Malaria Flashcards
What mosquito transmits malaria?
Female anopheles mosquito.
- Which species of malaria parasite afflict humans? (in order of increasing prevalence)
- Which causes most deaths?
- P. falciparum
- P. vivax
- P. ovale
- P. malariae
- P. knowlesi
- Falciparum most severe, causes most deaths
- What is the global burden of malaria disease?
- How many cases?
- How many deaths?
- 214 million cases per year
- 438,000 deaths
- How many deaths per year from Malaria?
- What percent in Africa?
- What percent in Kids?
- 438,000
- 90% in Africa
- 7% in SEARO
- 70% in kids
- How much has the incidence of malaria fallen this century?
- Since 2000 the incidence of malaria has fallen by 37%
- What is the geographic distribution of the various species of malaria in order of global prevalence?
- P. falciparum: throughout tropics and subtropics, esp. sub-Saharan Africa
- P. vivax: south, SE asia; East Africa, largely absent west Africa; Amazon
- P. ovale: pred West Africa, Phillipines, East Indonesia, Pap New Guinea
- P. malariae: throughout tropics & subtropics (but much less prev than falciparum)
- P. knowlesi: Zoonotic species, restricted to SE Asia: Borneo and peninsular Malaysia
- Name four geographic factors affecting the distribution of malaria.
- Temperature: affects life cycle of mosquito
- Altitude: restricted to altitudes below 1500 m
- Seasonality: more common in wet season due to mosq. life cycle
- Population movement.
- Name the 6 forms malaria parasite takes during its life cycle.
- Briefly describe each.
- sporozoites - dormant stage injected into human host via pregnant female anopheles salivary glands, travels to and infects liver cells
- schizonts - host liver or red blood cell containing mature forms soon to rupture, divides (schizogeny) then releases merozoites
- merozoites - parasite stage released from liver or rbc, then goes on to infect rbc’s
- trophozoites - developing intra-erythrocytic parasite phase visible on blood film
- gametocytes - sexual stage of parasite life-cycle that go on to infect mosquito, where they combine to form oocytes, which develop into sporozoites
- hypnozoites - a dormant form of P. ovale and P. vivax which can hide in the liver to cause relapses
- What are the usual symptoms of malaria?
- very non-specific
- fever
- rigors
- headache
- myalgias
- What species of plasmodium cause severe malaria?
- P. FALCIPARUM FAR AND AWAY MOST COMMON CAUSE OF SEVERE MALARIA, others known as “benign malaria”.
- P. vivax and knowlesi also cause it but much less common
- Describe the classical malaria fever patterns and which species of malaria they are associated with.
- Not a reliable guide, but pts may report “paroxysms” of rigor
- Tertian malaria, fever about every 48 hrs
- P. falciparum, vivax, ovale
- Quartan malaria, fever about every 72 hrs (q 3rd day)
- P. malariae
- What are WHO criteria for severe malaria due to P. falciparum.
- Peripheral blood parasitemia plus one of:
- impaired consciousness (including unrousable coma)
- prostration, i.e. generalized weakness so that the patient is unable to sit, stand or walk without assistance
- multiple convulsions: more than two episodes within 24h
- deep breathing and respiratory distress (acidotic breathing)
- acute pulmonary oedema and acute respiratory distress syndrome
- circulatory collapse or shock, systolic blood pressure < 80mm Hg in adults and < 50mm Hg in children
- acute kidney injury
- clinical jaundice plus evidence of other vital organ dysfunction
- abnormal bleeding
What makes falciparum more severe than the other “benign” species?
- ability to parasitize all ages of erythrocytes (and therefore reach high levels of parasitemia)
- ability to ‘sequester’ in blood vessels - adhere to capillary endothelial cells, obstructing microvasculature and causing ischemia
What is the treatment of severe falciparum malaria?
- IV artesunate
- if unavailable give iv quinine until available or follow with ACT
What is treatment for non-severe falciparum?
- Oral artenisin based combination therapy (ACT) x 3 days
- Which are the “benign” malarias and how are they treated?
