Malaria Flashcards
1
Q
What causes malaria?
A
Plasmodia species
2
Q
Where are the 2 places plasmodia bugs can live?
A
- Liver
2. RBC
3
Q
Which place are malaria bugs if you have symptoms?
A
RBC
if in liver- no symptoms
4
Q
What transmits malaria?
A
Mosquito (female anophele)
5
Q
How do plasmodia reproduce in mosquito and humans?
A
Sexual in mosquio
Asexual in human
6
Q
What do you see in the RBCs with malaria?
A
Ring forms
7
Q
What is plasmodia called when it initially affects you and then heads to the liver?
A
Sporozoites
8
Q
What is plasmodia called when it affects RBC?
A
Meroaotes
9
Q
What is the sexual stage of P. Falciparum called?
A
Gametocytes (these can be taken up by mosquitoes and then transmitted to other people)
10
Q
What is a hypnozoite?
A
When plasmodia is in the dormant stages in the liver
11
Q
What 2 species of plasmodia have hypnozoites and what can this cause?
A
P. Vivax and P. Ovale
-Causes relapses
12
Q
Fever?
A
IL-1, IL-6, TNF-alpha
13
Q
What cycle are the relapsing symptoms due to?
A
Asexual
14
Q
What is really important in diagnosing malaria?
A
History of travel
- Falciprum: Africa
- Vivax: SE Asia or SA
15
Q
Who will you see malaria in?
A
Travelers for foreign countries
Vets: Vivax (relapsing)
Peace Core
16
Q
How does plasmodia work?
A
It breaks gown hemoglobin leaving iron behind which is toxic, so it turns it into hemozoin (crystal that alters the host inflammatory mediator production)
17
Q
Where does plasmodia get it’s energy?
A
GLUCOSE
-Metabolizes it a lot faster than RBCs so you get hypoglycemia and lactic acidosis
18
Q
What do you die from in malaria?
A
Respiratory arrest because the RBCs cannot carry oxygen to tissues
19
Q
What 3 things cause anemia in malaria?
A
- Lysis of pRBC and RBC
- Suppression of hemtopoeisis
- Increased clearance of RBC by spleen
20
Q
What are 2 other things besides anemia that malaria can cause?
A
Thrombocytopenia and heptospenomegaly
21
Q
What’s the general description of symptoms with malaria?
A
Flu-like symptoms that cycle and repeat…. fever, chills, rigor
22
Q
What 2 species are benign tertian that cycle in 48 hours?
A
Vivax and ovale
23
Q
What species is malignant tertian malaria that cycles in 36-48 hours?
A
Falciparum
24
Q
What species is quartan malaria that cycles in 72 ours?
A
Malariae
25
Who is uncomplicated malaria seen in?
| -General symptoms with cyclical fevers
Semi-immune adults in P. Falciparum endemic areas
26
Who gets severe malarial amenia (Hb under 5)?
Infants and children in P. Falciparum endemic areas
| Have high parasite levels in blood and resp. complication
27
Who gets cerebral malaria?
Nonimmune people with low transmission areas
| lower parasite levels in blood... milder anemia
28
What type of malaria is the most common cause of death?
Cerebral: Coma, AMS, seizures
29
What other issue is seen in nonimmune adults with P. Falciparum?
Renal Failure
30
What is blackwater fever?
Hemoglobinuria (with hemolysis and hemoglobinemia) seen with P. Falicparum and it's treatment
-Dark urine, fever
31
What are 3 other manifestations associated with renal failure in malaria?
1. Hypoglycemia
2. Lactic acidosis
3. Hemolysis
32
What is used to dx. malaria?
Blood smears
33
What a thick smear for?
Detect organisms (drop of blood)
34
What is a thin smear for?
```
Detect species (1 RBC)
-Where you would see the ring form
```
35
Englarged RBC with Schuffner (Schueffner) dots?
P. Vivax
36
Oval shaped RBCs with Ragged cell walls and Schuffner dots?
P. Ovale
37
Bar and band forms with a rosette schizont?
P. Malariae
38
Ring form with in RBC
| Crescent/bannana/sausage shaped mature gametocyte?
P. Falicaparum (erythrocytic forms)
39
True or False: All species of malaria have the ring form, but only P. Falciparum has the gametocyte form
TRUE
40
What is hemozoin?
