MALARIA

BY
DR C.U. ONUBOGU

PAEDIATRICS DEPARTMENT NAUTH

 OUTLINE
• Definition
• Etiology
• Epidemiology
• Pathophysiology/pathogenesis
• Clinical features
• Complications
• Diagnosis
• Treatment
• Prevention
 Definition and etiology

• Definition: Malaria is an infectious disease caused by intracellular

protozoan parasite of the genus Plasmodium
• Etiology: Human malaria can be caused by 5 (predominantly 4)
species of plasmodium
 P. Falciparum –commonest species in Africa where it accounts for
more than 98% of cases. Accounts for almost all severe forms and
malaria deaths
 P. Vivax—Most widespread form. Dominant species in most
regions outside SSA (64% in America, 30% in South East Asia and
40% in Eastern Meditarranean)
 P. Ovale
 P. Malariae
 P. knowlesi – rare in man. Mainly a zoonotic infection seen in
forested regions of South East Asia
 BURDEN OF MALARIA

• Nearly half of the world's population are at risk.

• In 2021, estimated 247M cases and 619,000 deaths
occurred globally(229M cases and 409,000 deaths in 2019)
• Africa accounted for 95% of cases and 96% of deaths.
• < 5 year olds are the most vulnerable (account for 80% of
deaths in Africa).
• 4 African countries account for approx 50% of malaria
deaths: Nigeria (31.3%), the DRC (12.6%),Tanzania (4.1%),
Niger (3.9%).
• Nigeria has more reported malaria cases and deaths than
any other country in the world.
• In Nigeria, 97% of the population are at risk of Malaria
which accounts for 60% of outpatient visits, 30% of hospital
 Transmission of malaria
• Principally transmitted by bite of infected
female anopheles mosquito.
• About 30 out of over 400 anopheles species
can transmit the parasite. Important vector
specie bite between dusk and dawn
• Rare routes
 Transfusion of infected blood, organ transplant
 Needle stick injury, intravenous drug abusers
 Transplacentally ie congenital malaria
 Perinatally through mingling of maternal and
child blood during child birth
 Transmission of malaria contd
• Intensity of transmission and disease severity highly
dependent on interactions between
 The host (immune or non-immune, attractants)
 The parasite (predominant type, drug resistance)
 The mosquito vector insecticide resistance and predominant
type eg A. arabiensis of gambiae group is most efficient, found
only in Africa, prefer human blood meal and breed in a wide
variety of water collections)
 Environmental conditions which determine malaria endemicity
• Temperature
• Humidity
• Rainfall
• Altitude
 Endemicity of Malaria