- P. vivax, ovale, malariae, knowlesi
- Treate with Chloroquine or ACT
- ACT if any doubt about dx of parasite or mixed infection or if P. vivax infection from areas of chloroquine resistance (Indonesia and parts of Oceania).
- What is the ABCD of malaria prevention?
- Awareness of symptoms of malaria
- Bite Prevention: repelants, insecticide treated bednets
- Chemoprophylaxis of malaria if necessary
- Diagnose and treate symptoms promptly
What is Ro and what is its significance?
- the number of infections introduced into a fully susceptible host (human).
- If Ro>1, infection will spread.
- Goal for eradication is to get Ro<1.
- Describe the Blantyre Coma Scale and How to Score it.
- Motor
- Pressure to fingernail bed: 0=no response or extensor response only. If withdrawal then pressure to supraorbital ridge or sternum.
- withdrawal =1
- pushes the hand away =2
- Verbal
- no response = 0
- moan or abnormal cry = 1
- normal cry or speech = 2
- Visual
- unable to open eyes = 0
- able to close eyes to avoid light or blink to visual threat = 1
- able to track moving object, eg face of examiner = 2
What are the microscopic characteristics of P. Falciparum?
- immature ring forms predominate (more mature forms generally sequestered): nucleus stains red, cytoplasm appears as blue-stained ring
- RBC’s remain normal in size
- multiple invasion: may have single RBC infected by >1 trophozoite
- some rings have double chromatin rods
- accolé forms, parasite lies flat along membrane of cell
- high numbers of trophozoites
- older trophozoites:
- Maurer’s dots
- knobs (distinguish from artefactual crenation of rbc’s due to osmotic drying)
-
schizonts rarely seen except heavy parasitemia or resistant strain
- haemozin (haemosome, Malaria pigment) produced as end product of Hgb breakdown
- appears as brown-black refractive granules within infected red cell
- haemozin (haemosome, Malaria pigment) produced as end product of Hgb breakdown
- lipid trigger causes some parasites to develop into gametocyte
-
crescent shaped sexual forms which reinfect mosquito
- female bluish cytoplasm, compact nucleus
- male reddish cytoplasm, diffuse nucleus
-
crescent shaped sexual forms which reinfect mosquito
P. falciparum thick film:
What can be seen?
- red cells lyzed, so see
- trophozoites and
- gametes
- appearing to be extracellular
In what clinical situations do you see malarial pigment/haemozin?
- Red cells, late stage infections
- White blood cells
- may be seen in absence of other stages of parasites
- sometimes post treatment
- pts (esp children) with chronic malaria
- What are the factors that influence the severity and outcome of malaria?
- Host factors
- genetic
- specfic immunity
- age
- nutrition
- HIV
- adherence
- pharmacokinetics
- Parasite Factors
- species
- drug resistance
- ?virulence
- Circumstances
- access to health care and early treatment
- drug efficacy
- drug quality
How do incidence and prevalence of malaria relate to the age distribution?
- In areas of high incidence and prevalence the disease afflicts primarily children under 5 and pregant women.
- As the incidence and prevalence of malaria decline it afflicts relatively more older children and adults because they did not acquire immunity in early chilhood.
What technical factors may influence the diagnosis of malaria?
- diagnosis based primarily on interpretation of thick film
- exerptise may be lacking or thick film may not have been properly examined
- ngegative films do not exclude malaria due to
- poor interpretation
- partial treatment
- prophylaxis
- Rapid Diagnostic Tests are sensitive for falciparum and vivax
- Films should be repeated 3 x if clinical suspicion of malaria is high
4 terms referring to types of recurrent malaria.
Name and define them.
- Recurrence = any return of malaria after previous clear smear.
- Relapse = recurrence of malaria in P. vivax and P. ovale infection because of hypnozoite
- Recrudescence = recurrence of malaria in any malarie species due to failure to completely eliminate parasites (treatment failure)
- Re-infection = NEW infection with malaria (bitten by mosquito again).
What are the clinical features of uncomplicated malaria?
