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Transcript
Principles of malaria clinical
management/uncomplicated
malaria
Uncomplicated Malaria
• Symptoms: fever, chills, headache, body
pains, diarrhea, vomiting, cough
• Signs: anemia, thrombocytopenia
• Symptoms may be very nonspecific
• Synchronous infections with predictable
cycles of symptoms are rare
Features of severe malaria
•
•
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Decrease in conscious level, neurological signs or fits
Severe anemia – Hematocrit < 15%
Hyperpyrexia
Hyperparasitemia > 5%
Hypoglycemia (glucose < 2.2 mmol/L)
Renal impairment or oliguria
Pulmonary edema, hypoxia, acidosis
Circulatory collapse or shock
Hemostasis abnormalities – hemolysis, DIC
Principles of management of
uncomplicated malaria
• Prompt and accurate diagnosis
• Assess for signs of complicated/severe malaria
– Can occur with low parasitemias
– Can develop after parasites clear peripherally
• Prompt use of appropriate antimalarial drugs
• Monitor clinical and parasitological
improvement
• Cure – parasitic and/or clinical
• Ancillary treatment
• Instructions for future prevention of malaria
Information requested when
evaluating a potential case of
malaria
– Age
– Sex and pregnancy
status
– Travel history, travel
outside major or urban
areas
– Visitors from endemic
areas
– Exposure to
mosquitoes
– Malaria prophylaxis
used
– Receipt of blood
transfusions or
transplant
– Past history of malaria
– Drug allergies
– Clinical status of the
patient, esp.
neurological
– Lab results
Diagnosis
• Thick and thin blood smears are gold standard
– Identify species and quantify density
– If can not identify species, treat for P.f.
• Re-examine smears or use alternative diagnostic tool
• Suspect P.f.
– If critically ill, suspect P.f.
– If returned from Sub-Saharan Africa, > 95 % chance of P.f. pure
or mixed infection
– Parasitemia > 1%
– Doubly infected cells
Malaria Transmission Cycle
Exo-erythrocytic (hepatic) Cycle:
Sporozoites infect liver cells and
develop into schizonts, which release
merozoites into the blood
Sporozoites injected
into human host during
blood meal
Parasites
mature in
mosquito
midgut and
migrate to
salivary
glands
MOSQUITO
Parasite undergoes
sexual reproduction in
the mosquito
HUMAN
Some merozoites
differentiate into male or
female gametocyctes
Dormant liver stages
(hypnozoites) of P.
vivax and P. ovale
Erythrocytic Cycle:
Merozoites infect red
blood cells to form
schizonts
Drugs Used to Treat Malaria
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Chloroquine (Aralen, Dawaquine)
Amodiaquine (Camoquine)
Quinine and Quinidine
Sulfa combination drugs (Fansidar, Metakelfin)
Mefloquine (Lariam)
Halofantrine (Halfan)
Atovaquone-proguanil (Malarone)
Atemisinin derivatives (Paluther)
Malaria Treatment
non-falciparum infections

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
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Chloroquine (CQ) is the drug of choice
Some CQ-resistant P. vivax has been reported
from Oceania and South America
Mefloquine or quinine for proven resistant cases
Primaquine to eradicate liver phase in P. vivax
and P. ovale infections
Chloroquine







4-amino quinoline
acts on asexual intraerythrocytic forms
useful for treatment or prophylaxis
safe for children and in pregnancy
side effects: GI, headache, blurred vision,
pruritis
limited efficacy against P. falciparum
resistant strains of P. vivax emerging
Malaria Treatment
non-falciparum infections

If symptoms or parasites persist at end of
treatment

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Additional infection
Rarely, CQ- resistant strain
Repeat blood smears
Pruritis is major side effect of CQ

