Malaria

Motea Al-Awlaqi, MD
Assistant professor of cardiology, Aden University
Cardiologist Consultant, Al-Gamhouriah General Teaching Hospital
 Malaria

A protozoal infection caused by Six species of the genus Plasmodium that cause nearly all malarial
infections in humans
a. Plasmodium Falciparum
b. Plasmodium ovale (Curtisi,and Wallikeri)
c. Plasmodium vivax
d. Plasmodium malariae
e. P. Knowlesi- in Southeast Asia—the monkey malaria parasite
 Epidemiology
▪ Malaria is transmitted by the bite of female anopheline mosquitoes and occurs throughout the tropics and
subtropics at altitudes below 1500 meters
▪ Most cases are due to P. falciparum
▪ Who are susceptible to malaria?
- Those living in endemic areas
- Travellers
- Migrants from endemic countries
- Few people living near airports may have acquired malaria from accidentally imported mosquitoes
▪ Endemicity traditionally has been defined in terms of rates of microscopy-detected parasitemia or palpable
spleens in children 2–9 years of age and has been classified as
- hypoendemic (<10%),
- mesoendemic (11–50%),
- hyperendemic (51–75%), and
- holoendemic (>75%)
▪ In holo- and hyperendemic areas Constant, frequent, year-round infection is termed stable transmission
result in partial immunity and the repeated infections become increasingly likely to be asymptomatic but
symptomatic malaria may increase during the rainy season coinciding with increased mosquito breeding
and transmission
▪ In hypoendemic areas where transmission is low, erratic, or focal is termed unstable transmission; full
protective immunity is not acquired, and symptomatic disease may occur at all ages.
Malarial parasites life cycle
Relationships between life cycle of parasite
and clinical features of malaria
 Pathophysiology
The disease in human beings is caused by the direct effects of the asexual parasite—RBC invasion
and destruction—and by the host’s reaction
1. Haemolysis of infected red cells
2. Adherence of infected red blood cells to capillaries and post-capillary venules in brain, kidney,
liver, lungs and gut by the formation of ‘knob’ proteins
3. Formation of ‘rosettes’ and rouleaux with uninfected red cells
4. Vessel congestion results in organ damage
5. Rupture of schizonts, liberating toxic and antigenic substances which cause fever and other
pathologic effects
6. The host responds to malaria infection by activating nonspecific defense mechanisms. Splenic
immunologic and filtrative clearance functions are augmented, and the removal of both
parasitized and uninfected erythrocytes is accelerated
 Pathophysiology
Several factors retard the development of cellular immunity to malaria. These factors include
1. The absence of major histocompatibility antigens on the surface of infected RBCs, which
precludes direct T cell recognition
2. Malaria antigen–specific immune unresponsiveness
3. The enormous strain diversity of malarial parasites, along with the ability of the parasites to
express variant immunodominant antigens on the erythrocyte surface that change during the
course of infection
4. Parasites may persist in the blood for months or years (or, in the case of P. malariae, for
decades) if treatment is not given (not detected by immune system)
 Clinical features
▪ Malaria is a common cause of fever in tropical countries
▪ The clinical features of malaria are non-specific
▪ the diagnosis must be suspected in anyone returning from an endemic area who has features of
infection
▪ The classic malarial paroxysms, in which fever spikes, chills, and rigors occur at regular intervals,
are relatively unusual and suggest infection (often relapse) with P. vivax or P. ovale
 Clinical features
P. falciparum infection
▪ This is the most dangerous of the malarias
▪ The onset is often insidious, with malaise, headache and vomiting
▪ 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
▪ A patient with falciparum malaria, apparently not seriously ill, may rapidly develop dangerous
complications
▪ Children may die rapidly without any specific symptoms other than fever
▪ Malaria in Pregnant may complicated with Fetal distress, premature labor, and stillbirth or low
birth weight. Congenital malaria occurs in fewer than 5% of newborns whose mothers are
infected
Clinical features
Clinical features
 Clinical features
Features Indicating a Poor Prognosis in Severe Falciparum Malaria
A- Clinical
▪ Marked agitation
▪ Hyperventilation (respiratory distress)
▪ Low core temperature (<36.5°C; <97.7°F)
▪ Bleeding
▪ Deep coma
▪ Repeated convulsions
▪ Anuria
▪ Shock
 Clinical features
Features Indicating a Poor Prognosis in Severe Falciparum Malaria
B- Laboratory
Biochemistry Hematology
• Hypoglycemia (<2.2 mmol/L) • Leukocytosis (>12,000/μL)
• Hyperlactatemia (>5 mmol/L) • Severe anemia (PCV <15%)
• Acidemia (arterial pH <7.25, base deficit >8 meq/L, or • Coagulopathy