- fever in over 90%
- Non-specific symptoms
- fever, ‘flue-like’ illness, headache, rigors, sweats, jaundice, respiratory or GI symptoms.
- high index suspicion necessary
Which species of malaria form liver hypnozoites?
P. vivax
P. ovale
In which species of malaria does sequestration play a big role in pathogenesis?
In which species will parasitemia reflect the total parasite load?
- Sequestration of p. falciparum plays a large role in pathophysiology via impaired microcirculation leading to widespread tissue ischemia and acidosis.
- In P. vivax, ovale and malariae, parasitemia reflects total parasite load
What are the four cardinal features of severe malaria in children?
- cerebral malaria
- severe anemia
- respiratory distress/acidosis
- hypoglycemia is common
- due to impaired liver glycogenolysis
- poss effect of quinine
What is the clinical significance of respiratory distress in severe malaria?
- represents acidosis due to widespread tissue ischemia due to impaired microcirculation and anemia
- indicator of physiological decompensation and a powerful predictor of mortality in children not given a blood transfusion
-
HOWEVER
- as incidence of malaria declines, overdiagnosis remains a possibility and
- parasitemia in high transmission setting does not always mean the cause of presentation is malaria.
- ALWAYS consider other diagnoses as well
- How common is raised ICP in cerebreal malaria?
- Should children with suspected cerebral malaria have Lumbar puncture?
- ICP is common in children with cerbral malaria (up to 50%).
- however in over 1000 children with suspected cerebral malaria, no evidence of LP’s leading to excess mortality, even if signs of raised ICP.
- So yes, they should have LP unless there are signs of impending herniation.
- How common are seizures in children with severe malaria?
- very common
- may be febrile seizure brief with quick recovery of consciousness.
- true seizures occur in 80% of children with Cerebral Malaria
- often complex, or prolonged, may be subtle
- may only be detectable on EEG = a trial of treatment may be warranted.
What is the pattern of severe malaria in adults?
- most symptoms are attributable due to sequestration of falciparum and disruption of micro-circulation leading to multi-system failure including shock, DIC, acidose
- cerbral malaria
- renal failure
- severe anemia relatively rare
- pulmonary edema problematic
- older children behave like adults
- What species of malaria cause severe disease?
- falciparum most commonly associated with severe disease because most prevalent in sub-Saharan Africa and because of sequestration and effects on microcirculation.
- however increasing recognition that p. vivax and p. knowlesi can also cause severe malaria
- What is the pattern of mortality for children with severe malaria?
- For adults?
- case fatality rates for severe malaria remain between 15 & 20%
- children tend to die early
- in first 24 hours of admission
- adults die later with multi-system disease
- What supportive therapies are useful in Severe Malaria?
- Which ones are NOT?
- YES
- antipyretics, acetaminophen
- transfuse if appropriate
- renal support if required
- glucose
- anticonvulsants if required
- fluids
- NO
- hyperimmune serum
- dexamethasone
- mannitol
- adrenaline
- dopamine
- heparin
- prophylactive anticonvulsants
- anti-TNF monoclonals
- desferrioxamine
What are the indications for transfusion in severe malaria?
- low transmission setting
- hgb<7g/dl (hct 20%) if clinically stable and AT ANY HGB IF SIGNS OF DECOMPENSATION
- High transmission setting
- hgb<4 g/dl (hct 12%) if clinically stable and AT ANY HGB IF SIGNS OF DECOMPENSATION
- use lower thresholds (<7g/dl) if resp distress, acidosis, heart failure or shock, impaired consciousness (rapid if resp distress/acidosis).
How dow you define and manage hypoglycemia in severe malaria?
- severe malaria definition <2.2, in practice <3.0
- Initial tx:
- 5 ml/kg 10% D10W IV rapidly
- Maintenance
- D10W in NS or RL for maintenance
- Avoid concentrations over 20%
- At what levels of parasitemia should malaria be considered and treated as severe?
- Discuss
- What is the realationship between parasitemia and regional levels of transmission.
