Malaria 4th 2023

MALARIA
Dr. Jane Kimanthi

Consultant Paediatrician
Monday 15 April 2024

• Introduction
• Epidemiology
• Pathogenesis and life cycle
Outline • Pathophysiology
• Clinical features
• Management
• Prophylaxis
• Vaccine

Introduction
Malaria is caused by the parasite
plasmodium, transmitted by the
anopheles mosquito
• Major vectors in Kenya:

There are hundreds of species • Anopheles gambiae s.s.,
but there are 5 main ones that • Anopheles arabiensis,
cause disease in humans: • Anopheles merus
• Anopheles funestus
• Plasmodium falciparum • They are
• • Crepuscular
Plasmodium vivax
• Peak times 5pm-10pm
• Plasmodium ovale • Endophilic.
• Plasmodium malariae
• Have an average lifespan of 2-3
• Plasmodium knowlesi weeks

Comparing the malaria species

Global Distribution of Malaria

Epidemiology
In 2019, there were an estimated 229 million cases of
malaria worldwide and an estimated 409 000
deaths.
Children aged under 5 years are the most vulnerable group

affected by malaria; in 2019, they accounted for 67% (274
000) of all malaria deaths worldwide.
According to WHO, African Region carries a disproportionately

high share of the global malaria burden accounting for 94% of
malaria cases and deaths.

Global trends in 2019
a) malaria cases incidence rate (cases per 1000 population at risk),
b) mortality rate (deaths per 100,000 population at risk)

Malaria in Kenya
• One of the leading causes of morbidity and mortality in
Kenya
• In Kenya, there are an estimated 3.5 million new clinical
cases and 10,700 deaths each year, and those living in
western Kenya have an especially high risk of malaria
• 70% of Kenya’s population live in areas of high
transmission (MOH 2014)
• About 3.5 million of children are at risk of infection and
developing severe malaria
Every two minutes , a child under 5 years dies of malaria

Kills about 34,000 children <5yrs in Kenya every yr.
The World Health Organization’s (WHO’s) World malaria report 2019

Monday 15 April 2024 From presidents malaria initiative 2019
Four Epidemiologic zones determined by altitude, rainfall
patterns and temperature
% Kenya Region Transmission Prevalence of P
Population Falciparum
affected malaria
1. Endemic 29% Around Lake high and intense 20% and 40%.
Victoria throughout the year
Coast province
2. Epidemic 20% Western Seasonal with 1% to less than 5%
Highlands, considerable year-to-
year variation in some areas
tandem with prevalence
temperature and between 10% and
rainfall variation. 20%.
3. Seasonal 21% Arid/semi-arid short periods of less than 5%.
Transmission zones in malaria transmission
Northern, South during the rainfall
& Eastern parts seasons
of Kenya
4. Low risk 30% Central highlands little to no disease
of Kenya transmission.
Prevalence in
children
Population-adjusted P.
falciparum prevalence
in children 2 – 10 years
of age
(PfPR2-10) in 2015

Pathogenesis
• Malaria is caused by protozoan parasites called

Plasmodium
• Parasites are inoculated into the human host by a
feeding female Anopheles mosquito.
• Can be transmitted through blood transfusion, use
of contaminated needles and transplacentally.
• Plasmodium species life cycle is in 2 phases that
enables them to survive in different cellular
environments
• human host (asexual phase)
• the mosquito (sexual phase)

Pathogenesis
• The exoerythrocytic phase begins with inoculation of sporozoites
(sexual forms) into the bloodstream by a female Anopheles
mosquito.
• Sporozoites enter the hepatocytes in minutes and form schizonts,
which are asexual forms.
• These mature and multiply in pre-erythrocytic or hepatic schizogony.
• In P vivax and P ovale infection, some sporozoites convert to dormant
forms, called hypnozoites, which can cause disease after weeks,
months or years (upto 5 years)
• The tissue schizonts of P.falciparum, P. malariae, and P. knowlesi
rupture once and do not persist in the liver.
• The primary type ruptures in 6-9 days, and the secondary type
remains dormant in the liver cell before releasing merozoites and
causing relapse of infection.

