MALARIA Flashcards
List the causative agents of human malaria
- Plasmodium vivax: Benign Tertian Malaria
- Plasmodium falciparum: Malignant Tertian Malaria
- Plasmodium malariae: Benign Quartan Malaria
- Plasmodium ovale: Benign Tertian Malaria
- Plasmodium knowlesi (monkey-derived malaria)
Frequency of fever in tertian and quartan malaria
=”Tertian Malaria” (P. falciparum, P. ovale and P. vivax)
*fever occurs every third day.
=“Quartan Malaria” (P. malariae)
*fever occurs every fourth day.
Where is P. vivax distributed?
=Asia
=North Africa
=Central and South America
*Nearly Worldwide, 16 Degrees North -20 degrees South. P. vivax
rare in West Africa
Where is P. falciparum distributed?
Predominant species in:
=Africa
=Papua New Guinea
=Haiti
Rapidly spreading in:
=South-east Asia and India
Where is P. malariae distributed?
=Present in most places but is rare, except in Africa
Which plasmodium parasite is endemic to West Africa
=P. ovale
- Tropics, esp W.Africa, Burma, China, S.E.Asia, Ethiopia
How is malaria transmitted?
=Female Anopheles mosquito bite; dusk until dawn
=blood transfusion
=congenitally acquired disease
=organ transplantation
=sharing of contaminated needles
What is meant by “Airport Malaria”?
→ infected mosquitoes can enter a country via airplane thereby transmitting infection
Explain how Malaria can both be endemic and epidemic?
–Endemic, when it occurs constantly in
an area over a period of several successive years and
–Epidemic, when periodic or occasional sharp rises occur in its incidence
Hypoendemic (Transmission pattern)
- Transmission is low
Mesoendemic (Transmission pattern)
- Transmission is moderate
Hyperendemic (Transmission pattern)
- Transmission is intense but seasonal
Holoendemic (Transmission pattern)
- Transmission of high intensity
What is the habitat of P. falciparum?
=RBCs of all ages
Describe the Morphology of P. falciparum
- Trophozoite, ring stage. multiple infections, High parasitaemia.
- Schizont infected cell ruptures to release up to 32 merozoites.
- Gametocytes: enclosed in rbc membrane Banana shaped, called crescents
- Zygote, Ookinete, Oocyst, Sporozoites
- Infected rbc show stippling on the surface (Maurer’s clefts)
What is the habitat of P. vivax?
=Young RBCs
Describe the Morphology of P. vivax
1.Trophozoites- large, fragmented amoeboid cytoplasm.
* infected rbcs enlarged and pale,
* Schuffner’s dots in infected rbc cytoplasm
- Schizonts 8-24 merozoites,
* schizogony 48hourly - Gametocytes compact and round,
* fill rbc without sign of schizogony - Hypnozoites: Latency for several years
* Dormant sporozoites in hepatocytes
* Uninucleate, Explains clinical malaria relapses. - No Knobs,no sequestration, all stages seen in blood smears.
What is the habitat of P. ovale?
Young RBCs
Describe the morphology of P. ovale
- Trophozoites: compact cytoplasm, not amoeboid, large prominent nuclei
- Schuffner’s dots, infected rbc slightly enlarged
- 20-30% parasitised rbcs oval, show fimbria, ragged end, artifact
- Low merozoite numbers 8-10, central darker pigment
- Gametocytes: oval, rbcs fimbriated, show Schuffner’s dots.
- Hypnozoites present
What is the habitat of P. malariae?
Old RBCs
Describe the morphology of P. malariae
- Trophozoites form bands around rbc, invades mature cells
- Schizogony 72 hourly
- No Schuffner’s dots, Zieman’s
stippling - Schizonts: 6 - 12 merozoites,
with malaria pigment at the
center forming Daisy heads or marguerites - Gametocytes oval
- No Hypnozoites: 40 year recrudescence
Summarise the malaria parasite life cycle
- Malaria parasite passes its life cycle in 2 hosts.