Detoxified heme which alters the inflammatory mediator production in monocytes
41
What are 3 other options for diagnosing malaria that aren't really too useful?
1. Antigen detection (ELISA)
2. Molecular diagnosis (PCR)
3. Serology (IFA/ELISA- HISTORY OF INFECTION)
42
What form of sickle cell anemia offers protection against malaria?
HbAS - Heterozygote
43
What offers 100% protections against Vivax?
Duffy antigen deletion (receptor on RBC for vivax)
44
What are 3 other diseases that offer protection against malaria?
G6PD deficiency, Thalassemia, HbC polymorphisms
45
What are 2 other ways you could get protection from malaria?
1. Inflammatory mediatory production: TNF-a, NO, COX-2, IL-1b, IL-10
2. Cell surface adhesion proteins: ICAM1, CD34, ect.
46
What is the treatment for malaria for non-severe, non-resistant cases?
Chloroquine
47
What is the treatment for malaria for severe cases (or resistant ones)?
Quinine
48
What are 2 toxicities that quinine can cause?
Renal and oto
49
What is given for anti-relapse therapy for vivax and ovale that is active versus hypnozoites only?
-LIVER
Primaquine
50
Who can you not give primaquine to?
Children, preggers, G6PD
51
Would you give primaquine to someone with falciparum?
NO
52
If someone had vivax (like they had malaria a long time ago and now it's back) how would you treat it?
Chloroquine and primaquine
53
How do heme metabolism inhibitors work?
They stop parasite enzymes from making hemozoin from heme...you get a build-up of heme which is toxic to parasites
54
What are some heme matabolism inhibitors?
Cholorquine, quinine, mefloquine (Lariam), halofantrine
55
What are the 3 proposed mechanisms of actions of heme metabolism inhibitors?
1. Bind to ferriprotoporphyrin 9 released from Hb- Heme build-up
2. Raise pH of parasites intracellular acid vesicles (intereferes with Hb degradation)
3. Bind to DNA and interfere with DNA replication
56
When do you use quinoline derivatives?
Erythrocytic malaria (NOT FOR HEPATIC STAGE)
57
What are 2 properties of chloroquine?
1. Rapid onset of action
| 2. Long half life
58
What is the mechanisms of resistance to chloroquine?
Drug efflux (falciparum and vivax)
59
Who do you need to be careful in giving chloroquine to?
G6PD and preggers
60
Who do you see toxicity and SE due to chloroquine in?
SLE and RA patients (b/c they are treated with higher doses)
61
What are the 3 areas of SE from chloroquine?
SKIN: pruritus (dark skin)
HEART: conduction/cardiomyopathy
NEURO: reinopathy ,general
62
What is qunine and quinidine?
Cinchona alkaloids
63
With chloroquine-resistant strains, what do you give quinine and quinidine with?
Doxy or clindamycin
64
Can you give quinine or quinidine to preggers?
YES
65
How do you give quinine/quinidine?
Oral: Mild
IV: Acute (multidrug-resistance P. Falciparum
66
Why can't you give quinine/quinidine as prophylaxis?
short half life
67
What are the 2 main toxicities of quinine and quinidine?
Renal and oto
68
Is quinine and quinidine effective against the asexual stage of malaria?
YES... it's gametocidal for vivax and malaria (BUT NOT FALCIPARUM)
69
SE (Cinchonism) with normal dosing of quinine and quinidine?
TINNITUS.... flushed/sweaty skin, burry vision, confusion, drug-induced lichenoid reaction, vertigo, vomiting/diarrhea
70
Large doses of quinine/quinidine can lead to?
Skin rashes, deaf, blind, conduction cardiac, BLACKWATER FEVER (hemolysis, hemoglinemia, hemoglobinuria, renal failure)
71
What other 2 things can qunine/ quinidine cause?
Hypoglycemia (IV) and hypotension
72
Who needs precaution for quinine/quinidine?
```
G6PD deficient (but okay for preggers)
Class 1A antiarrythmic (inhibit P450)
```
73
What are the 2 synthetic quinoline compounds?
Mefloquine and halofantrine
74
What is mefloquine used for?
Monotherapy prophylaxis and treatment of malaria (ORAL)
75
What is the toxicity of mefloquine?
