Malaria Flashcards

1
Q

What mosquito transmits malaria?

A

Female anopheles mosquito.

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2
Q
  • Which species of malaria parasite afflict humans? (in order of increasing prevalence)
  • Which causes most deaths?
A
  1. P. falciparum
  2. P. vivax
  3. P. ovale
  4. P. malariae
  5. P. knowlesi
  • Falciparum most severe, causes most deaths
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3
Q
  • What is the global burden of malaria disease?
    • How many cases?
    • How many deaths?
A
  • 214 million cases per year
  • 438,000 deaths
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4
Q
  • How many deaths per year from Malaria?
    • What percent in Africa?
    • What percent in Kids?
A
  • 438,000
  • 90% in Africa
  • 7% in SEARO
  • 70% in kids
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5
Q
  • How much has the incidence of malaria fallen this century?
A
  • Since 2000 the incidence of malaria has fallen by 37%
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6
Q
  • What is the geographic distribution of the various species of malaria in order of global prevalence?
A
  1. P. falciparum: throughout tropics and subtropics, esp. sub-Saharan Africa
  2. P. vivax: south, SE asia; East Africa, largely absent west Africa; Amazon
  3. P. ovale: pred West Africa, Phillipines, East Indonesia, Pap New Guinea
  4. P. malariae: throughout tropics & subtropics (but much less prev than falciparum)
  5. P. knowlesi: Zoonotic species, restricted to SE Asia: Borneo and peninsular Malaysia
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7
Q
  • Name four geographic factors affecting the distribution of malaria.
A
  1. Temperature: affects life cycle of mosquito
  2. Altitude: restricted to altitudes below 1500 m
  3. Seasonality: more common in wet season due to mosq. life cycle
  4. Population movement.
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8
Q
  • Name the 6 forms malaria parasite takes during its life cycle.
  • Briefly describe each.
A
  1. sporozoites - dormant stage injected into human host via pregnant female anopheles salivary glands, travels to and infects liver cells
  2. schizonts - host liver or red blood cell containing mature forms soon to rupture, divides (schizogeny) then releases merozoites
  3. merozoites - parasite stage released from liver or rbc, then goes on to infect rbc’s
  4. trophozoites - developing intra-erythrocytic parasite phase visible on blood film
  5. gametocytes - sexual stage of parasite life-cycle that go on to infect mosquito, where they combine to form oocytes, which develop into sporozoites
  6. hypnozoites - a dormant form of P. ovale and P. vivax which can hide in the liver to cause relapses
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9
Q
  • What are the usual symptoms of malaria?
A
  • very non-specific
    • fever
    • rigors
    • headache
    • myalgias
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10
Q
  • What species of plasmodium cause severe malaria?
A
  • 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
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11
Q
  • Describe the classical malaria fever patterns and which species of malaria they are associated with.
A
  • 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
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12
Q
  • What are WHO criteria for severe malaria due to P. falciparum.
A
  • 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
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13
Q

What makes falciparum more severe than the other “benign” species?

A
  • 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
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14
Q

What is the treatment of severe falciparum malaria?

A
  • IV artesunate
  • if unavailable give iv quinine until available or follow with ACT
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15
Q

What is treatment for non-severe falciparum?

A
  • Oral artenisin based combination therapy (ACT) x 3 days
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16
Q
  • Which are the “benign” malarias and how are they treated?
A
  • 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).
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17
Q
  • What is the ABCD of malaria prevention?
A
  • Awareness of symptoms of malaria
  • Bite Prevention: repelants, insecticide treated bednets
  • Chemoprophylaxis of malaria if necessary
  • Diagnose and treate symptoms promptly
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18
Q

What is Ro and what is its significance?

A
  • 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.
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19
Q
  • Describe the Blantyre Coma Scale and How to Score it.
A
  • 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
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20
Q

What are the microscopic characteristics of P. Falciparum?

A
  • 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
  • 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
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21
Q

P. falciparum thick film:

What can be seen?

A
  • red cells lyzed, so see
  • trophozoites and
  • gametes
  • appearing to be extracellular
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22
Q

In what clinical situations do you see malarial pigment/haemozin?

A
  • 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
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23
Q
  • What are the factors that influence the severity and outcome of malaria?
A
  • 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
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24
Q

How do incidence and prevalence of malaria relate to the age distribution?

A
  • 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.
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25
Q

What technical factors may influence the diagnosis of malaria?

A
  • 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
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26
Q

4 terms referring to types of recurrent malaria.

Name and define them.

A
  1. Recurrence = any return of malaria after previous clear smear.
  2. Relapse = recurrence of malaria in P. vivax and P. ovale infection because of hypnozoite
  3. Recrudescence = recurrence of malaria in any malarie species due to failure to completely eliminate parasites (treatment failure)
  4. Re-infection = NEW infection with malaria (bitten by mosquito again).
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27
Q

What are the clinical features of uncomplicated malaria?

A
  • fever in over 90%
  • Non-specific symptoms
    • fever, ‘flue-like’ illness, headache, rigors, sweats, jaundice, respiratory or GI symptoms.
  • high index suspicion necessary
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28
Q

Which species of malaria form liver hypnozoites?

A

P. vivax

P. ovale

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29
Q

In which species of malaria does sequestration play a big role in pathogenesis?

In which species will parasitemia reflect the total parasite load?

A
  • 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
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30
Q

What are the four cardinal features of severe malaria in children?

A
  • cerebral malaria
  • severe anemia
  • respiratory distress/acidosis
  • hypoglycemia is common
    • due to impaired liver glycogenolysis
    • poss effect of quinine
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31
Q

What is the clinical significance of respiratory distress in severe malaria?

A
  • 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
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32
Q
  • How common is raised ICP in cerebreal malaria?
  • Should children with suspected cerebral malaria have Lumbar puncture?
A
  • 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.
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33
Q
  • How common are seizures in children with severe malaria?
A
  • 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.
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34
Q

What is the pattern of severe malaria in adults?

A
  • 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
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35
Q
  • What species of malaria cause severe disease?
A
  • 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
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36
Q
  • What is the pattern of mortality for children with severe malaria?
  • For adults?
A
  • 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
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37
Q
  • What supportive therapies are useful in Severe Malaria?
  • Which ones are NOT?
A
  • 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
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38
Q

What are the indications for transfusion in severe malaria?

A
  • 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).
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39
Q

How dow you define and manage hypoglycemia in severe malaria?

A
  • 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%
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40
Q
  • 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.
A
  • 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.
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41
Q

How do you distinguish adult female anopheles from culicines?