– Definitive host: Female Anopheles mosquito
– Intermediate host: Man - an asexual phase occurring in humans, which act as the
intermediate host and= SCHIZOGONY - a sexual phase occurring in mosquito, which serves as a
definitive host for the parasite= SPOROGONY
What is the other name for the Plasmodium asexual phase in man?
vertebrate, intrinsic, or endogenous phase
In humans, schizogony occurs in 2 locations, these are?
– In the red blood cell (erythrocytic schizogony) and
– In the liver cells (exoerythrocytic schizogony or the
tissue phase)
- Products of schizogony, whether erythrocytic or exoerythrocytic, are called MEROZOITES (meros: a part,
zoon: animal)
What is the other name for sporogony?
=invertebrate, extrinsic, or exogenous phase
Where does sporogony occur?
=Takes place in female Anopheles mosquitoes
- Maturation and fertilization give rise to a large number of
SPOROZOITES (from sporos: seed) - Usually, 10–15 sporozoites are injected at a time
What is the infective form of Plasmodium?
=Sporozoite
Describe the pre-erythrocytic/Exoerythrocytic schizogony
Sporozoites=> Schizonts=> Merozoites
- Mature liver stage schizonts contain 2000–50,000 merozoites
- Mature schizonts rupture in 6–15 days and release thousands of merozoites into the blood stream
- The merozoites infect the erythrocytes
Describe the Erythrocytic schizogony
=> Merozoites from liver enter RBCs=> Ring form/ Young Trophozoites=> Late Trophozoites=> Schizonts/ Meronts=> Mature Schizonts with 8-32 merozoites and hemozoin=> The mature schizont bursts releasing the merozoites into
the circulation=> Merozoites infect RBCs===> REPEATS ++PARASITEMIA UNTIL ARREST BY HOST IMMUNITY
- Rupture of mature schizont= large quantities of pyrogens.
- This is responsible for the febrile paroxysms
- In P. falciparum, erythrocytic schizogony always takes place inside the capillaries and vascular beds of internal organs.
- The parasite feeds on the haemoglobin of the erythrocyte
- It does not metabolize haemoglobin completely and
– therefore, leaves behind a haematin-globin pigment called the malaria pigment or haemozoin pigment as residue
After a few erythrocytic cycles, gametogony starts, describe the human sporogony cycle
Merozoites=> Gametocytes
* Development of gametocytes takes place within the internal organs and only the mature forms appear in circulation
- The gametocytes do not cause any clinical illness in the host, but are essential for transmission of the infection
When do Gametocyte appear in circulation in P. vivax?
– 4–5 days after the first appearance of asexual form
When do Gametocyte appear in circulation in P. falciparum?
– and 10–12 days
Describe the mosquito phase of plasmodium sporogony
- Female Anopheles mosquito ingests parasitized erythrocytes with its blood meal:
– the asexual forms of malaria parasite are digested
– but the gametocytes are set free in the midgut (stomach) of mosquito and undergo further
development - The nuclear material and cytoplasm of the male
gametocytes divides to produce 8 microgametes with long, actively motile, whip-like filaments (exflagellating male gametocytes) - The female gametocyte does not divide but:
– undergoes a process of maturation to become the female gamete or macrogamete
– It is fertilized by one of the microgametes to produce the zygote - The zygote, which is initially a motionless round body, gradually elongates and:
– within 18–24 hours, becomes a vermicular motile form called the ookinete (travelling vermicule) - The ookinete develops into oocyst:
– which is yet another multiplicatory phase, within which numerous sporozoites are formed - The mature oocyst ruptures releasing sporozoites which find their way to the salivary glands
- The mosquito is now infective and when it feeds on humans:
– the sporozoites are injected into skin capillaries to initiate human infection - The time taken for completion of sporogony in the mosquito is about 1–4 weeks (extrinsic incubation period)
What’s the average incubation period of P. vivax?
—14 (8–31) days
What’s the average incubation period of P. falciparum?
—12 (8–14) days
What’s the average incubation period of P. ovale?
—14 (8–31) days
What’s the average incubation period of P. malariae?
- P. malariae —28 (18–40) days
What is meant by incubation period?
- This is the interval between the entry of sporozoites into the host and the earliest manifestation of clinical illness.
