Malaria (Plasmodium)

Mequanint H
(Assistant prof of Paediatrics &
child health)
 As a start up

1. Define relapse in malria

2. Define recrudescence
3. Define reinfection

07/17/2025 2
4. One has risk of relapse;
A. P. falciparum,
B. P. malariae,
C P. ovale ,
C.
D. P. knowlesi
E.
E P. vivax

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5. Which species of plasmodium are prevalent in Ethiopia?
6. What is tropical splenomegaly syndrome?
7. Which complications of malaria are more common in pediatrics
population than adults?

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8. Summarize the life cycle of malaria
9. Schizonts Vs Hypnozoites
10. List natural protective factors for malaria after an individual get infected.
11. Which species is associated with nephrotic syndrome and which one for AGN?

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 Malaria
• An acute illness characterized by paroxysms of:
• Fever, chills, sweats,
• Fatigue, anemia, and splenomegaly.
• Historically cause harm to more people than any other
infectious disease
• Estimated 214 million cases and 438,000 deaths in 2015.
• Malarial deaths in areas of high malaria transmission occur
primarily in children <5 yr of age
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 Etiology
• Intracellular Plasmodium protozoa
1. P. falciparum,
2. P. malariae,
3. P. ovale ,
4. P. vivax , and
5. P. knowlesi …. Discovored in 2004
• Transmitted to humans by female Anopheles mosquitoes.
• Can be transmitted through blood transfusion and use of
contaminated needles and transplacentally 07/17/2025 7
 Disease burden
• A major worldwide problem, occurring in 95 countries that
comprise ½ of the world's population
• The principal areas of transmission are Africa, Asia, and S
America.
• P. F and P. M are found in most malarious areas.
• P. F is the predominant species in Africa and New Guinea.
• P. V and P. F predominate in Southeast Asia, South
America, and Oceania.
• P. O is the least-common species and is transmitted
primarily in Africa. 07/17/2025 8

• Ethiopia = P.F and P. V

 Pathogenesis
• Plasmodium species exist in a variety of forms and have a
complex life cycle
• In the human host (asexual phase) and
• The mosquito (sexual phase)
• A marked amplification, from 102 to 1014 organisms, occurs
during a 2-step process in humans,
Exoerythrocytic phase (in hepatic cells) and ….. 1st phase
Erythrocytic phase (in the RBCs)…… 2nd phase 07/17/2025 9
• The exoerythrocytic phase begins with inoculation of
sporozoites into the bloodstream
• Within minutes, the sporozoites enter the hepatocytes;
develop and multiply asexually as a schizont .
• After 1-2 wk, the hepatocytes rupture and release
thousands of merozoites
• The tissue schizonts of P. falciparum, P. malariae, and P.
knowlesi rupture once and do not persist in the liver.
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There
are 2 • The primary type = ruptures in 6-9 days, and
types
• The secondary type = remains dormant in
of
tissue hepatocytes for weeks, months, or as long as 5 yr
schiz before releasing merozoites and causing relapse
onts of infection
for P.
ovale
and P.
vivax
. 07/17/2025 11
 Erythrocytic phase

• Begins when the merozoites penetrate erythrocytes.

• Then transforms into the ring form , which then enlarges to
become a trophozoite
These latter 2 forms can be identified with Giemsa stain on
blood smear
• The trophozoite multiplies asexually to produce small
erythrocytic merozoites that are released into the bloodstream
= fever.
• Over time, some of the merozoites develop into male and female
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• Gametocytes are ingested by the female anopheline mosquito =

complete the Plasmodium life cycle
• The male and female gametocytes fuse to form a zygote
in the stomach cavity of the mosquito.
• After a series of further transformations, sporozoites enter
the salivary gland of the mosquito and are inoculated into
a new host

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07/17/2025 14
 Why severe malaria in P. falciparum???

• Severe malaria is more common in P. falciparum

1. Higher-density parasitemia= excessive production of cytokines;
2. Cytoadherence
3. Infect both mature and imature RBC
4. Polyclonal activation= hypergammaglobulinemia & the formation of immune
complexes.

