Malaria

Question 1

What are the 5 types of malaria?

Answer 1

1. Plasmodium falciparum

(“Non-falciparum malaria”)

2. P.vivax
3. P.ovale
4. P.malariae
5. P.knowlesi

Question 2

What is the initial management of patients with falciparum malaria?

Answer 2

Hospital admission initially due to risk of rapid deterioration even after starting treatment

*if the infective species is not known or the infection is mixed and includes falciparum, initial treatment should be as for falciparum malaria

Question 3

What is the treatment of choice for uncomplicated P.falciparum malaria?

Answer 3

“Artemisinin combination therapy”

FIRST LINE:
- artemether with lumefantrine

SECOND LINE:
- artenimol with piperaquine phosphate

THIRD LINE:

• oral quinine
• atovaquone with proguanil hydrochloride

**quinine is highly effective but poorly tolerated in prolonged treatment and should be used in combination with an additional drug, usually oral doxycycline or clindamycin in pregnant women and young children

Question 4

What are the main contraindications to using artemether with lumefantrine? (5)

Answer 4

(Risk factors for cardiotoxicity)

1. Family history of congenital QT interval prolongation
2. Family history of sudden death
3. History of arrhythmias
4. History of clinically relevant bradycardia
5. History of congestive heart failure accompanied by reduced LVEF

Question 5

What are the main contraindications to using artenimol with piperaquine phosphate? (10)

Answer 5

(Risk factors for cardiotoxicity, torsades de pointes)

1. Acute MI
2. Bradycardia
3. Congenital long QT syndrome
4. Electrolyte disturbances
5. Family history of sudden death
6. Heart failure with reduced LVEF
7. History of symptomatic arrhythmias
8. LVH
9. Risk factors for QT interval prolongation
10. Severe hypertension

Question 6

What are the main contraindications to chloroquine use? (4)

Answer 6

1. Hemoglobinuria
2. Myasthenia gravis
3. Optic neuritis
4. Tinnitus

(Caution used in patients with risk factors for cardiac toxicity eg Afib, cardiac disease, conduction defects, heart block, etc. as well as first trimester pregnancy and G6PD deficiency)

Question 7

What are the key features of quinine overdose? (2)

Answer 7

Quinine is very toxic in overdose

1. Life-threatening arrhythmias (can be very rapid onset)
2. Convulsions (can be intractable)

Question 8

What are the main side effects of quinine? (7)

Answer 8

1. Tinnitus (may be permanent)
2. Deafness (may be permanent)
3. Blindness (may be permanent)
4. GI upset
5. Prolongs QT interval, may cause arrhythmias
6. Hypoglycemia
7. Leg cramps

Question 9

Quinine should be prescribed with caution in which patients? (3)

Answer 9

1. Existing hearing or visual loss
2. First trimester pregnancies (teratogenic)
3. G6PD deficiency

Question 10

What are the main contraindications to the use of atovaquone with proguanil hydrochloride?

Answer 10

None

Caution used if diarrhea or vomiting (reduced absorption)

Question 11

What are the neuro-psychiatric side effects of some antimalarial drugs?

Answer 11

Neuro:

• movement disorders
• neuromyopathy
• seizure

Psychiatric:

• hallucinations
• psychotic disorder
• personality change
• insomnia
• anxiety
• confusion

**particularly with chloroquine and mefloquine; frequency rare or not known

Question 12

What is the treatment of choice for severe or complicated falciparum malaria?

Answer 12

Should be managed in a high dependency unit or intensive care setting

FIRST LINE:
- IV artesunate min 24 hours followed by a full course of oral artemisinin combination therapy

SECOND LINE:
- IV artesunate min 24 hours followed by a full course of oral quinine with doxycycline (or clindamycin) OR atovaquone with proguanil

Question 13

How should patients with severe or complicated falciparum malaria be managed in the absence of artesunate therapy?