Pathogenesis
• Pre-erythrocytic schizogony takes 1-2 weeks and results in the host
cell (hepatocyte) bursting and releasing thousands of merozoites into
the blood.
• These enter the erythrocytes and initiate another asexual
reproductive cycle, known as erythrocytic schizogony.
• The parasite successively passes through the stages of trophozoite
(ring form) and schizont.
• The trophozoite multiplies asexually to produce a number of small
erythrocytic merozoites.

Pathogensis
• Upon maturation of merozoites, the erythrocyte ruptures, releasing
the merozoites and multiple antigenic and pyrogenic substances into
the bloodstream…this release is associated with fever.
• These merozoites again infect new erythrocytes.

• After a few cycles of this erythrocytic schizogony, some merozoites
differentiate into the sexual forms: the male and female
gametocytes.
• A mosquito that takes a blood meal from a patient with
gametocytemia acquires these sexual forms and plays host to the
sexual stage of the plasmodial life cycle

Pathogenesis
• 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
with the next blood meal.
• There is a marked increase in the number of Plasmodia during the 1st
phase in hepatic cells (exoerythrocytic phase) and the 2nd phase in
the RBCs (erythrocytic phase).

Pathogenesis
• Mechanism that contribute to severe disease:
Cytoadherence
Sequestration
Rosetting
• Cytoadherence of infected erythrocytes to vascular endothelium

allows them to escape clearance by the spleen and to hide from
the immune system.
• It is mediated by P. falciparum erythrocyte membrane protein 1
(PfEMP1), which is expressed on surface of parasitized RBC
• Cytoadherence leads to sequestration of the parasites in various
organs- heart, lung, brain, liver, kidney, intestines, adipose tissue,
subcutaneous tissues, and placenta.
• This provides the growing parasite with the microaerophilic
venous environment that is better suited for their maturation
Pathogenesis
• Due to the sequestration , only the ring-stage trophozoites
of P. falciparum are seen circulating in the peripheral blood.
• More mature trophozoites and schizonts are bound in the
deep microvasculature, hence seldom seen on peripheral
blood examination.
• Cytoadherence and sequestration lead to obstruction of
blood flow and capillary damage, with resultant vascular
leakage of blood, protein, and fluid and tissue anoxia.
• This may lead to cerebral, cardiac, pulmonary, renal and
hepatic failure.

Pathogenesis
• The infected red cells also adhere to the uninfected
red cells, resulting in the formation of red cell
rosettes (rosetting).
• Rosetting is found to be lesser in blood group O
erythrocytes compared with groups A, B, and AB,
• Cytoadherence-rosetting-sequestration of infected
and uninfected erythrocytes ultimately
• blocks blood flow,
• limits the local oxygen supply,
• hampers mitochondrial ATP synthesis, and
• stimulates cytokine production
• All these contribute to development of severe
disease
Pathogenesis
• Malaria parasite has immune-evasive strategies e.g.
intracellular replication,
vascular cytoadherence preventing infected erythrocytes from
circulating through the spleen,
rapid antigenic variation, and
alteration of the host immune system.
• The human host has natural immune mechanisms like
several alterations in erythrocyte physiology that prevent or
modify malarial infection and prevent infection by other
Plasmodium spp., such as those of birds or rodents.
• These lead to partial immunity with repeated episodes of
malaria

Life cycle of malaria

Pathophysiology
• Lysis of infected erythrocytes to release merozoites releases red cell
membrane products, hemozoin pigment, and
glycosylphosphatidylinositol (GPI) into the blood.
• This activates macrophages and endothelial cells to secrete cytokines
and inflammatory mediators such as TNF, IFN-γ, IL-1, IL-6, IL-8,
macrophage colony-stimulating factor, and lymphotoxin, superoxide
and nitric oxide(NO).
• Severe malaria- more common in P. falciparum because of higher-
density parasitemia causing excessive production of proinflammatory
cytokines; cytoadherence of P. falciparum -infected erythrocytes to
the vascular endothelium; and polyclonal activation, resulting in both
hypergammaglobulinemia and the formation of immune complexes.
• The various manifestations of malaria are largely due to the release
of these cytokines

Pathophysiology- hypoglycemia
• The intracellular parasites derive energy from anaerobic

glycolysis of glucose to lactic acid, which may contribute to
clinical manifestations of hypoglycemia and lactic acidosis
• Diminished hepatic gluconeogenesis and glycogenolysis
• Depletion of liver glycogen stores
• Quinine induced hyperinsulinemia
• Increased metabolic demand of the febrile illness
Hypoglycemia is associated with a poor prognosis,

particularly in children and pregnant women.