• Based on the parasite and spleen rates in children aged 2-9

years.
• Spleen rate is number of palpable enlarged spleens per 100
individuals of similar age group.
• Parasite rate is number of persons with parasitaemia per
100 individuals of similar age group
 Hypoendemic-Spleen or parasite rates 1–10%
 Mesoendemic-Spleen or parasite rates 11–50%
 Hyperendemic – Spleen or parasite rates persistently > 50%
and < 75%, adult spleen rates > 25%
 Holoendemic – Spleen and parasite rates persistently >
75%, low adult spleen rates < 25%
 Other epidemiological terminologies
Stability of Malaria
• Stable malaria : Seen in Holoendemic and hyperendemic
malaria regions. High rate of transmission throughout the year
with little or no seasonal variation. P. Falciparum is the
dominant species, herd immunity is high and epidemics do not
occur. Pregnant women and children especially under-fives
mostly affected. Found in SSA countries like Nigeria.
• Unstable Malaria: Seen in hypoendemic and mesoendemic
areas. Transmission rate is low and varies considerably from
season to season and year to year. Immunity is low and
epidemics can occur. All strata of the population are at risk of
malaria during transmission seasons.
• Epidemic Malaria: Periodic or occasional sharp increase of
malaria incidence in a given community  
 Life cycle of plasmodium
• Involves 2 hosts (human and vector). In humans involves the asexual hepatic
(exo-erythrocytic) and sexual erythrocytic cycles. Sporogony last 10-18 days
• Incubation period is 9-14 days for P. falciparum, 18-37 days for P. malariae, 12-
17 days for P. vivax and 16-18 days for P. ovale,
• Duration of tissue schizogony ranges between 8–30 days depending on the
specie.
• In cases of P. vivax and P. ovale, some sporozoites may go into hybernation
(dormant phase) called hypnozoites which may cause clinical relapse months
or years later.
• The erythrocytic schizogony lasts for about 48 hrs in P. falciparum, P. vivax, P.
ovale infections and 72 hours in P. malariae infection and determine the
pattern of fever.
• The malaria clinical paroxysms occur when enough cycles have occurred to
produce the amount of parasitic materials, pigments (hemozoin from Hb
consumption by parasite, RBC debris)
• The contents of lysed RBC stimulate TNF and other cytokines, which results in
the characteristic clinical manifestations of the disease.
LIFE CYCLE OF MALARIA PARASITE
 MALARIA IMMUNITY
• Natural Immunity : Nonspecific intense proliferation of
macrophages of the spleen, liver and bone marrow which
phagocytize parasitized RBC
• Acquired immunity:
 Passive via transplacentally transferred IgG which is reinforced
by antibodies in breastmilk and protective till 6 months.
 Active : depends on repeated contact with MP and is
incomplete. Prevents severe and repeated attacks.
• Other factors that influence immunity against malaria include
HbS, C, E status, thalassemia, Duffy negative genotype, G6PD
deficiency status, Fetal Hb concentration all of which reduce
ability to parasitize RBC
• Low immune status of the individual, age (> 6 months <5years),
pregnancy increases risk of malaria
 Immunity in infants
• Newborns and young infants seldom have malaria and when they do, the
infection is rarely severe because of natural protection from the following
mechanisms:
 Antibodies tend to pass from the mother via the placenta to the baby during
pregnancy.
 The protection is further reinforced by antibodies against malaria that pass to
the baby via breast milk.
 The foetal haemoglobin that persists in young infants usually up the age of six
month tends to be relatively resistant to parasitisation particularly by P.
falciparum.
 The breast milk is also relatively poor in para-aminobenzoic acid (PABA); PABA is
needed in abundance for the growth of plasmodium.
 Some of the drugs the mother take against malaria infection will also protect the
baby via the breast milk (using the rule of thumb, about 10% of the dose gets
transferred).
 The vector-avoidance behaviour of the mother also minimises the exposure of
the baby to the biting of the mosquitoes and consequently of the transfer of the
sporozoites
 Pathophysiologic mechanisms

• Fever, anaemia, immunopathologic events and tissue anoxia are

four major pathologic processes in malaria.
• Anaemia caused by
 Haemolysis
 sequestration of erythrocytes in the organs particularly, the
spleen
 suppression of erythrocyte production in the bone marrow.

