MMI 426 - Lec 1 Malaria + Babesia

after what taxonomic rank does malaria and babesia diverge

after class (aconoidasida)

name of parasite that causes malaria

plasmodium

Charles Louis Alphonse Laveran

saw parasites inside RBCs and won nobel prize

malaria vector

Anopheles spp. mosquitoes

parasites that cause malaria human infection

• P. falciparum

• P. malariae

• P. ovale

• P. vivax

• P. knowlesi (zoonotic)

Quinine

fever tree bark used during the 19th century to treat malaria

Artemisinin

used to treat malaria today

which plasmodium sp causes the most death/is most severe

P. falciparum

which plasmodium sp can remain dormant in liver and cause relapsing infections

P. vivax

common regions for P. falciparum

• Sub-Saharan Africa

• New Guinea

• Central and South America

• Southeast Asia

banana-shaped gametocyte

feature exclusive to P. falciparum

common regions for P. vivax

• Central and South America

• India

• Southeast Asia

• Eastern Africa

parasite that primarily causes malaria in primates

P. knowlesi (SE Asia) but human cases also rising

malaria symptoms

fever

malaria severe manifestations

cerebral malaria

malarial parasites with longest incubation time

P. ovale (18-40d)

malarial parasites with shortest incubation time

P. falciparum (9-14d)

main cause of returning travellers to Canada with fevers

malaria (20-30%) of cases-- therefore we check pt travelling history FIRST

cerebral malaria

• most morbid complication of malaria

• affects 1% of children w/ P. falciparium

PfEMP1

• major virulence and immune-evasion protein of P. falciparum

• expressed on infected RBC surfaces

• extracellular domains can bind to different host endothelial receptors

PfEMP1 expression

• cytoadherence

• sequestration

• microvascular obstruction/inflammation

• tissue injury

clonal antigenic variation

• switching expression from one gene to another when host antibodies develop against one gene = defense mechanism for parasite against host antibody response

• PfEMP1 does this

how many genes is PfEMP1 encoded by

~60 var genes

gold standard for malaria diagnosis

microscopy: thick and thin blood smears

BinaxNOW

• a rapid antigen test for malaria (immunochromatigraphic test)

• T1 targets HRP2 for P. falciparum

• T2 targets pan-malarial antigen common to all other malaria species (pan-aldolase)

cons of using BinaxNOW

may miss HRP2/3 mutants

malaria diagnostics

• microscopy

• RATs (BinaxNOW)

• PCR

• LAMP Assay

Illumigene/Alethia

• malaria LAMP assay

• detects Plasmodium spp. DNA in EDTA whole blood by targetting 214 bp sequence of mitochondrial noncoding region

LOD for P. falciparum using LAMP

2 parasites/uL of blood

LOD for P. vivax using LAMP

0.125 parasites/uL of blood

how does LAMP work

• uses 4-6 primers targetting 6-8 regions of DNA for highly specific amplification at a constant temperature

• DNA Pol allows primers to bind and make look structures for amplification of the loops and additional annealing of primers

• visualize by eye (can also add Mg Pyrophosphate to observe white ppt)

treatment for liver parasites

primaquine and tafenoquine

resistant malarial parasites

confirmed in P. falciparum and vivax

RTS,/AS01

- vaccine against malaria, recommended for children >5 months in regions with high P. falciparum transmission
- targets P. falciparum CSP
- protection short lived; waning immunity

R21/Matrix-M

another vaccine against malaria recomended by WHO in 2023

elimination definition

interruption of local transmission of a specified malaria parasite species in a defined geographical area as a result of deliberate activities

elimination strategies for malaria

vector control

what must malaria treatment target

both blood and liver stages as drug resistance increasingly encountered

first case of Babeisa

discovered by Victor Babes in 1888 inside RBCs of cattle suffering from a severe hemolytic disease

Babesia epidemiology

Ixodes spp. ticks infects a range of wild + domestic animals

Babesia vector

Ixodes spp. ticks

Babesia microti

responsible for most cases in NA

B. duncani

found in PNW

B. divergens

detected sporadically

primary host for B. microti

white-footed mouse

definitive host for B. microti

tick

dead-end host for B. microti

humans

clinical manifestation of Babesia

mostly asymptomatic

Babesia symptoms

• fever

• chills

• sweating

• muscle aches and pains (myalgias)

• fatigue

• hepatosplenomegaly

• hemolytic anemia

Babesia incubation period

1-4 wks

Babesia diagnostic methods

• microscopy

• PCR

• serological tests (IFA

microscopy for Babesia diagnosis

• make thick and thin films

• look for maltese cross (tetrads)

• looks similar to P. falciparum

IFA

detects fluorescently tagged antibodies bound to parasite antigens on slides

ELISA

detects host antibodies against the parasite antigen in serum

Babesia treatment

• target mitchondria and apicomplast using atovaquone + azithromycin

• clindamycin + quinine also used

vaccines for Babesia

no current approved vaccines for huan babeiosis