Pathophysiology-coma
• Cause not clear

• Decreased cerebral blood flows, increased CSF lactate levels
• Increase in inducible nitric oxide synthase activity by cytokines
resulting in inhibition of neurotransmission.
• Durck’s granuloma – accumulation of glial cells surrounding
hemorrhagic foci
• Hemorrhages

Pathophysiology-anaemia
• Intracellular parasites make the red cell membrane less deformable,

resulting in hemolysis and accelerated splenic clearance.
• Alterations to uninfected RBCs by the addition of P. falciparum GPI to
the membrane, leading to increased clearance of uninfected cells by
the spleen
• TNF suppress haemopoiesis
• Destruction of RBCs
• Bone marrow dyserythropoiesis
• Serum erythropoietin levels usually elevated
• ?role of Coomb’s positive hemolysis

Pathophysiology
Acidosis Jaundice
• Anaerobic glycolysis in host • Haemolysis
tissues where sequestered • Hepatocellular injury
parasites interfere with
• cholestasis
microcirculatory flow
• Parasite lactate production
• Hypovolemia
• Insufficient hepatic and renal
lactate clearance
• Parasite anaerobic
metabolism may also lead
to hypoglycemia and
metabolic acidosis.
Pathophysiology
Pulmonary oedema Fever
• Increase in pulmonary • Release of
capillary permeability not proinflammatory
seen in other vascular cytokines that in turn
beds induce COX-2-
• Pulmonary capillary upregulating
wedge pressure usually prostaglandins leading to
normal fever induction.
• May also occur in vivax
unlike renal failure,
severe metabolic
acidosis, coma
More in adults
Pathophysiology-Renal issues
1. Renal failure-More common in adults
• Renal vasoconstriction
• Renal injury due to Acute Tubular necrosis presumably from
microvascular obstruction and cellular injury from sequestration of free
hemoglobin, myoglobin, and other cellular material
• Study showed elevated TNF associated with renal impairment
• Mechanical obstruction by infected erythrocytes
• Immune mediated
• Fluid losses due to alterations in renal microvasculature
2. Nephrotic syndrome is a rare complication of P. malariae infection

and is poorly responsive to corticosteroids
Pathophysiology-Shock (Algid malaria)
• Characterised by circutory collapsy and hypothermia.
• Dehydration due to high-grade fever, excessive sweating and
inadequate fluid intake, vomiting+/- diarrhoea.
• Pulmonary oedema.
• Metabolic acidosis.
• Associated Gram negative septicemia(endotoxin).
• Massive gastrointestinal haemorrhage.
• May be fatal due to adrenal crisis
Coagulopathy and DIC
• Accelerated coagulation cascade activity with
increased fibrin degradation products (FDPs)
• Coagulation pathway activated via intrinsic pathway
• All 5 types of malaria spp associated with
thrombocytopenia due to increased splenic platelet
clearance
• Accelerated fibrinogen turnover, consumption of
antithrombin III, reduced factor 8 and increased FDPs.
• DIC occurs in less than 5% of severe malaria, and
lethal hemorrhage is extremely rare
Pathophysiology-Blackwater fever
• Massive intravascular hemolysis leading to jaundice, hemoglobinemia
and hemoglobinuria
• Possible mechanisms:
• G6PD deficiency taking oxidant drugs e.g. Sulfonamides
• G6PD deficiency with malaria and receive quinine
• Even quinine treatment in patients with normal G6PD levels
• Why quinine causes hemolysis not clear
Pathophysiology- Hyperreactive malarial
splenomegaly/syndrome(HMS
• Also known as tropical Splenomegaly syndrome
• Spleen contributes to parasite clearance following treatment by
removing damaged intraerythrocytic parasites and returns the once
infected rbcs to the circulation (‘pitting’).
• Pitting is a specialized process by which the spleen extracts particles,
including malaria parasites, from within circulating RBCs during their
passage through the interendothelial slits (IES) in the splenic cords.
• Hyperreative malarial splenomegally (HMS) follows chronic or repeated

