AAU,School of Med

Department of Ped
Presented by Se
Samuel.T,Samra

March

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 Understand the
 Etiology
 Epidemiology
 Pathogenesis
 Clinical manifestations
 Complication
 diagnosis
 management & treatment
 prognosis of malaria
 Congenital malaria
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 Malaria is a protozoan disease transmitted by female
Anopheles mosquitoes.
 Is one of the major causes of disease for people living in
tropical and subtropical areas.

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 Is caused by intracellular plasmodium protozoa
 There are 4 species of plasmodium causing infection in
humans
 P.falciparum
 P.vivax
 P.ovale
 P.malariae

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 Is transmitted to humans by the bite of infected female Anopheles
mosquito
 Transmission requires high environmental temp and collected water
body, both of which are ideal for breeding of mosquitoes. so
transmission is common in lowland areas during rainy seasons.
 It can also be transmitted through
 Blood transfusion
 Use of contaminated needles
 Transplacentally
 Organ tranplantation
 The incubation period in transfusion malaria is often short b/c there is
no exo-erythrocytic stage
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 Global Epidemiology
 Occurs in over 100 countries
 Approximately 40% of the world’s population at risk of
infection
 300-500 million clinical cases each year
 1.5-2 million deaths mainly infants and young children
 80%-90% of deaths occur in sub-Saharan Africa
 The prevalence of malaria is increasing due to emergence of
DDT resistant Anopheles mosquitoes, drug resistant plasmodia
and global whether change

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 LBW,pre-term delivery, cerebral malaria, and severe malarial
anemia are major causes of deaths
 Its economic impact is tremendous.These include direct cost
for treatment and prevention
 Indirect cost such as lost productivity from morbidity and
mortality,time spent seeking treatment etc
 So malaria is not a disease of poverty but is also a contributor
of poverty

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 High land areas (2000m and above) and arid areas
typically have less malaria.Although are prone to
epidemic malaria
 Areas below 2000m altitude are considered
malarious.

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 Assessed by spleenomeglly and asymptomatic parastemia rate
in children under 10yrs
 -hypoendemic-<10%
 -mesoendemic-10-50%
 -hyperendemic-51-74%
 -holoendemic->75%
 In holo and hyperendemic- stable transmission
 In hypo and mesoendemic- unstable transmission

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 Is leading cause of morbidity and mortality in Ethiopia
 Accounts for 15.5% out patient consultations 20.4%
admissions and 27% in patient deaths
 68% of population of Ethiopia is at risk of malaria and 75% of
the country is malarious(<2000m)

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 Two malaria transmission seasons
 Major one from SEP to NOV - following main rainy season from
June to august
 Minor one from April to may - following a short rainy season from
Feb. to march

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 The actual number of malaria cases that occur annually
throughout the country may be estimated in range of 4-5
million
•Due to the topography and climatic conditions of the
country the nature of malaria transmission in most part of
Ethiopia is unstable
•Unstable malaria -Stable malaria
- seasonal - perennial
- lack of immunity - epidemic uncommon
- all age groups affected - children and pregnant
women more affected

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 Children below 5yrs of age are one of the most affected groups
of population with malaria.
 360,000 Ethiopian under 5 children die each year and malaria
accounts for 20%

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 P.falciparum (60%) and p.vivax (40%) are the most dominant
malaria parasites in Ethiopia.
 P.malariae and p.ovale accouts for less than 1% of all cases

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 Sexual cycle in the definitive host-A.mosquito
 Asexual cycle in humans which includes
 Two phases exo-erythrocytic-in hepatic cells
 erythrocytic-in red blood cells
 Mosquito inoculates sporozoites
 Sporozoites will infect the liver with in 1\2-2hrs
 Sporozoites undergo multiple nuclear division to produce hepatic
schizont(hepatic schizogony)
 Hepatocytes burst to produce merozoites
 P.vivax and p.ovale may remain in the hepatocytes as
hypnozoites to cause disease later in life
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 Merozoites invade the RBC
 P.vivax-Duffy blood group antigen
 P.falciparum-glycophorin
 In RBC parasite feed on hemoglobin
 Initial form ring then enlarge to become trophozoites
 Trophozoite undergoes asexual nuclear division to produce
schizonts
 Degradation product of hemoglobin forms malarial pigment
hemozoin

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 Schizont cause RBC lysis and each releases about 8-24
merozoites which infect other RBC
 A subpopulation of merozoites differentiate to
gametocytes.These are necessary for sexual reproduction.
 Mosquito picks up female and male gametocytes during
feeding
 Fusion and meiosis then occurs in the mosquito stomach to
produce zygote_ookinte_oocyte_sporozoite

