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The Pharmacology of Travel Health Medicine
Jacinda Wagner BscH(biology), Bsc(Pharm)
Introduction Medications to prevent travel related illnesses are becoming more commonly prescribed. This talk will discuss medications and vaccines and their methods of action. Important contraindications and interactions with other medications will be discussed.
I. Hepatitis A - An infectious virus that causes inflammation of the liver - Transmission occurs via contaminated food or water - Individual presents with nausea, vomiting, diarrhea and fever - Active disease may last up-to 12 weeks with some developing jaundice +/- proving fatal - Vaccination is available: Havrix, Avaxim, Vaqta, and Twinrix
A. Havrix 1440 (18yrs +), Havrix 720 (2-18 yrs), Vaqta, Avaxim
1. Dose and schedule - Initial dose at day 1 provides immunity up-to 12 months - Booster dose between 6 & 18 months after initial dose may provide immunity up-to 10 yrs + - Shake vial well prior to IM administration into deltoid (avoid gluteal region due to sub-optimal response as it deposits into fat tissue rather than muscle)
2. Precautions - Consider delaying administration in those who present with acute febrile illness - Use with precaution in those with thrombocytopenia or bleeding disorders due to risk of bleeding following IM injection - Those with immunodeficiency, receiving radiation therapy or taking high dose Corticosteroids may have a dampened immune response to vaccination and thus require additional doses to achieve immunity
3. Contraindications - Because Havrix may contain trace amounts of neomycin, individuals with allergies to this substance - Relative contraindication: consider delaying administration in those who present with acute febrile illness
4. Drug interactions - Since these are inactivated vaccines, concomitant administration with other inactive vaccines is generally unlikely to cause interference with the immune response
Note: Havrix, Vaqta and Avaxim are considered interchangeable and equal
B. Twinrix (18 yrs +), Twinrix jr (2-18 yrs) - When administered appropriately, provides immunity against hepatitis A and B • since hepatitis D does not tend to occur in the absence of the hepatitis B virus, it is thought, in theory, twinrix should • protect against hepatitis A, B, and D
• Dose and schedule -Traditionally a 3 dose schedule with the 2 nd dose a minimum of 4 weeks after the initial dose and the 3 rd dose 6 months after the initial dose. - Dose 1 gives some protection, but needs a 2 nd dose which gives up-to 12 months of immunity, and a third scheduled dose gives prolonged protection of 10-20 yrs + for hepatitis B and ~10-20 yrs for hepatitis A 2. Precautions - Consider delaying administration in those who present with acute febrile illness - Use with precaution in those with thrombocytopenia or bleeding disorders due to risk of bleeding following IM injection - Those with immunodeficiency, receiving radiation therapy or taking high dose Corticosteroids may have a dampened immune response to vaccination and thus require additional doses to achieve immunity
3. Contraindications - Relative contraindication: consider delaying administration in those who present with acute febrile illness
4.Drug interactions • since this is an inactivated vaccine, concomitant administration with other inactive vaccines is generally unlikely to cause interference with the immune response
II. Hepatitis B - An infectious inflammation of the liver, which may progress into chronic liver disease or liver cancer - Individual presents with nausea, vomiting diarrhea, fever +/- yellowing of the skin, abdominal pain and anorexia - Transmission occurs via contaminated bodily fluids
A. Engerix B 1mL (adults) and 0.5 mL (jr £ 19 yrs) and Recombivax HB
1. Dose and schedule • Canadian pediatric society recommends routine vaccination of all infants; this is just a recommendation not a guarantee & so Inquire! - Traditionally patient receives 2nd dose 1 month after the first, and the 3rd dose 6 months after the first - Doses should be separated by a minimum of 4 weeks -Shake vial gently prior to administration - An accelerated induction may be achieved by dosing at 0, 1 and 2 months with a 4th dose 12 months after the first for those who desire prolonged protection - A rapid induction at 0, 7, and 21 days (adults only) is currently used for those previously non-vaccinated individuals being vaccinated within 1 month prior to intended travel (last minute planners!) The 1st 3 doses in this schedule provide immunity for up-to 12 months, while a 4th dose may provide prolonged immunity up-to 10-20 yrs + - Intended for IM injection into deltoid region - Avoid gluteal region due to sub optimal immune response when vaccine deposits into fatty tissue rather than muscle - Infants and newborns should receive IM injection into their anterolateral region due to the small size of their deltoids. • in special circumstances SC injection may be administered for those with severe bleeding disorders