- Laloo: consider as severe hyperparasitemia (>10% circulating erythrocytes infected)
- (also treat as severe, monitor closely if parasitemia 4-10% because of risk of rapid progression).
- WHO: high parasitemia undoubtedly a risk factor for mortality, but level at which sig varies with regional transmission rates. In areas of low transmission, parasitemia >2% may be associated with sig mortality. In areas of higher transmission areas of higher transmission tolerated. Levels > 20% associated with high risk in any epidemiological context.
How do you distinguish adult female anopheles from culicines?
- Different palp lengths: female anopheles have long palps, longer than their antennae; culicines have short palps
- Resting position of abdomen relative to substrate: female anopheles tilted up, culicines down
- large spots on anterior edge of wing in Anopheles
- How are female anopheles wings different from culicines?
- The anterior edge of their wings have spots.
- How do you tell femal anopheles from culicines by palp lengths?
- anopheles female palps are longer than antennae, culicines are short
- How do you tell female anopheles from culicines by body position when feeding?
- anopheles tail points up to sky, culicines is angled down
- How do you tell anopheles larvae from culicines?
- orientation: anopheles larvae are parallel to surface of water, whereas culicines are angled down and anchored to the surface by a
- siphon
- What diseases or parasites do anopheles transmit?
- malaria
- plasmodia
- lymphatic filiarisis
- Wuchereria bancrofti
- Brugia malayi
- viral
- O’nyong nyong
How big is an erythrocyte?
- Approximatel 6-8 µm diameter
- 1-2.5 µm thick
Describe the gametocyte of p. falciparum.
- Crescent-shaped
- Male and female can be distinguished from each other by their different staining reactions; the female has a bluish cytoplasm and a compact nucleus, the cytoplasm of the male is much redder in colour.
Describe the appearance of P. vivax.
- Main criteria:
- large pale RBC
- Schuffner’s dots
- round gametocytes
- large ameboid trophozoite with pale pigment
- red cells are 1.5-2 times larger than normal
- shape normal or oval
- Schuffner’s dots present in all stages except early ring form
- occasional red cells with multiple parasites per cell
- all stages of trophozoite present in peripheral blood
- ring form: ring 1/2-1/2 diameter of cell
- heavy chromatin dot
- developing schizont:
- enlarged, chromatin divided into two or more discrete red areas, but cytoplasm not divided, malaria pigment present
- mature schizont: 12-24 merozoites in rosette filling entire RBC
- gametocytes round or oval
Describe the appearance of P. ovale
-
Main Criteria:
- Oval RBC with fimbriated edges characteristic but not alwasy present; generally like P. vivax
- In P.ovale although both parasite and red cell do increase in size, the red cell remains more oval in shape, with fimbriated (jagged) ends while the parasite is more compact.
- As for P. ovale, red cells are 1.5-2 times larger than normal
- shape normal or oval but differ from P. ovale in that some have irregular fimbriated edges
- As for P. ovale:
- Schuffner’s dots present in all stages except early ring form
- occasional red cells with multiple parasites per cell
- all stages of trophozoite present in peripheral blood
- ring form: ring 1/2-1/2 diameter of cell
- heavy chromatin dot
- As for P. ovale and P. malariae:
- developing schizont: enlarged, chromatin divided into two or more discrete red areas, but cytoplasm not divided, malaria pigment present.
- Mature shizont : 8-12 merozoites (P. vivax has 12-24)
Describe P. vivax (Main Criteria only)
- Main criteria:
- large pale RBC
- Schuffner’s dots
- round gametocytes
- large ameboid trophozoite with pale pigment
Describe the appearance of P. Malariae.
- In P.malariae the parasite is quite solid and stretched across the red cell which is often smaller than normal, termed microcytic.
-
Main Criteria:
- Red Cell normal or slightly smaller
- trophozoites compact and intensely stained
- band form suggestive
- no Schuffner’s dots
- coarse and dark pigment
Describe the schizont of P. vivax
- Schizonts are round with
- 12-24 merozoites in rosette filling entire RBC
- Schuffner’s dots visible
- haemozin may also be seen
Describe P. vivax gametocytes.