PSYCHIATRIC DISORDERS, gi issues, seizures, bradycardia, qt long, arrythmia
76
What can mefloquine cause?
Still births
77
What are the 2 oxidative phosphorylation inhibitors?
Atovaquone and primaquine
78
What is primaquine used for?
Radical cure of vivax/ovale (hypnozoites)
RELAPSE THERAPY
(LIVER)
(ORAL)
79
How does primaquine work?
Inhibits ETC increasing ROS in parasite
80
What are the SE of primaquine?
GI distress, pruritus, methemoglobinemia, HA
81
What are the contraindicatations of primaquine?
```
G6PD deficiency (hemolytic anemia)
Preggers
```
82
What is atovaquone?
Hydroxynapthoquinone
83
What does atovaquone do?
Inhibits ETC in parasitic mitochondria
(it inhibits malaria cytochrome C complex and collapses mitrochondrial membrane potential...this blocks nucleic acid synthesis and inhibits replication)
84
What is atovaquone used for?
Treat liver stage (hypnozoites), but not relapse
85
How is atovaquone best work?
Given with proguanil (folate?)
| -Oral absorption is also increased with fatty foods
86
What the mechanism of resistance for atovaquone?
mutations in mitochondrial B-gene
87
Toxicity and SE of atovaquone?
Abd pain, N/V, HA, Diarrhea
88
What are some precautions for atovaquone?
Rifampin induces p450 which reduces atovaquone effectiveness (induces metabolism of atovaquone)
89
What are contraindications of atovaquone?
Preggers, lactating mothers, children
90
What is a folic acid antagonist used for malaria?
Sulfadoxine- pyrimethamine
91
Why are protozoa susceptible to folate synthesis inhibitors?
Can't absorb exogenous folate and need it for nucleic acid synthesis
92
What do diaminopyrimidines do?
Inhibit dihydrofolate reductase
| proguanil, pyrimethamine, trimethoprim
93
What do sulfonamides do?
Inhibit the conversion of aminobenzoic acid to dihydropteroic acid
(sulfadoxine and sulfamethoxazole)
94
What combo is used for malaria?
Sulfadozine/pyrimethamine
95
What combo is used for toxoplasmosis?
TMP/SMX
96
What are the 3 SE for folic acid antagonists?
1. BM depression (pancytopenia)
2. Erythma multiforme
3. Epidermal necrolysis
97
Who are folic acid antagonists contraindicated in?
Lactating mothers and infants under 2 months
-precaution in IC patients
98
What drug is a combo of atovaquone and proguanil?
Malarone
99
What is proguanil?
Antifolate that inhibits plasmodia dihydrofolate reductase
| -Synergizes with atovaquone to inhibit ETC
100
True or false: Malarone is effective against all stages of P. Falciparum
TRUE
101
What can malarone be used for?
Prophylaxis and treatment of erythrocytic stage of vivax and ovale
102
What are 2 inhibitors of protein synthesis?
Doxy and clindamycin
103
What is dozy used for?
Prevention (short-term) not treatment (unless combo)
104
How does doxy work?
Slow-acting blood schizontocide that prevents apicoplast function (which is an essential biosynthetic organelle)
-In bacteria it is a 30S inhibitor
105
What are toxicities of doxy?
Bone and teeth
106
Who can't you give doxy to?
Kids under 8 and preggers
107
What is the only disease where you can give doxy to a child?
Rocky mountain spotted fever
108
What are sesquiterpenes?
Artemisnin derivatives (artemether and artesunate)
109
What do artemisinins treat?
Erythrocytic malaria by reacting with the heme moiety (bind heme itself to block enzyme)
110
How are arteminsinins the most active antimalaria compound?
They are effective against small-ring forms and maturing schizonts and the reduce gametocyte carriage and transmission
111
Who do you need to be precautious with in artemisinins?
Preggers and infants
112
Chloroquine is the DOC for malaria in non-sever cases, but in high areas of resistance what can be given?
Mefloquine, malarone, anti-folates
113
What are the 3 main drugs for prevention of malaria?
Doxy (no in children or preggers), mefloquine*, malarone
114
Even though there is no effective malaria vaccine, what is the best shot they have at it and what are the problems right now with it?
Irradiated sporozoites... problems with cost and storage