2. Precautions - ?????speculation that immune response to Hepatitis B vaccination may be reduced in those > 40 years of age???????? - Use with precaution in those with thrombocytopenia or bleeding disorders due to risk of bleeding following IM injection - Those with immunodeficiency, receiving radiation therapy or taking high dose Corticosteroids may have a dampened immune response to vaccination and thus require additional doses to achieve immunity - A preservative (thimersol) free product is available and recommended for newborns and infants
3. Contraindications - Hypersensitivity or allergies to yeast and /or other components of the vaccine - Relative contraindication: consider delaying administration in those who present with acute febrile illness
4. Drug interactions • since these are inactivated vaccines, concomitant administration with other inactive vaccines is generally unlikely to cause interference with the immune response
Note: Engerix B and Recombivax are considered equal and interchangeable
III. Traveler's Diarrhea - Advise your patients to take necessary precautions "cook it, peel it, boil it or forget it" - Drink bottled water - Avoid raw eggs, meat and fish - Avoid milk or milk products (uncertain about pasteurization practices) - Eat items off menus in restaurants - Eat foods that physically hot - Wash foods with iodinated water - Wash your hands frequently
A. Pepto Bismol - Bismuth
1. Dose and schedule Prevention - starting 1 to 2 days before traveling and continue up-to 2 weeks 0-3 yrs ½ tsp (2.5 mLs) QID* 3-6 yrs 1 tsp (5 mLs) QID* 6-9 yrs 2 tsp (10 mLs) QID* 9-12 yrs 1 tbsp (15 mLs) QID* Adults 2 tablets QID* * Regular strength liquid and tablets Treatment - Pepto Bismol may be used for mild symptoms but antibiotics are recommended for short-term treatment 0-3 yrs ½ tsp (2.5 mLs) q 30-60 minutes Maximum 20mL/24 hours 3-6 yrs 1 tsp (5 mLs) q 30-60 minutes Maximum 40mL/24 hours 6-9 yrs 2 tsp (10 mLs) q 30-60 minutes Maximum 80mL/24 hours 9-12 yrs 1 tbsp (15 mLs) q 30-60 minutes Maximum 120mL/24 hours Adults 2 tablet q 30-60 minutes maximum 8 tablets/24 hours
2. Precautions - Salicylates should be used with caution in those less than 18-21 years of age due to the risk of Reye's Syndrome especially in the presence of a viral infection (which may be silently present!) - Due to its salicylate nature Pepto Bismol should be avoided during pregnancy, there are enough treatment alternatives available that its use need not be contemplated. - Use with caution in those with a history of GI bleeds - Black tongue is likely with prolonged use
3. Contraindications - Avoid in active GI bleed - Avoid in ASA allergy - Avoid in 3rd trimester of pregnancy (preferred that its use be avoided all together during pregnancy) - Avoid in hemophiliacs
4. Drug interactions - Warfarin (due to increased effect of anti-coagulant) - Acetazolamide (due to increased effect of cationic anhydrase inhibitor) - Ciprofloxacin, tetracycline, doxycycline, levofloxacin (due to the formation of non-absorbable complexes) - Prednisone (due to decreased effect of salicylate)
B. Septra - Sulfamethoxazole + trimethoprim
1. Prevention - prophylactic antibiotics are not recommended except occasionally in high-risk individuals (people with compromised immune function &/or disorders of the digestive tract) Treatment- worldwide misuse and overuse has led to worldwide resistance
2. Precautions - Worldwide resistance, not drug of choice anymore - Use with caution in those with blood dyscrasia (avoid if possible) - Photosensitivity - Requires plenty of water with use therefore have to consider the availability of non-contaminated water - G6PD deficiency (avoid if possible) - Caution in hepatic insufficiency and alcoholism due to risk of liver toxicity and disulfiram reaction
3. Contraindications - Sulfa allergies - Avoid in 3rd trimester of pregnancy especially the last 2 weeks prior to anticipated delivery date due to risk of kernicterus