Answer 13

Do not delay treatment if artesunate is not immediately available; quinine by IV infusion should be given until the patient can take oral quinine to complete a full course

Question 14

What is meant by “Artemisinin combination therapy?”

Answer 14

Artemisinin derivatives include artesunate, artenimol, and artemether. These drugs are combined with a second drug to increase efficacy against malaria

FIRST LINE:
- artemether with lumefantrine

SECOND LINE:
- artenimol with piperaquine phosphate

Question 15

Why are chloroquine and mefloquine avoided in treatment of malaria?

Answer 15

P.falciparum is now resistant to chloroquine in most parts of the world

Mefloquine is no longer recommended use to severe adverse effects leading to non-completion of drug courses (ie neuropsychiatric symptoms)

Question 16

What is the main concern regarding falciparum malaria in pregnancy?

Answer 16

Falciparum malaria in pregnancy carries a higher risk of severe disease, requiring prompt treatment by specialists in hospital and close observation

Question 17

What is the treatment of choice for uncomplicated falciparum malaria in pregnancy?

Answer 17

Second and third trimesters:

FIRST LINE: Artemether with lumefantrine

All trimesters:

FIRST LINE: Quinine with clindamycin

**NB: quinine can increase the risk of uterine contractions and hypoglycemia

Question 18

What are the main concerns regarding quinine use during pregnancy?

Answer 18

Quinine can increase the risk of uterine contractions and hypoglycemia

Question 19

What is the treatment of choice for severe or complicated falciparum malaria during pregnancy?

Answer 19

FIRST LINE:
- IV artesunate in any trimester

SECOND LINE:
- IV quinine with clindamycin

Question 20

What is the treatment of choice for non-falciparum malaria?

Answer 20

FIRST LINE:

• artemisinin combination therapy
• chloroquine

*artemisinin combination therapy may be preferred in Indonesia, Malaysia, and eastward of Southern Vietnam due to reported chloroquine resistance, but either can be used with appropriate follow-up

Question 21

What additional measures may be taken in cases of P.vivax and ovale infection?

Answer 21

P.vivax and ovale undergo a dormant hypnozoite stage in the host liver. Thus, with chloroquine treatment alone, hypnozoites are not killed and the individual is vulnerable to relapse. To provide “radical cure” in these patients, primaquine should be given along with chloroquine treatment

*whereas chloroquine therapy alone is adequate for P.malariae and knowlesi infection

Question 22

What should be done before initiation of primaquine treatment?

Answer 22

Screening for G6PD deficiency; may cause hemolysis in individuals with G6PD deficiency

Question 23

What is the treatment of choice for severe or complicated non-falciparum malaria?

Answer 23

Same as treatment of severe or complicated falciparum malaria

FIRST LINE:
- IV artesunate

SECOND LINE:
- IV quinine

Question 24

What is the treatment of non-falciparum malaria during pregnancy?

Answer 24

Chloroquine can be given throughout pregnancy

Artemisinin combination therapy can be used in the second and third trimester with quinine used in the first trimester if there is concern about chloroquine-resistant P.vivax

**in cases of P.vivax or ovale infection, radical cure with primaquine should be postponed until pregnancy and breastfeeding are over due to risk of neonatal hemolysis and methemoglobinemia in the third trimester in G6PD-deficient infants

Question 25

Can artemisinin combination therapy be used in the first trimester of pregnancy?

Answer 25

Toxicity in animal studies with artemether; manufacturer advises use only if potential benefits outweigh risks

Question 26

How is radical cure attained in pregnant patients?

