Malaria Diagnosis Flashcards
False positive causes on RDTs?
- 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
False negative causes on RDTs?
-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)
Types of RDTs?
BinaxNOW - HRP2 (Pf), and aldolase (pan-malarial)
OptiMAL-IT - PfLDH and pan-Plasmodium lactate dehydrogenase
SD Bioline and Humasis - HRP2, pLDH (pan)
Modes of testing for malaria?
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
Pros of malaria microscopy?
-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
Cons of malaria microscopy?
- Requires equipment (stains and microscope)
- Requires staff training
- Microscopist dependent
RDT pros?
- Detect 2 parasite antigens: HRP2/LDH
- Good for low resource settings
- Low user training needed
RDT cons?
- Less sensitive than microscopy
- Remain positive after treatment (up to 5 weeks)
- Pan-antigen is poor for P malariae and P ovale
Malaria species?
P falciparum
P vivax
P knowlesi
P ovale (Pov curtisi and Pov wallikeri)
P malariae
P falciparum clinical
Inc: 7-14d
-Malignant
-Tertiary fever (48h growth cycle)
-High fatality
P falciparum distribution?
-All malarious zones
-Sub-Saharan Africa primarily
-Rare in South America
P vivax clinical
Inc: 17-17d
-“Benign”
-Tertiary fever pattern
-Relapses occur (hypnozoites)
P vivax distribution
-All malarious areas
-More temperate zones, widest distribution
-Partial limitation by Duffy blood group (full protection disproved)
P knowlesi clinical
-Zoonotic
-Fast growth cycle (27h)
-Unpredictable fever
-High mortality rate
P knowlesi distribution
-Southeast Asia (Malaysia)
Host: long and pig tailed macaques
P ovale clinical
Inc: 12-17d
-“Benign”
-Tertiary fever (q48h)
-Low parasitemia
-Relapses occur (hypnozoite)
P ovale distribution
-Tropics only
-Widespread in Africa
-Present in Asia and Oceania
-Absent in South America
P malariae clinical
Incubation: 18-40d
-“Benign”
-Quartan malaria (72h growth cycle)
-Persistent (up to 70 years)
-Can cause kidney pathologies
-Low parasitemia
-Rare fatalities
P malariae distribution
-All malarious areas
-Used to be considered rare however thought to be much more prevalent than previous
P falciparum trophozoite features
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
P falciparum schizont features
RBC: same size, can fill RBC
Pigment: dark pigment in one mass
Merozoites: 8-24
P falciparum gametocyte features
Banana shaped
P vivax trophozoite features
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
P vivax schizont features
RBC: enlarged, may fill cell
Merozoites: 12-24
Pigment: yellowish-brown contained in one place
P vivax gametocyte features
RBC: enlarged, almost fill cell
Pigment: scattered light brown pigment
Shape: round to oval
Dots: Schuffner’s dots, finer than ovale
P ovale trophozoite features
RBC: enlarged, may have fimbriation, can have multiple
Cytoplasm: compact
Chromatin: large dot
Dots: Schuffner’s dots, larger than vivax
P ovale gametocyte features
RBC: enlarged, almost fill RBC, fimbriation
Pigment: brown, more coarse vs vivax
Shape: round to oval
Dots: Schuffner’s dots visible
P ovale schizont features
RBC: enlarged, fimbriation
Pigment: mass of dark brown
Merozoites: 6-14 with large nuclei
P malariae trophozoite features
RBC: smaller
Cytoplasm: sturdy, may have band forms or basket forms
Chromatin: large dot
Pigment: coarse, dark brown
P malariae schizont features
RBC: smaller, often fill RBC
Merozoites: 6-12 with large nuclei
Pigment: coarse, dark brown, can rosette
P malariae gametocyte features
RBC: smaller, almost fill RBC
Shape: round to oval
Pigment: scattered dark brown
What is HRP2?
Histidine-rich protein 2
-Specific for cytoplasm of P falciparum
-Cross-reacts with HRP3
-Can have deletions in this (horn of Africa)
What is pfLDH?
-Plasmodium falciparum specific lactate dehydrogenase
-Expressed in intra-erythrocytic stage of life cycle
