Malaria - prophylaxis and treatment

What do you already know about malaria?

It is caused by a protozoa - parasite.
Commonly caused by Falciparum parasite but there are other types which are endemic to certain regions
around the world.
Prophylaxis is better than treatment. Bite prevention and chemoprophylaxis are important in preventing
someone from contracting malaria. Monitoring for fever or other symptoms of malaria e.g. feeling hot and
shivery, muscle pain, diarrhoea and vomiting is important not just during stay but after stay.

Malaria is a serious and potentially life-threatening febrile illness.

It is caused by infection with the protozoan parasite plasmodium.
Plasmodium is transmitted to humans by the bite of the female Anopheles mosquito. It is one of the most
common causes of fever among people returning from abroad and is the most common tropical disease in
the UK.

Malaria is preventable and treatable.

Types of malaria:
- Plasmodium falciparum (82% UK cases) - most common type in UK and most dangerous, causes
majority of deaths
- Plasmodium vivax (9%) - can persist in liver for months - relapsing
- Plasmodium ovale (7%) - can persist in liver for months - relapsing
- Plasmodium malaeiae (2%)
- Plasmodium knowlesi (0.1%)
- Mixed (0.5%)

When mosquito bites and feeds on person’s blood, plasmodium sporozoites are injected into the
bloodstream which are taken up by the liver and the species develop in the liver forming shizonts.
Parasites are then released and they invade and develop in the red blood cells. For vivax and ovale species
there is a dormant stage in the liver where the parasite may live for many months before infecting the
blood cells which is why there is a relapsing effect.
As parasites lives as shizonts in the liver for a while so it make take time from when the mosquito bites to
when the patient develops symptoms.

Parasites multiple in red blood cells through asexual reproduction which leads to clinical illness. At this
point the person’s blood has parasites in it and if they get bitten by a mosquito that is not yet infected, the
mosquito then picks up infected blood and can transmit it to someone else.
Tropical and subtropical regions:

Statistics from WHO

- 3.4 billion people in 92 countries are at risk globally
- 219 million cases in 2017
- 0.5 million deaths in 2017

What about in the UK?

In 2018, there were 1683 cases of malaria in the UK. The vast majority of these were acquired in west
Africa. Of these cases they were most commonly picked up by those visiting family (80%) in country of
origin. The other 20% are equally split between people travelling on business and people travelling for
holidays.

In 2016:
- Half of the cases were picked up in London, median age of 41 and about 67% were male.
- 85% of people who picked up malaria and brought it back to the UK had not taken
chemoprophylaxis
- 6 deaths due to Falciparum malaria and picked up in West Africa
- UK cases peak in July - September, smaller peak in January
LECTURE TWO - PREVENTION
A - awareness of risk
B - bite prevention
C - chemoprophylaxis
D - diagnose promptly and treat without delay

Awareness of risk:
- Risk depends on temperature, altitude (high above sea-level) and season
- Optimum conditions for malaria transmission are high humidity and a temperature between 20 and
30 degrees Celsius.
- Parasite maturation in the mosquito usually stops above 2000 metres.
- Rural versus urban - staying in a hotel in the middle of the city has a lower malaria risk compared to
sleeping in a rural area where there may be ponds which attract mosquitos.
- Type of accommodation - hotels often have air-conditioning which creates a draught as well as
mosquito screens in windows
- Being outdoors between dusk and dawn is the main risk for getting bitten
- Length of stay
- Patient factors

Patient factors
- Some have genetic or immunological factors which are protective or lead to less severe disease e.g.
sickle cell gene
- Some immunity develops after years of exposure - but lost within a year e.g. if someone has lived in
a malarious area who return to the UK without taking chemoprophylaxis can still pick it up when
they go back
- Pregnancy puts people more at risk because of the effect of pregnancy on the immune system (it
becomes weaker)
- Immunocompromised people e.g. due to immunosuppressant drugs for RA or cancer or because
they are asplenic (have no spleen). People are advised to not travel to malarious areas.

Bite avoidance:
- Physical barriers e.g. mosquito nets are essential
- Personal protection is essential even for those taking chemoprophylaxis
- Mosquito nets impregnated with an insecticide like permethrin. Peak biting time at 2am but varies
by species. Retreat with permethrin every 6 months, replace every 3 years.
- Mosquito nets are estimated to be about 50% effective.
- People can use vapourised insecticides.
- Wear long sleeves and long trousers worn after dusk, tuck trousers into socks
- Diethyltoluamide (DEET) 20-50% on any bare skin and under thin clothes (avoid eyes and lips)
- Duration of protection 1-3 hours for 20% for up to 6 hours for 30% and up to 12 hours for 50%
- Contradictory advice about DEET after sunscreen or vice versa. DEET may reduce the efficacy of
sunblock so use high SPF; DEET efficacy also reduced. Can use combination products. It may need
reapplying more often.
- Purchase in the UK as not available in some countries
- Do not swallow or inhale

https://www.nhs.uk/conditions/malaria/prevention/
There's no evidence to suggest homeopathic remedies, electronic buzzers, vitamins B1 or B12, garlic, yeast
extract spread (such as Marmite), tea tree oils or bath oils offer any protection against mosquito bites.

