Neobook — clinical reference

Personal protection measures
Chemoprophylaxis
High-risk groups
Chemoprophylaxis regimens
Dose schedule
Interactions between malaria chemoprophylaxis and other drug treatment
Drug choice according to Traveller’s condition/situation
Diagnosis of malaria – early diagnosis is essential
Rapid diagnostic tests (RDTs)

Malaria risk map RSA 2018

September to May is the main malaria season in South Africa

Kruger National Park, neighbouring areas
The risk of malaria during this period is moderate and chemoprophylaxis needs to be considered for all travellers.

KwaZulu-Natal
The risk remains and is confined to far northern KZN.

Other countries
Mozambique has year-round malaria and the risks in southern Zambia, Zimbabwe (Victoria Falls), Botswana (Okavango delta) and Namibia (Caprivi) will likewise increase during the rainy season.

Personal protection measures are essential

Insect repellent (DEET) application
Wearing of long pants, socks
Sleeping under a repellent impregnated mosquito net
Use air-conditioning / fans

Chemoprophylaxis

Consider for all travellers to moderate and high-risk areas
Adherence to chemoprophylaxis is critical – completion of the course is essential
It does not mask the symptoms of malaria

Travellers who have been to a malaria area and develop a fever must seek medical assistance promptly even if they have taken chemoprophylaxis

High-risk groups

The following should be advised not travel to malaria areas:

pregnant women
young children under age of five years
immunocompromised individuals,
persons on chemotherapy,
immunosuppressant doses of cortisone,
HIV infection with a CD4 count below 250 cells/mm³,
splenectomised individuals.

The following are a summary: download the complete guidelines from www.santhnet.co.za

Chemoprophylaxis regimens

	Doxycycline	Mefloquine	Atovaquone-Proguanil
Efficacy	Highly effective	Highly effective	Highly effective
Side effects	Skin photosensitivity, oesophageal ulceration, GIT upset, candida infections	Nausea, strange dreams, dizziness, insomnia, headaches	Headache, abdominal discomfort
Contraindications	Pregnancy, lactation, children under 8 years, OC use	History of psychiatric illness, cardiac arrhythmia, infants < 5 kg	Renal impairment (GFR <30), children under 11 kg
Special precautions	Use sunscreen, take with full glass of water, avoid lying down after taking dose	Travellers requiring fine motor co-ordination (pilots, divers)	Take with milk or food to increase absorption
Dosage interval	Daily	Weekly	Daily
Time to start before entering malaria area	24-48 hrs	1 week	24-48 hrs
Time to continue after leaving malaria area	30 days	4 weeks	7 days
Benefit	Cost-effective	Good for long term travellers	Good for short term travellers
Resistance	Rare	Rare but has been described in SE Asia	Rare

Although mefloquine is given as an option for chemoprophylaxis, there are currently no mefloquine-containing products available in South Africa – Lariam® has been discontinued in this country and Cipla have manufacturing issues regarding Mefliam® that will take a while to be resolved.
This means that there is currently no product that can be used for pregnant travellers or children weighing less than 11 kg. As these are also the travellers at highest risk of complicated malaria, they should be strongly advised not to go to malaria risk areas. If they have no option but to go, they should use all methods available to prevent getting bitten by the mosquitoes, and should seek immediate medical attention should they have any signs of illness.
Both doxycycline and atovaquone-proguanil are now S2 and are available from pharmacies without a prescription

Dose schedule

Option	Mefloquine		Doxycycline	Atovaquone-proguanil
Adult dose	250 mg (1 tablet) once weekly		100 mg once daily	250 mg atovaquone/100 mg proguanil (1 tablet) once daily
Paediatric dose	Infants over 3 months of age or weighing more than 5 kg:		Contraindicated in children under 8 years of age	Paediatric formulation (62.5 mg atovaquone and 25 mg proguanil) for children weighing more than 11 kg
	Weight(kg)	Weekly Dose	Children over 8 years of age: 2 mg/kg	Weight (kg)	Daily dose (paed tablet)
	5-20 21-30 31-45 > 45	¼ tablet ½ tablet ¾ tablet Adult dose		11-20 21-30 31-40 > 40kg	1 tablet 2 tablets 3 tablets Adult dose
Administration in relation to meals	Best taken with food and adequate fluid		Take after a meal with a full glass of water. Do not lie down for at least one hour after dosing	Take with food and with adequate fluid