4. Drug interactions - Warfarin may risk of increase effect of anticoagulant?
C. Ciprofloxacin
1. Dose and schedule Treatment dose: 500 mg BID x 3 days Or 1000 mg (one dose)
2. Precautions - Not recommended in those 15 years of age or younger or during pregnancy -(potential damage in bone/joint formation)
3. Contraindication allergy to cipro
4. Drug interactions - Warfarin (increased anticoagulant effect) calcium, aluminum, magnesium, iron, and zinc may form insoluble, non-absorbable complexes and potentially rendering ciprofloxacin inactive)
D. Azithromycin (Zithromax)
1. Dose and schedule Treatment dose: Adults 500mg once daily x 3 days Children 10mg/kg/24 hours x 3 days Pregnant women 500mg once daily x 3day • Precautions Since the major route of elimination for azithromycin is via the liver, precaution should be adhered to in the case of significant hepatic disease/disorder • Contraindications Those having known hypersensitivity or allergic reaction to the erythromycin family or macrolide antibiotics
4. Drug Interactions - Antacids, dairy and other products containing calcium, magnesium, aluminum, iron and zinc should not be administered simultaneously with this agent due to the risk of formation of non-absorbable complexes.
Note: treatment antibiotics should show optimal results and significantly decrease symptoms within the first 24-48 hours but if the individual is still sick after 2 to 3 days he/she should contact the nearest Canadian embassy and get their assistance in finding medical attention locally
E. Loperamide 2mg (Immodium) 1. Dose and schedule - Treatment dose: (adults) 2 tablets at onset then 1 tablet after each substantial loose bowel movement to a maximum of 8 tablets in a 24-hour period (children) routine use not recommended but for acute diarrhea in 1st 24 hours (maintain hydration!!!!) -2 to 5 yrs (10 to 20 kg) 1mg TID (3 mg daily dose) -6 to 8 yrs (20 to 30 kg) 2 mg BID (4 mg daily dose) -8 to 12 yrs (> 30 kg) 2 mg TID (6 mg daily dose)
2. Precautions -Exceeding the maximum recommended dose of 16mg/24 hours could bring about rebound constipation - Ensure proper hydration, replacing electrolytes if the problem persists beyond the first 24 hours, showing no signs of improvement despite treatment - Use with caution in the case of hepatic insufficiency 3. Contraindications - Avoid its use in those in whom constipation must be avoided - Avoid in the case where blood, mucous and/or fever accompanies stool - Avoid in psuedomembranous colitis - Avoid in shigellosis 4. Drug interactions - None mentionable
• Malaria - A disease caused by a parasite and spread through the bite of an infected mosquito - Initial symptoms are minor and flu-like and can go on to result in severe complications such as respiratory and kidney failure, liver problems, anemia and even prove fatal - It is always better to prevent than treat when you consider the long-term consequences of malaria • Chloroquine - The drug of choice in chloroquine sensitive areas - Available in tablet form for adults and can be compounded into a weight based suspension and flavored to taste for children and infants - Suitable in pregnancy and "for all ages" but over-doses are frequently fatal so verify the dose if uncertain - Symptoms of overdose may include headache, drowsiness, visual disturbances, CV collapse, seizures, respiratory and cardiac arrest - Acidification of the urine enhances its elimination • Dose and schedule (Prevention) (adults) 500mg/week* (on the same day each week) (children) 8.3mg/kg/week* *Doses are expressed in terms of the chloroquine phosphate salt (250mg of the phosphate salt = 150mg base and either can be used in the compounding of tailored doses) - Dosing should begin 1 week prior to intended departure to the malarious area and continue weekly while in the malarious area and for 4 consecutive weeks after departing from the malarious area.