Chemoprophylaxis:

Choice of prophylactic drug

- Different drugs recommended for different geographical areas - need up to date recommendations
- Rarely indicated outside sub-saharan Africa and other areas (particularly if patient is
immunocompromised). This might change as patterns of malaria change and resistance change and
guidance is always changing.
- Take into account risk of exposure, extent of drug resistance, efficacy of recommended drugs, side
effects and patient factors and contraindications: pregnancy, age, renal or hepatic impairment, co-
morbidities and other drugs.

HCPs:
www.TravelHealthPro.org.uk and/or Public Health England’s guidelines for malaria prevention in travellers
from the UK - 2019.

For the public - hospital for tropical diseases has produced advice on all aspects of travel and health
including malaria guidance - www.fitfortravel.nhs.uk

GENERAL PRINCIPLES OF MEDICATION FOR PREVENTION:

- Length of prophylaxis - start one week before travel (preferably 2-3 weeks for mefloquine which
gives opportunity to change to a different drug if it causes intolerable side effects)
- Continue for 4 weeks after leaving because of the way the parasite cycles through the body as it is
released from the dormant stage in the liver (except Malarone - one week)
- Obtain antimalarials in the UK if possible - greater counterfeit risk in some countries
- Protection against bites are also essential
- Be aware of illness up to 1 year after return - especially for the first 3 months as chemoprophylaxis
is not 100% effective

TWO APPROACHES:
- Causal - prevent plasmodium parasite leaving liver and infecting red blood cells to prevent
presenation of symptoms when red blood cells get infected- must be taken at least 7 days after
leaving area e.g. proguanil/atovaquone
- Suppressive - acts on parasite after it has infected red blood cells - must be taken for several weeks
after a bite - continue for 4 weeks after leaving malarious area
- Mefloquine, doxycycline, chloroquine and proguanil.

DRUGS USED:
Proguanil
- Mild side effects - rarely used alone
- Atovaquone/proguanil (Malarone) - GI side effects and headaches common
- Chloroquine is only used when chloroquine resistance is low and not in patients who have history
of epilepsy. Ocular toxicity can be caused if used long-term (avoid in someone who is going to live
or work in a malarious area), GI side effects and headaches common. It has a lot of drug
interactions - contraindicated with amiodarone as it can cause problems with arrythmias.
Chloroquine can increase cyclosporin levels and digoxin levels (be cautious in general with drugs
who have a narrow therapeutic index).
Mefloquine (not used as often because of side effects)
- Used where high risk chloroquine-resistance falciparum
- Taken once a week - need to remember! (TELL PEOPLE MONDAY MALARIA)
- Do not use in cardiac conduction disorders, epilepsy or psychiatric illness (including depression) as
mefloquine can make this worse. This is why we start it 3-4 weeks before travelling so if someone
finds they experience bad side effects they can start another treatment.
- Dizziness - may affect driving.
- Nightmares - psychosis, GI side effects

Doxycycline
- Not in children as with all tetracyclines (WHY IS THIS?)
- Children can develop permanent brown discoloration of the teeth due to drug deposition, probably
due to its chelating property and the formation of a tetracycline– calcium orthophosphate complex.
Therefore, the risk is when the teeth are being calcified
- Various dietary interactions - divalent cations and can lead to photosensitivity

Specific groups
- Certain groups of patients especially vulnerable - avoid travel to malarious areas if at all possible if
you are pregnant, asplenic or immunocompromised.
- Settled immigrants (or long term visitors) in the UK are at risk on return to previous home area so
they may have lost previous in built immunity. Areas where they previously lived may have now
become malarious.

Emergency standby treatment.

- Emergency standby treatment should be recommended for those taking chemoprophylaxis and
visiting remote areas where they are unlikely to be within 24 hours of medical attention.
- Written instructions for use required - available from PHE
- Not a substitute for prophylaxis
Lecture three - Malaria treatment

Drug treatment - UK malaria treatment guidelines 2016

- Early diagnosis and recognition of severity is essential to avoid deaths

- Applies to all febrile/ill patients with history of travel to malarial area
- Suspect in anyone with a history of travel to affected area in the last 12 months

Diagnosis - what are the symptoms?

