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Uncomplicated Malaria. Symptoms: fever, chills, headache, body pains, diarrhea, vomiting, coughSigns: anemia, thrombocytopeniaSymptoms may be very nonspecificSynchronous infections with predictable cycles of symptoms are rare. Features of severe malaria. Decrease in conscious level, neurologi
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1. Principles of malaria clinical management/uncomplicated malaria
2. 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
3. Features of severe malaria 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
4. 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
5. 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
6. 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
7. Malaria Transmission Cycle
9. 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
10. 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
11. 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
12. 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
13. 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
14. Malaria TreatmentPlasmodium falciparum infections Acquired in CQ-sensitive areas
Chloroquine alone
Acquired in CQ-resistant areas
Quinine + tetracycline
Quinine + sulfadoxine/pyrimethamine
15. 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
16. 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
17. 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
18. Considerations when managingPlasmodium falciparum infections Potentially complicated case, with no other risk factors
Pregnancy
Hyperpyrexia ( > 39o)
Parasite count > 2%
Mature parasites ( schizonts or late trophozoites) on blood film
19. 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
20. 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
21. 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
22. Personal Protection Protective clothing
Insect repellants
Household insecticide products
Window and door screens
Bed nets
23. 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
24. 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 Ū
Tetra or doxycycline
Quinine
Hydroxychloroquine PlaquenilŪ
Atovaquone
Clindamycin
Meds received abroad
Artesunates
Halofantrine
25. 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
26. 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
29. 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
30. 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
31. 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
32. Fansidar? antifol combination drug (sulfadoxine-pyrimethamine)
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
33. 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 < 5 kg
side effects: neuropsychiatric reactions, cardiac dysrhythmias, vomiting in children
resistance is limited to SE Asia
34. 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)
35. 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
36. 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
37. 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