Malaria Clinical - Presentation + Treatment

Question 1

Pathologic features of P. falciparum?

Answer 1

-Intravascular sequestration
-Adherence of endothelial cells + knob-like projections (PfEMP1) on RBC membrane (ICAM-1)
-Infected RBCs bind vessels = sequestration
-Infected RBCs bind each other = agglutination
-Infected RBCs bind uninfected cells = rosetting
-All leads to sequestration and obstruction
-Symptoms depend on organ affected

Question 2

Danger signs for severe falciparum malaria for children 2-59 mo?

Answer 2

Fever or hx of fever in past 24h OR palmar pallor + one or more of the following signs:
-Unable to drink or breastfeed
-Vomiting everything
-Multiple convulsions
-Lethargy
-Unconsciousness
-Stiff neck
-Chest indrawing or stridor

Question 3

Danger signs for severe falciparum malaria for older children and adults?

Answer 3

Fever or hx of fever in past 24h + one or more of the following danger signs:
-Very weak or unable to stand
-Convulsions
-Lethargy
-Unconsciousness
-Stiff neck
-Resp distress
-Severe abdo pain

Question 4

WHO definition of severe falciparum malaria?

Answer 4

One or more of the following with P falciparum in the absence of an alternative cause:
- Impaired LOC (GCS <11, BCS <3)
-Prostration (too weak to sit/stand/walk)
-Multiple convulsions (>2 within 24h)
-Acidosis (lactate >5, bicarb <15, base deficit >8)
-Hypoglycemia (<2.2)
-Severe anemia (<5 in children under 12, <7 in adults)
- Renal impairment (Cr >265)
-Jaundice (bili >50)
-Pulm edema (O2 <92%, RR>30)
-Sig. bleeding
-Shock (SBP<70 children, <80 adults, impaired perfusion)
-Hyperparasitemia (>10%)

Question 5

3 Factors to rely on for treatment determination?

Answer 5

1. Malaria testing (repeat q12-24h)
2. Falciparum or non-falciparum?
3. Severe or uncomplicated?

Question 6

Treatment options for uncomplicated falciparum?

Answer 6

Children and adults should be treated with an ACT x3d:
-Artemether + lumefantrine
-Artesunate+amodiaquine
-Dihydroartemisinin + piperaquine
-Artesunate + pyronaridine*
-Artesunate + mefloquine
-Artesunate + sulfadoxine-pyrimethamine*

*Cannot use in 1st trimester

Question 7

Reasons for treatment failure?

Answer 7

• Drug resistance
• Suboptimal dosing
• Poor adherence or vomiting
• Substandard medicines

Question 8

Approach to investigating recurrent falciparum malaria?

Answer 8

-Determine if reinfection or recrudescence (treatment failure)
-Confirm recurrence with microscopy (not RDTs)
-May be difficult to differentiate in high transmission areas

Question 9

Management of treatment failure within 28d of initial treatment?

Answer 9

2nd line treatment - alternative ACT

Question 10

Management of treatment failure after 28d of initial treatment?

Answer 10

Consider new infection, treat with first line ACT
-Retreatment with AS+MQ within first 60d is not recommended due to neuropsychiatric rxns

Question 11

Alternative non-ACTs for uncomplicated falciparum?

Answer 11

Atovaquone-proguanil x3d
Quinine+doxycycline x7d
Quinine+clindamycin x7d

Question 12

Treatment of uncomplicated falciparum in pregnancy?

Answer 12

1st trimester –> artemether-lumefantrine
2nd + 3rd trimester –> treat with an ACT, safe

Mefloquine - safe in 2nd and 3rd trimester, use with artemisinin derivative
Quinine - increased risk of hypoglycemia in late pregnancy, use with clinda only if alternatives not available
Primaquine - don’t use
Tetracyclines - don’t use

Question 13

Treatment of uncomplicated non-falciparum malaria?

Answer 13

Chloroquine sensitive area –> ACT or CQ
Chloroquine resistant area –> ACT

In vivax + ovale –> primaquine x14d following G6PD status for relapse prevention

Question 14

Vivax and ovale relapse prevention in pregnant women?

Answer 14

-Weekly chemoprophylaxis with chloroquine until delivery and breastfeeding complete
-Following, pending G6PD status, give primaquine x14d

Question 15

What is Primaquine standard dose?

Answer 15

0.25-0.5 mg/kg BW per day, once daily, x14d

Question 16

What is the alternative primaquine standard dose for a short course regimen?

Answer 16

0.5 mg/kg/d x7d for children and adults

Question 17

Dosing of primaquine in those with G6PD deficiency?

Answer 17

0.75 mg/kg/bw once a week x8 weeks
-Monitor for possible primaquine-induced hemolysis

Question 18

Primaquine mechanisms of action?

Answer 18

-Kills mature gametocytes

Question 19

Types of severe malaria?

Answer 19

1. Cerebral malaria
2. Severe anemia
3. Pulmonary (PnA - children, edema/ARDS/PnA - adults)
4. Metabolic acidosis
5. Hypoglycemia
6. Renal complications
7. Bacteremia (non-typhi Salmonella)
8. Jaundice (common in adults), DIC, shock

Question 20

Clinical features of cerebral malaria?

Answer 20

• Impaired consciousness
• Presence of retinopathy
• Convulsions common
• Increased ICP (>80% in children, NL in adults)
• Cerebral edema (more common in chidlren)

Mortality 10-40%

Question 21

Clinical features of severe malaria anemia?

Answer 21

• Hb <5 in children, <7 in adults

Causes: spleen filters both infected and uninfected cells, intravascular hemolysis, bone marrow suppression, repeat infections

Question 22

AQUAMAT trial finding re: treatment?

Answer 22

-Mortality with AS 8.5%
-Mortality with QNN 10.9%

Relative reduction in mortality 22.5%

Question 23

SEAQUAMAT trial finding re: treatment?

Answer 23

-Mortality with AS 15%
-Mortality with QNN 22%

Absolute mortality reduction 34.7%

Question 24

Treatment of severe falciparum malaria?

Answer 24

Artesunate x24h until they can tolerate oral for everyone

Artesunate IV 2.4 mg/kg, dose at 0, 12 and 24h

Once 24h of IV and can tolerate PO, move to 3d treatment with an ACT