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e-mail: [email protected]: http://www.cmp.dk
Malaria prophylaxisMalaria prophylaxis
Jørgen KurtzhalsCentre for Medical Parasitology
Rigshospitalet, Copenhagen, Denmark
e-mail: [email protected]: http://www.cmp.dk
Indication for chemoprophylaxisIndication for chemoprophylaxis
• Risk groups in populations of endemic countries
• Pregnant women
• Infants
• Travel to high risk areas
e-mail: [email protected]: http://www.cmp.dk
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
e-mail: [email protected]: http://www.cmp.dk
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
e-mail: [email protected]: http://www.cmp.dk
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
e-mail: [email protected]: http://www.cmp.dk
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
e-mail: [email protected]: http://www.cmp.dk
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
e-mail: [email protected]: http://www.cmp.dk
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
e-mail: [email protected]: http://www.cmp.dk
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)
e-mail: [email protected]: http://www.cmp.dk
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?)
e-mail: [email protected]: http://www.cmp.dk
Drugs for prophylactic useDrugs 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
e-mail: [email protected]: http://www.cmp.dk
Drugs for prophylactic useDrugs for prophylactic use
• 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
e-mail: [email protected]: http://www.cmp.dk
Drugs for prophylactic useDrugs for prophylactic use
• Mefloquine – II
• Side effects
• Sleep disorders
• Neuropsychiatric
• Cardiac arrythmia
• GI – vomiting
• Public opinion!
e-mail: [email protected]: http://www.cmp.dk
Drugs for prophylactic useDrugs 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 (<12 years)
• One daily dose (NOT with milk products or iron)
• Broad spectrum antibiotic – ecological perspective
e-mail: [email protected]: http://www.cmp.dk
Drugs for prophylactic useDrugs for prophylactic use
• Doxycycline – II
• Side effects
• GI – potentially severe (e.g. Cl. difficile)
• Vaginal candidiasis
• Photo sensitivity
e-mail: [email protected]: http://www.cmp.dk
Drugs for prophylactic useDrugs 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)
e-mail: [email protected]: http://www.cmp.dk
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
e-mail: [email protected]: http://www.cmp.dk
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
e-mail: [email protected]: http://www.cmp.dk
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
e-mail: [email protected]: http://www.cmp.dk
Standby treatmentStandby treatment
• Definition
• Self administration of antimalarial
• When malaria is suspected
• And when medical care is unavailable within 24 hours
e-mail: [email protected]: http://www.cmp.dk
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
e-mail: [email protected]: http://www.cmp.dk
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
e-mail: [email protected]: http://www.cmp.dk
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
e-mail: [email protected]: http://www.cmp.dk
Choice of standby treatmentChoice 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
e-mail: [email protected]: http://www.cmp.dk
Choice of standby treatmentChoice 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
e-mail: [email protected]: http://www.cmp.dk
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
e-mail: [email protected]: http://www.cmp.dk
RiskRisk
• The doctor
• Responsibility
• Standard procedure
• All deviations recorded
• Signed contract for all sub-optimal choices?
• E.g. long term travellers
• Insurance!
e-mail: [email protected]: http://www.cmp.dk
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
e-mail: [email protected]: http://www.cmp.dk
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)
e-mail: [email protected]: http://www.cmp.dk
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?
e-mail: [email protected]: http://www.cmp.dk
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
e-mail: [email protected]: http://www.cmp.dk
Case 1 – ctd.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
e-mail: [email protected]: http://www.cmp.dk
Case 1 – ctd.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)?
e-mail: [email protected]: http://www.cmp.dk
Case 1 – ctd.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
e-mail: [email protected]: http://www.cmp.dk
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?
e-mail: [email protected]: http://www.cmp.dk
Case 2 – ctd.Case 2 – ctd.
• 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
e-mail: [email protected]: http://www.cmp.dk
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?
e-mail: [email protected]: http://www.cmp.dk
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?
e-mail: [email protected]: http://www.cmp.dk
Case 3 (ctd.)Case 3 (ctd.)
• Returned to Denmark at end of contract period
• Routine check including 3 blood films: Anaemia, no malaria parasites found
• What next?
e-mail: [email protected]: http://www.cmp.dk
Case 3 (ctd.)Case 3 (ctd.)
• 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?
e-mail: [email protected]: http://www.cmp.dk
Case 3 (ctd.)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
e-mail: [email protected]: http://www.cmp.dk
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?