Principles of malaria clinical management/uncomplicated malaria

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Principles of malaria clinical management/uncompli
cated malaria
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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

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Features of severe malaria

• Decrease in conscious level, neurological signs
  or fits
• Severe anemia Hematocrit lt 15
• Hyperpyrexia
• Hyperparasitemia gt 5
• Hypoglycemia (glucose lt 2.2 mmol/L)
• Renal impairment or oliguria
• Pulmonary edema, hypoxia, acidosis
• Circulatory collapse or shock
• Hemostasis abnormalities hemolysis, DIC

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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

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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

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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, gt 95
  chance of P.f. pure or mixed infection
• Parasitemia gt 1
• Doubly infected cells

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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
Dormant liver stages (hypnozoites) of P. vivax
and P. ovale
HUMAN
MOSQUITO
Erythrocytic Cycle Merozoites infect red blood
cells to form schizonts
Some merozoites differentiate into male or female
gametocyctes
Parasite undergoes sexual reproduction in the
mosquito
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Drugs Used to Treat Malaria

• Chloroquine (Aralen?, Dawaquine?)
• Amodiaquine (Camoquine?)
• Quinine and Quinidine
• Sulfa combination drugs (Fansidar?, Metakelfin?)
• Mefloquine (Lariam?)
• Halofantrine (Halfan?)
• Atovaquone-proguanil (Malarone?)
• Atemisinin derivatives (Paluther?)

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Malaria Treatmentnon-falciparum infections

• 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

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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

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Malaria Treatmentnon-falciparum infections

• If symptoms or parasites persist at end of
  treatment
• Additional infection
• Rarely, CQ- resistant strain
• Repeat blood smears
• Pruritis is major side effect of CQ
• More common in dark-skinned people
• Can offer antihistamines, continue use

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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

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Primaquine (PQ) use in P. vivax and P. ovale
infections

• Use to achieve radical cure and prevent relapses
• Check glucose-6-phosphate dehydrogenase (G6PD)
  level first
• PQ can cause hemolysis in G6PD-deficient patients
• If mildly deficient, consider weekly PQ dosing
  instead of daily
• Partial resistance in Oceania and Southeast Asia
• Double usual dose if exposed in these areas
• Contraindicated in pregnancy
• Pregnant women and newborns use prophylactic CQ
  weekly until delivery or until end of
  breast-feeding
• Then use primaquine

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Malaria TreatmentPlasmodium falciparum infections

• Acquired in CQ-sensitive areas
• Chloroquine alone
• Acquired in CQ-resistant areas
• Quinine tetracycline
• Quinine sulfadoxine/pyrimethamine

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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

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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

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Considerations when managingPlasmodium
falciparum infections

• Can underestimate severity
• 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
• Severe malaria and antimalarials can cause
  hypoglycemia
• Pregnant women are at particular risk

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Considerations when managingPlasmodium
falciparum infections

• Potentially complicated case, with no other risk
  factors
• Pregnancy
• Hyperpyrexia ( gt 39o)
• Parasite count gt 2
• Mature parasites ( schizonts or late
  trophozoites) on blood film

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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

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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

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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

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Personal Protection

• Protective clothing
• Insect repellants
• Household insecticide products
• Window and door screens
• Bed nets

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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

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Dont forget to ask

• Occupational history
• Healthcare workers
• Exposure to mosquitoes
• Needle exposure
• IV drug abuse
• Needlestick injuries
• Tattoos
• Acupuncture

• Other meds used with potential antimalarial
  effect
• Sulfa Bactrim
• Tetra or doxycycline
• Quinine
• Hydroxychloroquine Plaquenil
• Atovaquone
• Clindamycin
• Meds received abroad
• Artesunates
• Halofantrine

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All malaria is not malaria

• 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

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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

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The Malaria Transmission CycleSites of Action
for Antimalarial Drugs
TISSUE SCHIZONTOCIDES primaquine pyrimethamine pr
oguanil tetracyclines
HUMAN
MOSQUITO

• BLOOD SCHIZONTOCIDES
• chloroquine
• mefloquine
• quinine/quinidine
• tetracyclines
• halofantrine
• sulfadoxine
• pyrimethamine
• artemisinins

SPORONTOCIDES primaquine pyrimethamine proguanil
GAMETOCYTOCIDES primaquine
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Malaria Life Cycle
Exo- erythrocytic (hepatic) cycle
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Primaquine

• 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

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Doxycycline

• 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

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Quinine

• 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

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Fansidar?

• antifol combination drug (sulfadoxine-pyrimethamin
  e)
• 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

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Mefloquine

• 4-quinolinemethanol
• acts on asexual intraerythrocytic forms
• effective prophylaxis against CRPF
• treatment doses less well tolerated
• not licensed for use in pregnancy or infants lt 5
  kg
• side effects neuropsychiatric reactions, cardiac
  dysrhythmias, vomiting in children
• resistance is limited to SE Asia

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Other Medications--Clindamycin

• common antibiotic
• weak antimalarial activity alone
• may be used for treatment in combination with
  quinine, especially for pregnant women and young
  children
• still need to give full course of quinine
• more effective drugs can be used in these groups
  (MQ, SP)

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Other Medications--Halofantrine

• 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

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Other Medications--Malarone?

• 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

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Other Medications--Artemisinins

• 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