• Hemolysis : accounts for anaemia, jaundice and black water fever in

intense cases. Hemolysis is caused by
 destruction of parasitized RBC
 auto-antigenic changes
 increased osmotic fragility of RBC
 effect of antimalarials like quinine or SP in G6PD deficient individuals
 Pathophysiologic mechanisms contd
• Fever : occurs when RBC rupture and release
merozoites and pyrogens. The paroxysms of fever is
related to the periodicity of the erythrocytic
schizogony
• Microvascular obstruction: due to occlusion of the
deep microvasculature. This results from increased
rigidity and adhesiveness of parasitized RBC to
which unparasitize RBC also adhere to forming
rossettes which causes obstruction and varying
degree of organ involvement
• Immunopathologic events : include formation of
immune complexes and immunosuppression
 Clinical features
• For a focused management of malaria the WHO recommends that
every case of malaria should be classified as uncomplicated or
complicated malaria
• Uncomplicated malaria
 This is symptomatic infection without evidence of vital organ
dysfunction.
 Most cases of malaria in children in the tropics belong to this
group.
 The main manifestations of malaria in this group include bouts of
intermittent fever accompanied by other features like malaise,
chills, rigors, headaches, and body pain, nausea, vomiting, and
joint weakness, pallor, hepatosplenomegaly etc
• Severe malaria: Life threatening form of malaria
 This is malaria with evidence of vital organ dysfunction in the
asexual P. Falciparum parasitaemia of peripheral blood.
 Complicated malaria Diagnostic features
1 Cerebral malaria Unarousable coma > 30 minutes in the absence of other causes of
encephalopathy, ring haemorrhage
2 Prostration generalised weakness with inability to sit or stand without
assistance
3 Hyperparasitaemia Asexual Parasite density >250,000/UL of blood or > 5% of RBC
parasitized by asexual forms of P. falciparum
4 Severe Anaemia Hb < 5g/dl, packed cell volume < 15%
5 Hyperpyrexia Rectal temperature > 40 0C
6 Severe jaundice SB > 51micromol/L
7 Hypoglycaemia blood glucose <2.2mmol/L or <40mg/dl
8 Shock or circulatory hypotension, rapid thready pulse
collapse
9 Renal impairment serum creatinine >265mol/L, oliguria or anuria
10 Pulmonary oedema Clinical or radiologic evidence
11 Metabolic acidosis plasma bicarbonate <15mmol/L, pH < 7.2, acidotic breathing
12 Clotting disturbances abnormal spontaneous bleeding

13 Others Multiple convulsions, black water fever with massive intravascular

hemolysis and hemoglobinuria
 Patient Evaluation
• History: fever, chills rigor, headache in the older
patient, look out for symptoms suggestive of severe
malaria like extreme weakness, change in behaviour,
convulsions, drowsiness or unconsciousness, timing of
last feed or drink, fast breathing (may be due to
pulmonary oedema, acidosis or aspiration or coexisting
pneumonia), reduced urinary output, urine colour
Also enquire about treatment already received.
• Physical Examination:
 Assessing for the presence of signs of severe malaria.
 Look out for signs of other possible causes of disease
 Do thorough systemic examination
• Investigation : For diagnosis and determining severity
of disease
 PARASITOLOGICAL DIAGNOSIS
• Peripheral Blood Smear :The Gold Standard
• Both thick & thin smears should be examined.
 Thick film: parasite detection and quantification.
 Thin film: Identify the Plasmodium species.

• Degree of Parasitaemia : The “plus system” is less precise.

 + = 1–10/ 100 thick fields.
 ++ = 11–100/ 100 thick fields.
 +++ = 1–10/ thick field.
 ++++ = >10/ thick field
 Microscopy contd
• Microscopic by a highly skilled microscopist has
a sensitivity of 86-98% with a lower sensitivity at
low parasitaemia (≤ 320/μl)
• P. falciparum smears best obtained after a
febrile paroxysm
• Stage of the malaria infection and previous
medication may reduce parasitaemia below the
detectable threshold and necessitate repeat
examination.
• A single negative blood smear does not exclude
malaria.
 DIAGNOSIS OF MALARIA contd

• Quantitative Buffy Coat (QBC) test ‑ A

microscopic test that consist of mixing blood with
acridine orange then centrifuging in a capillary
tube which is the read directly with a fluorescent
microscope.
• Non-microscopic tests:
 Rapid Diagnostic tests :
 Polymerase Chain Reaction
 Detection of antibodies by Radio immuno assay,
immunofluorescence or enzyme immuno assay
 Malaria Rapid Diagnostic Tests (mRDT)
• Detects specific antigens (proteins) produced by malaria parasites.
• The commonest ones are broadly of two categories;
 Those based on the identification of the Plasmodium falciparum
histidine rich protein 2 (PfHRP2). It is rapid, sensitive and specific
for P. Falciparum. This detects the presence of the plasmodium
protein whether dead or alive. Therefore very sensitive, but
slightly less specific because test may remain positive after death
of the parasite for up to 5-weeks. Hence a positive test may not
always indicate an active infection
 Those based on the identification of the plasmodium lactate
dehydrogenase enzyme (pLDH) and aldolase enzyme.
 Since pLDH is produced only by live Plasmodium parasites, this test
has the ability to differentiate live from dead organisms. Therefore
slighly less sensitive but more specific
 mRDT Contd
Most RDTs have a sensitivity of 95% at parasite
densities of 200/μl of blood.
The sensitivity of malaria RDTs is determined by the:
• Species of parasite (poor sensitivity in detecting P.
malariae and P. ovale)
• Number of parasites present in the blood
• Condition of the RDT
• Correctness of technique used to perform the test
• Correctness of interpretation by the reader
• Parasite viability and variation in production of
antigen by the parasite.
 Treatment: Aim
Severe malaria
Uncomplicated malaria 1. To prevent death.
1. To cure the infection.
2. Prevent progression to severe 2. To prevent recrudescence.
disease
3. Prevent transmission of 3. To Avoid adverse effects.
disease
4. To prevent neurological deficit
4. To prevent the emergence of (cerebral malaria).
resistance to anti-malarials.

