Archive for the ‘malaria prophylaxis’ Category

What are the components of the fixed-combination antimalarials?   Leave a comment

Conventional formulations
Fansidar: sulfadoxine 500mg + pyrimethamine 25mg

Malarone: atovaquone 250mg + proguanil 100mg
(paeds Malarone tab: atovaquone 62.5mg + proguanil 25mg)

Maloprim: dapsone 100mg + pyrimethamine 12.5mg
 

Artemisinin-based
Coartem (Riamet): artemether 20mg + lumefantrine 120mg

Artekin: dihydroartemisinin 40mg + piperaquine 320mg

DNP: dihydroartemisinin 160mg + naphthoquine 400mg + trimethoprim 200mg

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Posted February 24, 2010 by absinthemisia in malaria, malaria prophylaxis

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What are some non-pharmacological interventions in prophylaxis against malaria?   Leave a comment

  • malaria endemic areas (see WHO world map)

  • Anopheles mosquitoes bite between dusk and dawn; the lifetime range of flight of an Anopheles mosquito is 1km. Hence, daytime side trips to areas where malaria is endemic present little risk, if the traveler restricts nighttime hours to air-conditioned hotels or other environments where there are few mosquitoes.

  • travel restricted to capital cities and other urban areas (as is typical of business travel) is associated with an insignificant risk of malaria, despite the risk in areas nearby, with the exception of sub-Saharan Africa and certain cities in India.

  • take into account the possibility of deviation from the preset itinerary brought to the pretravel consultation.

 
Non-pharmacological interventions

  • wear long sleeves, long pants, and fully closed shoes with socks after dark.

  • use permethrin-treated mosquito nets if accommodations are neither well screened nor air-conditioned.

  • repellent containing 30-50% DEET (N,N-diethyl-3-methylbenzamide) should be applied to exposed areas of skin every 4-6 hours; more frequent applications is required for agents containing lower concentrations.
    Children: up to 30% DEET is considered to be safe (higher concentrations have not been tested).
    Pregnancy: up to 20% DEET has been shown to be safe.

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Chemopropylaxis & dosage for travel to malaria-endemic countries   Leave a comment

CQ-sensitive areas
chloroquine (or hydroxychloroquine) as first line, if contraindicated then one of the others
(map: see here)
Pregnancy: avoid travel to malaria-endemic areas; if travel is unavoidable, use CQ as first line, otherwise mefloquine (but data limited for use of MQ in first trimester).

CQ-resistant areas
mefloquine as first line, if contraindicated then Malarone or doxycycline
(map: see here)
Pregnancy: MQ only. Both the WHO and the CDC recommend that pregnant women try not to travel to malaria-endemic areas. If travel is unavoidable, the trip should preferably be delayed to after the first trimester, as data is limited on use of MQ in the first trimester.

MQ-resistant areas
doxycycline or Malarone
(map: see here)
Pregnancy: consult infectious disease/malaria specialist

Terminal prophylaxis or presumptive anti-relapse therapy
primaquine. Indicated only for persons who have had prolonged or obvious intense exposure to infective mosquitoes in areas where there is a substantial risk of P. vivax or P. ovale transmission (for eg. missionaries and Peace Corps volunteers).
Pregnancy: PQ is contraindicated as it causes haemolytic anaemia in utero. When terminal prophylaxis is indicated, continue CQ/MQ prophylaxis until delivery, after which PQ may be started.

Legend:
CQ = chloroquine; HCQ = hydroxychloroquine
MQ = mefloquine
PQ = primaquine

 

Notes on other regimes:

  1. Halofantrine is not recommended by CDC for malaria prophylaxis.

  2. Primaquine may be used by itself as a primary prophylaxis regime in special circumstances when patients cannot tolerate any of the other drugs, but only after consulting with an infectious disease/malaria expert. Dosage is orally 30mg base daily (0.5mg base/kg/day for children up to adult dose) starting 1-2 days before entering, and continuing for 7 days after leaving the malarious area.

  3. Chloroquine + proguanil (CQ+PG) was still offered as an alternate regime by UK guidelines in 2007 for UK residents who travel to chloroquine-resistant areas (except sub-Saharan Africa), the rationale being that chloroquine resistance is considered incomplete in many areas and protection could be extended by the addition of proguanil. Although theoretically safer (especially for pregnant women), this regime is complicated; and, in light of waning efficacy in many parts of the world, and better availability and experience with using Malarone and mefloquine, I do not advise traveler to Asia take the CQ+PG combination, unless recommended by an infectious-disease expert.

