malaria Flashcards
Plasmodium falciparum is responsible for ~500,000 deaths yearly
yeppp; major cause of morbidity and mortality in the developing world
most aggressive
Causes of Human Malaria:
- Plasmodium falciparum (Pf)
- P. vivax (Pv)
- P. ovale (Po)
- P. malariae (Pm)
- P. knowlesi (Pk)
- Plasmodium falciparum (Pf)
Occurs worldwide
Responsible for greatest morbidity + mortality - P. vivax (Pv)
Occurs in Latin America, Asia, Middle East, North and East Africa - P. ovale (Po)
Only found in Central-West Africa - P. malariae (Pm)
Limited worldwide distribution - P. knowlesi (Pk)
Recently identified cause of human malaria in Malaysia, Borneo, other parts of SE Asia
what are we looking in a parasite smear in malaria?
trophozoites (ring forms)
some forms of parasites in malaria are latent in the
liver
Parasites reduce RBC membrane deformability resulting in hemolysis and increased splenic clearance leading to
anemia
Once within RBCs, parasites digest hemoglobin
toxic metabolite (hemozoin) is stored in the parasite’s food vacuole
why is P. falciparum so mean?
no latent stage goes directly to do the RBC and invades them alllllll.
No latent stage (no hypnozoites)
Only invade senescent (old) RBCs
Mildest form of malaria, can persist at low levels for years
No sequestration
P. malariae
After the initial liver stage, some parasites remain dormant as hypnozoites for weeks-years, allows for clinical relapses
Only invade reticulocytes (young RBCs)
Generally less severe disease
No sequestration
P. vivax/Ovale
increased disease severity for malaria (4)
- children
- pregnancy
- non-immune host
- HIV infection
decreased severity for malaria (4)
- premunition- sustained repeated infection but last only a couple of months
- sickle cell trait
- absence of Duffy blood group- no infection
- certain HLA types and thalassemia traits
Mean incubation period for malaria
= 10-15 days
Acute malaria attack classically has three stages:
- Chills or rigors (30-60 mins)
- High fever with diaphoresis, HA, GI symptoms
- Period of intense sweating
Do we see some enlargement of an organ in malaria?
yep, splenomegaly and hepatomegaly is seen
severe malaria
badddddd, mortality is >20%, there is an intense cytokine response to parasite proteins released during shizont rupture and there are metabolic derangements
** pregnancy is a risk for severe disease
cerebral malaria
cuased by P. falciparum that results in sequestration and resultant host immune response
We see Sludging of Capillaries.
it leads to confusion, seizures and coma and about 10% of children who survive will have long term neuro-psychological deficits
malaria diagnosis
use a thick and thin smear; where the thick is more sensitive but thin is more specific
**stained with Giemsa/Wright’s
Normal size RBCs; Small ring forms (”stereo headphones”);
Multiply infected cells; High grade parasitemia
Rare banana shaped gametocytes;
Developing forms almost never seen
P. falciparum:
Rapid Antigen Detection Tests (RDTs)
Detect parasite proteins (histidine rich protein-2 of Pf and parasite specific LDH or aldolase antigens) in finger prick blood samples
- Advantage: easy to use, require minimal equipment/ skill
- Disadvantage: cannot quantify parasitemia, cannot pick up low level infection, remain positive for 7-14 d post-Rx
other diagnostic tests for malaria
- PCR
Can detect <10 parasites per 10L of blood; species specific
>90% sensitive; ~100% specific
Turnaround time is slow and testing is expensive
Can remain positive for several weeks after curative treatment
Can be done at CDC for free (along with resistance testing) - Serology
Detects Ab against malaria parasites
Does not detect current infection per se, but rather measures past exposure
Principles of Management: Definitions:
Prophylaxis
Medication taken at regular intervals to kill one or more life stages of the parasite to ______ clinical illness
Critical to prophylactic treatment is administration _______________; dosing/duration is drug dependent
Treatment
1. __________ eradication of RBC trophozoites and schizonts
- ________ eradication of RBC trophozoites, schizonts and hepatic schizonts(hypnozoites)