Interactions between malaria chemoprophylaxis and other drug treatment

Antimalarial	Other drug	Comment
Mefloquine	Amiodarone	Both increase QT interval. Increased risk of torsade des pointes.
	Antipsychotics e.g. phenothiazines, pimozide	Increased risk of ventricular arrhythmias. Mefloquine should not be used in patients with a history of a psychiatric illness.
	Antiretrovirals; efavirenz, nevirapine protease inhibitors	Theoretical risk of reduced levels of mefloquine, (not clinically significant). Theoretical risk of reduced levels of protease inhibitors, (not clinically significant).
	Beta blockers e.g. atenolol, propranolol etc.	Potential for increased risk of electrocardiographic abnormalities, bradycardia and cardiac arrest. Therefore, mefloquine is not recommended for patients with cardiac conduction abnormalities, but mefloquine prophylaxis may be used safely in individuals without arrhythmia who are using beta blockers.
	Calcium channel blockers e.g. nifedipine, verapamil, diltiazem etc.	Possible increased risk of severe bradycardia. However, CDC states that there is no evidence to justify precautions for concomitant mefloquine therapy in patients using calcium channel blocking agents.
	Digoxin	Increased plasma levels of digoxin. Use with caution. Monitor levels.
	Halofantrine	Concurrent use may result in serious cardiac effects. Treatment with halofantrine is contraindicated when mefloquine has been used for prophylaxis.
	NOACs	May increase plasma levels of dabigatran and rivaroxaban, which may increase risk of bleeding.
	Oral cholera and typhoid vaccines	Inactivation of the immunisation possible. Complete immunisation three days before taking mefloquine.
	Primaquine	May increase the serum levels and side effects of mefloquine.
	Quinine or quinidine	Quinine may inhibit the metabolism of mefloquine, thereby increasing mefloquine levels. The combination may produce electrocardiographic abnormalities, cardiac arrest, or could result in potentially serious cardiac conduction abnormalities. On the other hand, a small, limited study conducted in 13 adults with single doses of both drugs showed a lack of a clinically significant cardiovascular pharmacodynamic interaction. The combination may increase the risk of seizures. A loading dose of quinine should not be given if mefloquine has been used for prophylaxis in the preceding 24 hours.
	Rifampicin	Decreased plasma concentration of mefloquine via induction of mefloquine metabolism.
	Tricyclic antidepressants	Increased risk of ventricular arrhythmias. Mefloquine should not be used in patients with a history of a psychiatric illness.
	Valproic acid	Accelerated sodium valproate metabolism may result in low valproic acid serum concentrations and loss of seizure control. Monitor valproic acid levels. Mefloquine is contraindicated in epileptics.
Doxycycline	Alcohol	In alcoholic patients the serum levels of doxycycline may fall below minimum therapeutic concentrations, but this does not apply to acute intake of alcohol.
	Antacids containing: calcium, bismuth, aluminium, magnesium, calcium supplements	Reduces the absorption and serum concentrations of doxycycline significantly, compromising therapeutic efficacy. If possible use alternative therapy, or administer doxycycline at least two hours before, or four to six hours after antacids.
	Antiretrovirals	No theoretical or known interaction
	Carbamazepine, barbiturates and phenytoin	Reduce the plasma half-life of doxycycline by approximately 50 per cent and may result in a reduction of efficacy. (See Epilepsy Section)
	Iron	Decreased absorption of doxycycline and iron salts. Efficacy may be reduced. Separate dosages by as much as possible. Give iron at least three hours before or two hours after the doxycycline dose.
	Methotrexate	One case report exists of a cancer patient who was receiving high-dose methotrexate and developed methotrexate-induced gastrointestinal and haematological toxicities in association with increased methotrexate levels after a course of doxycycline was introduced. Monitor patients closely, especially when methotrexate is administered in high doses.
	Isotretinoin	An increased incidence of pseudotumour cerebri has been reported in patients on other tetracyclines. It is unknown whether doxycycline is also potentially problematic.
	Milk and dairy products	Absorption of doxycycline may be reduced by up to 30 per cent because of the calcium ions found in milk. Avoid for at least one hour before or two hours after taking doxycycline. The small amounts of milk used in coffee and tea appear not to matter.
	Oral contraceptives	May reduce efficacy of contraceptives, if diarrhoea or vomiting occurs.
	Rifampicin	Increased doxycycline clearance. Potential loss of doxycycline efficacy. Monitor patient response.
	Warfarin	Potentiation of anticoagulant effect possible, monitor INR.
Atovaquone - proguanil	Antiretrovirals: protease inhibitors, zidovudine	Theoretical risk of reduced level of atovaquone. Theoretical risk of reduced level of indinavir. Zidovudine levels may be increased.
	Live typhoid vaccine	A decreased immune response to typhoid vaccine. Allow 10 days to elapse between the last dose of live typhoid vaccine and the administration of proguanil.
	Magnesium trisilicate	Reduces absorption of proguanil. Separate doses as much as possible (two to three hours).
	Metoclopramide	Atovaquone plasma levels reduced, resulting in therapeutic failure.
	Rifampicin, rifabutin	Atovaquone plasma levels reduced, resulting in therapeutic failure.
	Tetracycylines	Atovaquone plasma levels reduced, resulting in therapeutic failure.
	Warfarin	May potentiate effect of Warfarin, monitor INR.