A
  1. Different palp lengths: female anopheles have long palps, longer than their antennae; culicines have short palps
  2. Resting position of abdomen relative to substrate: female anopheles tilted up, culicines down
  3. large spots on anterior edge of wing in Anopheles
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42
Q
  • How are female anopheles wings different from culicines?
A
  • The anterior edge of their wings have spots.
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43
Q
  • How do you tell femal anopheles from culicines by palp lengths?
A
  • anopheles female palps are longer than antennae, culicines are short
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44
Q
  • How do you tell female anopheles from culicines by body position when feeding?
A
  • anopheles tail points up to sky, culicines is angled down
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45
Q
  • How do you tell anopheles larvae from culicines?
A
  • orientation: anopheles larvae are parallel to surface of water, whereas culicines are angled down and anchored to the surface by a
  • siphon
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46
Q
  • What diseases or parasites do anopheles transmit?
A
  • malaria
    • plasmodia
  • lymphatic filiarisis
    • Wuchereria bancrofti
    • Brugia malayi
  • viral
    • O’nyong nyong
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47
Q

How big is an erythrocyte?

A
  • Approximatel 6-8 µm diameter
  • 1-2.5 µm thick
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48
Q

Describe the gametocyte of p. falciparum.

A
  • 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.
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49
Q

Describe the appearance of P. vivax.

A
  • 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
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50
Q

Describe the appearance of P. ovale

A
  • 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)
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51
Q

Describe P. vivax (Main Criteria only)

A
  • Main criteria:
    • large pale RBC
    • Schuffner’s dots
    • round gametocytes
    • large ameboid trophozoite with pale pigment
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52
Q

Describe the appearance of P. Malariae.

A
  • 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
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53
Q

Describe the schizont of P. vivax

A
  • Schizonts are round with
    • 12-24 merozoites in rosette filling entire RBC
    • Schuffner’s dots visible
    • haemozin may also be seen
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54
Q

Describe P. vivax gametocytes.

A
  • 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)
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55
Q

Describe P. ovale trophozoites.

A
  • parasites generally more compact than p. vivax
  • Schuffner’s dots
  • Oval shape, with some having fimbriations is diagnostic (up to 30% will have this)
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56
Q

Describe the P. ovale Schizont.

A
  • Round form
  • 8-12 merozoites
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57
Q

Describe P. ovale gametocyte

A
  • round form, solid in appearance, filling most of RBC
  • Schuffner’s dots may be seen around periphery
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58
Q

Describe the appearance of p. malariae younger trophozoites.

A
  • 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
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59
Q

Describe older trophozoites of p. malariae

A
  • 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
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60
Q

Describe P. malariae Schizonts

A
  • 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
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61
Q

Describe P. malariae Gametocytes

A
  • compact, tend to fill host rbc
  • nucleus and cytoplasm often deeply stained
  • no enlargement of rbc and may be microcytic
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62
Q
  • Insect Repellants
    • List 5 types and efficacy
A

*

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63
Q

What is the differential for typical xray picture of miliary TB?

A
  • histoplasmosis
  • sarcoid
  • varicella
  • pneumonitis
  • berylliosis.
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64
Q

Describe the identifying characteristics of P. vivax shizont & gametocyte.

A
  • 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
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65
Q

Describe the appearance of P. vivax gametocyte.

A
  • P. vivax gametocytes are round to oval with scattered brown pigment and may almost fill the rbc
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66
Q

What is this?

What are the diagnostic features?

A
  • 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)
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67
Q

Describe the features of p. falciparum on a thin smear.

A
  • multiple invasion
  • high rate of parasitemia
  • accolé form
  • double chromatin dot
  • in attached picture note scanty cytoplasm of young ring form trophozoites
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68
Q

What is this?

What are the distinctive features?

A
  • 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.
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69
Q

What is this?

Describe the characteristics.

A
  • 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
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70
Q

What is this?

A
  • 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
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71
Q

What is this?

What are the advantages, differences from thin film?

A
  • P. falciparum thick film
  • red cells piled thickly, irregularly, not fixed with methanol prior to staining.
  • aqueous stain allows red cells to hemolyze, leaving purple staining white cells
  • malaria parasites appear extracellular
72
Q

What is this?

A
  • P. falciparum gametocyte in thick film
  • likely male because of reddish tinge to cytoplasm
  • crescent shape identifies as p. falciparum
73
Q

What is this?

A
  • as p. falciparum infections often intense, WBC’s containing hemozoin may often be seen after phagocytozed
74
Q

Describe malaria life cycle.

A
75
Q

What is this?

Characteristics?

A
  • P. vivax mature trophozoite
  • both parasite and red cell become very enlarged and ameboid in shape
  • Schuffner’s dots present in both Ovale and Vivax
76
Q

what is this?

Characteristics?

A
  • P. ovale
  • both parasite and red cell increase in size but red cell remains more oval in shape, with fimbriated ends in 20%
  • parasite more compact
  • Schuffners dots present in both Ovale and Vivax, but there are more present in Ovale
77
Q

What is this?

A
  • P. malariae thin film - basket form
  • In the picture below parasite is solid and streteched across red cell, which is often smaller than normal (microcytic)
  • no Schuffner’s dots
78
Q

What is this?

In what species is it found?

How are they treated?

A
  • hypnozoites in liver ceslls, found in P. Vivax and P. Ovale
  • dormant stage leading to Relapsing Malaria occurring months or years after initial infection
  • round, intra-cytoplasmic, non-dividing, uni-nucleate bodies about 5 µm in size.
  • similar to but smaller than schizonts, also found in liver tissue
  • detectable by immunofluorescence (right) 36-40 hours after sporozoite inoculation
79
Q

What is this?

Characteristics?

A
  • P. vivax trophozoites, mature
  • parasitized red cell enlarged and irregular in shape, increasing as parasite develops
  • parasite also irregular or ameboid shape
  • large red nucleus, often to one side
  • cytoplasm blue, forming large, irregular mass
  • Schuffner’s dots visible.
80
Q

What is this?

Characteristics?

A
  • P. vivax trophozoite, mature
  • parasitized red cell enlarged and irregular in shape, increasing as parasite develops
  • parasite also irregular or ameboid shape
  • large red nucleus, often to one side
  • cytoplasm blue, forming large, irregular mass
  • Schuffner’s dots visible.
81
Q

Describe the features of P. vivax

A
  • large (macrocytic) red cell
  • ameboid irregular cytoplasm of parasite
  • ameboid shape to parasitized cell
  • trophozoite cytoplasm stains blue with large heavily staining red nucleus
  • cytoplasm increasinly large and ameboid as parasite matures
  • Schuffner’s dots
82
Q

What is this?

Characteristics?

through maturation?

How long does it take?

