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MALARIA

Dr. Paulos Efrem


Department of Internal medicine,
School of Medicine

27-Jun-21
Definition
• Malaria is a protozoan disease transmitted to man by the bite of the female
anopheles mosquitoes. (Anopheles arabiensis)

• Five species of the genus Plasmodium cause nearly all malarial infections in humans.

• P. falciparum, P. vivax, P. ovale, P. malariae,

• P. knowlesi —in Southeast Asia


Epidemiology
• Malaria has a global prevalence of 500 million people affected every year

• Approximately 52 million people (68%) live in malaria risk areas in Ethiopia,


primarily at altitudes below 2,000 meters.

• On average, 60% of malaria cases have been due to P. falciparum, with the
remainder 40% caused by P. vivax. P. ovale and P. malariae cause <1%.
Cont.
• Malaria is common in both low and high land areas.

• Stable Vs. Unstable transmission

• Epidemics are common during the months between September and December (Major) & April
to May (Minor) .

• Endemicity of malaria is based on splenic rates (palpable spleen) in children between 2 & 9
years,
• Hypo endemic - < 10% Unstable
• Meso-endemic - 10-50% transmission

• Hyper-endemic - 51-75% Stable


• Holo-endemic - > 75% transmission
Life cycle and pathogenesis
Clinical features
• Incubation period is 10-14 days in P. vivax, P. ovale, & P. falciparum, and 18 days
to 6 weeks in P. malariae.
• Early non-specific symptoms.
• Classical regular paroxysms of high grade fever, chills and rigors occurring
every
• 2 days (Tertian) in P. vivax and P. ovale,
• 3rd day (Quartan) in P. malariae,
• Irregularly in P. falciparum
Uncomplicated vs Complicated

• Uncomplicated malaria: - fever, malaise, and mild anemia, a palpable


spleen and liver and mild jaundice.

• Complicated Malaria: - Is defined as life threatening malaria caused


by P. falciparum, and the asexual form of the parasite demonstrated
in a blood film.
Clinical Criteria for Complicated malaria
1. Cerebral Malaria
• Failure to localize or respond appropriately to noxious stimuli;

• coma persisting for >30 min after generalized convulsion.

• The onset may be gradual or sudden

• Manifest as diffuse symmetric encephalopathy (No meningeal signs).

• Convulsions, usually generalized (50%);


Cont.
• Causes of neurological manifestations in malaria:
• High-grade fever
• Antimalarial drugs
• Hypoglycemia
• Hyponatremia
• Severe anemia
• May have residual neurologic deficit such as: hemiplegia, cerebral palsy, cortical
blindness, deafness, and impaired cognition and learning (all of varying duration).
• The majority of these deficits improve markedly or resolve completely within 6
months.
2. Hypoglycemia

• Plasma glucose level of <2.2 mmol/L (<40 mg/dL).

• is associated with a poor prognosis and is particularly problematic in children and


pregnant women.

• Results from: -
• Failure of hepatic gluconeogenesis

• Increase in the consumption of glucose by both host and the malaria parasites.

• Quinine - Hyperinsulinemic hypoglycemia


3. Acidosis
• Arterial pH of <7.25 or plasma bicarbonate level of <15 mmol/L; venous lactate level of >5
mmol/L.

• Results from:
• Anaerobic glycolysis in host tissues where sequestered parasites interfere with microcirculatory flow
• Parasite lactate production
• Hypovolemia
• Insufficient hepatic and renal lactate clearance

• Manifest as laboured deep breathing often termed “respiratory distress”


4. Noncardiogenic pulmonary edema

• The pathogenesis is uncertain but may be related to,


• Sequestration of parasitized red cells in the lungs and/or

• Cytokine induced leakage from the pulmonary vasculature.

• This complication may develop even after several days of antimalarial therapy,

• Can be aggravated by overly vigorous administration of intravenous fluid

• The mortality rate is >80%.


5. Renal Failure
• Urine output (24 h) of <400 mL in adults; no improvement with rehydration; serum
creatinine level of >3 mg/dL.

• is common among adults with severe falciparum malaria

• Results from:
• Erythrocyte sequestration and agglutination interfering with renal microcirculatory flow and
metabolism (acute tubular necrosis).

• In survivors, urine flow resumes in a median of 4 days, and serum creatinine levels return
to normal in a mean of 17 days.
6. Anemia
• Severe normochromic, normocytic anemia with Hematocrit of <15%, Hgb <5g/dl
• In non-immune individuals and areas with unstable transmission, develop acute
anemia.
• Results from:
• Hemolysis of parasitized red cells
• Increased splenic sequestration and clearance of erythrocytes with diminished
deformability
• Cytokine suppression of hematopoiesis
• Shortened erythrocyte survival
• Repeated infections and ineffective treatments
7. Liver dysfunction

• Serum bilirubin level of >3 mg/dL if combined with other evidence of vital-organ
dysfunction.