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

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 Incubation period p.falciparum-7-9 days
P.vivax & p.ovale-days to yrs
 Rupture of hepatocytes –no symptoms
 Rupture of RBc’s-fever,malaise,muscle aches,chills
 Infected RBC’s are removed by spleen causing spleenomegally
 Only p.falciparum causes potentially fatal complicated &
severe malaria

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 Four important pathologic processes identified in patients with
malaria
 Fever
 Anemia
 Immunopathologic events
 Tissue anoxia

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 Fever occurs when erythrocytes rupture and release merozoites
into the circulation
 Anemia is caused by
 Hemolysis
 Sequestration of erythrocytes in spleen and other organs
 Bone marrow suppression
 Immunopathologic including polyclonal activation resulting in
both hypergammaglobulinemia and formation of immune
complexes, immunodepression and excessive production of
proinflammatory cytokines(TNF)

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 Cytoadherence of infected RBC to vascular endothelium
occurs with p.falciparum leading to obstruction of blood flow
 Hypoglycemia and lactic acidosis are due to anaerobic
metabolism
 Cumulative effect cerebral, cardiac, pulmonary, intesinal, and
hepatic failure

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 Non specific host defense mechanisms stop the infection’s
expansion & the subsequent specific immune response controls
the infection
 Is specific to species & strain of infecting malarial parasite
 Both humoral & cellular immunity are necessary
 Protect from high level parastemia & disease not from
infection

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 A state of infection without illness (premunition),
asymptomatic parasitemia, is common among adults & older
children living in regions with stable & holo or hyperendemic
areas.
 This immunity to disease declines when a person lives outside
an endemic area for several months or longer.

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 Immune evasion by the parasite
 Intracellular replication
 Rapid antigenic variation
 Alteration of host immune system that includes parial immune
suppression
 RBC containing HBs(sickle erythrocytes) resist malaria
parasite growth
 Erythrocytes lacking Duffy blood group antigen resist p.vivax

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 RBC containing HBF(fetal HB)are resistant to p.falciparum
 In hyperendemic areas newborns rarely become ill with
malaria in part owing to passive maternal antibody and high
levels of fetal HB
 Children 3month to 2-5yrs have little specific immunity to
malaria and therefore suffer yearly attacks of deblitating and
potentially fatal disease.

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 The specific immune response to malaria following repeated
infections confers protection from hyperparasitemia and
disease but not from infection in adults (premunition)
 Immunity is species and strain specific
 Maternal antibody transferred to new born confers protection
against severe disease in the few months of life
 The immunity wanes with in months after leaving malaria
endemic area.

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 Variable depending on √ species involved
 √ patients age and
 √ immune status

 Symptoms are most severe in falciparum and is associated with

intense parastemia

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1. Uncomplicated malaria
Symptomatic malaria without signs of severity or evidence
of vital organ dysfunction
Commonly presentation is nonspecific like lack of sense of well-
beingness, muscle aches, headache, fatigue
Less common paroxysms of chills, rigor, fever and sweeting
Tertian malaria: vivax, ovale, falciparum
Quartan malaria: malariae
Anemia, mild jaundice, splenomegaly, hepatomegaly

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2. severe and complicated malaria
Patients with P. falciparum asexual parsitemia
and no other obvious cause of their
symptoms, in the presence of one of the
following symptoms, signs, or lab findings
should be considered to have sever malaria

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 Clinical
 Parasitological
 Microscopic blood smear gold standard
 RDT ( Rapid diagnositic testing)

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 BROAD & INCLUDES
 TB
 Typhoid fever
 Brucellosis
 Relapsing fever
 Infective endocarditis
 Influenza
 Poliomyelitis
 Yellow fever
 Trypanosomiasis
 Kala-azar
 Amebic liver abscess

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 Complications of P.flaciparum malaria
1. Metabolic (Lactic) Acidosis • Complications of
2. Cerebral malaria P.vivax/P.malaria
3. Hypoglycemia
1. Rupture of spleen
4. Pulmonary edema
5. Renal failure 2. Hepatic dysfunction
6. Jaundice 3. Malarial nephropathy
7. Haematologic abnormalities
4. Thrombocytopenia
1. Severe anemia
2. Thrombocytopenia 5. Severe anemia
8. Algid Malaria
9. Hyperparasitemia
10. Hyperpyrexia
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 The onset may be gradual or sudden following a convulsion
 Is associated with a fatality rate of 20–40%
 Symptoms include
 Fever(37.5-41◦c)
 Vomiting and cough
 Decreased level of consciousness and range from drowsiness and severe
headache to confusion
 Delirium, hallucinations, convulsions before or after the onset of coma
 Laboured and noisy breathing
 In patients with profound coma, corneal reflexes and ‘doll’s eye’
movements may be absent
 The abdominal and cremasteric reflexes are absent

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 Hypoglycemia is associated with increased mortality and
neurologic sequelae.
 Is associated with a poor prognosis
 Results from a failure of hepatic gluconeogenesis and an
increase in the consumption of glucose by both host and, to a
much lesser extent, the malaria parasites; also from decreased
intake and administration of some antimalarials with
hypoglycemic effect(quinine).