2. Precautions - Get the advise of a travel health expert based on each individuals travel itinerary and medical history to determine the most appropriate anti-malarial to use - Appears to be a safe choice in pregnancy and while breast-feeding (keep in mind that although considered safe during breast-feeding, maternal administration does not protect the suckling infant) - Take with food - Bitter to taste - May cause discoloration of urine - May cause reversible yellowish corneal deposit in prolonged use (i.e. long term trip) - Avoid taking antacids at the same dosing time as chloroquine - Use with caution in the case of alcoholism - May? Exacerbate symptoms of psoriasis - May cause photo-sensitivity
3. Contraindications - Allergies to chloroquine, hydroxy-chloroquine or primaquine - Avoid in dialysis (hemo and peritoneal)
4. Drug interactions - Methotrexate, as it may reduce the efficacy of methotrexate temporarily - Cyclosporin, as it may increase the blood concentrations of cyclosporin requiring temporary dosage reduction during such co-administration - Chlorpromazine, as it may increase the blood concentration of chlorpromazine thus requiring close monitoring for signs of increased neuroleptic effects
B. Hydroxy-chloroquine (Plaquenil) - Traditionally used for arthritis but may be indicated as an anti-malarial 1. Dose and schedule (prevention) - Prevention (adults) 400mg/week# (pediatric/children) 6.5mg/kg/week# - Starting 2 weeks prior to travel, continuing while in malarious area and for 8 consecutive weeks after leaving malarious area # Doses are expressed in terms of the hydroxy-chloroquine sulfate salt (200mg sulfate salt = 155 mg base) 2. Precautions - Since related to chloroquine, it is extrapolated that hydroxy-chloroquine is safe for use during pregnancy although its actual safety is unknown - Its appear to be safe for use while breast-feeding due to lack of evidence suggesting otherwise but benefit must always outweigh possible risk in terms of both pregnancy and breast-feeding when it comes to the use of chemicals and drugs - Bitter to taste - May cause reversible yellowish corneal deposit in prolonged use (i.e. long term trip) - Avoid taking antacids at the same dosing time as hydroxy-chloroquine - Use with caution in the case of alcoholism - May? Exacerbate symptoms of psoriasis - May cause photo-sensitivity - Take with food
3. Contraindication - Pre-existing retinopathy of the eye
4. Drug interactions - Concomitant use with digoxin therapy may result in elevated serum digoxin levels thus necessitating the close monitoring of patients receiving both; watch for signs of nausea, vomiting, anorexia, visual disturbance (unfortunately arrhythmias may be the first recognized sign)
C. Mefloquine (Larium) 1. Dose and schedule (prevention) - Adults and pediatric patients > 45kg • 1 tablet at least 1 week prior to travel to malarious area • 1 tablet once weekly (on same day of the week) while in malarias area • 1 tablet once weekly for 4 weeks after leaving malarious area - > 30kg to 45kg • ¾ of a 250mg tablet = 187.5mg - > 20kg to 30kg • ½ of a 250mg tablet = 125mg - 5kg to 20kg • ¼ of a 250mg tablet = 62.5mg
2. Precautions - May want to limit or avoid activity that requires mental alertness or fine motor control - Use with caution in those with cardiac conduction disorders, mild anxiety disorders or seizure disorders or tendencies - May use during pregnancy and breast-feeding but does not protect the infant (some suggest that its use be postponed until after 16 weeks of pregnancy due to lack of studies revolving around teratogenicity)
3. Contraindications - Concomitant administration of Mefloquine with quinine, quinidine, chloroquine or anti-epileptics may increase the risk of convulsions and minimize seizure control, respectively - In patients with unstable psychiatric disturbances or overt, uncontrolled anxiety alternative suggestions should be considered
4. Drug interactions - None mentionable (see precautions and contraindications)
D. Doxycycline (Vibramycin) 1. Dose and schedule (prevention) (adults) 100mg daily (children 9yrs +) 2mg/kg daily (maximum daily 100mg) - Starting 2 days prior to intended travel, while in malarias area and continue for 4 consecutive weeks after leaving malarious area 2. Precautions - Not recommended in pregnancy, especially beyond 14 weeks gestation week the fetus' teeth are scheduled to begin calcification process - Classified as a code D in pregnancy by Briggs: Drugs in Pregnancy and Lactation - Little to no evidence of harm to a breast-fed infant - Overall recommend avoidance during pregnancy - Photo-sensitivity - Avoid use in children < 9 yrs due to increased risk of permanent tooth discoloration - Women prone to yeast infection while on antibiotic treatment should make typical lifestyle/dietary modifications while on antibiotic treatment (i.e. yogurt acidophilus/lactobacillus)
3. Contraindications - Individuals with hepatic or renal insufficiency - Allergy to tetracyclines