infections.
• Abnormal immunologic response characterized by massive
splenomegaly, hepatomegaly, marked serum IgM, malarial Ab, hepatic
sinusoidal lymphocytosis and peripheral B cell lymphocytosis.
Pathophysiology- HMS
• Prevalent in native residents of regions
where malaria is endemic and visitors
to those regions.
• Patients with HMS have high levels of
antibody for P. falciparum, P.vivax, or
P.ovale.
• Genetic factors, pregnancy, and
malnutrition may play a role in the
etiology of HMS.
• Relative protection against HMS is
observed in patients with sickle cell
trait
• Results in anemia and regress in 40%
by 6 months of therapy
Pathophysiology

Pathophysiology
• Hemolysis of infected RBCs and BM suppression leading to
anemia
• Severe parasitemia leading to excessive inflammatory
reactions
• Cytoadherance of infected RBCs on vascular endothelium
and polyclonal activation leading to hypogammaglobinemia
and immune-complex activation.
• Cytoadherance can result to obstruction of blood flow and
capillary damage.
• Parasitic anaerobic metabolism can result in hypoglycemia
and metabolic acidosis
• All these pathologic processes can lead to cerebral, cardiac,
pulmonary, renal and hepatic failure
Pathophysiology

Differences in severity
Parasite factors Immunological

factors

Host factors
Majority of severe malaria and related mortality are caused by P.

falciparum infection although complications can occur in non-falciparum
(P. vivax and P. knowles) infections as well.
Reasons
• P. falciparum has the ability to invade RBCs of all ages.
• P. vivax preferentially infects only young RBCs, thus limiting its
reproductive capacity and resultant parasite loads.
• P. falciparum is associated with high parasitemia even exceeding 20-
30%, whereas in vivax malaria it rarely exceeds 2%.
• Intracellular replication,
Immune • Vascular cytoadherence that prevents infected
evasive erythrocytes from circulating through the spleen,
strategies • Rapid antigenic variation
• Alteration of the host immune system resulting in
partial immune suppression.
The Host
Several genetic polymorphisms
and mutations appear to Hemoglobin and red cell antigens
influence the severity of malaria can confer variable protection
infection against malaria.
HbAS
Thalassemia
Duffy blood group factor
Ovalocytosis
Pyruvate kinase
deficiency
G6PD

Difference in immunity
• Individuals living in endemic areas develop partial immunity to malaria
following repeated infections
• Individuals not living in endemic areas (eg, travelers) infected with malaria
form a detectable antibody response (which can be measured by ELISA).
• This response is not protective against the initial infection of malaria and
may serve only as a marker of past exposure

Clinical manifestations
• Children with malaria often lack the typical paroxysms
in adults and may have nonspecific symptoms,
including fever (may be low-grade but is often >40°C,
headache, drowsiness, anorexia, nausea, vomiting,
and diarrhea.
• Fever patterns are based on schizont rupture
• Every 48 hr with P. vivax and P. ovale- fever every other day
• Every 72 hr with P. malariae – fever every 3rd day
• P. knowlesi takes 24 hours
• P. falciperum and mixed infection- periodicity is less
apparent and may not be apparent early on infection
Clinical manifestations
• The classic attack lasts 6-10 hours with 3 stages
• A cold stage(sensation of shivering).
• A hot stage(fever, headache, vomiting, seizures in young children.)
• A sweating stage(sweats, return to normal temp, tiredness)
• Patients with primary infection (eg travelers) lack

classic malaria fever pattern with irregular
symptomatic episodes for 2-3 days before regular
paroxysms begin
Classification of Malaria
1. Uncomplicated malaria
2. Complicated malaria/
severe malaria

Classification of malaria
Uncomplicated Malaria
• Asymptomatic during incubation period:
• Prodromal symptoms include headache, fatigue, anorexia,
myalgia, slight fever, and pain in the chest, abdomen, and
joint pains 2-3 days before evident parasitemia.
• Children often lack periodicity of fever followed by chills
then diaphoresis
• Common presentation:
• low grade fever or >40 degrees Celsius, headache,
drowsiness, anorexia, nausea, vomiting, and diarrhea.
• physical signs: pallor, splenomegaly ,mild jaundice

