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Rationale. CDC malaria prophylaxis recommendations made by Malaria Epidemiology Branch with input from Division of Global Migration and QuarantineInformally have sought external input
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1. Evidence-based review of malaria chemoprophylactic drugs
2. Rationale
CDC malaria prophylaxis recommendations made by Malaria Epidemiology Branch with input from Division of Global Migration and Quarantine
Informally have sought external input – e.g. ASTMH; phone and email communications from providers
Expert meeting on Malaria Chemoprophylaxis held at CDC in January 2003: a more formal mechanism to elicit expert opinion/input on policies and recommendations
3. Preparation for meeting Extensive literature review
Creation of evidence-based documents
Main points summarized in 2-3 page “Guidelines” documents
Points that are potentially unclear or controversial were raised as Discussion Points at the meeting
4. Evidence-based documents (I)
Recommended dosing
Efficacy and effectiveness
Data from various studies listed in table format
Pharmacokinetics
Adherence
Safety
Information also in table format
Severe and mild/moderate ADRs*
5. Evidence-based documents (II) Contraindications
Duration of use
Therapeutic index/overdosage
Drug interactions
Special populations – children, pregnant women, persons with pre-existing medical conditions
Cost
6. Topics discussed (I)
Overall recommendations:
Areas with CQ (chloroquine)-sensitive Plasmodium falciparum: CQ is drug of choice (hydroxy-CQ alternative)
Areas with CQ-resistant P. falciparum - 3 options:
Mefloquine
Doxycycline
Atovaquone/proguanil
7. Topics discussed (II)
6 drugs recommended for prophylaxis, including terminal prophylaxis, were covered in individual sessions:
CQ
Hydroxychloroquine
Doxycycline
Atovaquone/proguanil
Mefloquine
Primaquine
8. Topics discussed (III)
Additional sessions:
Health communications
Self-treatment and the low risk traveler
9. Example of discussion points raised: Mefloquine (I) Indication
Dosing
How much time to start before travel?
Loading dose?
Split dose? (twice weekly)
Efficacy
ADRs
How can we better communicate?
What about long term neuropsychiatric ADRs?
Are there gender differences?
Interaction with alcohol?
Need to monitor LFTs* or ophthalmologic exam?
10. Example of discussion points raised: Mefloquine (II) Contraindications
Use in persons with history febrile seizures?
Precautions
Cardiovascular disease?
Pilots?
Divers?
Drug interactions
Use during pregnancy
Concerns about spontaneous abortions/stillbirths?
Use during breastfeeding
Use in children
11. Overall recommendations (I) Confirmed drug choices in both areas with chloroquine (CQ)–sensitive and CQ-resistant P. falciparum
Areas with CRPF
Alphabetize by generic name
No drug of choice
Primaquine (PQ) at 30 mg/day added as 2nd-line choice
12. Overall recommendations (II) Elimination of CQ/proguanil as option in areas of CRPF
Explicitly state that in areas with CSPF* if cannot tolerate CQ (or hydroxy-CQ) use one of the drugs for CRPF
If concerned about drug tolerance could start as early as 3-4 weeks before travel
Specific warning: avoid purchase of chemoprophylactic drugs overseas - may be of suboptimal quality
13. Overall recommendations (III) Disseminate more information on ADRs
Focus group data also supported this concept – people want information to make informed decision
Advantages and disadvantages of the various options in a table
Try to provide rates of mild/moderate and severe ADRs
Provide information on rates of discontinuation of drug due to ADRs
Important to communicate some key points
Risk of malaria
Prevention works
14. CQ & hydroxy-CQ CQ 1st choice (much more data than hydroxy-CQ)
No eye exams needed even with long-term use since risk very low at malaria prophylaxis doses
Maintain option of twice weekly dosing (but caveat is no data)
No G6PD screening needed prior to use
Further discussion needed: tolerance of CQ vs hydroxy-CQ; longterm use of hydroxy-CQ in children
15. Doxycycline No evidence that doxycycline interferes with effectiveness of oral contraceptives
Doxycycline preferred to minocycline for malaria prophylaxis (if on minocycline, recommend change to doxy if at all possible)
Further discussion needed: use during breastfeeding; long-term use
16. Primaquine Increase dose for terminal prophylaxis (all geographic areas) to 30 mg base/day
No new insights on refining decisions on who are candidates for terminal prophylaxis
Avoid use for primary or terminal prophylaxis in those w/ G6PD deficiency
Further discussion needed: use in young children and in persons with myelosuppression
17. Atovaquone/proguanil Efficacy adequate to recommend as 1st line option for non-immune persons
Efficacy adequate against P. vivax to recommend for use in areas with substantial P. vivax transmission
Still need terminal prophylaxis with primaquine in those persons where it is indicated (may not prevent establishment of hypnozoites)
Further discussion needed: long-term use; use in children 5-11 kg
18. Mefloquine (I) Comment from panel: getting hard to prescribe…
No good explanation for long-lasting neuropsychiatric ADRs
Should include information on gender differences in tolerance in health communications materials
People need to know ADRs can last weeks given the long half life
OK for use in those w/ history febrile seizures
19. Mefloquine (II) No precautionary statement planned on use of concomitant use of alcohol and mefloquine (MQ)
Can use in those who performing tasks that require fine motor coordination (eg pilots) but best to start 3-4 weeks early
Permissive language to use loading dose
Needs further discussion: split dosing (twice weekly); need for monitoring LFTS*; use in those with cardiovascular problems; safety concerns during pregnancy
20. Self-treatment and treatment Sulfadoxine-pyrimethamine (SP) no longer recommended – therefore, atovaquone/proguanil is 1st choice agent
Stronger language on avoiding halofantrine
21. Next steps Summary report – review by panel
Revise evidence-based documents
Revise overall and drug-specific recommendations, indicating level of evidence for each recommendation
Update all health communications materials – Health Information for International Travel, website, travelers’ brochure
Peer-reviewed publications as well as possible publication in MMWR