• Mild hemolytic jaundice is common in malaria.

• Severe jaundice is associated with P. falciparum infections; is more common


among adults than among children.

• Results from hemolysis, hepatocyte injury, and cholestasis.


Chronic complications of malaria
1. Hyperreactive Malarial Splenomegaly ( Tropic splenomegaly syndrome)

• Is mainly due to P. vivax and P. malariae.

• Due to overproduction of IgM in response to repeated infection, with subsequent


formation of immune complexes that cause prolonged stimulation of splenic
reticuloendothelial cells.

• Present with an abdominal mass or a dragging sensation in the abdomen

• Anemia and some degree of pancytopenia are usually evident.


Chronic complications of malaria
2. Quartan Malarial Nephropathy

• Is due to repeated infections with P. malariae causing soluble immune-complex


injury to the renal glomeruli, resulting in nephrotic syndrome.

3. Burkitt's Lymphoma

• Is due to immune dysregulation by malaria resulting in increased risk for EBV


infection.
Diagnosis
• There are two approaches of malaria diagnosis: -

1. Clinical Diagnosis: is made when a patient


• has fever or history of fever in the last 48 hours and

• Lives in malaria-endemic areas or

• Has a history of travel within the last 30 days to malaria-endemic areas.

• Basing the diagnosis on clinical features alone is not recommended.


Cont.
2. Parasitological diagnosis:
• Microscopic diagnosis and Multispecies RDTs are the methods used.
• Light microscopy:
• Thick blood films used for detecting as few as 20 parasites/μl.
• Thin blood film stained with Giemsa is useful for identifying the malaria
parasite species.
• The recommended method to determine parasite load is by quantifying the
percentage of parasitized red blood cells.
• Multispecies RDTs: can detect both P. falciparum and P. vivax.
Cont.
• CBC, Blood group & Rh

• Renal function test

• Liver function test

• Coagulation profile

• Blood glucose level

• Serum Na
Species Diagnosis
P. falciparum P. vivax P. ovale P. malariae

Enlarged, and oval


Size of RBCs Normal size Enlarged Normal size
in shape

Number of parasites
multiple Usually one Usually one Usually one
per RBC

Typical form of Amoeboid, often Compact and


Rings Compact
trophozoite fragmented regular

Schuffner's
Band forms,
Other Banana-shaped granules,
Schuffner's granules gametocytes fill
characteristics gametocytes gametocytes fill
cytoplasm
cytoplasm
P. Falciparum & P. Malariae
P. Vivax & P. Ovale
Treatment
• Classified as Uncomplicated Vs. Severe malaria

• Further classified into – First line

Second line &

Supportive Treatments.

- Objective is cure -- reduce transmission of infection.

- Prevent the emergence & spread of resistance.


Treatment of Uncomplicated Malaria
➢First line Drugs – P. Falciparum or Mixed Infection

• Artemisinin-based Combination Therapy (ACTs),

- artemether-lumefantrine (AL) – 120mg + 20mg po BID x 3 days

➢Second line Drugs

• Oral Quinine – Recommended first line in infants <5kg, pregnant women

10mg/kg po TID for 7 days


Cont…
➢First line Drugs – P. Vivax – ovale, malariae, knowlesi

• Chloroquine – 10mg/kg base, same after 24hrs, 5mg/kg at 48hrs.(4+4+2)

➢Second line Drugs

• Oral Quinine - 10mg/kg po TID for 7 days


➢Primaquine - given for radical cure – 15mg daily x 14 days
- patients who are not living in malaria endemic areas
- to eliminate hypnozoite
Treatment of severe falciparum malaria

• A medical emergency !!

• IV or IM Artesunate preferred - 2.4 mg/kg on admission, at 12h and 24h, then daily x
5-7 days

• IV quinine 20mg/kg loading, then 10mg/kg 8hrly maintenance infusion in 5%


dextrose as alternative

• Once patient conscious and tolerates oral therapy - oral AL or quinine

• Continued supportive care is as vital as the antimalarials


Prevention

▪ 2 Components

1. Vector Control, and

2. Chemoprophylaxis
1. Vector Control

• Environmental management

• Larviciding

• Indoor Residual Spraying (IRS)

• Insecticide Treated Nets (ITN) or LLIN

• Insect repellants – DEET

• Proper clothing
2. Chemoprophylaxis

• For all visitors to and residents of the tropics who have not lived
there since infancy, including children of all ages

• Based on the resistance patterns.


• Atovaquone/proguanil (Malarone), 1-2 days before, taken daily, up to 7 days
after.

• Mefloquine, 1-2 wks before, up to 4 wks after – 250mg once weekly


Thank you!!

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