A
  • P. vivax schizont
  • in early schizonts as nucleus begins to divide, cytoplasm remains dense
  • as nuclear division continues cytoplasm also begins to divide and surround nuclei forming merozoites
  • mature schizont may contain 16-24 merozoites
  • schizogony complete after ~48 hrs
  • parasitised rbc enlarged, Schuffners dots present
  • haemozoin may also be seen
83
Q

What is this?

Characteristics?

A
  • P. vivax gametocytes
  • large, solid, usually rounded, filling most of rbc
  • Single chromating mass (nucleus) either compact (female gametocyte) or more diffuse (male)
  • left male, right female
84
Q

What is this?

characteristics?

A
  • P. vivax thick film
  • enlarged late trophozoites of P. vivax ameboid, irregular in shape and size on thick film
  • cytoplasm may appear fragmented
  • Schuffners dots may be seen as pink ‘halo’ around some of larger parasites, giving useful indication of size and shape of original red cell before lysis
  • large round or oval gametocytes and developing schizonts may be seen
85
Q

What is this?

Characteristics?

A
  • P. ovale younger trophozoite
  • well stained, compact ring form
  • red cell slightly enlarged, round or oval shape
  • parasites gen more compact than P. vivax with Schuffner’s dots
    *
86
Q

What is this?

Characteristics?

A
  • P. ovale older trophozoite
  • large nucleus, large solid cytoplasm
  • red cell macrocytic
  • schuffners dots clearly visible
  • some fimbriation (seen about 30%, diagnostic)
    *
87
Q

Describe characteristics of P. ovale.

Of late troph.

A
  • macrocytic red cell, but not as large as P. vivax, may be better defined
  • oval shaped
  • fimbriation diagnostic, but only seen in 20-30%
  • Schuffner’s dots
  • large parasite with more cytoplasm than early trophozoite
88
Q

What is this?

characteristics?

A
  • P. ovale schizont
  • red cells sl enlarged, round or oval shape
  • up to 30% fimbriated ends
  • parasites more compact than p. vivax, with Schuffner’s dots visible
  • Schizonts 8-12 merozoites when mature
89
Q

What is this?

characteristics?

A
  • P. ovale gametocyte
  • macrocytic cell, but smaller than p. vivax
  • Schuffner’s dots
  • gametocyte round and solid, filling most of infected cell , schuffner’s dots around periphery
  • malarial pigment (hemozin) in later stages
90
Q

What is this?

Characteristics.

A
  • P. malariae
  • infected cell is normal size or smaller
  • younger ring form may appear superficially like young P. falciparum ring form, but both nucleus and cytoplasm are thicker and stain more deeply.
91
Q

what is this?

characteristics

A
  • microcytic red cell
  • chromatin round or streaky
  • cytoplasm usually fairly compact
  • “solid ring form”
92
Q

What is this?

Birds eye form of P. malariae

A
  • microcytic rbc
  • some rings may appear to have nucleus located in middle
  • “bird’s eye” form
93
Q

what is this?

characteristics?

A
  • P. malariae Band form
  • now as trophozoites mature, nucleus may be stretched across middle forming “band form”
    • diagnostic as P. malariae
    • malarial pigmen granules become larger, tend to have more peripheral arrangement, may be yellowish and refractive
94
Q
A
  • P. malariae basket form
95
Q

Describe characteristics of P. malariae

A
96
Q
A
  • P. malariae young schizont
  • microcytic red cell
  • 8-12 merozoites
97
Q
A
  • P. malariae mature schizont
  • 8-12 merozoites, arraged in rosette or irregular cluster
  • nearly fill host red cell , pigment is coarse, golden brown and usually cntral
  • Schizonts can be common in peripheral blood circulation
98
Q

What is this?

A
  • P. malariae gametocyte
  • compact, tend to fill hospt RBC
  • nucleus and cytoplasm often deeply stained
  • abundant dark refractile pigment may be scattered through the cytoplasm
99
Q

What is this?

What groupings of organism may be seen?

Where.

A
  • mixed infection with P. falciparum and P. vivax
  • common in South-East Asia, this one from Thailand
  • P. falciparum mixed with p. malariae often seen West Africa
100
Q

What are the Characteristics of P. vivax on a thick film?

A

Plasmodium vivax Trophozoites, Thick Film

  1. Trophozoites range in size from small to large.
  2. Broken rings and irregular shapes are common.
  3. Cytoplasm is irregular or fragmented.
  4. Mature trophozoites are compact and dense.
  5. Pigment is scattered and fine.
101
Q

What are the characteristics of P. vivax Schizonts on thin film?

A

Plasmodium vivax Schizonts, Thin Film

  1. Schizonts usually contain between 12 and 24 merozoites.
  2. Schizonts are irregularly shaped and can fill the infected RBC.
  3. Pigment usually occurs in one or two masses.
102
Q

What are the characteristics of P. vivax schizonts on a thick film?

A

Plasmodium vivax Schizonts, Thick Film

  1. Schizonts are large and occur in few to moderate numbers.
  2. Mature forms have 12 - 24 merozoites, usually 16 in an irregular cluster.
  3. Pigment is seen in a loose accumulation.
103
Q

What are the characteristics of P. vivax gametocytes?

A

Plasmodium vivax Gametocytes, Thin Film

  1. Immature forms are similar to mature trophozoites.
  2. Mature gametocytes are large and rounded with a fine, abundant, scattered mass of pigment and not vacuolated.
  3. Microgametocytes have light-blue cytoplasm with diffuse pink chromatin.
  4. Macrogametocytes have darker blue cytoplasm and compact eccentric mass of dark-red chromatin.
104
Q

What are the characteristics of P. ovale trophozoites on thin film?

A

Plasmodium ovale Trophozoites, Thin Film

  1. Infected RBCs might be enlarged, often stretched into ovoids with fimbriated edges, and can have coarse James’s stippling.
  2. Immature trophozoites bear similarities to P. vivax and P. malariae and have a single prominent nucleus.
  3. Mature trophozoites are less vacuolated than P. vivax, resemble P. malariae, and have coarse and scattered pigment.
105
Q

What are the characteristics of P. ovale schizonts in thick film?

A

Plasmodium ovale Schizonts, Thick Film

  1. P. ovale schizonts are few in number and resemble those of P. malariae.
  2. P. ovale schizonts contain 4-12 merozoites, usually 8, in a rosette-like cluster.
  3. Pigment in a P. ovale schizont occurs in a concentrated mass.
106
Q

What are the characteristics of P. ovale gametocytes in thin film?

