Malaria

Dr Md Mamunul Abedin Shimul

MBBS, BCS(Health)
Medical Officer (Dept of Medicine)
General Hospital, Jamalpur
Epidemiology
• Malaria is a systemic protozoal infection, in human it is caused by-
• Plasmodium falciparum
• P. vivax
• P. ovale
• P. malarie
• P. knowlesi
• Transmitted by the bite of female anopheline mosquitoes
• Occurs throughout the tropics and subtropics at altitudes below 1500
metres
Distribution of Malaria
Life Cycle of Malarial Parasite (in Mosquito)
Life Cycle of Malarial Parasite (in Mosquito)

Human Blood containing Mosquito become

GAMETOCYTE
infected

Development of Gametocyte
for 7-20 days
-Accumulate within
Mosquito’s salivary gland
-Enter Human by SPOROZOITE INFECTIOUS FORM
Mosquito bite
Life Cycle of Malarial Parasite (in HUMAN)
Life Cycle of Malarial Parasite (in HUMAN)

SPOROZOITES SPOROZOITES
In Mosquito’s Salivary Gland in Human Blood

MEROZOITES leave the After some

SPOROZOITES Disappear from
Enter the LIVER blood within ½ Hour
Liver & invade RBC days
(Primary Exo-Erythrocytic cycle)
-Releases more
Within RBC
MEROZOITE in
After multiplication Rupture of Blood
SCHIZONTS are produced SCHIZONTS
(Erythrocytic cycle)
-Causes FEVER
Pathophysiology (exceptions)
• P. vivax & P. ovale may persist in the Liver as HYPNOZOITES, capable of
developing into MEROZOITES- months or years later.
-First Attack of Malaria may occur very lately.
-May relapse after Rx with drugs that only kill Erythrocytic Stage.

• P. falciparum, P. knowlesi, P. malariae have no persistent Exo-

Erythrocytic phase.
-Recrudescence of fever may result from multiplication of
parasites in RBC that have not eliminated by treatment.
Relationships between
Life cycle of parasite and clinical features
Feature P. vivax, P. ovale P. malariae P. falciparum
Minimum Incubation 8–25 days 15–30 days 8–25 days

Exo-erythrocytic cycle Persistent as hypnozoite Pre-erythrocytic only Pre-erythrocytic only

Asexual cycle 48 hrs 72 hrs < 48 hrs
synchronous synchronous asynchronous

Fever periodicity Alternate days Every third day None

Delayed onset Common Rare Rare
Relapses Common up to Recrudescence Recrudescence
2 years many years later up to 1 year

Affects RBC Reticulocytes Normoblasts RBC of all age

CLINICAL FEATURES
• The First symptoms of malaria are Non-Specific and same as minor
systemic viral illness.
- Headache, Lassitude, Fatigue, Abdominal discomfort, Muscle &
Joint aches
-Usually followed by Fever, Chills, Perspiration, Anorexia,
Nausea, Vomiting, Worsening Malaise
-In young children, may present with Lethargy, Poor Feeding,
Cough.
• The diagnosis must be suspected in anyone returning from an
endemic area who has features of infection.
CLINICAL FEATURES (cont.)
P. vivax and P. ovale infection
• The illness starts with several days of continued fever before the
development of classical bouts of fever on alternate days.
• Fever starts with a rigor. The patient feels cold and the temperature
rises to about 104°F. After half an hour to an hour, the hot or flush
phase begins. It lasts several hours and gives way to profuse
perspiration and a gradual fall in temperature.
• The cycle is repeated 48 hours later.
• Gradually, the spleen and liver enlarge and may become tender.
• Anaemia develops slowly.
CLINICAL FEATURES (cont.)
P. malariae and P. knowlesi infection
• This is usually associated with mild symptoms and bouts of fever
every third day.
• Parasitaemia may persist for many years, with the occasional
recrudescence of fever or without producing any symptoms.
• Chronic P. malariae infection causes glomerulonephritis and long-
term nephrotic syndrome in children.
• P. knowlesi is usually mild but can deteriorate rapidly.
CLINICAL FEATURES (cont.)
P. falciparum infection
• Most dangerous of the malarias.
• The onset is often insidious, with malaise, headache and vomiting.
Cough and mild diarrhoea are also common.
• The fever has no particular pattern.
• Jaundice is common due to haemolysis and hepatic dysfunction.
• The liver and spleen enlarge and may become tender.
• Anaemia develops rapidly, as does thrombocytopenia.
CLINICAL FEATURES (cont.)
Severe Malaria
• Complication of P. falciparum infection
• May present with delirium, seizures or coma (Cerebral malaria )
• Other features may include Metabolic acidosis, Severe Anemia,
Hypoglycemia, Acute Renal Failure or Acute Pulmonary Oedema.
• Children die rapidly without any specific symptoms other than
fever.
• Abortion and intrauterine growth retardation in pregnancy.
• Previous splenectomy increases the risk of severe malaria.
Investigations
1. Giemsa-stained thick and thin blood films
-should be examined whenever malaria is suspected
-Thick film: Diagnosis of disease
-Thin film: -Confirm the Diagnosis, Confirm the Species.
-Quantify the parasite load of P. falciparum.
2. Rapid Diagnostic Test (RDT) -Immunochromatographic test (ICT)
-extremely sensitive & specific for falciparum malaria but less
so for other species.
3. Fluorescence microscopy – QBC Malaria test
4. PCR- Research Purpose
Management
Treatment of Non-falciparum MALARIA
• P. vivax, P. ovale, P. knowlesi and P. malariae infections should be treated
with oral chloroquine;
• if resistant, treat with ACT (Artemisinin-based Combination Therapy)
Preferred Therapy
• CHLOROQUINE:
1st day: 10 mg base/kg
2nd day: 10 mg base/kg
3rd day: 5mg base/kg
If Chloroquine Resistant
• ACT (Artemisinin-based Combination Therapy)
• In 1st Trimester of Pregnancy: Quinine should be used in place of ACT
Management
Treatment of Non-falciparum MALARIA
Liver Stages (Hypnozoites) of P. vivax & P. ovale
• To prevent relapse
• Before starting Rx, G6DP deficiency should be evaluated.
• If G6PD not deficient:
PRIMAQUINE for 14 days
30 mg orally daily for P. vivax, or
15 mg orally daily for P. ovale
• If G6DP deficient:
PRIMAQUINE 0.75mg base/kg bw, once a week for 8weeks.
*close medical supervision needed for adverse haematological effects.
Management
Treatment of Mild falciparum/ Uncomplicated MALARIA
• Definition: A patient who presents with symptoms of malaria and a positive
parasitological test (microscopy/ RDT) but with no features of Severe
malaria is defined as having uncomplicated malaria.
• Treatment option: ACT: Artemisinin-based Combination Therapy
• Five ACTs are recommended.
-Artemether + Lumefantrine
-Artesunate + Amodiaquine
-Artesunate + Mefloquine
-Artesunate + SP
-Dihydroartemisinin + Piperaquine
• ACT should not be given in 1st Trimester of Pregnancy
Management
Treatment of Mild falciparum/ Uncomplicated MALARIA

