DIAGNOSTIC TEST
• Negative RDT should not preclude treatment in a strongly
suspected case, especially in severe clinical disease
• PfHRP-2 based kits may show positive result up to four weeks
after successful treatment and parasite clearance.
• Aldolase and pLDH fall rapidly to undetectable levels after
treatment but these antigens may be expressed in
gametocytes which may appear after clinical infection has
cleared
 Parasite Index
• PI is calculated as the number of asexual and/or sexual parasites
present in 1 μL of peripheral blood
• WHO: 8,000 leucocytes/μL for the calculation of PI
• Indicates: severity of disease and effectiveness of treatment
• Detected by microscopy and RDT
• Assuming that 1 μl of blood contains 5 × 106 RBC; 1% parasitemia will
contain 1 parasite/100 RBC or 50,000 parasites/μl of blood.
• Similarly, a 0.1% parasitemia will contain 5,000 parasites/μl of blood.

Levels of parasitemia:
• Low parasitemia: 5–10,000 parasites/µl.
• Intermediate parasitemia: 10,000–100,000 parasites/µl.
• High parasitemia: > 100,000 parasites/µl.
 Malaria Serology

• Immunologic assays to detect host response

• Antibodies to asexual parasites appear some days after
invasion of RBCs and may persist for months
• Positive test indicates past infection
• Not useful for treatment decisions
 Polymerase Chain Reaction
• Detect parasite DNA

• Highly sensitive

• Very useful for detecting mixed infection, particularly at low

parasite density

• Identify drug resistance

• Differentiate b/w P. Knowlesi and P. Malariae can’t be done by

microscopy.

• Not routinely available

 Case
• 4-year-old girl
• Fever X 15 days
• Paleness X7 days
• No bleeding/rashes/jaundice/abdominal
distention/loose stools/cough/joint pains
• No H/O contact with kochs
• Examination
• Pallor++, Icterus+-, LAD-
• P/A: Spleen 3 cm, firm; Liver 3 cm BCM, span: 6cm
 What possibilities?
• Infection: Malaria, Leptospirosis, TB,
Rickettsial illness, Enteric fever
• Malignancy: Acute leukemia
• Nutritional anemia: Megaloblastic
• Hemolytic anemia: AIHA, G6PD
Plasmodium falciparum Plasmodium vivax
High-grade parasitemia: P. Reticulocyte infection: Low-grade
falciparum can infect RBCs of parasitemia, with ring
any age trophozoites in the largest red
Crescent-shaped / banana- blood cells.
shaped gametocytes Schuffner’s dots
Appliqué forms: Trophozoites Absence of RBC shape changes
may look like they are on the
surface of the RBCs
 Treatment: On basis of severity
• Uncomplicated malaria
• P vivax
• P falciparum: Antimalarial combination therapy; WHO recommendation:
artemisinin-based combination therapy (ACT)
• Rapidly eliminated: Tetracycline, Clindamycin X 7d
• Slowly eliminated: Lumefantrine, SP, MQ (3 d therapy); Better
compliance

• Complicated malaria

• Artemesinin most rapidly acting, produce 10,000-fold reduction in parasites

per asexual cycle
 Uncomplicated Plasmodium vivax malaria

• Chloroquine should not be given in empty stomach or when

there is a high fever. Control fever first.
• If there is vomiting within 45 minutes, dose should be repeated
after ondansetron or domperidone is given.
Uncomplicated Plasmodium falciparum malaria

• Artesunate 4 mg/kg orally once daily for 3 days + Sulfadoxine +

Pyrimethamine (ASP) (S 25 mg/kg and P 1.25 mg/kg) on day 1

Or
• Artesunate 4 mg/kg orally once daily for 3 days + mefloquine
25 mg/kg in two divided doses on day 1 followed by 15 mg /kg
on day 2 and 10 mg/kg on day 3.
• Day 2: Primaquine 0.75 mg/kg, PO: For gameticidal action
Uncomplicated Plasmodium falciparum malaria

• Artemether 20 mg + lumefantrine 120 mg (AL) as

twice daily, six doses, 3 days treatment

Primaquine 0.75 mg/kg single dose.

AL Should not be given to <5 kg children.

 Uncomplicated Mixed Infection (Plasmodium
Vivax and Falciparum)

• Artemisinin-based combination therapy (ACT) regimen

plus primaquine for 14 days as for vivax malaria.