5. To prevent the spread of

resistance to anti-malarials.
 TREATMENT

• UNCOMPLICATED MALARIA
• All cases should be confirmed parasitologically
• WHO now recommends the use of Artemisinin-based
Combination Therapy.
• The recommended ACTs include:
 Artemether-lumefantrine @ 1.5/9 mg/kg twice daily for
three days
 Artesunate+Amodiaquine (@ Artesunate 4 mg/kg dly for
3 days + Amodiaquine 10mg /kg for 3 days)
 Artesunate+Mefloquine
 Dihydroartemisinin-piperaquine
 
 Treatment of severe malaria
Initial antimalarial therapy must be parenteral
 Artesunate Injection : Give 2.4 mg/kg IV bolus @ 0, 12, 24, 48hrs. Give full
course of ACT as soon as patient can take orally
•   In the absence of IV artesunate other alternatives include
 Intramuscular Artemether:- 3.2 mg/kg IM on the first day and then 1.6
mg/kg daily for a maximum of 3 days until the patient can take oral
treatment, then give a full 3-day course of ACT OR
 Alpha-beta arteeter 3mg/kg/day
 Intravenous quinine 20 mg/kg of Quinine dihydrochloride salt loading dose
diluted in 10 ml/kg of 5% dextrose over a period of 4 hours. Then 8 hours
after the start of the loading dose, give 10 mg salt /kg infusion over 4 hours 8
hourly until when patient is able to take orally. Change to oral ACT once
patient can tolerate oral medication OR
• Intramuscular Quinine: Where IV access is not possible give quinine
dihydrochloride at a dosage of 20 mg/kg salt (loading dose), then 8hours
after the start of the loading dose give 10mg/kg 8hourly until patient is able
take orally, then ACT 
 