What is meant by pre-patent period?
- This is the interval between the entry of the parasites into the host and the time when they first become detectable in blood
What is meant by Recrudescence?
=Recurrence of malaria from ineffective treatment that did not CLEAR the infection.
*common in places with high anti-malarial resistance
- Recrudescence may be due to
– waning immunity of the host, or possibly due to antigenic variation, drug resistance or under-dosage - In P. falciparum infections=> 1–2 years
- In P. malariae infection=> up to 50 years
What happens in malarial relapse?
Blood is cleared of merozoites but hypnozoites persist in the liver
* occurs in P. vivax and P. ovale
=24 weeks to 5 years
list the stages in the Pathogenesis of Malaria
- Erythrocytic infection
- Cytoadherence, rosetting and sequestration - P. f
- Host defense mechanism -immunopathology
What are the consequences of erythrocytic infection?
Anaemia: Normocytic, hemolytic
a. Parasite multiplication and survival=> Hb digestion
b. Destruction of parasitized rbcs at end of schizogony
c. Auto-antibodies specific for unparasitized cells: - autoimmune, nonspecific sensitization, rbcs bind
Ab/Ag complexes that fix complement.
What are the consequences of Cytoadherence, sequestration and rosetting in Pf?
- altered deformability and fragility of parasitized erythrocytes;
- endothelial activation,
what leads to sequestration of RBCS?
Cytoadherance=> Sequestration
- Sequestration of the growing P. falciparum parasites in these deeper tissues provides them the microaerophilic venous environment
- that is better suited for their maturation and the adhesion to endothelium allows them to escape clearance by the spleen and to hide from the immune
system.
which proteins help P. falciparum erythrocyte bind to endothelial membrane?
=P. falciparum erythrocyte membrane protein 1(PfEMP1) =Histidine rich protein II (HRP II)
which proteins help P. falciparum erythrocyte bind to placenta?
– chondroitin sulfate A (CSA) protein (placenta)
Which ligands are involved in sequestration?
=CD36
=thrombospondin
=vascular cell adhesion molecule1 (VCAM 1)
=intercellular adhesion molecule II (ICAM II)
=E-selectin
Describe rosetting
=The infected red cells also adhere to the uninfected red cells resulting in the formation of red cell rosettes
- Rosetting is mediated by binding of:
- PfEMP1-DBLα on the surface of infected red cells to
complement receptor 1 - CD31, and heparin sulfate-like glycosaminoglycans of
uninfected RBCs
=only the ring-stage trophozoites of P. falciparum are seen circulating in the peripheral blood, Why?
Due to the sequestration
Describe the immunopathology in malaria?
- Anemia
= autolysis of unparasitized rbcs, increases splenic clearance, drug induced hemolysis, dyserythropoeisis in BM
2a. Nephropathies
= Ab/Ag complexes cause lesions
in Kidney glomerular walls
* In P. falciparum: Acute nephropathy, reversible, oliguria,
renal failure due to IgM,
* Malaria antigen and Complement
* Clears after treatment
2b. Nephropathies
= In P. malariae: Nephropathy is
Chronic
* - progressive, severe
* - Deposits of IgG, IgM, complement
* and Pm antigen in glomerular walls
* - Auto immune response to damaged tissue
* - Quartan Malaria nephrosis with persistent heavy proteinuria, hypoalbinemia, edema,
* - Deterioration of renal functions
* - Hypertension.
* - Treatment - little effect
- Splenomegaly:
* Oedema of the pulp, RES hyperplasia, increased phagocytic fxn
* Tropical Splenomegaly Syndrome (TSS) in young and adults - Immunodepression:
. Bone marrow depression (iron sequestration- dyserythropoeisis; dysthrombopoeisis)
. Auto antibodies
. Pregnancy
. Burkitt’s lymphoma; endemicity correlating with malaria endemicity
What are the clinical presentations of Uncomplicated (Benign) Malaria?
- Prodromal phase:
– Severe headache, nausea, and vomiting are common &
intermittent fever or paroxysms of chills - Paroxysms of chills (intermittent fever)= Sudden attack of fever 104- 105 F (40-40.6 C).