Complicated malaria/ severe malaria

Detection of Plasmodium falciparum in the peripheral blood in
the presence of any of the following features :
• >2 convulsions/24hrs
• AVPU<A
• Hypoglycemia <2.5mmol/l
• Severe anemia<5g/dl
• Metabolic acidosis
• Acute renal failure, hemoglobinuria
• Respiratory distress/ARDS
• Hepatic failure
• Coagulopathy /DIC
• Hyperpyrexia >40 degrees
National malaria treatment guidelines 2016


Physical Findings
Pallor,
Petechia,
Jaundice,
Splenomegaly,
and/or Hepatomegaly
Deep Acidotic Breathing
Splenic Rupture
National malaria treatment guidelines 2016


• Hypoglycaemia (blood glucose <2.5 mmol/l or < 45 mg/dl)
• Metabolic acidosis (plasma bicarbonate <15 mmol/l)
• Severe normocytic anaemia (hb < 5 g/dl, packed cell volume
<15%)
• Haemoglobinuria
• Hyperparasitaemia
>2% or 100, 000/μl in low intensity transmission areas
or
>5% or 250, 000/μl in areas of high stable malaria
transmission intensity)
• Hyperlactataemia (lactate >5 mmol/l)
• Renal impairment (serum creatinine >265 μmol/l).
Monday 15 April 2024 National malaria treatment guidelines 2016
Metabolic changes
Hypoglycemia Acidosis
occurs as a result of the caused by;
following factors:
Anaerobic glycolysis in
Diminished hepatic host tissues where
gluconeogenesis
sequestered parasites
Depletion of liver glycogen interfere with
stores microcirculatory flow
Increase in the consumption of
glucose by the host (and, to a
Parasite lactate production
much lesser extent, the parasite) Hypovolemia
Quinine-induced Insufficient hepatic and
hyperinsulinemia renal lactate clearance
Hematologic abnormality
Causes of Anemia in the setting of malaria :

1. Hemolysis of parasitized red cells
2. Increased splenic sequestration and clearance of
erythrocytes with diminished deformability
3. Cytokine suppression of hematopoiesis
4. Shortened erythrocyte survival
5. Repeated infections and ineffective treatment.

Coagulopathy and
thrombocytopenia
• Accelerated coagulation cascade activity with increased

Fibrin Deposition Products (FDPs)
• Thrombocytopenia is due to increased splenic platelet

clearance

FLUID AND ELECTROLYTE CHANGES
Plasma renin activity,
Aldosterone
Antidiuretic hormone
Reflecting an appropriate activation of homeostatic mechanisms
to maintain adequate circulating volume in the presence of
general vasodilatation and a falling haematocrit.
• Mild hyponatraemia and hypochloraemia are common in severe

malaria
SPLEEN
• considerable splenic
enlargement in malaria occurs
as a result of
cellular multiplication and
structural change which occur
due to an increased capacity to
clear red cells from the
circulation
There is considerable
accumulation of parasitized
erythrocytes
GASTRIC DYSFUNCTION
• Gut sequestration and visceral
vasoconstriction leads to
reduced splanchnic perfusion
manifest as
Abdominal pain,
minor stress ulceration of the
stomach and duodenum,
 malabsorption of sugars, fats
and amino acids
• Increase in gut permeability is

associated with reduced local
defenses against bacterial
toxins, or even whole bacteria in
severe disease
LIVER DYSFUNCTION
• Sequestration in the hepatic

microvasculature  • Reduced clotting factor
reduced hepatic blood flow synthesis
Hepatic injury • Reduced metabolic
clearance of anti-malarial
drugs
• Jaundice
• Failure of gluconeogenesis
contributes to lactic acidosis
and hypoglycaemia.
Complications of malaria
Cerebral malaria
Defined as encephalopathy that presents with
impaired consciousness, delirium, and/or seizures;
focal neurologic signs are unusual.
• Clinical criteria for diagnosis of cerebral malaria
1. Blantyre coma score ≤2
2. P. falciparum parasitemia (any density)
3. No other identifiable cause of coma (e.g,
hypoglycemia, meningitis, or a postictal state
• Risk factors: children, nutritional status, HIV,
genetic susceptibility
• Investigations
1. Lumbar puncture
2. fundoscopic exam done to detect malarial
retinopathy(white-centered hemorrhages,
papilledema, vessel changes, and whitened
areas of the retina)