A

Plasmodium ovale Gametocytes, Thin Film

  1. Erythrocytes infected with P. ovale are smaller than those infected with P. vivax and are stippled.
  2. P. ovale gametocytes are similar to gametocytes in P. malariae and have prominent chromatin.
  3. P. ovale with mature macrogametocytes fill the host cell, and the microgametocyte is smaller with coarse, scattered pigment.
107
Q

What are characteristics of P. malariae trophozoites on thin film?

A

Plasmodium malariae Trophozoites, Thin Film

  1. Infected cells are normal or slightly smaller in size, occasionally with Ziemann’s stippling in trophozoite-infected RBCs.
  2. Ring trophozoites have a single nucleus with denser cytoplasm and smaller vacuoles than P. vivax; binucleate trophozoites are occasional.
  3. Trophozoites may form bands without vacuoles and with peripheral coarse chromatin and black or greenish-brown pigment.
  4. “Basket-form” trophozoites with eccentric circular vacuoles are seen more often in P. malariae than in other species.
108
Q

P. malariae trophozoites in thick film.

A

Plasmodium malariae Trophozoites, Thick Film

  1. Trophozoites are small and few in number.
  2. Trophozoites range in shape from ring to rounded.
  3. Trophozoite chromatin is single and large.
  4. Trophozoite cytoplasm is dense with scattered pigment that varies in color

from black to greenish brown.

109
Q

What are the characteristics of P. malariae schizonts on thin film?

A

Plasmodium malariae Schizonts, Thin Film

  1. Schizonts are small and compact with 6-12 merozoites. Usually, eight are in a rosette arrangement.
  2. Schizonts contain a single mass of black or greenish-brown pigment.
110
Q

Appearance of P. malariae schizonts in thick film.

A

Plasmodium malariae Schizonts, Thick Film

  1. Schizonts are small and compact with 6-12 merozoites. Usually, eight merozoites are in a rosette arrangement and resemble those of P. ovale.
  2. Pigment occurs in a concentrated mass.
111
Q

What is babesiosis?

A
  • a disease of cattle and other livestock, transmitted by the bite of ticks. It affects the red blood cells and causes the passing of red or blackish urine
  • in humans ranges from assymptomatic to fulminant in splenectomized pts. Hemolytic anemia, fever, etc.
  • Babesia microti is transmitted in nature by Ixodes scapularis ticks (also called blacklegged ticks or deer ticks).

Tickborne transmission primarily occurs in the Northeast and upper Midwest, especially in parts of New England, New York state, New Jersey, Wisconsin, and Minnesota.

  • parasite can resemble P. falciparum, but larger vacuole, reproduces by budding rather than schizont formation - typical “Maltese Cross” appearance
112
Q

What are the complications of severe malaria?

A
  • P. falciparum
    1. Cerebral coma
    2. anemia
    3. pulmonary edema
    4. renal failure
    5. shock
    6. lactic acidosis
    7. hypoglycemia
    8. tropical splenomegaly
    9. pregnancy
      1. maternal death
      2. stillbirth
      3. low birth weight
      4. anemia
  • P. vivax and P. ovale
    1. splenic rupture
    2. anemia (mild)
    3. debilitating fevers
    4. higher TNFalpha per parasite
  • P. malariae
    1. immune complex glomerulonephritis leading to nephrotic syndrome (poor px)
113
Q

Tertian fever?

Quartan Fever?

A
  • Tertian fever - P. vivax + P. ovale
  • Quartan fever - P. malariae
114
Q

What diseases are associated with non-immunological mechanisms of refractoriness to malaria?

A
  • Hemoglobinopathies e.g. thallasemia
  • RBC enzyme deficiency eg. G6PD deficiency
  • RBC surface components eg Duffy blood group
  • Sickle Cell Hgb, gene frequency in Nigeria >20%
115
Q

Which malarian parasite has a reservoir in the macaques?

Where?

Clinical disease?

Identification?

A
  • P. knowlesi “the fifth species”
  • distribution limited by distribution of mosquito vector (Anopheles leucosphyrus)
  • SE Asia, but predominantly Brunei, Borneo
  • microscopically same as P. malariae
  • dx by PCR
116
Q

Treatment of uncomplicated Malaria?

In pregnancy?

Role of primaquine?

A
  • ACT on days 123 for adults & children (except 1st trimester pregnancy)
  • Primaquine x 14 days to follow to prevent relapse in P. ovale and P. vivax but have to test for G6PD deficiency
  • if G6PD deficient can consider lower dose primaquine x 8 wks with close monitoring for hemolysis
  • Pregnancy
    • ACT ok in trimester 2&3
    • otherwise Quinine & Clindamycin for 7 days instead of 3
    • [But WHO is changing imminently to allow ACT in all 3 trimesters]
  • In low transmission countries give Primaqine 0.25 mg/kg one dose in addition to ACT for anti-gametocyte effect as part of malaria elimination programme
  • G6PD screening not needed because dose low enought that hemolysis not a worry
117
Q

What are the ACT drugs?

Choice guided by local sensitivities.

A
  • Artemether +
    • lumefantrine
    • amodiaquine
    • mefloquine
    • SP (sulfadiazine & pyremethamine)
  • Dihydroaretemisinin (DHA) + piperaquine
118
Q

What considerations drive antimalarial choice in HIV pts with malaria.

A
  • should not use artesunate + Sulfidiazine/Pyrimethamine with co-trimoxazole (too much anti-folate)
  • should not use artesunate + amodiaquine with evafirenze or AZT (hepatotoxicity)
119
Q

How do you treat severe malaria (WHO rec)?

Dosing in kids<20 kg?

What if IV tx not available (i.e. pre-hospital)?

Which trials led to this recommendation?

What complication should you watch for AFTER treatement with iv artesunate?

A
  • IV artesunate minimum 24 hrs or until pt can tolerate oral meds
  • then 3 days ACT
  • (followed by single dose low dose PQ in low transmission areas)
  • Dosing for kids<20 kg higher (3 mg/kg vs 2.4 mg/kg to ensure equivalent exposure.
  • Give IM artesunate, artemether or quinine prior to transfer
  • watch for delayed hemolysis
  • SEAQUAMAT & AQUAMAT
120
Q

How does chloroquine and derivative quinolones work against malaria parasite?

A
  • he mechanism of plasmodicidal action of chloroquine is not completely certain. Like other quinoline derivatives, it is thought to inhibit heme polymerase activity. This results in accumulation of free heme, which is toxic to the parasites. … During this process, the parasite produces the toxic and soluble molecule heme.
121
Q

What are the effects of pregnancy on malaria?

How does the risk differ for women in high transmission areas (eg. Sub Saharan Africa) from that for women in low transmission areas (e.g. Thailand).

