Malaria Diagnosis

Question 1

False positive causes on RDTs?

Answer 1

• High levels of circulating RF
• Acute typhoid fever
• Some evidence for Schisto mekongi, Hepatitis C, toxoplasmosis, dengue, leishmaniasis, Chagas disease and Trypanosoma brucei cross-reacting

Question 2

False negative causes on RDTs?

Answer 2

-HRP2 deletion
-P ovale curtisi (RDTs often fail)
-Operator error
-Poor storage conditions
-P knowlesi (sensitivity only roughly 10% with RDTs with the pan-LDH)

Question 3

Types of RDTs?

Answer 3

BinaxNOW - HRP2 (Pf), and aldolase (pan-malarial)
OptiMAL-IT - PfLDH and pan-Plasmodium lactate dehydrogenase
SD Bioline and Humasis - HRP2, pLDH (pan)

Question 4

Modes of testing for malaria?

Answer 4

RDT - HRP2 (P falciparum antigen, cross-reacts with HRP3), and LDH (less sensitive but helpful in deletions)
Microscopy - thick and thin smear
Molecular - PCR (often fails with Pow)
Whole genome sequencing

Question 5

Pros of malaria microscopy?

Answer 5

-Able to determine parasitemia
-Able to determine species
-Able to assess for schizonts (help predict future parasitemia)
-Relatively good for low resource settings
-Can ID non-malarial diseases

Question 6

Cons of malaria microscopy?

Answer 6

• Requires equipment (stains and microscope)
• Requires staff training
• Microscopist dependent

Question 7

RDT pros?

Answer 7

• Detect 2 parasite antigens: HRP2/LDH
• Good for low resource settings
• Low user training needed

Question 8

RDT cons?

Answer 8

• Less sensitive than microscopy
• Remain positive after treatment (up to 5 weeks)
• Pan-antigen is poor for P malariae and P ovale

Question 9

Malaria species?

Answer 9

P falciparum
P vivax
P knowlesi
P ovale (Pov curtisi and Pov wallikeri)
P malariae

Question 10

P falciparum clinical

Answer 10

Inc: 7-14d
-Malignant
-Tertiary fever (48h growth cycle)
-High fatality

Question 11

P falciparum distribution?

Answer 11

-All malarious zones
-Sub-Saharan Africa primarily
-Rare in South America

Question 12

P vivax clinical

Answer 12

Inc: 17-17d
-“Benign”
-Tertiary fever pattern
-Relapses occur (hypnozoites)

Question 13

P vivax distribution

Answer 13

-All malarious areas
-More temperate zones, widest distribution
-Partial limitation by Duffy blood group (full protection disproved)

Question 14

P knowlesi clinical

Answer 14

-Zoonotic
-Fast growth cycle (27h)
-Unpredictable fever
-High mortality rate

Question 15

P knowlesi distribution

Answer 15

-Southeast Asia (Malaysia)
Host: long and pig tailed macaques

Question 16

P ovale clinical

Answer 16

Inc: 12-17d
-“Benign”
-Tertiary fever (q48h)
-Low parasitemia
-Relapses occur (hypnozoite)

Question 17

P ovale distribution

Answer 17

-Tropics only
-Widespread in Africa
-Present in Asia and Oceania
-Absent in South America

Question 18

P malariae clinical

Answer 18

Incubation: 18-40d
-“Benign”
-Quartan malaria (72h growth cycle)
-Persistent (up to 70 years)
-Can cause kidney pathologies
-Low parasitemia
-Rare fatalities

Question 19

P malariae distribution

Answer 19

-All malarious areas
-Used to be considered rare however thought to be much more prevalent than previous

Question 20

P falciparum trophozoite features

Answer 20

RBC: same size
Number: can have multiple in cell
Trophozoite: single or double chromatin dots, thin, delicate cytoplasm
Dots: can have Maurer’s clefts, uneven and faint

Question 21

P falciparum schizont features

Answer 21

RBC: same size, can fill RBC
Pigment: dark pigment in one mass
Merozoites: 8-24

Question 22

P falciparum gametocyte features

Answer 22

Banana shaped

Question 23

P vivax trophozoite features

Answer 23

RBC: enlarged
Cytoplasm: can become amoeboid, can have band forms
Chromatin: large single dot
Pigment: yellow-brown pigment as they develop
Dots: Schuffner dots, finer than ovale, many

Question 24

P vivax schizont features

Answer 24

RBC: enlarged, may fill cell
Merozoites: 12-24
Pigment: yellowish-brown contained in one place

Question 25

P vivax gametocyte features

Answer 25

RBC: enlarged, almost fill cell
Pigment: scattered light brown pigment
Shape: round to oval
Dots: Schuffner’s dots, finer than ovale

Question 26

P ovale trophozoite features

Answer 26

RBC: enlarged, may have fimbriation, can have multiple
Cytoplasm: compact
Chromatin: large dot
Dots: Schuffner’s dots, larger than vivax

Question 27

P ovale gametocyte features

Answer 27

RBC: enlarged, almost fill RBC, fimbriation
Pigment: brown, more coarse vs vivax
Shape: round to oval
Dots: Schuffner’s dots visible

Question 28

P ovale schizont features

Answer 28

RBC: enlarged, fimbriation
Pigment: mass of dark brown
Merozoites: 6-14 with large nuclei

Question 29

P malariae trophozoite features

Answer 29

RBC: smaller
Cytoplasm: sturdy, may have band forms or basket forms
Chromatin: large dot
Pigment: coarse, dark brown

Question 30

P malariae schizont features

Answer 30

RBC: smaller, often fill RBC
Merozoites: 6-12 with large nuclei
Pigment: coarse, dark brown, can rosette

Question 31

P malariae gametocyte features

Answer 31

RBC: smaller, almost fill RBC
Shape: round to oval
Pigment: scattered dark brown

Question 32

What is HRP2?

Answer 32

Histidine-rich protein 2
-Specific for cytoplasm of P falciparum
-Cross-reacts with HRP3
-Can have deletions in this (horn of Africa)

Question 33

What is pfLDH?

Answer 33

-Plasmodium falciparum specific lactate dehydrogenase
-Expressed in intra-erythrocytic stage of life cycle