 Supportive treatment continued
• Pulmonary oedema : Prop up the patient, give oxygen and
furosemide 2-4 mg/kg IV and exclude anaemic heart failure.
•  Renal failure : Initial renal challenge with 20 ml/kg of normal
saline and furosemide 1-2 mg/kg, monitor fluid-input output,
restrict fluid to 300ml/m2 + previous day’s output in
established renal failure. If patient does not pass urine within
24 hours, consider peritoneal or haemodialysis. 
• Profuse bleeding: transfuse with screened fresh whole blood
• High temperature: Give paracetamol (oral/rectal) if
temperature is > 38.5 o C, tepid sponge and apply other
measures to reduce body temperature
 Supportive treatment for severe malaria
• Coma or unconscious patient : Ensure airway is patent; gentle
suction of nostrils and the oro- pharynx, make sure the patient is
breathing, nurse the patient lying on the side, naso-gastric tube
feeding, establish IV line for fluid and drugs
• Hypoglycaemia: correct with 4ml/kg of 10% dextrose and maintain
with dextrose containing fluid.
• Convulsions: Ensure patent airway and that the patient is breathing,
correct hypoglycaemia or control temperature, give rectal diazepam
0.5 mg/kg or IM paraldehyde 0.1 ml/kg. If convulsions continue, give
IM phenobarbitone 10-15 mg/kg.
• Severe dehydration or shock : Give 20-30 ml/kg of normal saline and
reassess the patient within 30 minutes to decide on the next fluid
requirement according to the degree of dehydration. Place the
patient on maintenance fluid as soon as the patient is well hydrated. 
• Severe Anaemia : Urgent blood transfusion. The blood must be
screened to ensure that it is HIV, Hepatitis B and C negative.
 Nursing care in severe malaria
• Monitor and document vital signs (Pulse, Temperature,
Respiratory rate, Blood pressure) at least 6 hourly but may be
more frequent at the initial stages. 
• Monitor input and output
• A strict 24-hour input /output chart should be kept in all
patients with severe malaria. Examine regularly for signs of
dehydration or fluid overload. 
• Monitoring unconscious patient : Monitor the level of
consciousness at least 6 hourly, regular turning to avoid
bedsores. 
• Drug chart : Keep a clear drug chart where all name, dosage
and timing of all given drugs are recorded.
•  Laboratory Monitoring : monitor parasitaemia by daily blood
smear. If still high after 2-3 days, review adequacy of the
drug dose. Monitor blood glucose and PCV as indicated 
 Key recommendations for malaria tmt
• Prompt parasitological confirmation by microscopy or RDTs in all
patients suspected of malaria before treatment.
• Use Artemisinin-based combination therapies (ACTs) for uncomplicated
P. falciparum malaria.
• ACTs recommended for use in Nigeria are; Artemether-lumefantrine,
Artesunate-amodiaquine.
• Artemisinin and its derivatives should not be used as monotherapy in
the treatment of uncomplicated malaria.
• Oral Quinine is the recommended medicine for the treatment of
uncomplicated malaria in the first trimester of pregnancy.
• ACTs is the recommended treatment of uncomplicated malaria in the
second and third trimesters of pregnancy.
• Treat infants less than 5kg with ACTs under supervision by the health
care provider
 Key recommendations for malaria tmt contd
• Severe malaria is a medical emergency. Commence immediate
treatment with parenteral medication using intravenous artesunate .
• Children weighing < 20 kg should receive a higher dose of artesunate (3
mg/kg bw per dose) than larger children and adults (2.4 mg/kg bw per
dose) to ensure equivalent exposure to the drug.
• Parenteral artemether or quinine is an acceptable alternative only if
artesunate is not available.
• Give parenteral medication for a minimum of 24 hours once started
(irrespective of the patient’s ability to tolerate oral medication earlier)
and thereafter, complete treatment with a complete course of an ACT.
• Where complete treatment of severe malaria is not possible, patients
should be given pre-referral treatment and referred immediately to an
appropriate facility for further treatment.
• The recommended pre-referral treatment options include; artesunate
IM or rectal artesunate or quinine IM, in the order of preference
 Antimalarial resistance
• Cure : clearance of asexual parasitaemia within 7 days of
starting treatment and no recrudescence
• Drug resistance: ability of the parasite to survive at a
concentration of a drug equal to or higher than that
obtained by recommended dosage.
 R1 = clearance of asexual parasitaemia within 7 days of
starting treatment with recrudescence
 R11: marked reduction in asexual parasitaemia but no
clearance
 R111 : no marked reduction in asexual parasitaemia
• Mechanisms for drug resistance include baseline genetic
predisposition, host immunity and drug pressure (poor
compliance, low dosage, adulterated drug)
 PREVENTION OF MALARIA
o Use five levels of prevention
o ROLL BACK MALARIA
• The Roll Back Malaria (RBM) Partnership was launched on 31 st July 1998 by the
WHO, UNICEF, UNDP and the World Bank.
• This is a global partnership to fight malaria building on existing framework of
national governments, international organizations and private sector with
original goal of halving malaria burden by 2010 in affected population.
• RBM involves multiple strategies targeted to meet local malaria control needs.
• Six Principles of RBM
 Early detection
 Rapid diagnosis and effective treatment
 Multiple prevention
 Focused research
 Well coordinated actions
 Dynamic movement