Renal impairment:
• Common in adults than in children.
• Renal impairment can manifest as acute tubular necrosis due
to RBC sequestration impairing renal flow, hemolysis and
hypovolemia
Concomitant bacterial infection
• E.G. Salmonella bacteremia,
• Catheter induced UTIs,
• Chest infections
Non cardiogenic pulmonary oedema :

• Mostly in adults.
• It occurs due to sequestration of RBCs in the lungs and
cytokine production leading to leakage from the pulmonary
vasculature

Congenital malaria
• Acquired from the nonimmune mother prenatally or perinatally with P.
vivax or P. malariae infection, but can be observed with any of the
human malaria species.
• First sign or symptom typically occurs between 10-30 days of age (range:
14 hr to several months).
• Signs and symptoms include fever, restlessness, drowsiness, pallor,
jaundice, poor feeding, vomiting, diarrhea, cyanosis, and
hepatosplenomegaly.
Tropical Splenomegaly syndrome
• Hyperactive malarial syndrome (HMS) after excluding all

other causes of splenomegally.
• prevalent in native residents of regions where malaria is
endemic and visitors to those regions.
• Patients with HMS have high levels of antibody for
P.falciparum, P.vivax, or P.ovale.
• Genetic factors, pregnancy, and malnutrition may play a role
in the etiology of HMS. Relative protection against HMS is
observed in patients with sickle cell trait, as it is with malaria

• Antimalarial treatment is effective in
decreasing the size of the spleen,
but premature discontinuation of
treatment may lead to relapse.
• Effective malarial chemoprophylaxis
and eradication measures have been
associated with a decrease in the
incidence of HMS.
• The currently recommended
prophylactic medicine for those with
HMS is proguanil.

Laboratory diagnosis
Microscopy 2.Rapid diagnostic tests
• The standard tool for • RDTs provide a qualitative
diagnosis of malaria; result but cannot provide
• It allows identification of quantitative information
the Plasmodium species regarding parasite density
as well as quantification • Detects histidine-rich
of parasitemia. protein 2
• Thick films are (HRP2), Plasmodium lacta
recommended for te dehydrogenase (pLDH),
parasite detection and and aldolase
quantification
• Thin films are
recommended for species
identification
Monday 15 April 2024 Molecular diagnostics e.g PCR

P. Vivax P. Ovale
P. falciparum P. Malariae
A, Multiple signet-ring Plasmodium falciparum trophozoites, which are visualized outside erythrocytes. B,
A multiply infected erythrocyte containing signet-ring P. falciparum trophozoites, including an accolade
form positioned up against the inner surface of the erythrocyte membrane. C, Banana-shaped gametocyte
unique to P. falciparum. D, Ameboid trophozoite characteristic of Plasmodium vivax. Both P. vivax– and
Plasmodium ovale–infected erythrocytes exhibit Schuffner dots and tend to be enlarged compared with
uninfected erythrocytes. E, P. vivax schizont. Mature P. falciparum parasites, by contrast, are rarely seen on
blood smears because they sequester in the systemic microvasculature. F, P. vivax spherical gametocyte. G,
P. ovale trophozoite. Note Schuffner dots and ovoid shapes of the infected erythrocyte. H, Characteristic
band form trophozoite of Plasmodium malariae, containing intracellular pigment hemozoin.
Other Laboratory tests
• Complete blood count
• Reticulocyte count
• Urea and electrolytes
• Liver function tests
• Blood gas analysis
• Random blood sugar

Management of malaria
If a high-quality blood slide is negative with signs of SEVERE

malaria, start presumptive treatment BUT REPEAT testing and
STOP treatment if test is negative


Supportive management of malaria

Manifestation/ Immediate management
complication
Coma( cerebral Maintain the airway, intubate if necessary, provide
malaria) nursing care to avoid aspiration and pressure sores.
Fever Paracetamol 10-15mg/kg 6hourly.
Convulsions Follow the paediatric protocols for treatment of
convulsions. Check blood glucose and control
temperature.
Hypoglycemia A bolus of 5mls/kg of 10% dextrose then continue with
maintenance intravenous fluids and monitor RBS.
Severe anemia Transfuse if HB <5g/dl
Fluid and electrolyte Ensure adequate fluid and electrolyte balance. Fluid
imbalance management is vital in the comatose patient. Fluid
used in administration of medications and blood
transfusions must be calculated as part of total fluid
requirement of the patient.