serum HCO3 <15 mmol/L) • Decreased platelet count (<50,000/μL)
• Elevated serum creatinine (>265 μmol/L) • Prolonged prothrombin time (>3 s)
• Elevated total bilirubin (>50 μmol/L) • Prolonged partial thromboplastin time
• Elevated liver enzymes (AST/ALT 3 times ULN) • Decreased fibrinogen (<200 mg/dL)
• Elevated muscle enzymes (CPK ↑, myoglobin ↑)
Parasitology
• Elevated urate (>600 μmol/L)
Hyperparasitemia
• Increased mortality at >100,000/Μl
• High mortality at >500,000/μL
• >20% of parasites identified as pigment
containing trophozoites and schizonts
• >5% of neutrophils contain visible
malaria pigment
 Clinical features
P. vivax and P. ovale infection
▪ In many cases, 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 40°C. 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
▪ Relapses are frequent in the first 2 years after leaving the malarious area and infection may be
acquired from blood transfusion
 Clinical features
P. malariae and P. knowlesi infection
▪ P.malariae 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
 Chronic complication of malaria
1. Hyperreactive splenomegaly
2. Quartan malariae nephropathy
3. Burkitt's lymphoma and Epstein Barr virus infection
Investigations
 Laboratory findings in acute malaria
▪ Normochromic, normocytic anemia is usual
▪ The leukocyte count is generally normal, although it may be raised in very severe infections
▪ There is slight monocytosis, lymphopenia, and eosinopenia
▪ Reactive lymphocytosis and eosinophilia in the weeks after acute infection
▪ The platelet count is usually reduced to ~105/Μl
▪ ESR, plasma viscosity, and levels of C-reactive protein and other acute-phase proteins are
elevated
▪ Severe infections may be accompanied by
- prolonged prothrombin and partial thromboplastin times and
- by more severe thrombocytopenia.
- Antithrombin III levels are reduced even in mild infection
▪ In uncomplicated malaria, plasma concentrations of electrolytes, blood urea nitrogen (BUN), and
creatinine are usually normal
 Laboratory findings in acute malaria
▪ Findings in severe malaria may include
- Metabolic acidosis
- Low plasma concentrations of glucose, sodium, bicarbonate, phosphate, and albumin
- Elevations in lactate, BUN, creatinine, urate, muscle and liver enzymes, and conjugated and
unconjugated bilirubin.
▪ Hypergammaglobulinemia is usual in immune and semi-immune subjects living in malaria-
endemic areas
▪ Urinalysis generally gives normal results
▪ In adults and children with cerebral malaria
- The mean cerebrospinal fluid (CSF) opening pressure at lumbar puncture is ~16 CM H2O
- The CSF content is normal or there is a slight elevation of total protein level (<1.0 g/L [<100
mg/dL]) and cell count (<20/μL)
 Malaria treatment
Mild malaria
Preferred therapy
• Co-artemether (CoArtem or Riamet); contains artemether and lumefantrine (4 tablets orally at 0, 8, 24, 36,
48 and 60 hrs)
Alternative therapy
• Quinine (600 mg of quinine salt 3 times daily orally for 5–7 days), together with or followed by doxycycline
(200 mg once daily orally for 7 days)
Use clindamycin not doxycycline if the patient is a pregnant woman or young child
or
• Atovaquone–proguanil (Malarone, 4 tablets orally once daily for 3 days)
Pregnancy
• Co-artemether but avoid in early pregnancy.
• If not using co-artemether, use quinine plus clindamycin (450 mg 3 times daily orally for 7 days
Other regimens
• Artesunate (200 mg orally daily for 3 days) and mefloquine (1 g orally on day 2 and 500 mg
orally on day 3
 Malaria treatment
Severe malaria
Preferred therapy
• Artesunate 2.4 mg/kg IV at 0, 12 and 24 hrs and 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
Alternative therapy
• Quinine, loading dose 20 mg/kg IV over 4 hrs, up to a maximum of 1.4 g, then maintenance doses of 10 mg/kg quinine
salt given as 4-hr infusions 3 times daily for the first 48 hrs then twice a day, up to a maximum of 700 mg per dose or until
the patient can take drugs orally. Combine with doxycycline (or clindamycin if there are contraindications to doxycycline)
• Note the loading dose should not be given if quinine, quinidine or mefloquine has been administered in the previous 24
hrs
• Patients should be monitored by ECG while receiving quinine, with special attention to QRS duration and QT interval
Non-falciparum malaria
Preferred therapy
• Chloroquine: 600 mg chloroquine base orally, followed by 300 mg base in 6 hrs, then 150 mg base twice daily for 2
more days plus primaquine (30 mg orally daily (for P. vivax) or 15 mg orally daily (for P. ovale) for 14 days) after confirming
G6PD-negative
Patients with mild to moderate G6PD deficiency and P. vivax or P. ovale
• Chloroquine plus primaquine 0.75 mg/kg weekly orally for 8 weeks
Chloroquine-resistant P. vivax
• Co-artemether as for P. falciparum
Chemoprophylaxis of malaria