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More common in dark-skinned people
Can offer antihistamines, continue use
CQ-resistant P. vivax
• Emerged in Southeast Asia
• Indonesia, Papua New Guinea, Birma
• Also documented in Latin America
• Guyana
• Also documented in South Asia
• India
• CQ therapy still recommended
• Quinine after documented treatment failure
Primaquine (PQ) use in P. vivax
and P. ovale infections
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Use to achieve radical cure and prevent relapses
Check glucose-6-phosphate dehydrogenase (G6PD) level
first
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Partial resistance in Oceania and Southeast Asia
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PQ can cause hemolysis in G6PD-deficient patients
If mildly deficient, consider weekly PQ dosing instead of daily
Double usual dose if exposed in these areas
Contraindicated in pregnancy

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Pregnant women and newborns use prophylactic CQ weekly until
delivery or until end of breast-feeding
Then use primaquine
Malaria Treatment
Plasmodium falciparum infections

Acquired in CQ-sensitive areas
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
Chloroquine alone
Acquired in CQ-resistant areas


Quinine + tetracycline
Quinine + sulfadoxine/pyrimethamine
CQ-resistant P. falciparum
• Emerged in Southeast Asia
• Near global distribution
• Few areas of susceptibility remain
– Middle East
– Central America/Caribbean
• CQ is still the first-line drug in most
African countries
• Non-immune migrant populations may be
at higher risk
Multidrug-resistant P. falciparum
• Focus in Southeast Asia
• Border areas, forest transmission
• Recommendations
• Prophylaxis: Doxycycline
• Treatment:
– Quinine combinations, longer duration of therapy
– High-dose MQ,artemisinin combinations
• Identifying and documenting treatment
failure is critical
Considerations when managing
Plasmodium falciparum infections

Can underestimate severity
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Significant damage occurs at certain times during repeated
cycles of development and reproduction
Patient can deteriorate quickly
Low parasite density does not mean infection is trivial
Complications can arise after parasites clear peripheral
blood, parasites can sequester in tissues
Monitor for neurological changes and hypoglycemia
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Severe malaria and antimalarials can cause hypoglycemia
Pregnant women are at particular risk
Considerations when managing
Plasmodium falciparum infections

Potentially complicated case, with no other risk
factors
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Pregnancy
Hyperpyrexia ( > 39o)
Parasite count > 2%
Mature parasites ( schizonts or late trophozoites) on
blood film
Management of induced or
congenital cases
• No sporozoites are injected into the human
by mosquito
• Therefore no exo-erythrocytic (hepatic)
cycle
• No need for primaquine
Adjunct treatment of
uncomplicated malaria
• Fever
– Acetominophen, paracetamol
• Avoid aspirin in kids due to risk of Reyes Syndrome
– Sponge baths
• Anemia
– Transfusion of RBCs may be needed
– Iron, folic acid
• Rehydration
– Solutions with extra glucose
Antimalarial Chemoprophylaxis
• Prevents disease, not infection
• Appropriate for non-immune travelers
• Practical only for some populations in
endemic areas
• Consider:
•
•
•
•
immune status
intensity/duration of exposure
parasite drug resistance
resources for diagnosis and treatment
Personal Protection
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•
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Protective clothing
Insect repellants
Household insecticide products
Window and door screens
Bed nets
Evaluation of febrile illnesses
– Age
– Sex and pregnancy
status
– Travel history, travel
outside major or urban
areas
– Visitors from endemic
areas
– Exposure to
mosquitoes
– Malaria prophylaxis
used
– Receipt of blood
transfusions or
transplant
– Past history of malaria
– Drug allergies
– Clinical status of the
patient, esp.
neurological
– Labs
Don’t forget to ask
– Occupational history
• Healthcare workers
• Exposure to mosquitoes
– Needle exposure
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•
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•
IV drug abuse
Needlestick injuries
Tattoos
Acupuncture
– Other meds used with
potential antimalarial effect
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Sulfa – Bactrim ®
Tetra – or doxycycline
Quinine
Hydroxychloroquine –
Plaquenil®
• Atovaquone
• Clindamycin
– Meds received abroad
• Artesunates
• Halofantrine
All “malaria” is not malaria
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Incubation periods unlikely
Parasite density very high for nonfalciparum
Species not likely given travel history
Drug resistance?
Misdiagnosis – species or parasite or negative
Miscalculation of density
Previously undetected mixed infection
Antimalarial drug actions
• Actions
– Causal (true) – drug acts on early stages in liver, before release
of merozoites into blood
– Blood schizontocidal drugs (suppressive or clinical)– attack
parasite in RBC, preventing or ending clinical attack
– Gametocytocidal – destroy sexual forms in human, decreases
transmission
– Hypnozoitocidal – kill dormant hypnozoites in liver, antirelapse
drugs
– Sporontocidal – inhibit development of oocysts in mosquito,
decreases transmission
The Malaria Transmission Cycle
Sites of Action for Antimalarial Drugs
TISSUE SCHIZONTOCIDES:
primaquine
pyrimethamine
proguanil
tetracyclines
MOSQUITO
SPORONTOCIDES:
primaquine
pyrimethamine
proguanil
HUMAN
GAMETOCYTOCIDES:
primaquine
BLOOD
SCHIZONTOCIDES:
chloroquine
mefloquine
quinine/quinidine
tetracyclines
halofantrine
sulfadoxine
pyrimethamine
artemisinins
Malaria Life
Cycle
Oocyst
Sporozoites
Mosquito Salivary
Gland
Zygote
Exoerythrocytic
(hepatic) cycle
Gametocytes
Erythrocytic
Cycle
Hypnozoites
Primaquine