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 Acidosis, an important cause of death from severe malaria,
results from accumulation of organic acids.
 Acidotic breathing, sometimes called respiratory distress, is a
sign of poor prognosis.
 Lactic acidosis is caused by the combination of anaerobic
glycolysis in tissues where sequestered parasites interfere with
microcirculatory flow, hypovolemia, lactate production by the
parasites, and a failure of hepatic and renal lactate clearance.

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 May occur several days after therapy has begun and is
commonly associated with excessive intravenous therapy

 It can develop rapidly and may be fatal. Thus, great care

should be taken not to overhydrate patients with P. falciparum
malaria.

 Can also develop in otherwise uncomplicated vivax malaria,

where recovery is usual.

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 Rare among children.
 Results from deposition of hemoglobin in renal tubules,
decreased renal blood flow, and acute tubular necrosis; i.e.
prerenal and intrinsic renal causes.

 Blackwater fever is a clinical syndrome that consists of severe

hemolysis, hemoglobinuria, and renal failure.
 It is a rare complication that occurs when the combination of
antibody directed against parasite-laden erythrocytes(?
AUTOIMMUNE?) and complement result in severe hemolytic
anemia, hemoglobinuria, oliguria, and jaundice.
 Renal failure usually requires peritoneal dialysis or hemodialysis.
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 Anemia results from accelerated RBC removal by the
spleen, obligatory RBC destruction at parasite
schizogony, and ineffective erythropoiesis.
• May present with tachycardia and dyspnea.
• HCT <15% needs transfusion.

 Thrombocytopenia is a common complication of P. falciparum

and P. vivax malaria.
• Platelet counts can decrease to 10,000–20,000/mm3.

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 Mild hemolytic jaundice is common in malaria.
 Severe jaundice is associated with P. falciparum infections; is
more common among adults than among children; and results
from hemolysis, hepatocyte injury, and cholestasis.

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 Is GI focus sepsis secondary to GI ischemia due to
 Is a rare form of P. falciparum malaria that occurs with
overwhelming infection, hypotension, hypothermia, rapid weak
pulse, shallow breathing, pallor, and vascular collapse.
 Death may occur within a few hours.
 Correct hypovolemia with plasma expander, take blood culture
and start patient on broad spectrum antibiotics – ampicillin +
gentamycin.

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 Septicemia may complicate severe malaria
 Systemic Salmonella infections are common complications among
African children with falciparum malaria.
 Chest infections and catheter-induced urinary tract infections are
common among patients who are unconscious for >3 days.
 Aspiration pneumonia may follow generalized convulsions.
 Splenic rupture is a rare complication that may occur with acute
infection owing to any malaria species. Splenic rupture can occur
spontaneously but is usually the result of trauma that includes
overly vigorous palpation on physical examination. It causes severe
internal hemorrhage and may result in death if removal of the
spleen and blood transfusion are not performed in a timely manner.

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 Key: –, rare; +, infrequent; ++, frequent; +++, very frequent

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 Tropical Splenomegaly
(Hyperreactive Malarial Splenomegaly)
 Quartan Malarial Nephropathy
 Burkitt's Lymphoma and Epstein-Barr Virus Infection

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 Supportive and
 Specific

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 Supportive treatment may include the following:

1. Reducing the temp. if hyperpyrexia, rectal temp>39 is present

specially common with P. falciparum infection  paracetamol
2. Rehydration specially when vomiting and diarrhea have been
prominent and in acidosis  ORS, in case of infants encourage
breast feeding
3. Monitoring renal output and taking corrective measures if necessary
(such as hypovolemia and oliguria maintain careful flood balance
4. Monitoring the need for blood transfusion which may be life-saving.

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5. Terminating convulsion with appropriate drugs-a slow iv
injection or rectal diazepam
6. Monitoring of blood glucose and correction of hypoglycaemia
7. Reducing acidosis. Rehydration, blood transfusion, and anti
malaria therapy are usually sufficient for this purpose
8. Treating DIC if this complication is sever enough to cause
bleeding; fresh whole blood platelet-rich plasma and fresh frozen
plasma may be given according to availability.

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 Terminate the parasitaemia as rapidly as possible.
 Drug of choice depends on national policy in the particular
country and on the likely place of origin.

