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1
Malaria prophylaxis

• Jørgen Kurtzhals
• Centre for Medical Parasitology
• Rigshospitalet, Copenhagen, Denmark

2
Indication for chemoprophylaxis

• Risk groups in populations of endemic countries
• Pregnant women
• Infants
• Travel to high risk areas

3
The headlines

• Principles of malaria prophylaxis
• Individual counselling
• Geographical
• Traveller
• Available drugs
• Standby treatment
• Risk
• The need of the traveller
• The need of the doctor

4
Purpose of malaria prophylaxis

• Give the traveller a tool to
• Reduce risk of malaria
• Minimise risk of severe malaria
• Avoid fatal malaria
• NOT a guarantee against malaria

5
Principles of malaria prophylaxis

• A awareness about the risk of malaria
• B bites of mosquitoes should be avoided
• C chemoprophylaxis and compliance
• D diagnosis of febrile illness without delay

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Awareness about the risk

• The risk of contracting malaria
• In spite of taking prophylaxis
• Alert your doctor
• The risk of dying from malaria (P. falciparum)
• Particularly if treatment is delayed
• Adjust level of information to the traveller

7
Mosquito bite prophylaxis

• Malaria transmitted by anopheline mosquitoes
• Bite at night (dusk to dawn)
• Stay indoor at night
• Mosquito screen
• Impregnated bed nets
• Air conditioning
• Long clothing and repellent outdoors at night
• Also repellent in face apart from proximity of
  eyes and mouth

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Chemoprophylaxis

• Take prescribed drug exactly as advised
• Start one dose interval before (Lariam 3-4
  weeks)
• Continue 4 weeks after (Malarone 1 week)
• Side effects
• Serious Discontinue. Seek immediate medical
  advise
• Mild/moderate Continue. Seek medical advise
• Will chemoprophylaxis blurr symptoms?
• Possibly, but no cause to discontinue

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Diagnosis and treatment

• Incubation period 1 week - months
• Fever must be examined without delay
• Fever fluctuates (not always clear periodicity)
• Other symptoms can vary (nausea, headache,
  pains.)
• Falciparum malaria may become severe in 24-48
  hours
• Standby treatment
• Only when no other possibility
• Always medical care (certify cure, differential
  diagnosis)

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Drugs for prophylactic use

• Chloroquine
• Benign malaria or sensitive P. falciparum
• Acceptable in pregnancy and infants
• One weekly dosage
• Rare and acceptable side effects
• GI
• Vision
• Itching
• May worsen psoriasis (and epilepsy?)

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Drugs for prophylactic use

• Proguanil (Paludrine)
• In combination with Chq for sensitive P.
  falciparum
• Acceptable in pregnancy folate 5 mg daily
• Acceptable in infants no syrup available
• One daily dosage (evening meal)
• Acceptable side effects
• GI
• Mouth ulceration, hair loss

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Drugs for prophylactic use

• Mefloquine I (Lariam)
• Documented effect against P. falciparum (not S-E
  Asia)
• Useful from 5 kg body weight and gt 3 months
• Contra indicated in pregnancy and lactation
• One weekly dose
• Begin 3-4 weeks before (tolerance testing)
• Quinine use relative contra indication

13
Drugs for prophylactic use

• Mefloquine II
• Side effects
• Sleep disorders
• Neuropsychiatric
• Cardiac arrythmia
• GI vomiting
• Public opinion!

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Drugs for prophylactic use

• Doxycycline I
• Prevention of P. falciparum in S-E Asia (and
  alternative in other areas)
• Absolutely contraindicated in
• Pregnant and lactating women
• Growing children (lt12 years)
• One daily dose (NOT with milk products or iron)
• Broad spectrum antibiotic ecological
  perspective

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Drugs for prophylactic use

• Doxycycline II
• Side effects
• GI potentially severe (e.g. Cl. difficile)
• Vaginal candidiasis
• Photo sensitivity

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Drugs for prophylactic use

• Atovaquone proguanil (Malarone)
• Apparently effective against all P. falciparum
• Not documented against other plasmodia
• Used from 10 kg
• Contra indicated in pregnancy and lactation
• One daily dose (with food or milk product)
• Expensive
• Well tolerated (head ache, GI, mouth ulcers, hair
  loss rare)

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Choice of prophylaxis

• Destination
• WHO International travel and health
• www.who.int/ith
• National guidelines
• Duration and type of travel
• Short term, business
• Low risk, high economic performance
• Long term, adventure
• High risk, low economic performance

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Choice of prophylaxis

• Long term, residence
• Mosquito free housing
• Increased risk during journeys/field work
• Awareness about malaria
• Take responsibility
• Knowledge about good local clinics
• Long duration of drug intake
• Side effects (real/perceived)
• Economy

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Choice of chemoprophylaxis
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Standby treatment

• Definition
• Self administration of antimalarial
• When malaria is suspected
• And when medical care is unavailable within 24
  hours

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Rational for standby treatment

• Rapid progression from symptom start to possible
  complications
• High risk area Prophylaxis only 50-90 effective
• Low risk area Toxicity from prophylaxis may
  outweigh benefit of avoiding malaria

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Indication for standby treatment

• Tp gt 37.50C /- malaise, head ache etc.
• Medical aid unavailable within 24 hours
• Minimum 7 days after entering malarious area
• Take standby treatment
• Seek medical care without delay