Preferred therapy: ARTEMETHER + LUMEFANTRINE

Dosage: Twice a day for 3days (total 6 doses); First two doses
should be given 8hour apart (0, 8, 24, 36, 48, 60)
Dose: Body Weight (Kg) Dose of Artemether + Lumefantrine
5 to < 15 20 + 120
15 to < 25 40 + 240
25 to < 35 60 + 360
≥ 35 80 + 480

Comment: These should be taken immediately after food/fatty diet.

Management
Treatment of Mild falciparum/ Uncomplicated MALARIA

Alternate therapy:
• QUININE (600 mg ,3 times daily orally for 5–7 days), plus
DOXYCYCLINE (200 mg once daily orally for 7 days)
(In Pregnant Woman or Young Child: Use CLINDAMYCIN in place
of doxycycline)
or,
• ATOVAQUONE–PROGUANIL (Malarone, 4 tablets orally once
daily for 3 days)
Management
Treatment of Mild falciparum/ Uncomplicated MALARIA

In Pregnancy
• ACT (avoid in early pregnancy)
• If not using co-artemether, use:
QUININE +
CLINDAMYCIN (450 mg 3 times daily orally for 7 days)
Other regimens
• ARTESUNATE (200 mg orally daily for 3 days) PLUS
• MEFLOQUINE (1 g on day 2 and 500 mg on day 3, orally)
Management
Treatment of Severe MALARIA
Preferred therapy
• ARTESUNATE (Intravenous/Intramuscular)
2.4 mg/kg IV at 0, 12 and 24 hrs (1st Day) & then once daily for 7 days.
Once the patient is able to recommence oral intake, switch to 2 mg/kg
orally once daily, to complete a total cumulative dose of 17–18 mg/kg.

[Artesunate is dispensed as a powder of artesunic acid, which is

dissolved in sodium bicarbonate (5%) to form Sodium Artesunate. The
solution is diluted in 5ml of 5% dextrose and given by IV or by IM into
anterior thigh.]
• When IV Artesunate is not available, Per Rectal Artesunate can be
given in Child < 6years.
Management
Treatment of Severe MALARIA
Alternative therapy
• QUININE
Loading dose: 20 mg/kg IV over 4 hrs, (max 1.4 g),
Maintenance doses: 10 mg/kg, given as 4-hr infusions 3 times
daily for the first 48 hrs; then twice a day, (max 700 mg/ dose) or
until the patient can take drugs orally.
• Combine with DOXYCYCLINE (or CLINDAMYCIN)

• Patients should be monitored by ECG while receiving quinine, with

special attention to QRS duration and QT interval
Severe manifestations/ complications of
falciparum malaria and their Immediate Management
Coma (Cerebral Malaria) (GCS score < 11 in adults)
Mx:
• Maintain airway
• Nurse on side
• Exclude other treatable causes of coma (e.g. hypoglycaemia,
bacterial meningitis)
• Avoid harmful ancillary treatments such as glucocorticoids,
heparin and adrenaline (epinephrine)
• Intubate if necessary
Severe manifestations/ complications of
falciparum malaria and their Immediate Management
Hyperpyrexia (Temp > 106.7° F)
Mx:
• Tepid sponging, fanning, cooling blanket
• Antipyretic drug (Paracetamol/ Ibuprofen)