• Glucose-6-phosphate dehydrogenase (G6PD) screening

is highly recommended. In G6PD deficient children, dose
of primaquine is 0.6–0.8 mg/kg once a week for 6 weeks
Treatment of Complicated Malaria
 Treatment of Complicated Malaria
Cerebral malaria
• Convulsions—lorazepam/midazolam as local intensive
care unit (ICU) protocol; Phenytoin
• Phenobarbitone is avoided
• Steroids are contraindicated
• Mannitol and other anticerebral edema treatment is not
required as raised intracranial pressure (ICP) is not a
feature of cerebral malaria and it can be harmful
 Treatment of Complicated Malaria
Anemia
• High-transmission settings: HCT ≤ 12% or hb ≤ 4g/dl is an
indication for blood transfusion, whatever the clinical
condition of the child.
• Low-transmission settings: HCT <20% a hb < 7g/dl is
recommended for blood transfusion (10ml of packed cells or
20 ml of whole blood per kg of body weight over 4h).
• In children with less severe anemia (HCT 13–18%, hb 4–
6g/dl), transfusion should be considered for those with any
one of the following clinical features: respiratory distress
(acidosis), impaired consciousness, hyperparasitemia (>
20%), shock or heart failure.
• Diuretic not needed as many are hypovolemic
 Treatment of Complicated Malaria

• Lactic acidosis: Monitoring arterial blood gas (ABG), blood

sugar every 4 hours, serum electrolytes once daily or more

often, and interventions to be done accordingly.

• Hypoglycemia: Bolus of 25% dextrose, 2 mL/kg followed by

appropriate glucose infusion rate (GIR) with hourly glucose

monitoring to maintain blood glucose >70 mg/dL.

 Treatment of Complicated Malaria
• Hyperpyrexia: Tepid sponging and paracetamol 15
mg/kg
• Acute renal failure: Slow fluid infusion, hemodialysis,
or renal replacement therapy (RRT)
• Antibiotics if pneumonia/shock/CNS infection is
suspected
• Disseminated intravascular coagulation (DIC):
Spontaneous gastrointestinal (GI) bleeding and
subcutaneous bleeding—fresh frozen plasma is
administered. Subcutaneous low molecular weight
heparin is reserved for cases with clinical and
laboratory evidence of DIC.
 Monitoring of treatment

• Follow up for 28 days for both clinical and parasitological assessment

• Parasitological assessment include detection of malaria parasite, species
determination and parasite density measurement.
• 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.
 Treatment Failure/Drug Resistance

• After treatment patient is considered cured if he/she

does not have fever or parasitemia till Day 28.
• Some patients may not respond to treatment which
may be due to drug resistance or treatment failure,
especially in falciparum malaria.
 Early Treatment Failure (ETF)
 Development of danger signs or severe malaria on Day 1, 2 or 3, in the
presence of parasitemia

 Parasitemia on Day 2 higher than on Day 0, irrespective of axillary

temperature

 Parasitemia on Day 3 with axillary temperature >37.5°C

 Parasitemia on Day 3, >25% of count on Day 0.

 Late Treatment Failure (LTF)
 Development of danger signs or severe malaria in the presence
of parasitemia Treatment failure Day
on any day between with4 chloroquine
and Day 28 (Day 42) in
in P. vivax malaria is rare in India
patients who did not previously meet any of the criteria of early
treatment failure

 The presence falciparum

of parasitemiamalaria
on any day between Day
- alternative 4 and Day
ACT
or quinine
28 (Day 42) with axillary with Doxycycline.
temperature >37°C in patients who did
not previously meet any of the criteria of early treatment failure.
Prevention
 Chemoprophylaxis

• Chemoprophylaxis is recommended for travellers,

migrant labourers and military personnel exposed to

malaria in highly endemic areas.

 Chemoprophylaxis
• Short-term • Long-term chemoprophylaxis
chemoprophylaxis (less than (more than 6 weeks)
6 weeks)
Mefloquine: 5 mg/kg body weight (up
Doxycycline: 100 mg daily in adults
and 1.5 mg/kg body weight for to 250 mg) weekly and should be
children more than 8 years old. administered two weeks before, during

The drug should be started 2 days and four weeks after leaving the area.

before travel and continued for 4

weeks after leaving the malarious
area
 Malaria Control Strategies

 Early case Detection and Prompt Treatment (EDPT)

 Vector Control: ITN (Dual insecticide)
Indoor Residual Spraying (IRS)

Pyrethroid–chlorfenapyr nets combine a pyrethroid and a pyrrole insecticide to enhance the killing effect of the
net; and pyrethroid–pyriproxyfen nets combine a pyrethroid with an insect growth regulator which disrupts
mosquito growth and reproduction

 Environmental Management & Source Reduction Methods

 Vaccination of children in high-risk areas: In October 2023, WHO
recommended a second vaccine, R21/Matrix-M (R21), to complement the
ongoing rollout of the first malaria vaccine, RTS,S/AS01 (RTS,S): starting 5
months age, 4-dose schedule. Act against sporozoite stage