Supportive management of malaria

Manifestation/ Immediate management
complication
Acute kidney injury Exclude prerenal causes and dialysis when indicated.
Coagulopathy Transfuse cryoprecipitate, FFP and platelets and give
vitamin K injection
Metabolic acidosis Exclude or treat hypoglycemia, hypovolemia and
septicemia, if severe consider dialysis
Shock Suspect septicemia, take blood cultures , give
parenteral broad spectrum antimicrobials, correct
hemodynamic disturbances
Pulmonary edema Prop up , give oxygen, intubate and add
PEEP/continuous positive airway pressure in life
threatening hypoxemia.

Classification of Antimalarial drugs
Cinchona alkaloids : Quinine, quinidine
Quinoline derivatives : Chloroquine,

primaquine
mefloquine,
halofantrine
Antifolates : Sulfadoxine,
dapsone,
proguanil,
pyrimethamine
Naphthoquinone derivatives: Atovaquone
Artemisinin compounds : Artesunate,

artether,
artemether
Antimicrobials : Tetracycline,
doxycycline,
clindamycin
Treatment of uncomplicated malaria
First line
• Artemether
+Lumefantrine
Second Line
• Dihydroartemesinin
and Piperaquine

Treatment of severe malaria

• Artesunate IV or IM;
• Quinine (IV infusion or divided IM injection);
• Artemether IM (should only be used if none of the
alternatives are available as its absorption may be erratic).
Quinine Artesunate
• Iv 20mg/kg loading dose over 4hrs, 3mg/kg(weight<20kg)
• 10mg/kg maintenance dose over 2hrs • At 0,12, and 24h then daily
• Mixed in 5%/10% dextrose for max 7 days
IM quinine 2.4mg/kg/dose of artesunate
• Loading dose 0.4mls/kg weight >20kg
• Maintenance dose 0.2mls/kg

Treatment failure
• Failure to achieve the desired therapeutic response after the
initiation of therapy.
• It should be suspected if patient deteriorates clinically at any time or
symptoms persists 3-14 days after initiation of drug therapy in
accordance with the recommended treatment regimen.
• Whenever possible, treatment failure must be confirmed
parasitologically preferably by blood-slide examination. Use of rdts
is not recommended.
• May result from poor adherence to treatment, unusual
pharmacokinetic properties in that individual or drug resistance.
• Development of symptoms 14 days after initiation of therapy where
there has been prior clearance of symptoms should be considered as
a new infection and be treated with the first line drug
Treatment failure
1. Consider other causes of illness / co-morbidity
2. A child on oral antimalarials who develops signs of
severe malaria (Unable to sit or drink, AVPU=V,U or P
and / or respiratory distress) at any stage should be
changed to iv artesunate (or quinine if not available).
3. If a child on oral antimalarials has fever and a positive
blood slide after 3 days (72 hours) then check compliance
with therapy and if treatment failure proceed to second
line treatment
The recommended second line treatment for uncomplicated

malaria in Kenya is dihydroartemisinin-piperaquine (DHA-
PPQ) 20mg dihydroartemisinin and 160mg of piperaquine.
These are administered once daily for three days
PREVENTION
Interventions to control malaria in Kenya include:
Provision of prompt and

effective treatment or Prevention and
malaria case treatment of malaria in
management pregnancy
Chemoprophylaxis
Epidemic preparedness
Vector control
and response

Results showed that pregnant women with malaria infection, both antenatally and during
delivery are at an increased risk of getting babies with low birth weight compared to the
uninfected women.
Chemoprophylaxis
Chloroquine resistant area
• Mefloquine
• Atovaquone/Proguanil
• Doxycycline
Chloroquine susceptible area
• Chloroquine phosphate
• Drugs used for chloroquine
resistant areas