A
  • malaria is more common and more severe in pregnancy
    • for both P. falciparum and P. vivax
  • placental immunity to malaria is specific
  • primigravids remain susceptible to malaria even if previous exposure to malaria, although such exposure attenuates the severity of the malaria
  • in high transmission areas, primigravids usually have some immunity to malaria, but still develop placental parasites in first and second pregnacies; subsequent pregnancies benefit from placental immunity.
  • in low transmission areas multigravidae are unexposed and unprotected and thus also at risk of adverse consequences
122
Q

What is the impact of malaria on the pregnancy and neonate?

How does this differ in high transmission and low transmission areas?

A
  • High Transmission Areas
    • mostly assymptomatic leading to
      • anemia and IUGR
      • Affects 1st and 2nd pregnancies most
      • (And all pregnancies in HIV +ve women)
  • Low Transmission Areas
    • All pregnancies are affected
    • assymptomatic as well as symptomatic
    • In symptomatic cases leads to pregnancy loss, preterm deliveries
123
Q
A
124
Q

Outline the treament of Malaria in Pregnancy.

How about treatment of Severe Malaria?

A
  • 1st Trimester: Quinine
  • 2nd & 3rd Trimesters: ACT’s
  • But changing based on Observational Study eg Thai-Burma border demonstrating no elevated risk compared with inadequately treated malaria. In mid-2018
    • ACT’s throughout pregnancy
  • Severe Malaria: treat with IV Artesunate throughout pregnancy
125
Q

Outline the Preventive Treatment of Malaria in Pregancy.

What is it called?

Where utilized?

What are the challenges?

What is the effect of reductions in malaria transmission rates on strategy?

A
  • Intermittent Preventive Therapy in Pregnancy (IPTp)
    • With SP (Sulfamethoxazole & Pyrimethamine) at each scheduled antenatal care visit has both antimalarial and some antimicrobial effects
    • High Transmission Areas: SubSaharan Africa and PNG.
    • Uptake very low after 10 yrs (25%)
    • Malaria Resistance to SP, the only drug currently recommended
    • New drugs (ACT-piperaquine) replacing SP are likely to be more expensive and will be 3 day instead of 1 day regimens.
    • (Studies with DHA-pip ongoing)
    • Reductions in malaria transmission chages the risk-benefit profile of IPT.
126
Q

Other than IPTp, what other strategies are being used or considered in Low Transmission areas?

What new technologies and strategies are under consideration?

A
  • Test with RDT (Rapid Diagnostic Tests) and treat only RDT-positive women with ACT’s, i.e. SST: Single Screen and Treat
  • SST used in many low transmission areas that don’t use IPTp
  • IST (Intermittent Screen and Treat) with current generation RDT’s no better than IPTp-SP in SP resistant areas BUT
  • 2017 new highly sensitive RDT available, may improve accuracy of dx, screening
  • any future screen and treat strategies for malaria should be integrated with screening for other Points of Care (HIV, syphilis, anemia)
127
Q

What is the effect of Malaria in Pregnancy on the Mother?

Compare Low Transmission with High Transmission Areas.

A
  • increases the rates of fever, severe anemia and severe malaria (cerebral malaria, hypoglycemia, renal failure, pulmonary edema)
    • this is more pronounced in areas of Low Transmission (because of lack of prior exposure and immunity)
    • in areas of High Transmission, these effects occur to a lesser extent and malaria infection is more likely to be assymptomatic
  • increases the rates of Heavy Placental Infection with malaria
    • more pronounced in areas of High Transmission because of density of infection and lack of placental immunity in primigravids and 2nd babies
  • in areas of high transmission, all effects are seen primarily in primigravids; in areas of low transmission the risk applies to all pregnancies.
128
Q
A
129
Q

What is the Effect of malaria in pregnancy on the fetus?

Compare High and Low Transmission Areas.

A
  • in areas of high transmission, affect primarily primigravids; in low transmission, applies to all parities
  • Increased risks include
    • Low Birth Weight
      • IUGR esp primis in HTA
      • preterm deliveries esp all preg in LTA
    • Abortion/stillbirth esp LTA
    • Congenital Malaria more likely to be symptomatic in LTA
    • Fetal anemia
    • additionally it appears that in HTA there is reduced placental transfer of Ab and cellular immunity to the fetus (e.g. to Tetanus, measles, Strep. pneumonia). This effect may be present in LTA, but has not been demonstrated.
    • Other possible effects include poor developmental and behavioural outcomes, poss increase risk of metabolic disease, short stature.
130
Q

What is the ABCDE Framework for Malaria Elimination?

A
  • Accelerate scale up for impact (SUFI) - existing prevention strategies & case management
  • Build information systems for action (surveillance phase-1)
  • Community clearance of malaria parasites (targeting the parasite infectious reservoir)
    • Mass Screen and Treat (MSAT)
    • Mass Drug Administration (MDA)
    • Optimal combination of interventions
    • Adjunctive therapy with primaquine and ivermectin
    • P. vivax specific challenges
  • Detect and investigate individual cases (reactive case detection)
  • Eliminate (how to maintain malaria-free status)
131
Q

Once infection rates have declined, why are the elimination of P. vivax, P. malariae and P. ovale potentially harder than eliminating P. falciparum?

A
  • because of the hypnozoite phase of the parasite in these species, whereby it can lie dorman in the liver for years
  • with P. falciparum a smaller proportion of merozoites transform into gametocytes and they develop later in the course of the infection. In P. vivax therefore the infected person is capable of transmitting the infection before he becomes symptomatic.
132
Q

How do the rates of assymptomatic infection compare in low transmission vs high transmission areas? What drives these differences.

A
  • In areas of high transmission there is a higher proportion of assymptomatic malaria infections.
  • the primary driver is the development, through repeated infections, of immunity against a wider variety of clones of malaria.
  • higher proportion of people with partial immunity allows them to develop low level assymptomatic parasitemia that may still be capable of transmission
  • other factors such as coinfections by nematodes and trematodes (roundworms and flukes) may also affect their immune response
133
Q

How sensitive is microscopy vs RDT’s for malaria?

What are the implications for Screen and treat programmes.

A
  • microscopy realistically detects parasitemia down to 50-100 p/µl under field conditions.
  • RDT’s have >90% specificity at levels > 200 p/µl
  • PCR is gold standard, but no currently available under field conditions 0.02 p/µl
  • clearly in programmes designed to detect assymptomatic pts for Screen and Treat in pregnancy or possible in programmes aimed at elimination transmission of malaria, currently available methods available under field conditions
134
Q

What are the existing interventions for malaria treatment and control?