- Gametocytes are large, solid, and usually rounded, filling most of the infected red cell. There is a single chromatin mass (nucleus) which is either compact (female gametocytes) or more diffuse (male gametocytes)
- The parasitised red cell is enlarged and schűffners dots are usually visible.
- Fine pigment granules may be scattered throughout the cytoplasm (centre and right above)
Describe P. ovale trophozoites.
- parasites generally more compact than p. vivax
- Schuffner’s dots
- Oval shape, with some having fimbriations is diagnostic (up to 30% will have this)
Describe the P. ovale Schizont.
- Round form
- 8-12 merozoites
Describe P. ovale gametocyte
- round form, solid in appearance, filling most of RBC
- Schuffner’s dots may be seen around periphery
Describe the appearance of p. malariae younger trophozoites.
- younger ring form may initially appear similar to young ring of p. falciparum; but both nucleus and cytoplasm are thicker and stain more deeply
- ‘solid ring’ form: chromatin may be rounded or streaky, cytoplasm is usually fairly compact
- ‘birds eye form’: nucleus situated in middle
- may be haemozin present in parasitized red cell
Describe older trophozoites of p. malariae
- band form diagnostic: nucleus and cytoplasm stretched across middle of host red cell
- basket form: parasite more oval with vacuole forming the basket
- chromatin usually single mas
Describe P. malariae Schizonts
- seen in normal sized or smaller (microcytic) red cells
- 8-12 merozoites often arranged in rosette or irregular cluster
- generally low level parasitemia but high proportion of circulating parasites may be schizonts
Describe P. malariae Gametocytes
- compact, tend to fill host rbc
- nucleus and cytoplasm often deeply stained
- no enlargement of rbc and may be microcytic
- Insect Repellants
- List 5 types and efficacy
*
What is the differential for typical xray picture of miliary TB?
- histoplasmosis
- sarcoid
- varicella
- pneumonitis
- berylliosis.
Describe the identifying characteristics of P. vivax shizont & gametocyte.
- developing schizont:
- enlarged, chromatin divided into two or more discrete red areas, but cytoplasm not divided, malaria pigment present
- mature schizont: 12-24 merozoites in rosette filling entire RBC
- gametocytes round or oval
Describe the appearance of P. vivax gametocyte.
- P. vivax gametocytes are round to oval with scattered brown pigment and may almost fill the rbc
What is this?
What are the diagnostic features?
- P. falciparum thin smear.
- nucleus (chromatin dot) stains red while cytoplasm of parasite stains blue
- some rings have double chromatin dots
- in some red cells parasite lies flat along membrane of the cell (accolé form)
- some red cells contina more than one parasite (multiple invasion of red cell)
Describe the features of p. falciparum on a thin smear.
- multiple invasion
- high rate of parasitemia
- accolé form
- double chromatin dot
- in attached picture note scanty cytoplasm of young ring form trophozoites
What is this?
What are the distinctive features?
- P. falciparum: older trophozoites
- both nucleus and cytoplasm have become thicker and coarser
- a few Maurer’s dots (clefts) may be seen in t the cytoplasm of the red cells
- these irregular reddish dots are another diagnostic feature of older trophozoites of P. falciparum and can be used to distinguish from Schuffners dots in P. vivax/P. ovale.
What is this?
Describe the characteristics.
-
P. falciparum Schizont
- normally occur in capillaries of spleen, liver and brain
- not often seen in blood except heavy parasitemia or resistant strain
- nucleus begins to divide, then cytoplasm, producing mature schizont with 16-32 merozoites
- nb hemozoin
- schizont rupture blocks brain caps leading to cerebral malaria, coma, death
- toxins produce typical malaria attack
What is this?
- P. falciparum gametocytes
- crescent shaped gametocytes diagnostic
- distinguish by different staining reactions: female bluish cytoplasm and compact nucleus, male redder or pink
- do not develop further unless ingested by female Anopheles mosquito