malaria prophylaxis and liver disease

Last edited 06/2023 and last reviewed 08/2023

use of malarial prophylaxis in special situations

Seek expert advice

Breastfeeding

• Mefloquine - experience suggests safe to use during lactation
• Doxycycline - Advisory Committee on Malaria Prevention in UK Travellers (ACMP's) view is that doxycycline should not be used in breast feeding unless there is no alternative agent and its use is felt to be essential
• Atovaquone/proguanil - not recommended because of the absence of data but can be considered if there is no suitable alternative
  • the amount of medication in breast milk will not protect the infant from malaria. Therefore, the breastfeeding child needs his or her own prophylaxis

Epilepsy

• Note: A history of febrile convulsions only does not contraindicate use of any of the currently available malaria chemoprophylactic drugs. The following advice applies to travellers with epilepsy where restrictions do apply
• in epilepsy:
  • doxycycline or atovaquone/proguanil can be used
  • chloroquine is unsuitable
  • mefloquine is unsuitable

Glucose 6-phosphate dehydrogenase (G6PD) deficiency

• Chloroquine - theoretical risk of haemolysis in some G6PD-deficient individuals. Haemolysis does not appear to be a problem when chloroquine is given in the dose recommended for malaria chemoprophylaxis so there is no need to withhold chloroquine prophylaxis from those known to be G6PD-deficient. This risk is acceptable in acute malaria (63) and G6PD levels are not usually checked before using chloroquine in treatment doses
• Atovaquone-proguanil, doxycycline, mefloquine or proguanil prophylaxis - can be used in those known to be G6PD-deficient
• Primaquine - not currently recommended as a first line agent for malaria prevention in UK travellers, but may be considered in special circumstances on expert advice. There is a definite risk of haemolysis in G6PD-deficient individuals. The traveller's G6PD level must be checked before primaquine is prescribed: G6PD deficiency contraindicates its use for prophylaxis

Sickle Cell disease and thalassaemia

• sickle cell trait provides some protection against but still require antimalarial prophylaxis.
• in homozygous sickle cell disease, malaria causes further haemolysis against the background of that due to sickle-cell disease itself, hence rigorous antimalarial protection should be given to these patients
• thalassaemia may provide protection against severe malaria, but there is currently no evidence it prevents uncomplicated malaria

Renal impairment

• Chloroquine is partially excreted via the kidneys while proguanil is wholly excreted via the kidneys
• Chloroquine - in severe renal impairment, dose reduction for prophylaxis is required
• Proguanil: should be avoided or the dose reduced
• Atovaquone/proguanil: not recommended for patients with an eGFR of less than  30mL/minute Not to be used in patients receiving renal dialysis
• Mefloquine and doxycycline can be used in normal dosage in severe renal failure

Liver disease

• majority of antimalarial drugs are excreted or metabolised by the liver
• severe impairment: patients with impaired hepatic function since it is excreted as an inactive chelated product via a process of back diffusion in the small bowel
  • note to prescribers: The BNF states that tetracyclines should be avoided or used with caution in patients with hepatic impairment. The manufacturer of atovaquone-proguanil combination preparation states that although no pharmacokinetic studies have been conducted in severe hepatic impairment, no special precautions or dosage adjustment are anticipated (SmPC)
• moderate impairment: doxycycline, proguanil, or atovaquone-proguanil combination preparation, or mefloquine may be used
• mild impairment: chloroquine, or proguanil, or chloroquine plus proguanil, or atovaquone-proguanil combination preparation, or mefloquine, or doxycycline may be used. the choice of chemoprophylaxis should be made after discussion with the patient’s specialist, who will be able to assess their degree of hepatic impairment.

Splenectomy

• patients who have undergone splenectomy or whose splenic function is severely impaired are at particular risk of severe malaria
• if possible these patients should avoid travel to malarious areas
• if travel is unavoidable, rigorous use of antimosquito precautions and strict adherence to appropriate chemoprophyaxis should be undertaken

Reference:

• (1) Public Health England (PHE) 2022. Guidelines for malaria prevention in travelers from the United Kingdom .