  4. Maloprim (pyrimethamine 12.5mg + dapsone 100mg) has largely been superseded by Malarone, mainly due to its requirement for daily dosing, low therapeutic ratio, and risk of agranulocytosis. It is not recommended anymore for malaria prophylaxis in several parts of the world, including UK and USA; however it remains useful as an alternate regime if travelers are unable to tolerate any of the other regimes.

 

Recommended Dosages

  1. Chloroquine: orally 300mg base once weekly (5mg base/kg/week in children, up to adult dose) starting 2 weeks before entering, and continuing for 4 weeks after leaving malarious area

    • SE: GI disturbance, headache, dizziness, pruritus in African descent, rarely blood dyscrasias; retinopathy in overdose

    • CI: epilepsy, psychosis, psoriasis, QTc prolongation, myasthenia gravis; caution in severe renal failure

    • DI: increases toxicity of mefloquine, cyclosporin, digoxin; increased risk of ventricular arrhythmias with amiodarone, moxifloxacin

    • Pregnancy: chloroquine has not been found to have any harmful effects on the fetus when used in the recommended doses for malaria prophylaxis

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  3. Hydroxychloroquine (Plaquenil): orally 310mg base once weekly (5mg base/kg/week in children, up to adult dose) same regime as chloroquine

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  5. Malarone(250mg atovaquone + 100mg proguanil): orally one adult tab daily, start 1-2 days before entering, and continuing for 7 days after leaving malarious area. (paeds dosing, see here)

    • SE: gastric intolerance, diarrhoea, headache; occasionally stomatitis and mouth ulcers with proguanil

    • CI: children <5kg; CCT<30ml/min and dialysis; avoid in pregnancy but no evidence of foetal harm in inadvertent conception

    • DI: possible interaction with indinavir, zidovudine

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  7. Mefloquine (Lariam): orally 228mg base weekly (4.6mg base/kg/week in children, up to adult dose) beginning 2 weeks before entering, and continuing for 4 weeks after leaving malarious area.

    • SE: GI, headache, seizures, psychosis, insomnia, abnormal dreams, mood changes, visual disturbances, sensory/motor neuropathies, tremor, ataxia, AV block, prolonged QTc; not recommended for pilots and other occupations that require fine psychomotor skills or coordination

    • CI: known psychiatric disorders, depression, seizures, cardiac conduction abn; no evidence to suggest CI in underwater diving but may complicate decompression sickness and narcosis by lowering seizure threshold, hence to be avoided if possible

    • preferably start 3 weeks before travel to assess for tolerability

    • safe for use in renal failure and dialysis

    • Pregnancy: considered safe after first trimester; data is limited on use during first trimester

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  9. Doxycycline: orally 100mg daily (2mg/kg/day in children up to adult dose) starting 1-2 days before entering, and continuing for 4 weeks after leaving malarious area

    • SE: photosensitivity, gastritis, esophagitis, candidiasis, vaginal thrush

      take with full glass of water, and remain upright 30min

    • CI: pregnancy, children <8y

    • DI: increases anticoagulant effect of warfarin; increases toxicity of cyclosporin; avoid taking oral typhoid vaccine Ty21a within 24h

    • safe for use in renal failure
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  11. Primaquine as terminal prophylaxis: orally 30mg base daily (children: 0.6mg base/kg/d) for 14 days, to start after leaving malarious area; usually coinciding with the final 2 weeks of primary prophylaxis, but may be taken immediately after regime is completed

    • SE: GI upset on empty stomach, methaemoglobinaemia

    • CI: G6PD deficiency, pregnancy; also in breastfeeding unless baby has documented normal G6PD levels

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Ref:

  1. Freedman DO. Malaria Prevention in Short-Term Travelers. N Engl J Med 2008 Aug 7;359(6):603-12.

  2. CDC Travelers’ Health — Yellow Book 2008. Chap 4: Prevention of Specific Infectious Diseases: Malaria [Internet]. Atlanta (GA): Centers for Disease Control and Prevention; 2007 June 20. [updated 2009 Apr 17; cited 2009 Apr 20]. Available at:
    http://wwwn.cdc.gov/travel/yellowBookCh4-Malaria.aspx

  3. Chiodini P, Hill D, Lalloo D, Lea G, Walker E, Whitty C and Bannister B. Guidelines for malaria prevention in travellers from the United Kingdom. London, Health Protection Agency, January 2007.