Answer 26

Radical cure with primaquine should be postponed until the pregnancy and breast-feeding are over Instead, weekly chloroquine prophylaxis should be continued until delivery or completion of breastfeeding

Question 27

Which anti-malarials are avoided during the first trimester of pregnancy? (4)

Answer 27

All should be avoided unless benefit of use outweighs risk… 1. Primaquine (risk of hemolysis) 2. Artemether (toxicity in animals) 3. Artenimol (teratogenic in animals, not to be used as first line) 4. Quinine (teratogenic at high doses, benefits may outweigh risks) (Proguanil may be used along with adequate folate supplementation in the mother)

Question 28

When considering malaria prophylaxis, what factors should be taken into account? (5)

Answer 28

1. Risk of exposure to malaria 2. Extent of drug resistance 3. Efficacy of the recommended drugs 4. Side-effects of the drugs 5. Patient-related factors eg. age, pregnancy, renal, hepatic impairment, compliance

Question 29

In addition to antimalarial prophylaxis medication, what measures should be taken to avoid infection? (3)

Answer 29

- Use of mosquito nets, particularly those impregnated with insecticide - Vaporised insecticide - Long sleeves and trousers worn after dusk

Question 30

When should prophylaxis be started?

Answer 30

Generally, before travel to an endemic area… 1-2 days before travel: - atovaquone + proguanil or doxycycline 1 week before travel: - Chloroquin - proguanil 2-3 weeks before travel: - mefloquine

Question 31

How long should prophylaxis be continued?

Answer 31

Continued until 4 weeks after leaving the area EXCEPT atovaquone with proguanil which should be stopped 1 week after leaving

Question 32

What drugs may be offered in those requiring long-term prophylaxis? (5)

Answer 32

1. Chloroquine 2. Proguanil 3. Mefloquine (licensed up to 1 year) 4. Doxycycline (up to 2 years) 5. Atovaquone with proguanil (up to 1 year)

Question 33

During what window of time should malaria be considered in returning travelers?

Answer 33

It is important to consider that any illness that occurs within 1 year and especially within 3 months of return might be malaria even if all recommended precautions against malaria were taken

Question 34

Which drugs are unsuitable for malaria prophylaxis in individuals with a history of epilepsy? (2)

Answer 34

1. Chloroquine 2. Mefloquine *offer doxycycline or atovaquone with proguanil instead; however doxycycline may interact with some antiepileptics so its dose may need to be adjusted

Question 35

In which patient population should additional anti-malaria prophylaxis measures be taken to avoid severe disease?

Answer 35

Asplenic patients or those with severe splenic dysfunction

Question 36

How should malaria prophylaxis be managed in pregnant women?

Answer 36

Travel to malarious areas should be avoided during pregnancy; if travel is unavoidable, pregnant individuals must be informed about the risks and benefits of effective prophylaxis. Drug choices: (depends on region) FIRST LINE in sensitive areas - chloroquine (safe in pregnancy) - proguanil (give with folic acid) In high risk areas or in cases of resistance: - mefloquine (during second or third trimester; in first trimester if benefits outweigh risks) - doxycycline (only if other regimens are unsuitable) - atovaquone with proguanil + folate (only if no suitable alternative)

Question 37

Is prophylaxis required in breast-fed infants?

Answer 37

Yes; antimalarials are present in breast milk but amounts are too variable to give reliable protection

Question 38

How is malaria prophylaxis managed in patients taking warfarin?

Answer 38

Travelers should begin chemoprophylaxis 2-3 weeks before departure and INR should be stable before departure *INR should be measured before starting prophylaxis, 7 days after starting, and after completing the course. For prolonged stays, the INR should be checked at regular intervals

Question 39

For patients already taking hydroxychloroquine, does this medication need to be stopped prior to initiation of chloroquine therapy?

Answer 39

No, can remain on hydroxychloroquine

Question 40

Does acquired immunity to malaria remain after emigrating from an endemic region?

Answer 40

Settled immigrants (or long-term visitors) to the UK may be unaware that any immunity they may have acquired while living in malarious areas is lost rapidly after migration to the UK

Question 41

Where can you find a list of countries where malaria is endemic?

Answer 41

BNF Treatment Summaries: Malaria, prophylaxis