Convulsions (more than 2 episodes within 24hrs)

Mx:
• Maintain airway
• Treat promptly with diazepam or paraldehyde injection
Severe manifestations/ complications of
falciparum malaria and their Immediate Management
Hypoglycaemia (Plasma glucose < 2.2mmol/L)
Mx:
• Measure blood glucose
• Give 50% dextrose injection followed by 10% dextrose infusion
(glucagon may be ineffective)

Severe Anaemia (PCV< 15%) (Hb ≤ 5gm/dL)

Mx:
• Transfuse fresh whole blood or packed cells if pathogen
screening of donor blood is available
Severe manifestations/ complications of
falciparum malaria and their Immediate Management
Acute Pulmonary Oedema (Radiologically confirmed /
O2 saturation < 92% with Resp rate > 30/min)
Mx:
• Nurse at 45°, give oxygen, venesect 250 mL of blood, give
diuretic, stop intravenous fluids
• Intubate and add PEEP/CPAP in life-threatening hypoxaemia
• Haemofilter
Severe manifestations/ complications of
falciparum malaria and their Immediate Management
Acute Kidney Injury (S. Creatinine > 3mg/dL)
Mx:
• Exclude pre-renal causes
• Fluid resuscitation if appropriate
• Peritoneal dialysis (haemofiltration or haemodialysis if available)
Metabolic Acidosis (Plasma bicarbonate < 15mmol/L)
Mx:
• Exclude & treat hypoglycaemia, hypovolaemia & Gram(-ve) sepsis
• Fluid resuscitation
• Give oxygen
Severe manifestations/ complications of
falciparum malaria and their Immediate Management
Spontaneous bleeding and coagulopathy
Mx:
• Fresh whole blood transfusion after screening
• Vitamin K injection

Hyperparasitaemia (> 10% of circulating erythrocytes

parasitized)
Mx:
• Consider exchange transfusion
Severe manifestations/ complications of
falciparum malaria and their Immediate Management
Shock (‘Algid Malaria’) (Cap refill > 3s; SBP < 80mmHg)
Mx: Suspect Gram-negative sepsis
Take blood cultures
Give parenteral antimicrobials
Correct haemodynamic disturbances
Aspiration Pneumonia
Mx: Give parenteral antimicrobial drugs
Change position
Physiotherapy
Give oxygen
Prevention
Chloroquine Resistance High
Antimalarial Adult Regimen
tablets prophylactic
dose

Mefloquine 250 mg weekly Started 2–3 weeks before travel

and continued until 4 weeks after

Doxycycline 100 mg daily Started 1 week before and continued

until 4 weeks after travel

Malarone 1 tablet daily From 1–2 days before travel until 1 week
after return
Prevention
Chloroquine Resistance Absent
Antimalarial Adult prophylactic Regimen
tablets dose
Chloroquine 300 mg weekly Started 1 week before and
and continued until 4 weeks after
Proguanil 100–200 mg daily travel
Prevention
• Prevention also involves advice about-
-the use of high percentage diethyl-toluamide (DEET),
-covering up extremities when out after dark, and
-sleeping under permethrin-impregnated mosquito nets.

• Chloroquine should not be taken continuously as a

prophylactic for more than 5 years without regular
ophthalmic examination, as it may cause irreversible
retinopathy.
• Pregnant and lactating women may take proguanil or
chloroquine safely.
Nice to Know
Q. Why Anemia occurs in Malaria?
Ans: Anemia is due to:
-Hemolysis of infected & uninfected red cells
-Dyserythropoiesis
-Spleenomegaly
-Reduction of Folate store
Nice to Know
Q. Which Red Cells are involved by different species of
Malaria?
Ans: As follows:
-falciparum: RBC of all ages,
-vivax & ovale: mainly Reticulocyte
-malariae & knowlesi: Normoblast
Nice to Know
Q. Which disease or Haemoglobinopathy protects
against Malaria?
Ans: As follows:
-P. falciparum can not grow well in RBC containing
haemoglobin F, C or S. Sickle cell disease protects against
falciparum malaria
-P. vivax can not enter RBC that lacks Duffy blood
group (West African, American Blacks are protected)
Nice to Know
Q. What is Pernicious Malaria?
Ans: It is a severe form of falciparum malaria in which there
is widespread capillary blockage by the parasitized RBC
causing multiple organ damage.
Clinical Type:
1. Cerebral
2. Algid
3. Septicemic
Nice to Know
Q. What is Blackwater Fever?
Ans: It is a severe manifestation of falciparum malaria occurs
in previously infected person, characterized by sudden
intravascular hemolysis, fever and haemoglobinuria.
Clinical Feature:
High fever with Chill & Rigor
Vomiting, Diarrhoea
Dark-to-Black urine
Collapse & Renal failure
QnA
THANK YOU