A
  • LLINS (Long-Lasting Impregnated Bednets)
  • IRS (Indoor Residual Spraying)
  • Timely diagnosis and use of RDT’s at community level.
  • Effective Treatment using artemisinin-based combination therapies (ACT’s) that combine fast acting compounds that kill the majority of parasites and reduce gametocytes with a slower acting drug that clears the remaining parasites
  • Chemoprevention: IPTp (Intermittent Preventive Treatment with pyrimethamine) and Seasonal Malaria Chemoprevention (SMC, in Sahel region).
135
Q

What is schizogeny?

A
  • schizogony. : asexual reproduction by multiple segmentation characteristic of sporozoans (such as the malaria parasite)
136
Q

What were the findings and recommondations of Walker et el, Lancet Global Health 2016: What is the optimal combination of interventions in Africa?

What is most cost-effective intervention?

Then others?

What about the possibility of elimination of malaria in Africa?

A
  • universal coverage LLINs most cost efficient to reduce both burden and transmission
  • irrespective of the ecology
  • Optimal combination to reach pre-elimination
    • MDA is 2nd intervention in areas with mostly outside biting vectors
    • IRS is 2nd if mostly indoor biting vectors
  • not possible to achieve pre-elimination levels within 20 yrs in 51% of Africa, even with 90% coverage of LLINs, IRS and SMC
  • additional interventions to reduce parasite reservoir will be necessary
  • adding MDA to ITN’s and IRS increases areas where pre-elimination is reached from 49% to 91% with 3 rounds per year
  • Avoid 1 size fits all
137
Q

Outline possible methods of enhanced MDA.

Promise and problems?

A
  1. Single low dose primaquine (0.25 mg/kg) as adjunct Rx to ACT’s for P. falciparum
    • low dose ok with G6PD def without screening ok (Bancone et al, PlosOne 2016)
    • reduces risk of detectable gametocytes by day 8 by 65-75%
    • however modelling suggests low dose primaquine may have limited impact on transmission
  2. MDA & Ivermectin
    • Ivermectin kills mosquitoes feeding on recently treated people
    • higher doses (up to 2000 µgm/kg) well tolerated than singe dose of 150-200 µgm/kg used for onchocerciasis and filiariasis
    • IVERMAL trial suggests 3 days of 300 mg has major effect on mosquito survival up to 28 days post-treatment
    • 3 x 300 µgm/kg added to DHA-piperaquine may boost impact on malaria prevalence by 44-61%
    • likely most cost effective of extended MDA alternatives
138
Q

What is the commonest cause of splenomegaly in the tropics?

What causes it?

Where most common?

Who gets it?

How best managed?

A
  • Hyper-reactive malarial splenomegaly, HMS, (‘tropical splenomegaly’) is caused by excessive removal of IgM by the spleen due to repeated attacks of malaria over many years. It is postulated that the malarial –induced IgM targets CD8 suppressor lymphocytes* allowing unopposed activity of helper CD4 lymphocytes on B cells. As a result one finds reticuloendothelial hypertrophy.
  • Nonantigen specific CD8+ suppressor T lymphocytes (CD8+ Ts). Shut down immune responses in other cells.
  • Note that other causes of splenomegaly may be more frequent in some areas, e.g. lymphoma and cirrhosis in northern Nigeria. Note also that the acronym HMS has replaced the acronym TSS (tropical splenomegly syndrome) that was used in the past to indicate a tropical splenomegaly for which no cause was found.
  • HMS is most common in young women between 20 and 40 years of age. After that the spleen tends to fibrose and get smaller. A mild lymphopenia <10 x 109/L is common along with little change in the thrombocyte count.
  • There is marked shrinkage after anti-malarial therapy and many authorities recommend life-long proguanil 100 mg daily. HMS has been reported occasionally in Caucasians who resided for long periods in the tropics.
  • Up to 80% of some ethnic groups in Papua New Guinea have massive splenomegaly from HMS. Other causes of massive splenomegaly include storage diseases e.g. Gaucher’s Disease, Myelofibrosis and Chronic myeloid leukaemia.
139
Q

Treatment of P. Vivax

A

Treatment of P. vivax infections

P. vivax infections should be treated with an ACT or chloroquine in areas without chloroquine-resistant P. vivax. In areas where chloroquine-resistant P. vivax has been identified, infections should be treated with an ACT, preferably one in which the partner medicine has a long half-life. With the exception of artesunate + sulfadoxine-pyrimethamine (AS+SP) combination, all ACTs are effective against the blood stage infections of P. vivax.

In order to prevent relapses, primaquine should be added to the treatment; dose and frequency of the administration should be guided by the patient’s glucose-6-phosphate dehydrogenase (G6PD) enzyme activity.

140
Q

Treating neonate with P. vivax

A
  • ok to treat with chloroquine
  • in congenital infection, no sporozoites, so do not form hypnozoites, does not need primaquine
141
Q

In what P. vivax or ovale infections do you not need primaquine for hypnozoites?

A
  • congenital infection
  • infection due to transfusion
    • neither has sporozoites so no hypnozoites
142
Q

Outline the treatment guidelines 2015 for treatment of Malaria in pregnancy.

A
  • nb quinine resistance for Vivax very rare.
143
Q

What are WHO guidelines wrt Primaquine?

A
  • Must check G6PD status
  • to prevent relapse in P. vivax and P. ovale tx with 14 days 0.25-0.5 mg base/kg body weight in all transmission settings except​
    • preg women, infants < 6 mo, or women breastfeeding infants < 6 mo - or older unless known not to be G6PD def.
    • if G6PD def, consider relapse prevention by primaquine 0.75 mg bas/kg per week x 8 wk with close supervision for hemolysis
    • for women preg or breast feeding consider weekly chemoprophylaxis with chloroquine until delivery and bf completed then primaquine if G6PD neg
144
Q

In treating a pt with HIV and Malaria with ACT, what specific drug interactions should be considered?