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• Immunity after Plasmodium sp. infection is incomplete;
• Preventing severe disease but still allowing future infection.
• In some cases, parasites circulate in small numbers = Not
multiplying/no severe illness.
• Repeated episodes of infection occur because the parasite has
developed immune-evasive strategies
• Intracellular replication,
• Vascular cytoadherence
• Rapid antigenic variation, and
• Alteration of the host immune system resulting in partial
immune suppression
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 Protective factors

• RBCs containing hemoglobin S = resist malaria parasite

growth,
• RBCs lacking Duffy blood group antigen = relatively resistant
to P. vivax , and
• RBCs containing hemoglobin F and ovalocytes = resistant to
P. falciparum .
• In hyperendemic areas, newborns rarely become ill with
malaria;
17
Passive maternal antibody and
 Clinical Manifestations
• Children and adults are asymptomatic during the initial phase
of infection, the IP
• The usual incubation periods are;
9-14 days for P. falciparum ,
12-17 days for P. vivax ,
16-18 days for P. ovale, and
18- 40 days for P. malariae .
• It can be as long as 6-12 mo for P. vivax and can also be
prolonged for patients with partial immunity or incomplete
07/17/2025 18

chemoprophylaxis.
 Clinical …
• A prodrome lasting 2-3 days is noted in some patients before
parasites are detected in the blood.
• Headache, fatigue, anorexia, myalgia, slight fever, & pain
(chest, abdomen, & joints).
• Children with malaria often lack the typical paroxysms in adults;
High fever, followed by shaking chills and then diaphoresis
May have nonspecific symptoms;
Fever ( often >40°C), headache, drowsiness, anorexia, N/V,
and diarrhea.
• A classic pattern of fevers is every other day for P. vivax and P.
ovale
• Rupture of schizonts occur every 48 hr
• Pattern of fever is every 3rd day for P. malariae
• Rupture of schizonts is every 72 hr
• Periodicity is less apparent with;
• P. falciparum, and
• Mixed infections and
• Early on in infection, when parasite broods have not yet
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synchronized.
• In contrast to P. ovale, P. V, and P. M, which usually result
in parasitemias of <2%, malaria caused by P. F can have
parasitemia levels as high as 60%.
• The differences reflect that;
P. falciparum infects both immature and mature
erythrocytes,
P. ovale and P. vivax primarily infect immature
erythrocytes and
P. malariae infects only mature erythrocytes.
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Mortality in children associated with CNS involvement,
acidosis, and uremia

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• Severe disease and death from P. vivax is also possible and is
usually caused by;
Severe anemia and splenic rupture.
• P. ovale malaria is the least common type of malaria.
• P. malariae is the mildest and most chronic of all malaria
infections.
• Nephrotic syndrome is a rare complication of P. malariae
• P. K malaria is most often uncomplicated but can lead to severe
malaria

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 Recrudescence Vs Relapse???
• Recrudescence
Occur from the survival of erythrocyte forms in the bloodstream.
• Long-term relapse caused by :
Release of merozoites from an exoerythrocytic source in the
liver (P. V and P. O , or
From persistence within the erythrocyte(P. M).
• A history of typical symptoms in a person >4 wk after return from
an endemic area is therefore more likely to be P. V, P. O, or P. M
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infection than P. F infection
 Malaria in pregnancy
• Is a major health problem in malaria endemic countries,
• Can be severe, and is associated with adverse outcomes in
the fetus or neonate, including;
• IUGR and Even in the absence of
• LBW , transmission from mother to child