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 Health post level
 First line of drug for Rx of all clinical malaria cases and for RDT
confirmed falciparum malaria cases  Artemether - lumefantrine
(adm 2 times a day for 3days)
 For all RDT negative tests with clear signs and symptoms of malaria
 convincing to consider vivax  chloroquine at dosage of
25mg/kg adm over 3days and pt is referred

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 Health center and hospitals
 First line
 P.falciparumartemether-lumefantrine: adm two times a day for 3days
 For infants less than 5kg first line, oral quinine adm three times a day
for 7days
 P.vivax, P.malariae or P.ovalechloroquine

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  In order to eliminate hypnozoite forms of P.vivax from liver and to bring abt
radical cure  primaquine adm daily for 14days starting after chloroquine
Rx is completed
 (in malarious areas where there is high risk of re-infection, where main
intention is to bring abt clinical cure, primaquine is not recommended)

 Second line :
 Oral quinine if condition of patient permits

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 Epidemic control
 Mass fever treatment with Artemether-lumefantrine and chloroquine
should be used

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 Management of cerebral malaria
 If a child has convulsion  diazepam 0.15mg/kg

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 Management of anemia
 A haematocrit <15% in a normally hydrated child is an
indication for blood transfusion
 IV frusemide1-2mg/kg may be given to avoid fluid overload

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 Management of hypoglycemia
 Iv injection of 50% glucose followed by iv infusion of 10%
glucose to prevent recurrence

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 Management of Pulmonary edema
 -keep patient up right, give high concentration of oxygen by
any method available, give the pt a diuretic

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 Management of fluid, electrolyte and acid base disturbances
 Careful rehydration with isotonic saline
 If after rehydration urine output over 24hrs is<4ml/kg of body wt, IV
furosemide can be given.

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 Management of hyperpyrexia
 Vigorous tepid sponging and fanning, give paracetamol 15mg/kg,
suppository or nasogastric tube

 Patients who develop spontaneous bleeding should be given

fresh blood and IV vitamin K.

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 First line treatment due to P. falciparum is either:
 IV or IM artesunate (preferred); OR
 IM artemether (alternate)
 If artesunate is not available: IV or IM quinine infusion
 Artesunate is given 2.4 mg/kg IV or IM given on admission, at
12hrs, at 24hrs then once a day for 5-7 days.
 Once the patient with severe malaria regains consciousness and
tolerates oral therapy, oral AL therapy should be started.

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 IV quinine
 Give a loading dose of quinine (20 mg/kg) in 10 ml/kg of IV fluid
over a period of 4 hours
 Some 8 hours after the start of the loading dose, give 10 mg/kg
quinine salt in IV fluid over 2 hours, and repeat every 8 hours until
the child is able to take oral treatment
 Then, give oral quinine doses to complete 7 days of treatment

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 Components of malaria prevention:
 Reduction of exposure to infected mosquitoes
 Promotion of early diagnosis and treatment of cases
 Chemoprophylaxis
 Immunoprophylaxis--Development of a Malaria Vaccine

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Strategies that are successful and should be considered include
Use of insecticides to kill the mosquito vector
Use of insect repellents containing DEET (10–35%) or picaridin (7%;
if DEET is unacceptable),
Insecticide-impregnated bed nets
Avoidance of exposure to mosquitoes at their peak feeding times
(usually dusk and dawn) and throughout the night
Suitable clothing  During the day the travelers should wear
clothing that covers the arms and legs, with trousers tucked into shoes
or boots.
Mosquito repellent should be applied to thin clothing and exposed
areas of the skin, with applications repeated every 1–2 hours.
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 For all visitors to and residents of the tropics who have not
lived there since infancy and Children of non immune women
 Chloroquine is the drug of choice for prophylaxis of P vivax, P
ovale, P malariae, and chloroquine-sensitive P falciparum
 In areas where chloroquine-resistant P. falciparum
exists,mefloquine is recommended for all ages
 Non immune travelers weekly mefloquine adm at 5mg/kg
 should be started 2 weeks before departure and 4wks after
return from malarious area

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Development of a Malaria Vaccine
Although a malaria vaccine is not available, it is hoped that this
goal will ultimately be achieved
RTS, S/AS01 malaria vaccine is in its Phase 3 trial in African
children

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 Death may occur with any of the malarial species, but is most
frequent with complicated P. falciparum malaria. The
likelihood of death is increased in children with preexisting
health problems
 Virtually all patients with P. vivax, P. ovale, or P. malariae
infection respond well to chloroquine and make an uneventful
recovery
 For patients with P. falciparum infection, the quantitative
parasite count is the best predictor of the outcome. Patients
with 5% parasitemia (250,000 parasites per microliter of
blood) are at increased risk of severe and complicated malaria,
including death.
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