Malaria Flashcards
Where is malaria endemic
The whole tropical belt
Especially subsaharan africa
Who is malaria most common in
Childhood, neonates and pregnant women
Vector for malaria
Female anopheline mosquitos
esp anophelese gambiae
Five plasmodial species of malaria - plasmodium:
Falciparum
Vivax
Ovale
Malariae
Knowlesii - infrequent, zoonotic
What strain of malaria is most fatal
Falciparum
What two species can cause a dormant liver stage and therefore relapses
Vivax and ovale
PLasmodium malariae features
Chronic low level infection years to decades fluctuating
Cases of malaria and UK
1500-2000 cases per year
Where do most cases of malaria in UK come from
West africa - nigeria
Often holidaymakers, people who have family there
What is the life cycle of mlaaria
Female anopheline mosquito injects sporozoites into blood stream -> liver -> enter hepatic cell -> hepatic schizont (binary fission)
After 7 dyas rupture -> merozoites -> infect RBCs
Each RBC -> trophpzoites, plasmodium replicates -> schizont (haemozoin made in metabolism)
60s
-> cycles of red cell rupture every 48 hrs ->
gametocytes - sexual infection.
What immune protection naturally get in endemic areas
Immune cells in skin - goes after 6 months outside of malaria endemic areas
Why get spikes in fever on 48 hour basis
RBC schizonts (infected RBCs) rupture and release sporozoites into bloodstream every 48 hours
What allows plasmodium vivax to remain dormant
Vivax -> hypnozoites in liver - remain dormant and only rupture far down line
Pathology of malaria
RBC schizont rupture -> haemolytic anaemia
Glucose decreased (used)
Decreased liver function - hepatitis and splenomegaly
Exposure to damaged tissue - complement cascades and platelet aggregation - DIC
Sequestrian of infected RBC malaria
Altered rheology - less flexible
Electrical charge positive
Intra-cellular adhesion
More difficult to pass through microcirculation - omre likely to adhere to each other, other cells and internal cell wall
What organs are particuarly sensitivie to RBC infected
Brain
Kidneys
bell mesentery
Extremities
Pulmonary bed
What are severe features of malaria
Cerebral malaria w reduced GCS/seizures
Renal failure + anuria
ARDS
Tissue acidosis - microinfarct
Coagulopathy - exacerbated by tissue damage
Symptoms of malaria
FEVER
Rigors
Headache +/- confusion
Myalgia, arthralgia,
Nausea, vommitting, diarrhoea, dark urine
When do blood film for mlalaria
Anyone with fever returingin from endemic area
Signs of malaria
May be present, may be absent
Doesnt rule out
Fever
Jaundice
Pallor
Splenomegaly, hepatomegaly
Altered consciousness
Focal neurological signs
Coma
Indications for IV treatmnet in malaria (sev)
Cerebral involvement - reduced GCS/sezirues
Anaemia - Hb<8
Lactic acidosis <7.3
Renal failure Cr>265, <0.4ml/kg/hr urine - dark
Pulmonary oedema/ARDS
hypoglycaemia - BM <2.2 mmol/L
Shock - BP <90/60 (refractory to fluid resus)
Bleeding/DIC
Haemoglobinuria
How is severity of malrai graded
Proportion of infected RBCs on microsocpe of thin films
How will severity increase soon if see schizon on blood film
10 fold extremely soon - schizon about to rupture and infect 10x more RBC
Uncomplicated malaraia criteria
Parasitaemia <2%
No schizonts
No clinical complications
Oral treamtnet
(WHO recommends 5% - globally not UK)
Potentially severe disease criteria
Parasitaemia >2%
<2% with schizons
<2% w clinical complications
(WHO 5%)
Severe disease malaria criteria
Complications present, regardless of parasitaemia
Where is p.vivax endemic
Asia, south america
Wheere is p.ovale more common
West and central africa
Features of benigin malraal disease
P.vivax, p.ovale, p.malariae
<2% paraesitaemia
Dormant liver stages - hypnozoites, relapsing malaria
What strain can cause neprotic syndrome in malaria
P.malariae
V rare malaria cause
Nephrotic syndrome is rare aswell
Treatment for severe/complicated malaria
IV quinine or artesunate
How does quinine treat malaraia
Prevents production of haemozoin in RBC - malaria parasite poisons itself
Dose of quinine treatment of malaria
Loading dose 20mg/kg in 5% dextrose or dextrose saline >4 hours
Then 10mg/kg/8 hours for first 48 hrs
Then reduced to 12 hrly quinine if ocntinued
Side effects of quinine
Cardiac toxicity
Cinchonism
What ECG monitoring in quinine can show
Na channel blocking - electrical conduction disturb
QT intervals prolonged, QRS braod
What conitnuing treating malaria with after IV quinine
Oral doxycyclcine, clindamycin
What is cinchonism
Tinnutus, vertigo, headahce, nausea, abdo pains, visual disturbance occasionally blind
CI to treatment with quinine
Heart condutction problems
Cinchonism causing visual disturbance
How is artesunate given for malaria
2.4mg/kg IV at 0, 12, 24 hours then daily
Minimum 24 hrs therapy
What can be seen after artesunate treatment
Delayed haemolysis (membrane instability)
Mechanism of artesunate
Disrupts electric transport chani - RBC membrane instability