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 Congenital malaria
• Is acquired prenatally or perinatally
• Usually occurs in the offspring of a nonimmune mother with P. V or
P. M.
• The first sign or symptom typically occurs:
Between 10 and 30 days of age (range: 14 hr to several months
of age).
• Signs and symptoms include;
Fever, restlessness, drowsiness, pallor, jaundice,
Poor feeding, vomiting, diarrhea, cyanosis, and 07/17/2025 26

hepatosplenomegaly.
 Diagnosis of Malaria

• Hx & P/E
• Blood smears
• RDT (rapid diagnostic test).
• PCR = especially to distinguish P. knowlesi from P.
malariae
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 Blood smears
Thick smear Thin smear

• Concentration of RBCs is • Identification of the

20-40X that on a thin species and
smear • Determination of the
• Quickly scan large percentage of infected
numbers of erythrocytes erythrocytes and
• Useful in following the
response to therapy.
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 WHO & most other
guidelines
• Thick and thin blood smears should be performed for each
suspected case

• It is generally recommended to do BF for 3 times, 12-24

hours apart to exclude malaria in children in whom
malaria is strongly suspected

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 Treatment
1. Supportive care
2. Antimalarial drugs:
• Generally based on;
• Severity
• Level of immunity
Outpatient therapy generally is not given to
nonimmune children
• Local sensitivity/resistance pattern 07/17/2025 30
 Supportive Therapy
• RBC transfusion(s) to maintain the hematocrit at >20%,
• IN oxygen and ventilatory support for pulmonary edema or
cerebral malaria,
• Careful IV rehydration for severe malaria,
• IV glucose for hypoglycemia,
• Anticonvulsants for cerebral malaria with seizures, and
• Dialysis for renal failure.
• Exchange transfusion for parasitemia >10% and evidence of
severe complications (e.g., severe malarial anemia, cerebral
malaria) = Controversy 07/17/2025 31

• Corticosteroids are not recommended for cerebral malaria

Out patient Rx Admission

• Immune children • Non-immune children

• Low-level parasitemia • High level of parasitimia
• No evidence of • Severity sign
complications • With complications
• A lack of toxic appearance • From remote areas
• Able to contact the
physician or emergency
department at any time
• Follow-up within 24 hr is
ensured. 07/17/2025 32
• Parenteral therapy should be continued until the
• Parasitemia is <1%, which usually occurs within 48 hr,
and
• The patient can tolerate oral medication.

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 Un-complicated PF = Artemether-lumefantrine
(Coartem)

• A 3-day treatment schedule with a total of 6 oral doses is

recommended based on weight.
• The patient should receive the initial dose, followed by
2nd dose 8 hr later, then 1 dose PO bid for the following 2
days
• 5-<15 kg: 1 tablet per dose
• 15-<25 kg: 2 tablets per dose
• 25-<35 kg: 3 tablets per dose 07/17/2025 34

• ≥35 kg: 4 tablets per dose

 Uncomplicated malaria/P. malariae or P. knowlesi

• Chloroquine phosphate:
• Hydroxychloroquine:

• Dose of Chloroquine phosphate & Hydroxychloroquine is

similar;
• 10 mg base/kg PO immediately, followed by 5 mg base/kg PO
at 6, 24,and 48 hr
• Total dose: 25 mg base/kg 07/17/2025 35
 Uncomplicated malaria/P. vivax or
P. ovale
• Chloroquine phosphate plus primaquine
phosphate
or
• Hydroxychloroquine plus primaquine phosphate
Dose of Primaquine phosphate: 0.5 mg base/kg PO qd × 14
days
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• Some strains may require 2 courses of primaquine.
• Testing for G6PD deficiency must be performed before
initiation of primaquine, because it can cause hemolytic
anemia in such patients .
• Unfortunately, no alternatives to primaquine currently
exists.