4. Drug interactions - Concomitant use with digoxin therapy may result in elevated serum digoxin levels thus necessitating the close monitoring of patients receiving both; watch for signs of nausea, vomiting, anorexia, visual disturbance (unfortunately arrhythmias may be the first recognized sign) - Antacids, dairy and other products containing calcium, magnesium, aluminum, iron and zinc should not be administered simultaneously with this agent due to the risk of formation of non-absorbable complexes. - ~Birth control, women who rely on the oral contraceptive may and should practice an alternate means of protection while using antibiotics in general
E. Atovaquone and proquanil (Malarone) 1. Dose and schedule - Adults 1 tablet daily starting 2 days before intended travel, continue daily while on trip and for an additional 7 days upon leaving malarious area
2. Precautions - Use with caution in those with a history of uncontrolled psychiatric disorder(s) or epilepsy -Little to no evidence surrounding its use in pregnancy or lactation (clinician and travel health expert should determine its need based on the potential risk vs. benefit in each individual case
3. Contraindications - Still fairly new medicine, none mentionable
4. Drug interactions - Avoid administration with other anti-malarial medications
V. Altitude Illness prevention Medicine
A. Acetazolamide (Diamox) - Aids the acclimation process when used in conjunction with safe acclimation practices
1. Dose and schedule (adults) 125 mg (1/2 of a 250mg tablet) twice daily starting 1 day prior to climbing and continuing for ~ 3days
2. Precautions - Best to avoid during pregnancy and breast-feeding (risk and tolerance is unknown) - Common side effects (> 10%) include diarrhea, generalized malaise, increase volume (dehydration?), muscle weakness and nausea
3. Contraindications - Avoid in those with known sulfonamide allergies (may be beneficial to look into nature of such allergies given that acetazolamide is one of the only options here)
4. Drug interactions - Salicylates tend to increase the effect of the carbonic anhydrase inhibitor
B. Dexamethasone (Decadron) 1. Dose and schedule (Adult) 4mg every 6 (~12) hours - Possibly given in the case of allergy to acetazolamide - Mainly reserved for rescue efforts to dampen the symptom when altitude gets the best of a climber, thus buying time in the rescue attempt -OR in those well trained individuals who cannot take acetazolamide but must ascend quickly - Be very careful of this drugs ability to quickly wear off leaving the individual with the risk of rebound altitude sickness symptoms
C. Viagra (Sildenafil) and Cialis (tadalafil) • ?may improve blood flow when pulmonary edema is a threat?
Summary Many of the immunizations and medications mentioned today may be novel for pharmacists and doctors but are becoming more frequently prescribed with newer products being developed. Understanding their mode of action will help avoid ineffective doses, conflicts with other medications and contraindications with specific diseases.
References :
.Grabenstein JD ImmunoFacts: Vaccines and Immunologic Drugs St.Louis, MO: Wolters Kluwer Health, Inc.; 2005 .CPS 2004 .http://7005/hw_vigilance_monograph .Dr. Gary Podolsky M.D.(personal communications)
Pharmacology ScenariosJacinda Wagner
Sarah and John and their 6-year-old son Arnold are going to the Dominican Republic. Their doctor has prescribed 500mg of Chloroquine per week for each adult and 165mg for their 20kg son. On checking at the pharmacy none of those doses exist. What should they do? Chloroquine (Aralen) has traditionally been prescribed as 300mg base or as 500mg chloroquine phosphate salt. In this case we are referring to the salt, which is the most common designation although the old notation may persist. In Canada, Chloroquine comes as a 250mg salt dose, so each adult will require 2 pills per week starting one week before exposure, and continued every week of their trip and for 4 weeks post trip. Arnold will need 8.3mg/kg salt once weekly. A 250mg tablet may be scored into quarters of 62.5 mg but for lower doses having a compounding pharmacist prepare exact doses is preferable. Chloroquine also has a very bitter taste.
Edmund is going mountain climbing and has been prescribed Acetazolamide (diamox) for the prevention of altitude illness but his pharmacist has noted a previous allergy to sulpha drugs. What should be done? First it would be best to find out what the previous allergy was and to what drug. Distinguishing a mild rash from a full-blown severe anaphylactic or Stevens Johnson Syndrome due to a sulphonamide drug is essential. Acetazolamide contains a sulfaryl group, which is distinct from a sulphonamide group. In the history of only a mild rash the Acetazolamide may be given however caution must be used when severe reactions had occurred in the past however unlikely. Given enough time a referral to an allergist could be arranged but this is unlikely to be practical. If Edmund urgently needs Acetazolamide a trial dose may be tried at home prior to departing on his trip.