(for others consult interactions database)

A
  • HIV +ve and P. falciparum
  • avoid artesunate-SP if being treated with co-trimoxazole (anti-folate)
  • avoid artesunate-amodiaquine if being treated with
    • efavirenze (FTC): LFT’s increased
    • AZT: pancytopenia, neutropenia
145
Q

Global Malaria Policy

Outline History

A
  • large scale vector programmes and mass drug administration began in early 20th century
  • 40’s & 50’s widespread spraying with DDT and use of chloroquine
  • 1955 WHO Global Malaria eradication programme eliminated malaria from 37 of 143 malaria endemic countries and 2 continents: Australia and Europe
  • In India Malaria fell from 110 million in 55 to <1 million in 1968, almost gone from Sri Lanka
  • Environmental movement , Silent Spring in 1962 led to end of use of DDT, subsequent dramatic resurgence and elimination programme abandoned in 1972
  • worse over next 30 yrs, min investment
  • recent improvements in Insecticide treated nets, ACT, RDT’s
  • malaria mortality fell globally but rebounded in SSA btw 1970 and 97
  • beginning in ‘98 with Roll Back Malaria program increased investment in control programmes
  • decline in incidence over last 25 yrs, ? due to programme or preceded it. ?other causes
  • 2005 President’s malaria initiative US govt
    • ITN’s
    • IRS
    • dx and tx with ACT’s
    • IPTp
    • basic environmental actoin
    • strengthening health systems and training of staff
    • national and local community involvement
146
Q

Distinguish between WHO definitions of Control, Elimination and Eradication of Malaria (2006)

A
  • in pre-elimination phase slide positivity rate in fever cases is <5%
  • in elimination phase <1 case/1000
  • between 2000 and 2015 17 countries eliminated malaria (0 cases for 3 yrs), 6 certified as having eliminated malaria, UAE, Morocco, Turkmenistan, Armenia, and most recently 2016 Kyrgyzstan and Sri Lanka.
147
Q

In how many countries has malaria been eliminated since 2000?

What are the targets for 2030?

A
  • 17
  • Targets 2030
    • reduce malaria incidence by 90%
    • reduce malaria mortality by 90%
    • eliminate malaria in at least 35 countries
    • prevent a resurgence of malaria in all countries that are malaria-free
148
Q

What is the Ross MacDonald Model?

  • What does it take account of?
  • What does it not account for?
A
  • Factors in the Ross-MacDonald model
    1. Mosquito factors
      • # of female mosquitoes per human host
      • average lifespan of mosquitoes
      • biting rate of mosquitoes on humans
      • (has to bite at least twice to spread infection)
      • extrinsic incubation period, i.e. time for a mosquito to become infectious after biting an infected human
      • mosquitoes must survive this incubation period to transmit disease
      • extremely important as temp affects development rate so highly affected by environment
    2. Human Factors
      • length of a human infection
    3. Mosquito/human interactions
      • susceptibility of mosquitoes to malaria, i.e prob of acquiring infection when biting
      • susceptibility of humans to malaria, ie prob of human acquiring infection when bitten
  • Does not account for human immunity or
  • “Superinfection” - where through repeated bites, a person is infected with more than 1 strain of parasite
149
Q

What is R0?

  • for measles?
A
  • the # of secondary infections produced by a single infection introduced into a fully susceptible human population
  • if R0 > 1, infection will spread
  • goal of eradication is to get R0<1
  • measles R0=12
  • pertussis, 16
  • smallpox 4
  • Ebola about 2
150
Q

What is aEIR?

A
  • (annual) Entomological inocculation rate
    • # of infectious bites per person per year
    • gold standard is human bite catches
    • other ways eg spray huts, count # of infectious mosquitoes, divide by # of people in hut
    • infectious mosquitoes defined as those with sporozoites detected in head
    • highly variable with small area and over time, may have seasonality
151
Q

hypo/meso/hyper/holo-endemicity

Define

A
  • prevalence of malaria infection in given area
    • holoendemic > 75%
    • hyperendemic 50-75%
    • mesoendemic 11-50%
    • hypoendemic < 10%
  • initially based on spleen counts in kids 2-9
  • now based on malaria smear surveys
152
Q

Stable vs Unstable malaria

What determines the difference?

A
  • stability determined by the average # of feeds that mosquito takes on human during its life - the stability index a/u. Threshold of 2.5 differentiates
    • stable malaria - insensitive to natural and man-made perturbations
    • unstable - very sensitive to climate and amenable to control
    • intermediate range between them
153
Q

What is the geographic distribution of the 5 species of malaria?

A
  • Falciparum
    • through tropics esp SSA & Melanesia
  • Vivax
    • Central/S. America, N. Africa, Middle East and India/Pakistan
  • Ovale: West Africa
  • Malariae: Worldwide
  • Knowlesi: Borneo and peninsular Malaysia
154
Q

What part of the human immune response is most responsible for protection against malaria?

How does malaria parasite avoid this?

A
  • antibodies are the main mediators of protection
  • spleen plays a major role in destroying infected red cells (p. falciparum avoid circulating through the spleen by sequestration)
  • P. falc var gene encodes large (>50) antigenic repertoire and expresses only one at a time, switching between expression of gene family members. This allows chronic infection to be establishe despite host immune response.
  • children develop repertoire of variant specific antibodies over time
155
Q

Why do women in high endemic malaria areas develop pregnancy-associated malaria affecting the baby with their 1st (sometimes 2nd) infections without getting very sick themselves.

A
  • since childhood they develop a large antibody repertoire against different strains of malaria where they live. This protects them from symptomatic parasitemia.
  • However placental tissue allows selection of a particular (PfEMP1) variant that binds to Chondroitin Sulfate in the placenta. The parasite infects the placenta, leading to low birth weight babies and high risk of maternal anemia, but relatively immune mom does not develop significant symptomatic parasitemia. After developing Ab against this, they are relatively protected in subsequent pregnancies.
  • In low endemic areas, mothers do not have repeated exposure to malaria so do not develop Antibody repertoire. If they contract malaria during pregnancy they both become parasitemic and develop placental malaria. Both Mom and baby are at risk.
156
Q

What is the status of malaria vaccines?

A
  • The only approved vaccine as of 2015 is RTS,S. It requires four injections, and has a relatively low efficacy (26–50%). Due to low efficacy, WHO does not recommend the use of RTS,S vaccine in babies between 6 and 12 weeks of age.[1]

The vaccine is going to be studied further in Africa in 2018.[2] Research continues into recombinant protein and attenuated whole organism vaccines.