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 Treatment of Severe Malaria in
general
1. Artesunate, 2.4 mg/kg IV/IM , followed by 2.4 mg/kg at 12 hr
and 24 hr;
Continue injection once daily if necessary
2. Artemether, 3.2 mg/kg by immediate IM, followed by 1.6 mg/kg
daily
• Note:
• Artesunate is the treatment of choice.
• Artemether should only be used if artesunate is unavailable.
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• Quinine dihydrochloride should be given only when the 2

Complications Of
Malaria

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WHO Criteria for Severe Malaria
1. Impaired consciousness
2. Prostration
3. Respiratory distress
4. Multiple seizures
5. Jaundice
6. Hemoglobinuria
7. Bleeding
8. Severe anemia
9. Circulatory collapse
[Link] edema 07/17/2025 40
Complications of P. F malaria

• Serious complications that appear unique to P. falciparum

include;
• Cerebral malaria,
• Respiratory distress from metabolic acidosis,
• Acute renal failure,
• Hypotension, and
• Bleeding diatheses
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Manifestations of severe falciparum malaria by age

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 Severe malarial anemia
• Hemoglobin level <5 g/dl
• The most common severe complication of malaria in
children
• Pathogenesis
• Hemolysis
• Removal of infected erythrocytes by the spleen and
• Impairment of erythropoiesis
• The primary treatment = blood transfusion.
07/17/2025 43

• With appropriate and timely treatment, it has a low

mortality ( 1%).
 Cerebral malaria
• The presence of coma in a child with P. F parasitemia and an
absence of other reasons for coma.
• Most common ;
In children in areas of midlevel transmission and
In adolescents or adults in areas of very low transmission
• Often develops after the patient has been ill for several days
• Has a fatality rate of 15–40% and is associated with long-term
cognitive impairment
• Repeated seizures are frequent in children with cerebral malaria
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 Respiratory distress
• Is a poor prognostic indicator in severe malaria
• Appears to be caused by metabolic acidosis rather than
intrinsic pulmonary disease.
• To date, no successful interventions for treatment of
metabolic acidosis in severe malaria
• Primary therapy of malaria appears to be the most
effective way

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 Hypoglycemia
• Is a complication of malaria that is more common in;
Children,
Pregnant women, and
Patients receiving quinine therapy.
• Patients may have a decreased level of consciousness that
can be confused with cerebral malaria.
• Hypoglycemia is associated with increased mortality and
neurologic sequelae 07/17/2025 46
 Algid malaria
• A rare complication of tropical malaria
• Occur on 0.4% of cases
• Characterized by hemodynamic instablities;
• Shock
• Metabolic acidosis
• Hypothermia
• Associated with gram negative sepsis
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Long-Term Complications of
Malaria
1. Neurocognitive impairment and behavioral and mental
health problems

2. Hyperreactive malarial splenomegaly (HMS)

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 Long-term cognitive
impairment
• Occurs in;
1. 25% of children with cerebral malaria and
2. Children with repeated episodes of uncomplicated
disease

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 HMS
• Is a chronic complication of P. falciparum malaria
• Massive splenomegaly persists after treatment of acute infection.
• Major criteria include:
1. Splenomegaly (>10 cm),
2. IgM > 2 SD above local mean,
3. High levels of antibodies to a blood-stage P. Falciparum
antigen, and
4. A clinical response to an antimalarial drug.
• Occurs exclusively in children in endemic areas
• Prolonged antimalarial prophylaxis (for at least 1 yr is required
to treat this syndrome
 Prevention
• Consists of :
1. Reducing exposure to infected mosquitoes
Permethrin-treated mosquito netting and spray
insecticides.
Avoiding conducive environments for malaria
2. Chemoprophylaxis … Based on local sensitivity pattern
3. Vaccination
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 Intermittent prevention
treatment
• During infancy has been particularly successful in reducing the
incidence of malaria.
• Sulfadoxine-pyrimethamine;
• Given to infants at the 2nd and 3rd doses of the DPT vaccine
• Is safe and relatively effective.
• Has also been given to pregnant women;
3 doses of sulfadoxine-pyrimethamine have resulted in a
reduction of LBW infants. 07/17/2025 52
 RTS,S vaccine
• The first malaria vaccine to have some degree of efficacy
• An efficacy of;
17–56% against uncomplicated malaria
38–50% against severe malaria in young children in
malaria-endemic areas
• Works for as long as 48 mo after vaccination

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