Malaria Flashcards
Species of Malria that can be dormant
P Vivax
P Ovale
- form hypnozoites in the liver which can lie dormant for months to years resulting in relapses
Sexual reproduction stage?
Occurs?
Sprogony
Occurs in anopheles mosquitoes
Mosquito takes gametocytes during blood meal
Male and female gametocytes form oocysts
Oocysts rupture to sporozoites
Asexual reproduction?
Schizogony
Occurs in human (ex-erythrocytic or erythrocytic)
Schuffners dots
P vivax
P ovale
Ziemanns stippling
P malariae
Sinton and Mulligans stippling
P Knowelsi
Maurers Clefts
P Falciparum
Quotidian fever
24hrs P Knowelsi
Tertian fever
48hrs:
P falciparum
P vivax
P ovale
Quartan fever
72hrs
P malariae
What is cytoadherence?
Occurs in P Falciparum
Knobs on RBC surface, cause cytoahderence
Reduces clearance from spleen as get sequestration of mature trophozoites
If you see mature schizonts in P Flaciparum smear?
Hyperparasitemia
Patent parasitemia
Sub patent
Pyrogenic Density
Detected by optic microscopy (>50 ul)
Parasites in blood but not detected by optic microscopy (<50)
PD is the level of parasitemia at which fever occurs (<10,000 in non immune)
Recrudescence vs relapse
Renewed detection of parasitemia arising from survival of undetectable erythrocytic parasites- often failed anti-malarial treatment
Relapse is due to hipnozoties (p ovale and p vivax)
Average incubation periods
P Vivax and Ovale (13 days)
P malariae (28 days)
P falciparum (12)
Hypoendemic
Spleen rate or parasite rate <10% in children
Mesoendemic
SR or PR 11-50% in children 2-9yrs
Hyperendemic
SR or PR >50% in children (2-9yrs)
Adult SR is also high
Holoendemic
SR or PR >75%
Adult SR is low
Stable vs Unstable Malari
Stable malaria is found in highly endemic populations who have high immunity, epidemics are unlikely.
Unstable is low endemicity and low immunity, transmission rates vary and epidemics likely
Which strain of P Vivax has long latency periods?
Temperate (Hibernans) and subtropical strains (St Elizabeth and Korean)
Relapse seen in 8-10 months
Which strain of P Vivax shows short latency?
Tropical strain (1 month)
Eg Chesson (New Guinea)
Premunition?
State of partial immunity seen in areas of stable malaria.
Asymptomatic parasitemia common, reduces asexual parasitemia and production of gametocytes. Controls, does not prevent infection
Loss of exposure, get loss of immunity (6 months)
Immunity in stable malaria
Infants partially protected for 3-6months (maternal IgG)
Infected young children have high parasitemia causing severe disease
Older children who survive develop premunition and adults typically have asymptomatic parasitemia, rarely severe malaria
Immunity in unstable Malaria
Immunity low
Severe infection in all age groups including adults
Nutritional factor affecting malaria in host
Iron deficiency associated with reduced risk of malaria
(In areas with good malaria controlz do not withhold iron in anaemic pts)
What is hereditary ovalocytosis?
Reduces invasion by P Falciparum and P Vivax seen in SE Asia
What is Duffy negative genotype
Resistant to invasion by P vivax
Seen in West Africa, African and American blacks
Genetic factors inducing immunity in host
1) Haemoglobin S (sickle cell trait), mainly protects against severe cerebral malaria (p falciparum)
2) Duffy antigen negative (West Africa stops P Vivax invasion)
3) Heredity ovalocytosis seen in SE Asia, protective against p falciparum and p vivax
Other host factors genetic immunity
B and alpha thalassemia
G6PD deficiency
Haemoglobin AC and CC- reduced cytoadherence
Anthropophily vs Zoophily
Anophele mosquitoe preference human vs animal blood
Dominant species in Peru
P Vivax
P Vivax appearance
-increased RBC size
-hipnozoites round ovid body
-irregular and pale
-male gamerocytes pinkish stain, female more blue
What are VSAs?
Found in P Falciparum parasites in placenta
Cause placental sequestration
P falciparum effects on newborn in stable malaria?