Mrs Smith is leaving to go to Guatemala in 2 weeks and has a history of Psoriasis and is on metaprolol, a beta-blocker, digitalis and adalat. Are antimalarials safe for her?
Chloroquine should not be prescribed for those with psoriasis. Mefloquine should not be used in those with heart conduction (it is not the beta blocker that is a contraindication but the underlying heart conduction defect), nor for those with underlying anxiety or depression. Doxycycline or Malarone would be good choices. Guatemala malaria strains are chloroquine sensitive all of the above medications are suitable choices provided the individual has no contraindications or medication interactions with the medications.
Mary wants to know the differences between the typhoid oral vaccine (Vivotif-ty21a, Berna) and injectable typhoid (typhim vi, Aventis; Typherix, Glaxo). Both brands of the injectable typhoid vaccines are inactivated and give protection for 3 years. They are much less side effects from modern typhoid injectable vaccines than from the injectable typhoid vaccines of the 70s that required 3 weekly injections and were painful. Injectable vaccine may be safely given to children, HIV infected individuals and to pregnant women.
The ty21 vaccine (vivotif) is a live attenuated oral vaccine taken in 4 dosed at 0,2,4,and 6 days and should not be taken by anyone whom a live vaccine could be unhealthy (such as pregnant women, AIDS patients). Some questions about the vaccine may be found at www.bernaproducts.com/abt_faq.cfm
Can Alcohol be taken with the oral dose? Alcohol should not be taken for 1 hour after the vaccine is given as this may dissolve the capsule in the stomach not in the intestine where it is absorbed effectively.
Can the capsule be opened up instead of swallowed whole?No the capsule must be taken whole so it is absorbed correctly in small intestine..
What happens if I miss a dose of Vivotif?If 3 doses are taken properly a delay of up to 72hrs is acceptable. If 2 doses are taken properly a delay of 24-48 hrs for the 3 rd dose is ok but the 4 th dose must be taken 2 days later.
If only one dose was taken, the course should be discontinued and the 4 capsule series must be restarted. Vivotif is the one exception to the general rule about immunizations that normally it is acceptable to allow extra time may pass between vaccination doses without penalty and without one having to restart the series.
Are Antibiotics all right to take with Vivotif?No, they kill off the attenuated typhoid
Are antimalarials all right to use at the concurrently with the oral typhoid?Both chloroquine and mefloquine may be used with no interaction with oral typhoid. Doxycycline is an antibiotic and will kill off the attenuated typhoid oral vaccine. Malarone should not be used until 10 days after vivotif is given for a theoretical interaction
A client asks about the use of antibiotics to stop travelers' diarrhea. Do they still recommend this? Current evidence supports that antibiotics do help with Traveller's diarrhea Antibiotics are no longer recommended to be taken prophylactically (that is before getting sick) as this increases bacterial resistance and increases side effects. Pepto-bismol taken at 2 pills four times daily will decrease the risk of traveller's diarrhea by 50% and may be used for up to 3 weeks.
Antibiotics are now recommended to be taken at the onset of symptoms. Septra was previously widely used but now has worldwide resistance and is no longer effective. Instead a broad-spectrum fluoroquinolone such as Ciprofloxacin will be helpful at 500mg po bid for up to 3 days. This will work against enteric bacteria that cause travellers diarrhea. It will of course not kill viruses and parasites. Recently Captylobacter bacteria in Cambodia have resistance to Ciprofloxacin.. Pregnant women and children under 15 may use Azithromycin instead of Ciprofloxacin.
A new antibiotic Rifaximin (Xifaxan) has been developed but is not yet available in Canada. It may perhaps replace Ciprofloxacin, as it may be more effective and safer for pregnant women.
Eve has called the pharmacy asking for Ledum Palustre or Malaria 0fficinalis to prevent malaria on the advice of a homeopathic website. She can buy these products through the site but wants to know if the pharmacy is cheaper.
A recent review of homeopathic medication for the prevention and treatment of malaria did not find these preparations to be helpful (British Medical Journal http:bmj.bmjjournals.com/cgi/content/full/321/7271/1288/a). At present the CDC, Health Canada and WHO have not authorized any homeopathic product for use in the prevention of malaria. One new natural product of interest is the Chinese shrub Artisinea that is a very good antimalarial. It is beginning to be marketed in North America and is use in other parts of the world.
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