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
8-aminoquinoline
acts on gametocytes, hypnozoites; weak against
asexual blood stage parasites
primarily used as post-exposure prophylaxis and
radical cure for P. vivax and P. ovale
contraindicated in G6PD deficiency and
pregnancy
decreased activity against some P. vivax
Doxycycline
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tetracycline antibiotic
sites of action unknown
daily dose is effective prophylaxis against CRPF
and MRPF (in SE Asia)
contraindicated in pregnancy and in children
side effects: GI problems, photosensitivity, yeast
infections
no identified resistance
compliance can limit its effectiveness
Quinine
•
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•
first isolated from cinchona bark in 1820
dextroisomer: QUINIDINE
acts against asexual erythrocytic stages
used for treatment of all 4 species
safe in pregnancy and for children
side effects: nausea, blurred vision, tinnitus
duration shortened by adding SP or TCN
diminished activity against some P. falciparum
from SE Asia
Fansidar


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antifol combination drug (sulfadoxinepyrimethamine)
acts on asexual intracellular stages
no longer recommended for CRPF
used for treatment of CRPF, alone and in
combination with quinine
benefits outweigh risks in pregnancy
side effects: sulfa allergy, severe cutaneous
resistance developed rapidly in SE Asia
Mefloquine
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4-quinolinemethanol
acts on asexual intraerythrocytic forms
effective prophylaxis against CRPF
treatment doses less well tolerated
not licensed for use in pregnancy or infants < 5
kg
side effects: neuropsychiatric reactions, cardiac
dysrhythmias, vomiting in children
resistance is limited to SE Asia
Other Medications--Clindamycin
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
common antibiotic
weak antimalarial activity alone
may be used for treatment in combination with
quinine, especially for pregnant women and young
children
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still need to give full course of quinine
more effective drugs can be used in these groups
(MQ, SP)
Other Medications--Halofantrine

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licensed and marketed in the United States
widely used in Africa, South Asia
GI absorption is highly variable
cardiac conduction abnormalities are a concern
increased risk after MQ prophylaxis or treatment
repeat dosing one week after initial treatment
Other Medications--Malarone



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
fixed combination of atovaquone and
proguanil
effective against asexual intraerythrocytic
stages
intrinsically expensive to produce
approval for treatment in UK
large donation planned in Africa
Other Medications--Artemisinins
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novel class of antimalarial drugs
derived from Chinese herb: qinghaosu
act on earlier parasite developmental stages
than CQ or Quinine
rapid parasite clearance
no resistance to date, but high rates of
recrudescence if used alone
effective in combination with MQ
neurological lesions in animal studies