Principles of Management: Definitions:
Prophylaxis
Medication taken at regular intervals to kill one or more life stages of the parasite to prevent clinical illness
Critical to prophylactic treatment is administration before, during and after exposure; dosing/duration is drug dependent
Treatment
1. Clinical cure: eradication of RBC trophozoites and schizonts
- Radical cure: eradication of RBC trophozoites, schizonts and hepatic schizonts(hypnozoites)
active against blood stage; used for treatment and prophylaxis
Blood schizonticide:
active against liver stages of parasite; used for treatment and prophylaxis
Tissue schizonticide:
active against sexual forms of parasite, interrupts transmission to mosquito
Gametocide:
malaria treatment caviat
requires more than 1 drug regimen…. resistance occurs
Arylaminoalcohols: Quinine and Quinidine
not really used clinically but for boards yes, this is a treatment choice. it needs to be combined with another drug. contraindication is QT prolongation and a classic SE is tinnitus/deafness
Oral agent for prophylaxis for sensitive Pf (taken weekly) and treatment of sensitive malaria species, particularly Pv
Resistant Pf strains widespread
Must be given with primaquine or tafenoquine for treatment of Pv/Po to prevent recurrence
Classic Side Effects:
Pruritis (w/o rash) in dark skinned persons; exacerbation of psoriasis
Irreversible retinopathy if prolonged exposure to high doses
chloroquine
Oral agent for prophylaxis for Pf (taken weekly) and treatment of malaria
Resistant falciparum seen in SE Asia
Classic Side Effects:
Neuropsychiatric: seizures, abnormal dreams, psychosis, anxiety, depression
CV: QT prolongation
Contraindication: if hx any of the above issues at baseline
mefloquine
Oral agent active against hypnozoite forms of Pv/Po
Prevention of relapse after infection with Pv/Poradical cure
Presumptive therapy against relapse after possible exposure to Pv/Poterminal prophylaxis
Resistance: Pv resistance in some areas
Classic side Effects
Acute hemolysis if G6PD deficiency—Must check G6PD prior to use
Contraindication: G6PD deficiency; pregnancy (because cannot know G6PD status of fetus)
primaquine
primaquine
treatment for latent phase of P. ovali
FDA approved 2018 for prophylaxis of Pf AND Pv in adults AND for radical cure of Pv
First new antimalarial approved in >60 years
Kills dormant liver stage of P. v
Side effects: generally well tolerated; occasional delayed hemolytic anemia
Contraidication:
G6PD deficiency, pregnancy; history of mental illness
tafenoquine
Oral fixed dose combination for prophylaxis (taken daily) and treatment of Pf
Resistance: develops rapidly to either agent when used alone; seen in parts of SE Asia
Side effects: generally well tolerated
Contraindication: significant renal dysfunction
atovaquone/proguanil
PO, IM, IV, PR: used in combination with other agents for treatment of Pf
Artemether-Lumefantrine fixed dose combination for uncomplicated Pf
IV Artesunate
Not FDA approved, but is recommended as first line choice for severe malaria
Available from CDC
Must be given with a second agent to prevent resistance
Superior to quinine: better efficacy and tolerability
Resistance: in parts of Asia
Side Effects: generally well tolerated
Artemisinin derivatives
Artemisinin derivatives
not FDA approved but it is main one for severe malaria
Always used in combination with another antimalarial drug, for treatment of Pf usually a rapidly active agent
Can also be used for prophylaxis
doxycyline
Always used in combination with another antimalarial drug for treatment of Pf, usually a rapidly active agent (e.g. artemesinin)
clindamyicin
usually to treat infection above the diapghram
recurrence of initial infection due to dormant liver stages (P. vivax and ovale)
Relapse:
incomplete eradication of initial parasitemia, most likely due to resistance or inadequate levels of antimalarials
Recrudescence:
in areas of intense transmission, new infection with a different malaria parasite, from additional mosquito bites
Re-infection:
loss of susceptibility to therapeutic levels of antimalarials
Resistance:
