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e-mail: [email protected]: http://www.cmp.dk

Malaria prophylaxisMalaria prophylaxis

Jørgen KurtzhalsCentre for Medical Parasitology

Rigshospitalet, Copenhagen, Denmark


Indication for chemoprophylaxisIndication for chemoprophylaxis

• Risk groups in populations of endemic countries

• Pregnant women

• Infants

• Travel to high risk areas


The headlinesThe headlines

• Principles of malaria prophylaxis

• Individual counselling

• Geographical

• Traveller

• Available drugs

• Standby treatment

• Risk

• The need of the traveller

• The need of the doctor


Purpose of malaria prophylaxisPurpose 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


Principles of malaria prophylaxisPrinciples 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


Awareness about the riskAwareness 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


Mosquito bite prophylaxisMosquito 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


ChemoprophylaxisChemoprophylaxis

• 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


Diagnosis and treatmentDiagnosis 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)


Drugs for prophylactic useDrugs 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?)



• 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



• Mefloquine – I (Lariam®)

• Documented effect against P. falciparum (not S-E Asia)

• Useful from 5 kg body weight and > 3 months

• Contra indicated in pregnancy and lactation

• One weekly dose

• Begin 3-4 weeks before (tolerance testing)

• Quinine use relative contra indication



• Mefloquine – II

• Side effects

• Sleep disorders

• Neuropsychiatric

• Cardiac arrythmia

• GI – vomiting

• Public opinion!



• Doxycycline – I

• Prevention of P. falciparum in S-E Asia (and alternative in other areas)

• Absolutely contraindicated in

• Pregnant and lactating women

• Growing children (<12 years)

• One daily dose (NOT with milk products or iron)

• Broad spectrum antibiotic – ecological perspective



• Doxycycline – II

• Side effects

• GI – potentially severe (e.g. Cl. difficile)

• Vaginal candidiasis

• Photo sensitivity



• 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)


Choice of prophylaxisChoice 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


Choice of prophylaxisChoice 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


Choice of chemoprophylaxisChoice of chemoprophylaxis

Regional malaria (q, u, x, z) Yes Real risk No Mosquitoprophylaxis

No Yes

Benign malaria (Q) Yes ChloroquineNoSensitive P. falciparum (U) Yes Chq+proguanilNoMalarone acceptable (X, Z) Yes MalaroneNoMefloquine acceptable (X) Yes MefloquineNoHigh malaria risk (X, Z) Yes Doxycycline acceptable Yes DoxycyclineNo NoLow risk, relatively sensitive Yes Chq+proguanil+warningNoLow risk, resistant Yes Mosquito proph+warning


Standby treatmentStandby treatment

• Definition

• Self administration of antimalarial

• When malaria is suspected

• And when medical care is unavailable within 24 hours


Rational for standby treatmentRational 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


Indication for standby treatmentIndication for standby treatment

• Tp > 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


Choice of standby treatmentChoice 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



• 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



• 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


RiskRisk

• The traveller

• The risk of malaria

• Transmission intensity

• Type

• Benefit

• Resistance

• Adverse effects (and cost)

• The level of awareness

• The willingness to be responsible


RiskRisk

• The doctor

• Responsibility

• Standard procedure

• All deviations recorded

• Signed contract for all sub-optimal choices?

• E.g. long term travellers

• Insurance!


Short cases 1Short 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


Short case 2Short 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)


Case 1Case 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?


Case 1 – ctd.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



• Malarone if cost is not an issue

• Chloroquine and proguanil plus warning!

• Mefloquine not nice to start in the middle of journey



• 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)?



• 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


Case 2Case 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?



• Could be malaria

• Local doctor suspects cystitis – antibiotic treatment

• Admitted after additional 3 days with 11% P. falciparum

• Lessons:

• Chq+proguanil not optimal in West Africa

• No prophylaxis is safe – always suspect malaria

• Symptoms of malaria can mimick many conditions


Case 3Case 3

• 38-year old Danish woman, had been living in northern Ghana for 3 years

• Developed fever with chills, malaise, womiting

• Local clinic found <1% P. falciparum

• Treated with halofantrine (Halfan®) 500 mg x 3 for one day

• What next?


Case 3 (ctd.)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?



• Returned to Denmark at end of contract period

• Routine check including 3 blood films: Anaemia, no malaria parasites found

• What next?



• Stool examination x 3: No bacterial pathogens, Entamoeba coli cysts ++, Chilomastix mesnili cysts

• Total WBC 8.7, <1% eosinophils, 102 thrombocytes

• Normal renal function

• Bilirubin 26 mol/l, liver enzymes normal

• No obvious clinical explanation for the tiredness and anaemia. Bone marrow investigation, cerebral CT, and other investigations considered

• What next?



• 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


Case 3 – lessons learnedCase 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?

e-mail: [email protected] internet: malaria prophylaxis jørgen kurtzhals centre for medical parasitology...

Documents

malaria slide

falciparum malaria

risk of severe malaria

risk of contracting

traveller slide

fatal malaria

purpose of malaria prophylaxis

mouth slide