Chemoprophylaxis
DRUG DOSAGE USE
Mefloquine 5mg/kg 2-3wks before travel

Throughout the period of
travel and 4 weeks after
Atovaquone/proguanil Weight based 1 day before trave,
(62.5mg/25mg) throughout travel and
1 week after
Proguanil 3mg/kg Daily dose for TSS and SCD
Doxycycline 1.5mg/kg 1 day before departure, daily

throughout the stay and 4
weeks after
Monday 15 April 2024 National Guidelines for the Diagnosis, Treatment and Prevention of Malaria in Kenya,
2016.
Vector Control
• Use of long lasting insecticidal nets: The use of
LLINs is encouraged for all persons living in
malaria endemic areas.
• Indoor residual spraying – both in endemic and
epidemic prone areas.
• Screening of house inlets with wire mesh to
reduce entry of mosquitoes.
• Larviciding – in focalized breeding sites.
• Environmental management for source reduction
of vector density e.g. drainage of breeding sites.
• Biological control measures where feasible –
larvivorous fish, growth regulators, BTI
(Bacillus thuringiensis var israeliensis).
• Repellents and fumigants.
Vaccine
• RTS,S/AS01 (commercial name: Mosquirix) which

started Phase III evaluation in May 2009. A
recombinant vaccine
• It is designed for children resident in malaria-endemic
areas who suffer the burden of disease and death
related to malaria.
• Administered in 4 doses- 6 months, 7 months, 9 months, and
24 months
References
• Kenya Malaria Indicator Survey 2015
• National Guidelines for the Diagnosis, Treatment and
Prevention of Malaria in Kenya, 2016.
• Centre for Disease control website (CDC)
https://www.cdc.gov/parasites/malaria/index.html
• Kenya Demographic Health Survey 2014
• Nelson textbook of paediatrics 20th edition
• UpTodate 20.3 version

THANK YOU


Malaria 4th 2023

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Malaria 4th 2023

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MALARIA

Dr. Jane Kimanthi

Monday 15 April 2024

Monday 15 April 2024

• Major vectors in Kenya:

Monday 15 April 2024

Monday 15 April 2024

Monday 15 April 2024

Children aged under 5 years are the most vulnerable group

According to WHO, African Region carries a disproportionately

Monday 15 April 2024

b) mortality rate (deaths per 100,000 population at risk)

Monday 15 April 2024

Every two minutes , a child under 5 years dies of malaria

The World Health Organization’s (WHO’s) World malaria report 2019

Monday 15 April 2024

• Malaria is caused by protozoan parasites called

Monday 15 April 2024

Monday 15 April 2024

Monday 15 April 2024

• These merozoites again infect new erythrocytes.

Monday 15 April 2024

Monday 15 April 2024

• Cytoadherence of infected erythrocytes to vascular endothelium

Monday 15 April 2024

Monday 15 April 2024

Monday 15 April 2024

Monday 15 April 2024

• The intracellular parasites derive energy from anaerobic

Hypoglycemia is associated with a poor prognosis,

Monday 15 April 2024

• Cause not clear

Monday 15 April 2024

• Intracellular parasites make the red cell membrane less deformable,

Monday 15 April 2024

2. Nephrotic syndrome is a rare complication of P. malariae infection

• Hyperreative malarial splenomegally (HMS) follows chronic or repeated

Monday 15 April 2024

Monday 15 April 2024

Parasite factors Immunological

Monday 15 April 2024

Majority of severe malaria and related mortality are caused by P.

Monday 15 April 2024

Monday 15 April 2024

• Patients with primary infection (eg travelers) lack

Monday 15 April 2024

Monday 15 April 2024

Complicated malaria/ severe malaria

National malaria treatment guidelines 2016

Complicated malaria/ severe malaria

National malaria treatment guidelines 2016

Complicated malaria/ severe malaria

Causes of Anemia in the setting of malaria :

Monday 15 April 2024

• Accelerated coagulation cascade activity with increased

• Thrombocytopenia is due to increased splenic platelet

Monday 15 April 2024

• Mild hyponatraemia and hypochloraemia are common in severe

• Increase in gut permeability is

• Sequestration in the hepatic

Monday 15 April 2024

Non cardiogenic pulmonary oedema :

Monday 15 April 2024

• Hyperactive malarial syndrome (HMS) after excluding all