1. e-mail: jkcmp@rh.dk Internet: http://www.cmp.dk Malaria prophylaxis Jørgen Kurtzhals Centre for Medical Parasitology Rigshospitalet, Copenhagen, Denmark

2. e-mail: jkcmp@rh.dk Internet: http://www.cmp.dk Indication for chemoprophylaxis Risk groups in populations of endemic countries Pregnant women Infants Travel to high risk areas

3. e-mail: jkcmp@rh.dk Internet: http://www.cmp.dk 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. e-mail: jkcmp@rh.dk Internet: http://www.cmp.dk 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. e-mail: jkcmp@rh.dk Internet: http://www.cmp.dk 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

6. e-mail: jkcmp@rh.dk Internet: http://www.cmp.dk 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. e-mail: jkcmp@rh.dk Internet: http://www.cmp.dk 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

8. e-mail: jkcmp@rh.dk Internet: http://www.cmp.dk 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

9. e-mail: jkcmp@rh.dk Internet: http://www.cmp.dk 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)

10. e-mail: jkcmp@rh.dk Internet: http://www.cmp.dk 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?)

11. e-mail: jkcmp@rh.dk Internet: http://www.cmp.dk 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

12. e-mail: jkcmp@rh.dk Internet: http://www.cmp.dk Drugs 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

13. e-mail: jkcmp@rh.dk Internet: http://www.cmp.dk Drugs for prophylactic use Mefloquine – II Side effects Sleep disorders Neuropsychiatric Cardiac arrythmia GI – vomiting Public opinion!

14. e-mail: jkcmp@rh.dk Internet: http://www.cmp.dk 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 (<12 years) One daily dose (NOT with milk products or iron) Broad spectrum antibiotic – ecological perspective

15. e-mail: jkcmp@rh.dk Internet: http://www.cmp.dk Drugs for prophylactic use Doxycycline – II Side effects GI – potentially severe (e.g. Cl. difficile) Vaginal candidiasis Photo sensitivity

16. e-mail: jkcmp@rh.dk Internet: http://www.cmp.dk 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)

17. e-mail: jkcmp@rh.dk Internet: http://www.cmp.dk 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

18. e-mail: jkcmp@rh.dk Internet: http://www.cmp.dk 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

19. e-mail: jkcmp@rh.dk Internet: http://www.cmp.dk Choice of chemoprophylaxis

20. e-mail: jkcmp@rh.dk Internet: http://www.cmp.dk Standby treatment Definition Self administration of antimalarial When malaria is suspected And when medical care is unavailable within 24 hours

21. e-mail: jkcmp@rh.dk Internet: http://www.cmp.dk 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

22. e-mail: jkcmp@rh.dk Internet: http://www.cmp.dk Indication for standby treatment Tp > 37.5 0 C +/- 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

23. e-mail: jkcmp@rh.dk Internet: http://www.cmp.dk 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

24. e-mail: jkcmp@rh.dk Internet: http://www.cmp.dk 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

25. e-mail: jkcmp@rh.dk Internet: http://www.cmp.dk 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

26. e-mail: jkcmp@rh.dk Internet: http://www.cmp.dk 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

27. e-mail: jkcmp@rh.dk Internet: http://www.cmp.dk Risk The doctor Responsibility Standard procedure All deviations recorded Signed contract for all sub-optimal choices? E.g. long term travellers Insurance!

28. e-mail: jkcmp@rh.dk Internet: http://www.cmp.dk 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

29. e-mail: jkcmp@rh.dk Internet: http://www.cmp.dk 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)

30. e-mail: jkcmp@rh.dk Internet: http://www.cmp.dk 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?

31. e-mail: jkcmp@rh.dk Internet: http://www.cmp.dk 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

32. e-mail: jkcmp@rh.dk Internet: http://www.cmp.dk 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

33. e-mail: jkcmp@rh.dk Internet: http://www.cmp.dk 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)?

34. e-mail: jkcmp@rh.dk Internet: http://www.cmp.dk 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

35. e-mail: jkcmp@rh.dk Internet: http://www.cmp.dk 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?

36. e-mail: jkcmp@rh.dk Internet: 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

37. e-mail: jkcmp@rh.dk Internet: http://www.cmp.dk 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 <1% P. falciparum Treated with halofantrine (Halfan®) 500 mg x 3 for one day What next?

38. e-mail: jkcmp@rh.dk Internet: http://www.cmp.dk 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?

39. e-mail: jkcmp@rh.dk Internet: http://www.cmp.dk Case 3 (ctd.) Returned to Denmark at end of contract period Routine check including 3 blood films: Anaemia, no malaria parasites found What next?

40. e-mail: jkcmp@rh.dk Internet: http://www.cmp.dk 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?

41. e-mail: jkcmp@rh.dk Internet: http://www.cmp.dk Case 3 (ctd.) 4 weeks after return, discontinuation of malaria prophylaxis (chloroquine and proguanil) Six days later rushed to hospital, reduced consciousness, tp. 39.7 0 C Lumbar puncture: CSF with 8 cells, glucose and protein normal Blood film: 8% P. falciparum Diagnosis: cerebral malaria

42. e-mail: jkcmp@rh.dk Internet: http://www.cmp.dk 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?