Drug choice according to Traveller’s condition/situation

Condition/situation	Mefloquine	Doxycycline	Atovaquone-proguanil
Pregnancy - Avoid travelling to a malaria area	Drug of choice if pregnant women is at risk of malaria	Not recommended, but there are some data to support its use within the first 15 weeks of pregnancy if the risk of malaria is high	Not recommended due to lack of information
Women of child-bearing potential or on oral contraceptives	Ideally use reliable contraception during and for three months after taking last dose. Will not compromise contraceptive efficacy.	Avoid pregnancy during and for one week after taking last dose. Contraceptive failure may occur if the traveller presents with vomiting or diarrhoea.	Avoid pregnancy during and for three weeks after taking last dose. Will not compromise contraceptive efficacy.
Breastfeeding - Baby must be given its own prophylaxis	Insufficient data, but WHO states that it is safe to use.	Only use if there is no other option. (ACIP* says it can be used)	Avoid use, as data are lacking
Young children - Avoid taking children under the age of 5 years to a high risk area	Can be used in children over 3 months of age or >5 kg. Generally well tolerated by children.	Only use in children >8 years of age.	Paediatric tablets can be given to children weighing more than 11kgs.
Diabetics.	Insufficient data - monitor blood glucose levels.	May increase hypoglycaemic effect of insulins - monitor blood glucose levels.	No known problems. Monitor blood glucose levels.
Epilepsy	Contraindicated. May also interact with valproic acid.	May interact with phenytoin, phenobarbitone and carbamazepine, reducing the half-life of doxycycline & possibly resulting in prophylaxis failure.	Can be used.
Hepatic impairment	Contraindicated in severe impairment	Administer with caution to hepatically impaired patients or those receiving hepatotoxic drugs.	Safe to use in mild to moderate hepatic impairment, but no data on use in severe hepatic impairment
Individuals requiring fine motor co-ordination and spatial discrimination e.g. pilots.	Do not use.	Safe to use.	Safe to use.
Persons on oral anticoagulants. Caution: Changes in INR can be very dangerous, resulting in bleeding or clotting. Preferably avoid high risk malaria areas.	Insufficient data - monitor INR. Start therapy in advance to monitor possibility of interaction.	May potentiate anticoagulant effect. Monitor INR.	Proguanil may potentiate the effect of oral anticoagulants. Monitor INR.
Persons requiring long-term therapy.	Can be used for up to 3 years and even longer if justified by risk of exposure.	Can be used for 2 years and even longer if justified by risk of exposure	Can used for up to 1 year and even longer if justified by risk of exposure

Diagnosis of malaria – early diagnosis is essential
Suspect malaria in any person presenting with fever with a travel history to or is resident in a malaria transmission area, irrespective of the time of year, irrespective of whether they have taken chemoprophylaxis.

Symptoms of malaria infections commonly develop 10 to 14 days after an infective mosquito bite but may be prolonged especially if prophylactic drugs have been taken.

RAPID DIAGNOSTIC TESTS (RDTs)
Combination tests are available but are less sensitive. Use of such tests in the South African context is discouraged.

RDT Limitations:

very scanty infections may be missed.
cannot be used to determine severity of infection: do not measure parasite load.
cannot be used to monitor progress of treatment or to confirm clearance of parasites
remain positive for some time after successful treatment.
occasional false negative or false positive results, so RDT results should be confirmed by conventional microscopy whenever possible,

Effective treatment
Malaria must be treated as a medical emergency. The sooner effective treatment is started, the better the prognosis.

Download the complete Guidelines at https://www.santhnet.co.za/

Last checked for updates with SASTM: Aug 2023

Malaria: Prevention Guidelines (Summary)

Drugs mentioned