  • It consists of the P. falciparum circumsporozoite protein (CSP) from the pre-erythrocytic stage. The CSP antigen causes the production of antibodies capable of preventing the invasion of hepatocytes and additionally elicits a cellular response enabling the destruction of infected hepatocytes.
  • It is conjugated with Hep B Ag and contains oil emulsion to boost immunogenicity. Efficacy trials in 2017, 2018.
157
Q

Epidemiology of malaria in returning travellers

  • How many cases UK, US?
  • What kinds?
  • Fatality rate?
A
  • Mean 1500 cases per year in UK
  • 2-10deaths per year
  • 75%-80% falciparum,10-15%vivax
  • 2000-2200 reported cases in France
  • 1700 cases in US
158
Q
A
159
Q
  • What kind of personal protection is available for travellers to malaria endemica areas?
  • What are available Personal mosquito repellants?
  • Which are effective
A
  • Personal Protection
    • knock down insecticides
    • pyrethroid impregnated nets
    • permethrin impregnated clothing
    • air conditioning
    • pyrethroid vaporizers
    • repellants
  • DEET 20-50% most effective, protects up to 12 hrs. Lower concentrations shorter.
  • Citronella for 30 min - not worth the trouble
  • Lemon Eucalyptus Oil 10-30% lasts 2-5 hrs (only proven “natural” repellant.
  • Picaridin 20% effective but not available
160
Q

Traveller malaria risk assessment

  • East Africa?
  • West Africa?
A
  • EA av risk 1.2%/ month
  • WA risk 7.6%/ month
  • related to location, activity and length of stay
161
Q
  • Distinguish between
    • Causal prophylaxis
    • suppressive prophylaxis
    • prophylaxis against hypnozoites
A
  • causal prophylaxis: prevents est of liver stage and development of blood forms
  • suppressive prophylaxis: directed agains rbc forms only
  • prophylaxis against hypnozoites
162
Q
A
163
Q

Re Malaria prophylactic drugs:

  • What areas are still chloroquine sensitive?
  • Where is chloroquine/mefloquin resistant plasmodium reported>
A
  • chloroquine sensitive: Central America and Caribbean, Egypt, northern parts of Arabian Peninsula, northern Argentina
  • Chloroquine/mefloquine resistance: South East Asia (Thai, Cambodia, Laos, Myanmar)
  • (one thing that may influence slowness to develop resistance is latitude. Cooler latitudes are areas of unstable malaria where mosquito barely has time to feed 3 times so likely very little mosquito superinfection and little opportunity for malaria genetic change.)
164
Q

Chloroquine/proguanil

Safety

Efficacy

contraindications

A
  • safe with limited side effects
  • declining efficancy, now only used for parts of South and Central America and Asian subcontinent
  • CI in epilepsy
165
Q

Mefloquine

adverse effects

Dosing

A
  • good protective efficacy
  • once weekly dosing
  • concerns about neuropsych side effects
    • cw atovaquone/proguanil mor commonn
  • nausea and dizziness also more common
  • s/e more common in women than men
  • 75% apparent by third dose
  • recent concerns about ?vestibular effects in US
  • Dosing:
    • start 2-3 wk before departure, take for 4 wk after
    • avoid in epilepsy, neuropsych probl
    • close fam hx of psych probls relative CI
    • need to warn pt to stop if they develop sx
166
Q

Doxycyline as malaria prevention

Effectiveness (which species)

dosinge

Contraindications

A
  • effective for falciparum, less effective against vivax
  • daily dosing: 1 wk before and 4 wk after
  • part useful in areas of high drug resistance in SE Asia
  • limited use in Children and pregnancy
  • concern about photosensitivity
  • vag candidiasis
  • occ heartburn
  • compliance very important
  • do NOT impair OC effectiveness
167
Q

Malarone

Whats in it?

How does it work?

Dosing

A
  • combination atovoquone 250 mg & proguanil 100 mg (1 tab daily)
  • Causal prophylactic - presents dev of parasites in liver
  • take 24-48 hr prior to arrival and 7 days after leaving
  • generic, costs much down
168
Q

Primaquine

How does it work?

A
  • causla prophylactic - potential unlicensed 2nd option - commonly used in USA (30 mg daily)
  • G6PD testing necessary
  • esp useful where vivax/ovale predominate - prevents hypnozoite development
  • can be used in kid
  • BUT CYP polymorphisms affect levels: ~5% of caucausians have inadequate levles
169
Q

Standby treatment for malaria

What is it?

Potential problems?

What about self dx?

A
  • alternative approach to prophylaxis
  • advise pts to take drugs for self treatment if they get a fever (common approach in Europe)
  • Potential problems
    • often used incorrectly
    • self dx poor
    • may prevent people from seeking med attention
    • 79% of travellers with fever did not use standby or seek med assistance, wrong regimen used
  • Self diagnosis
    • using RDT’s
    • accurate for p. falc, less for others
    • often poorly used
    • may be role for expeditions or very remote travel with careful training
170
Q

Standby Medication for malaria for travellers

Which drugs?

A
  • none licensed
  • should not replace chemoprophylaxis
  • may be appropriate for those at high risk, if far from med attention or travelling in countries with poor drug supplies
    • Atovoquone-proguanil
    • Co-artemether (Riamet)
    • Quinine (esp in preg)
    • Chloroquine (if no resistance)
    • Mefloquine - not recommended, poorly tolerated
171
Q

What is Presumptive anti-relapse therapy (PART)?

A
  • 14 day course of primaquine to eliminate potential hypnozoites after return
  • very effective
  • only approp after high risk visit to vivax-ovale area
  • should overlap with final week of standard prophylactic drug
172
Q

Special conditions

  • What Malaria prophylactic in
    • Renal failure
    • Hepatic failure
    • Epilepsy
A
  • Severe renal failure (<10 mg/ml)
    • mefloquine or doxy
    • atovaquone-proguanil can be used if CrCl>30 ml/min
    • Chloroquine can be used in mild/mod renal failure
  • Hepatic failure
    • severe liver disease: ltd data, consider atovoquone-proguanil
    • mod impairment: as above, mefloquine or proguanil
    • doxy can be used with caution if no alternative
  • Epilepsy
    • mefloquine and chloroquine should not be used: increase seizure threshold
    • doxy ok, currently recommend increase to 200 mg daily
      • atovoquone-proguanil emerging as best option but still limited data
173
Q

Anti-malarials and ART interactions

A
  • generally minor, all prophylactic regimens considered safe
174
Q

Children and antimalarials

Which can be used when?

A
  • Chloroquine/proguanil from birth
  • mefloquine from 5 kg
  • atovoquone-proguanil licenced above 11 kg, can be used from 5 kg
  • Doxy contraindicated under 12
  • No suitable regimen for child under 5 kg in resistant areas
  • Problems regarding breast feeding
175
Q

Conception and antimalarials:

How long should you wait?

A
  • need to allow enough time for drug to be eliminated form body
  • UK recommendations
    • mefloquine: 3 months
    • doxy: one week
    • Malarone: 2 wk
176
Q

Pregnancy and antimalarials

Which OK?

Breastfeeding?

A
  • C & P ok (extra folate)
  • doxy contraindicated (occ use before 15 wk)
  • mefloquine: some concerns about increased still birth rate. Caution in 1st trimester
  • No evidence for Atov-Proguanil but no evidence harm
    • may consider this in 2nd and 3rd trimesters in absence of other alternatives
  • Breastfeeding
    • no simple rec
    • mefloquine safe
    • doxy contraindicated (debate)
    • no evidence for atov-progu
    • in young children need to consider different regimens for mother and child