Broad spectrum anti arasite, v rapid clearance of parasite
Which drug has greater survival from malaria in children
Artesunate
Oral therapy for malaria
Artemether-lumefantrine (riomet/aloo)
4 tablets immediate, 8, 24, 36, 48 and 60 hrs
Atovaquone/proguanil (malarone) - 4 tablets daily for 3 days
Oral quinine sulphate 500mg 8hrly quinine for 5-7 days + doxycycline -200mg daily for 7 days or clindamycin (450mg 8hrly)
Why does doxycycline have to be prescribed with oral quinine/after IV quinine
Quineine is narrow spectrum antiparasitic - does not kill off maturing parasites
Doxycycline does
Hypnozoite therapy
Preventing relapse in vivax and ovale malaria
Primaquine 2 weeks
G6PD activity levels
Why check G6PD levels with primaquine treatment
Increased risk of haemolysis due to oxidative stress by metabolising drug - lower dose drug for longer period of time
Chemoprophylaxis for malaria - causal
Directe at hepatic stage - prevents enter blood
Continue for 7 days following last exposure
eg atovaquone/proguanil - maralone
Supressive chemoprophylaxis of malarai
Against erythrocytic stage
cont 4 weeks post exposure
Chloroquine, doxycycline, mefloquine
Why chloroquine used less for malarai prophylaxis
Global drug resistancce in malaria widespread
What pale skinned indivuals warn with doxycycline
hypersensitivity to sun
doxycycline side effects
gi upset
take with water while upright
moderate alcohol intake
who is mefloquine CI in
Major depressive disorders, psychiatric conditions, seizure s neuropsych profile
Physical prophylaxis malaria
Bed nets
Repellent esp after dusk
Long sleeved clothing
Accomodation
Lab tests for malaria
FBC
Quantiative buffy coats
Thick and thin films
Immunochromatographic rapid diagnositc tests
PCR
Antibody detection - immunoassays, flurorescence
What see on FBC in malaria
Low platelets
Leuco/neutropenia
DNA/RNA - fluroescent pops on haemotaology analysers on flow cytometry
What is quantitative buffy coat screen
Blood -> acridine orange coated capillary tubes and centrifugues
Nucleic acid fluroesces when excited with blue light under fluroscent microscope
Gold standard malarial screening and species differentiation
Thic and thin filmds
What are thin films stained with
Methanol fix, MGG stain pH 6.8
Giemsa stained thin films 7.2 = additional information
What stain are thick films used malaria
Fields stain - unfixed - needs to stand ofr an hour before stain
Mehtyl blue + stelin B = fields stain
Rapid malaria diagnostic tests what are they and what test for
Immunochromatography
HRP2/pLDH monoclonal antibodies tested for on strip
Which species are HRP2 and pLDH specific to
HRP2 - P.falciparum
pLDH = P.falciparu,, vivax, malariae, ovale
Positive RMT for malaria
P.falciparum = control and line 1
P.vivax, malariae, ovale - control and line 2
All 3 lines = p.falciparum +/- mixed infection
Can get false positives
PCR test for malaria
Parasiti nucleic acids detected by polymerase chain reaction
Sensitive, limitied use in acute health care settings - reference centres only. QUERY dual infection
What used to screen blood donations
mALARIAL antibody tests eg immunoassays, fluroescense
Routine investiations for mlaaria
FBC
Thick and thin films
Carestart combo rapid tests- HRP2, pLdh TESTS
Gametocytes on blood film
Characteristic crescent shape
Dont appear in blood for first 4 weeks
What se on blood film falciparum
Fine ring trophozoites
No red cell enlargement
Chromatin dots, multiple infestation
What stain shows mauers clefts
Giemsa stain
Dots inside red cells
P.vivax blood film
Red cells enlarged
Schuffners dots
Mature ring - large and coarse
P.malariae on blood film
Ring forms squarish appearance
bAND FORMS
mATURE SCHIZONTS - DAISY head appearance, up to 10 merozoites
No RBC enlarged
Chromatin dot on inner surg=face ring
Abundant haemozoin
P.ovale on blood film
Enlarged RBC
Large and coarse rings
Comet forms common, fimbriated - jagged edge
Mature schizonts large and coarse,6-1 merozoites similar to p.malariae
James dots - coarse
Microfilaria worms that can infect blood
Below in lymph and vessles
Most - Wuchereria bancrofti
Brugia malayi
Brugia timori
Loa loa - SC and subconjunctival tissue
Mansonella perstans - cavities
Mansonella ozzardi - mesenteric tissue
Samples taken for microfilia
MINIMUM of one day blood taken 1pm and one night blood at midnight
Test of choice for W.bancrofti infection
Antigen testing
ICT filiaris test card
Vector of loa loa (eye worm)
Manog fly
Microfiliaria - eye worms
Features of loa loa
west and central africa
Diurnal periodicity
Curves and kinks in body
Nuclei dense and dark stain extend to rounded tail
Fever patterns different strains
Vivax and ovale - tertian 48 hs
Malariea - quartian - 72 hrs
Falciparum - irregular spikes
What is chloroquine CI in
Epilepsy, pregnancy
When consider exchange therapy
if parasite count > 10% then exchange transfusion should be considered