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Choice of standby treatment

• Fansidar (Sulfadoxin-pyrimethamine)
• Easy administration, effective, well tolerated
• S/P resistance in East Africa and South East Asia
• Allergy
• Malarone
• Highly effective in all areas
• Very expensive

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Choice of standby treatment

• Mefloquine
• Highly effective except S-E Asia
• Common side effects at therapeutic dosage
• Not recommended for treatment if used as
  prophylaxis
• Quinine
• Highly effective in all areas
• Common side effects
• Compliance Long treatment duration
• Not if mefloquine used as prophylaxis

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Choice of standby treatment

• Chloroquine
• Effective against benign malaria and P.
  falciparum where there is no resistance (WHO)
• Well tolerated
• Artemisinin derivatives
• Not available in many countries available in
  Africa
• Effective in all areas
• Well tolerated
• Risk of recrudescence

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Risk

• The traveller
• The risk of malaria
• Transmission intensity
• Type
• Benefit
• Resistance
• Adverse effects (and cost)
• The level of awareness
• The willingness to be responsible

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Risk

• The doctor
• Responsibility
• Standard procedure
• All deviations recorded
• Signed contract for all sub-optimal choices?
• E.g. long term travellers
• Insurance!

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Short cases 1

• 18 year old girl, going on an international
  exchange programme to rural Kenya for 9 months
• Suggest prophylaxis
• Mefloquine
• Father has epilepsy alternative?
• Ask about specific risk plus treatment facilities
• Low risk, good facilities Chloroquine and
  proguanil
• High risk and/or doubtful facilities Doxycycline

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Short case 2

• 35 year old, pregnant woman (8 weeks) travelling
  to Solomon Islands on a 2 month trip
• Advise Stay at home
• Insists on going choose chemoprophylaxis
• Chloroquine and proguanil
• Suggest stand by treatment
• Fansidar (or quinine)

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Case 1

• 17 students of West African architecture (Mali,
  Ghana)
• Various prophylactic regimens
• Two febrile cases treated as malaria by local
  clinic (Ghana)
• Both were on doxycycline
• Contact by e-mail What do we do?

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Case 1 ctd.

• Your advise continue. Take care of mosquito
  bites
• Confirmed diagnosis?
• No better alternative
• Two students on doxycykline have moderate-severe
  side effects
• Suggest alternative

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Case 1 ctd.

• Malarone if cost is not an issue
• Chloroquine and proguanil plus warning!
• Mefloquine not nice to start in the middle of
  journey

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Case 1 ctd.

• One student on artemisia drops (herbal drug) x 2
  weekly
• Suggests this to fellow travellers, one takes the
  advise
• After 3 months total of 11 suspected malaria, all
  treated with chloroquine
• Who had malaria antibodies (merozoite IFAT)?

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Case 1 ctd.

• The 2 on artemisia had confirmed malaria
• Lessons learned
• Local diagnosis not always reliable
• Do not change accepted principles due to single
  event
• Artemisia not suitable for prophylaxis (short
  half life)
• Herbal artemisia unreliable content

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Case 2

• 64-year old woman with fever and hot sensation
  when passing urine
• Returned from the Gambia after beach journey 2
  weeks ago
• Good compliance with chloroquine and proguanil
  (ongoing)
• Diagnosis?

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Case 2 ctd.

• Could be malaria
• Local doctor suspects cystitis antibiotic
  treatment
• Admitted after additional 3 days with 11 P.
  falciparum
• Lessons
• Chqproguanil not optimal in West Africa
• No prophylaxis is safe always suspect malaria
• Symptoms of malaria can mimick many conditions

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Case 3

• 38-year old Danish woman, had been living in
  northern Ghana for 3 years
• Developed fever with chills, malaise, womiting
• Local clinic found lt1 P. falciparum
• Treated with halofantrine (Halfan) 500 mg x 3
  for one day
• What next?

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Case 3 (ctd.)

• No serious side effects
• No repeated dose after one week
• Prolonged convalescence not really well for 2
  months
• Anaemia, Hb 9.4 g/dl normal MCV and MCHC
• Repeated blood films Malaria parasites not found
• What next?

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Case 3 (ctd.)

• Returned to Denmark at end of contract period
• Routine check including 3 blood films Anaemia,
  no malaria parasites found
• What next?

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Case 3 (ctd.)

• Stool examination x 3 No bacterial pathogens,
  Entamoeba coli cysts , Chilomastix mesnili
  cysts
• Total WBC 8.7, lt1 eosinophils, 102 thrombocytes
• Normal renal function
• Bilirubin 26 mmol/l, liver enzymes normal
• No obvious clinical explanation for the tiredness
  and anaemia. Bone marrow investigation, cerebral
  CT, and other investigations considered
• What next?

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Case 3 (ctd.)

• 4 weeks after return, discontinuation of malaria
  prophylaxis (chloroquine and proguanil)
• Six days later rushed to hospital, reduced
  consciousness, tp. 39.70C
• Lumbar puncture CSF with 8 cells, glucose and
  protein normal
• Blood film 8 P. falciparum
• Diagnosis cerebral malaria

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Case 3 lessons learned

• Halfan is never first choice
• Halfan should always be repeated after one week
• Malaria prophylaxis is intended to suppress the
  infection
• This may sometimes blurr the clinical and
  laboratory picture
• HOWEVER Prophylaxis should be given in any case
• Thrombocytopaenia and anaemia are suggestive of
  malaria
• Choose most effective prophylaxis?