-Doubles risk of LBW (use chloroquine proph)
-IUGR main cause, will cause 70% IUGR and 36% preterm delivery
-Doubles risk of stillbirth
P Falciparum effects on pregnant women in stable area
-primigravid at greatest risk
-often severe anaemia, can be asymptomatic
-congential malaria usually clears spontaneously
P Falciparum effects on pregnancy in unstable area
Affects all parities of women
Cerebral malaria, pulmonary edema and death
Still birth, LBW and preterm delivery 4× as high
P Falciparum effects on Infant in unstable area
Increased risk of congenital malaria (risk continues up to 6wks post delivery)
Anaemia 3x risk
Reduced transplacental maternal antibodies (reduced response to infections)
Multigravid babies at increased risk
Increases risk of disease later in life
P Malariae Tx
Chloroquine Base (3 days)
P vivax Tx
Chloroquine Base (3 days)
And Primaquine Base (7 days) kills hipnozoites
Uncomplicated P Falciparum Tx
ACT: artesunate, mefloquine, primaquine
Uncomplicated P Falciparum in Pregnant woman (1st Trim)
Quinine Salt and Clindamycin
For 2nd and 3rd Trim ACT
Why can you not give primaquine to children <6mths
G6PD deficiency
Are hypnozoties present in congential malaria
NO!
What % parasitemia in severe malaria?
40%
Tx of P Falciparum in traveller
Atorvoquone/Proguanil or
Artemether/lumefatine or quinine and Doxy
Treatment of P Vivax relapse
Chloroquine 3 days
Primaquine 14 days
What drugs are hepatic schizonticides?
Atorvoquine Proguanil
Primaquine
What drugs are hypnozoiticides
Primaquine
What drugs are blood stage schizonticides?
Atrovoquone-proguanil
Doxycycline
Mefloquine
Chloroquine
Where is most imported Malaria from? Most common cases
88% Africa
61% west africa
Falciparum nearly every case- typically within 1 month
Clinical Manifestations of severe malaria?
Any one of:
Prostration
GCS <11
Resp distress
Convulsions
Circulatory collapse
Pulmonary oedema
Abnormal bleeding
Haemoglobinuria
Lab features of severe Malaria?
Severe anaemia
Hypoglycemia
Acidosis
Renal impairment
Lactate >5
Hyperbiliruninaemia
Hyperparasitemia (2% if non immune or 10% endemics)
Hyperparasitemia in P Falciparum
2% non immune
10% endemics
Binax card?
Malaria rapid test
Good sensitivity for P Falciparum, not the others
Tx of Complicated Malaria
IV artesunate
Tx of suspected resistant P falciparum (uncomplicated)
Aetemether/Lumefantrine
Atorvoquone/Proguanil
Quinine plus doxy
Mefloquine
What tx for P Falciparum do you not give if contracted in SE Asia?
Mefloquone
Quinine plus doxy
Give atorvoquone/proguanil
Where is P Knowelsi from?
Borneo (Malaysia)
Thailand
Philippines
Burma
Prophylaxis Tx in Traveller
Atorvoquone/Proguanil or Doxycyline or Tafenoquine or Mefloquine (not SE Asia!)
What must you do before giving tafenoquine
Check G6PD levels!!
Mefloquine prophylaxis Regimen
Important SE
Weekly and for 4 weeks post travel
Best for longer trips
NOT for people with psychiatric disorders
Doxycycline as prophylaxis Regimen and side effects?
Daily dosing including 4 weeks post travel
Photosensitivity, GI irritant esophageal ulcers, vaginal candida
Miss 1 day- get malaria
Atrovoquone/Proguanil Tx regimen
Highly effective especially against P vivax
Daily plus 7 days after
V expensive
Primaquine Phosphate as prophylaxis
Only recommended as alternative for P Vivax
Need to test G6PD
Tefanoquine as prophylaxsis Regimen
Not in Children
Must have >70% G6PD function
Need loaded dose of once weekly and then take every day in malaria zone for 3/7
Which countries account for almost half cases worldwide?
Nigeria
DRC
Uganda
Mozambique
What can cause recrudescence?
Resistance (Vivax)
Incomplete treatment
Unusual PK
Immunodeficiency
Where is seeing emerging resistance to Chloroquine in P Vivax?
Indonesia
Papa New Guinea
Sabha
P Falciparum Pre patent period
Incubation period
9-11 days
9-14 days
P vivax prepatent and incubation period
P vivax is mainly found in Asia, SA and horn of Africa
Prepatent 11-13 days
Incubation 12-17 days and 6-12months
P ovale incubation and prepatent period
Can infect Duffy negative immature RBCs
Mainly subsaharan Africa
Prepatent 10-14 days
Incubation 14-18 days
What is P Malariae associated with?
Nephrotic syndrome
Why do you sometimes need PCR to speciate P Knowelsi?
Appearance similar to p malariae, differentiate with PCR
Diagnosis of malaria principles
Need to diagnose quickly (<1hr)
Anticoagulant not recommended
Stain with giemmsa stain 7.2
Thin smear: quantification against RBC
Thick smear: quantification against WBC
How many merozoites in schizont of P Falciparum?