- Fever/sweats/chills
- Malaise
- Myalgia - muscle aches
- Headache
- Diarrhoea
- Confusion
- Seizures
- Haemoglobinuria (blood in urine) if parasite is destroying many red blood cells
These symptoms are quite non-specific (could be a bad flu).

These symptoms are very varied in people who get malaria. Not everyone gets fever. Some children may
present with predominantly GI side effects or a sore throat.

Relevant history

Imagine someone coming into the pharmacy asking for medicine for flu and they have some of the
symptoms above
- Country of travel?
- Length of time abroad and date of return? If they returned yesterday and they developed
symptoms, it is unlikely to be malaria because it has an incubation period of 6 days before
symptoms become apparent.
- Falciparum malaria most likely within 3/12 of return - majority within 1/12 of return
- Other strains of malaria can take up to one year to become apparent
What prophylaxis was taken?
- Did people take precautions with mosquito nets, did they take chemoprophylaxis, how was their
adherence, did they get any diarrhoea or vomiting which could affect the efficacy?
- Even if someone has taken the right chemoprophylaxis, it does not exclude malaria as it is still
possible.

Investigations:
If you suspect malaria, refer the person to have some tests
- Urgent blood films for lab examination
- Finger prick to produce spot of blood on slide
- Gold standard - thin and thick blood films
- There is greater chance of seeing evidence of malaria parasites with a thick blood film but it may be
difficult to see what type of parasite is in the film. This is where thin blood films may be better (can
identify species more easily).
- Rapid diagnostic tests nearly as accurate as blood films and check for for antigens for P Falciparum
and P Vivax

Standard blood tests e.g. full blood count, urea and electrolytes, liver function tests and C-reactive protein.
Blood culture to exclude other bacteraemia e.g. tyhphoid.
Urine dipstick to measure haemoglobin
Chest x-ray to exclude pneumonia
Pregnancy test for women of child-bearing age.

Principles of treatment:

- Eradication in blood stream to suppress the erythrocytic stage e.g. quinine (risk of hypoglycaemia
and cinchonsim (cluster of side effects including tinnitus, decreased hearing, headache, nausea,
vomiting and visual disturbances).
- Chloroquine
- Pyrimethamine
- Artemasein
- Artemether with lumefantrine

Eradication in the liver where parasite can lie dormant and primaquine is used.

Most important - to distinguish between falciparum and non-falciparum malaria.

Drug treatment - falciparum

- Uncomplicated falciparum malaria

- Usually admitted to hospital initially
- Artemether - lumefantrine 4 tablets initially, followed by 5 further doses of 4 tablets each at 8, 24,
36, 48 and 60 hours.
- If unavailable use proguanil/atovaquone (Malarone) 4 tablets daily for 3 days OR
- Oral quinine (600mg TDS for 5-7 days plus oral doxycycline 200mg OD for 7 days).

Hospital treatment needed:

Severe or complicated malaria:
- If patient has one or more of the following: > 2% of red blood cells have parasites in them
(estimated by looking at blood film), extreme weakness, seizures, jaundice (breakdown product of
haem), hypoglycaemia, severe anaemia due to damage to blood cells OR bleeding
- Treatment of choice is IV artesunate (unlicensed) - more specialist hospitals stock this drug so by
providing a license it can be more accessible
- Or quinine (IV for at least first 48 hours) plus a second drug such as doxycycline, for 7 days
- Oxygen therapy
- Monitoring of blood glucose, oxygen saturation, FBC, U&Es, LFTs, ECG
- May need ITU - supportive management

Treatment of non-falciparum malaria

- Outpatient treatment may be appropriate, if patient aware of action to be taken in case of relapse
- Artemether - lumefantrine OR chloroquine
Common errors in treatment of malaria:

Community pharmacists can play a key role in suspecting malaria.

Notifiable disease
Malaria is a statutorily notifiable disease in England and Wales and the clinician caring for the patient must
complete a notification form.

Malarial control
- Would require control of three living beings - humans, mosquitos and plasmodium parasite
- Various initiatives in 1950s and 1960s to try and eradicate it
- WHO currently recommends focus instead on personal protection and early diagnosis/treatment

CONCLUSION:
Correct use of prophylactic drugs and personal protection can prevent the vast majority of cases - no single
intervention is 100% effective - need a combination of approaches, and be aware of malaria as a possible
diagnosis.
Malaria is straightforward to treat if diagnosed promptly and treated correctly.