=Release of schizogony products - Paroxysm comprises of 3 successive stages i.e. cold stage, hot stage and sweating stage
What are the most nottsble complictions of severe malaria?
cerebral, algid, and
septicemic varieties
more complications
D. Gastrointestinal: vomiting, coughing, diarrhoea, or acute dysentery
E. Pulmonary oedema:
* Malaria Shock syndrome
* Fluid overload during treatment Induce diuresis and haemodialysis. Often fatal
* DIC
F. Respiratory distress (metabolic acidosis bicarbonate less
than 15 meq/l
G. Hepatorenal syndrome/Haemolytic jaundice =
jaundice and renal failure
=Liver failure,
however, occurs only in individuals in whom a concurrent viral hepatitis is present.
Malarial anaemia: is multifactorial
important cause of death in children under two years of age.
H. Jaundice and kidney failure
I. Blackwater fever:
=in repeated infections with Pf with inadequate quinine treatment Haemolysins formed against quininized and
unparasitised cells – autoimmine
Haemoglobinuria, bilirubinaemia, haemoglobinaemia
Fever, jaundice, nausea, vomiting, anuria,
=Haemoglobinuria can also
be drug induced in patients deficient in the enzyme glucose 6-phosphate dehydrogenase (G-6-PD).
J. Severe anaemia (haemoglobin less than 5g/dl or haematocrit less than 15%)
K. Renal failure-presenting as oliguria or anuria
L. Confusion or drowsiness with extreme weakness
Malaria complications in children
- Pf common
- Symptoms atypical
- Drowsiness, vomiting, diarrhoea, unproductive
cough, fever without periodicity. - Cerebral manifestations- convulsions and coma twitching
- High body temperature
- Spleen enlargement, jaundice
- Severe anaemia fatal in babies
Malarial anaemia: malarial anaemia is an important cause of death in children under 5 years
Malaria in children - Hyperpyrexia
- medical shock, renal involvement
- splenic enlargement, jaundice
- severe normocytic anemia
- Pv and Po - milder in children.
- Pm - Nephrotic syndrome, glomerulonephritis leads
to gross edema, proteinuria and hypoprotinemia
Malaria complications in pregnancy
- high prevalence: highly susceptible
- haemolytic anemia- jaundice, ,splenomegaly, death
- acute renal insufficiency
- abortions, stillbirths, awaken latent malaria
- low birth weight
- Treatment must not be withheld, Intermittent Preventive
Treatment (IPTp) or chemophylaxis for at least 3 months
How is malaria diagnosed?
- Clinical diagnosis – based on S/S being presented
by a patient - LAB diagnosis of malaria is confirmed by blood tests
i.e. microscopic and non-microscopic tests
Which microscopic methods are used in malaria diagnosis?
=Demonstration of malarial parasites in Thick and Thin blood smear Light Microscopy
* Giemsa-staining of thick and/or thin blood smears →conventional method of diagnosing malaria
– combination is gold standard
- smears allow species identification
- can calculate the parasite density (prognosis)
Advantages of rapid simple dipstick?
▪ Rapid immunochromatographic test (ICT/RDTs) for detection of malaria antigen (PfHRP2 and PLDH)
* A rapid simple dipstick test → results in 10-15 minutes
* useful in situations where diagnostic expertise or microscopic facilities are limited
List the Limitations rapid dipstick malarial testing
– cannot determine degree of parasitemia
– false positives
– not fully reliable for accurate species diagnosis
- 3 assays currently used for testing: these are?
=HRP-2
=aldolase
=pLDH
Polymerase Chain Reaction (PCR) in malarial diagnosis
- Has the ability to detect parasitemia at very low levels
- Is helpful in species identification when microscopy is
equivocal - Disadvantages are high cost, labor intensive
Treatment of malaria depends on the following factors: (4)
- Type of infection
- Severity of infection
- Status of the host
- Associated conditions/ diseases
What is the prognosis of Malaria?
- Mortality of untreated falciparum is almost 100% and 10-40% for treated
- Poor prognostic factors:
– Age<3
– Seizures
– Acidosis
– Respiratory distress
