E-mail: [email protected] Internet: Malaria prophylaxis Jørgen Kurtzhals Centre for Medical Parasitology Rigshospitalet, Copenhagen, Denmark.

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 Rigshospitalet, Copenhagen, Denmark.

Documents

malaria slide

falciparum malaria

risk of severe malaria

risk of contracting

traveller slide

fatal malaria

purpose of malaria prophylaxis

mouth slide