40
When is a thick smear inaccurate?
When parastie count is high
When can a thick smear slide be pronounced negative?
Only when minimum of 100 fields have been examined correctly
When is a thin smear inaccurate and when can it be pronounced negative?
Inaccurate when parasite count is very low
Only deemed negative when a minimum of 800 fields have been examined
What malaria has Maltese cross
Babesia Malaria
Resembles Falciparum!
Babesia species
B Microti (NE and Midwest USA)- usually asymptomatic
B Divergins (Europe) - severe disease
M01 found in Missouri
How do you treat babesia malaria?
Atovaquone and azithromycin
Clindamycin and quinine (if severe)
Key points for RDTs
1)The accuracy of diagnosis of uncomplicated P Falciparum infection is equal or superior to routine microscopy
2)Sensitivity decreases at low parasitemia
3) use in combination with microscopy!!
HRP2 is RDT for what?
P Falicparum
pLDH
Pan species
Can use ones with isomers for Vivax or Falciparum
P Aldolase
Pan Species
Certain requirements for a RDT to be allowed on market
P Falciparum and P Vivax detection score of >75%
False positive rate <10%
Invalid rate <5%
Also consider: ease, storage, price
What causes false negatives in RDTs?
Low P Falciparum parasitemia
Plasmodium other than Falciparium
User interpretation
HRP-2 causes of false negatives
High Falciparum parasitemia
Pfhrp2/3 Gene deletion
Causes of false positives in RDTs?
Persistence HRP-2
Delayed reading
Buffer substitution
Cross reaction between species
Concomitant conditions eg chagas disease, dengue, toxoplasmosis
Prozone effect
Cause of false negatives as high antibody titre interacts with formation of antibody-antigen lattice
Where is Pfhrp2/3 gene deleted?
Most commonly amazon basin
Now in Mali, India, Africa
40 countries have gene deletions
What species are RDTs not great for?
P Ovale
P Malariae
P Knowelsi
What do you do of testing for P Falciparum in area where >5% missed due to pfhrp2 deletion
Use a combination of HRP2 and pf-LDH or combination of pf-LDH and pan-LDH
PCR for malaria testing
Differentiates species
Good when low parasitemia on blood film
When do you use malaria serology?
NOT in acute malaria- takes time for antibodies
Useful for screening blood donors
When is LAMP good?
Context of malaria elimination
High NPV- good to r/o imported Malaria in non-endemic countries
Define uncomplicated hyperparasitemia
> 4% parasitemia but no features of complicated malaria
Severe malaria defined as? Clinical features
One of:
GCS<11
Prostration
More than two convulsions in 24hrs
Pulmonary oedema
Significant bleeding
Shock
Lab categories of severe malaria
Acidosis or lacate >5
Hypoglycaemia
Hb <7 or hct <20 and parasite count >10,000
Renal impairment
Jaundice and parasite count >100,000
Hyperparasitemia (>10% endemic and >2% non immune)
Examples of ACT
Artemether-lumefantrine
Artesunate-amodiaquine
Artesunate-mefloquine
How long ACT
3 days;
Minimise resistance
Good adherence
Less risk of failure
Less risk of gametocytaemia
How do you reduce transmission of P Falciparium
In low transmission areas give single dose of primaquine on first day of ACT tx
Do not need G6PD testing as v low dose
AVOID in pregnant woman and babies <6mths
What happens if recurrence of P Falciparum?
If within 28 days- alternative ACT
If after- use first like ACT but avoid use of mefloquine as increases neuropsychiatric reactions
Tx of pregnant woman in first trimester with P Falciparum?
Artemether-lumefantrine
What ACT to avoid during first trim pregnancy?
Sulfadoxine-pyrimethamine
What do you avoid in pregnancy and lactating women who have malaria?
Primaquine and tetracyclines
What to avoid in Tx uncomplicated P Falciparum in HIV taking co-trimoxazole?
Avoid Artesunate-SP
What to avoid in tx of P Falciparum malaria in HIV patient on efavirenz or zidovudine?
Artesunate- Amodiaquine
Tx when malaria species unknown?
ACT
Tx of Vivax, knowelsi, ovale, malariae
ACT or chloroquine
If chloroquine resistance what Tx
ACT
How to prevent relapse in Ovale and Vivax
14 days primaquine
G6PD Def common where?
Africa and Asia
G6PD genetics?
X linked
Much more common in men
What time do in females heterozygous G6PD def?
Need quantitative test, do not give them tenefoquine
What to do if G6PD def? (<30%)
8 week course of weekly primaquine
