2009 nov (89): treatment guidelines - advice for travelers

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Advice for Travelers.p 83
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Published by The Medical Letter, Inc. • 1000 Main Street, New Rochelle, NY 10801 • A Nonprofit Publication 2. Low-Risk Areas for Hepatitis A & B 6. Drugs of Choice for Malaria Prevention Advice for Travelers
Patients planning to travel to other countries often ask Patients who received a first dose of one vaccine will physicians for information about appropriate vaccines respond to a second dose of the other. Second doses and prevention of diarrhea and malaria. More detailed given up to 8 years after the first dose have produced advice for travelers is available from the Centers for Disease Control and Prevention (CDC) atwww.cdc.gov/travel. Guidelines are also available from Antibodies reach protective levels 2-4 weeks after the the Infectious Diseases Society of America (IDSA).1 first dose. Even when exposure to the disease occurssooner than 4 weeks after vaccination, the traveler is VACCINES
usually protected because of the relatively long incu-bation period of hepatitis A (average 28 days). For Common travel vaccines are listed in Table 1 on page immunosuppressed patients and those with chronic 84. In addition to travel-specific vaccines, all travelers liver disease who will be traveling to an endemic area (including children) should be up to date on routine in <2 weeks, immune globulin (0.02 mL/kg IM) vaccines. Guidelines for routine adult immunization should be given in addition to the initial dose of vac- have been published in a separate issue.2 cine. The same dose should be given to children Immunocompromised or pregnant patients generally under 1 year of age and other travelers who cannot should not receive live virus vaccines, such as those receive the vaccine if traveling for <3 months; a dose for measles and yellow fever, although in some situa- of 0.06 mL/kg IM should be given if traveling for >3 tions the benefit might outweigh the risk.
months. For travel durations of >5 months, the doseshould be repeated.7 CHOLERA — The risk of cholera in tourists is very
low. The parenteral vaccine previously licensed in the
HEPATITIS B — Vaccination against hepatitis B is
US is no longer available. An oral, whole-cell recom- recommended for travelers going to intermediate- or binant vaccine called Dukoral is available in some high-risk areas (see Table 2 for low-risk areas).
European countries (Crucell/SBL Vaccines) and in Travelers going anywhere who engage in behaviors Canada (Sanofi Pasteur). It is not currently recom- that may increase the risk of transmission, such as mended for routine use in travelers, but might be con- unprotected sexual contact with new partners, dental sidered for those who plan to work in refugee camps treatment, skin perforation practices (tattoos, acupunc- or as healthcare providers in endemic areas.
ture, ear piercing) or invasive medical treatment(injections, stitching), should be immunized against HEPATITIS A — Hepatitis A vaccine, which is now
part of routine childhood immunization in the US, isrecommended for all unvaccinated travelers going Two hepatitis B vaccines are available in the US: anywhere other than Australia, Canada, western Engerix-B and Recombivax-HB. Primary immuniza- tion usually consists of 3 doses given IM at 0, 1 and 6months. An alternate schedule of 3 doses given at 0, 1 Vaccination of adults and children usually consists of and 2 months, followed by a fourth dose at 12 months, two IM doses separated by 6-18 months. Additional is approved for Engerix-B in the US. A 2-dose sched- booster doses are not needed.4,5 Two hepatitis A vac- ule of adult Recombivax-HB at 0 and 4-6 months is cines are available in the US: Havrix and Vaqta.
approved in the US for adolescents 11-15 years old. An Federal copyright law prohibits unauthorized reproduction by any means and imposes severe fines.
Advice for Travelers
Table 1. Some Vaccines for Travel
Pediatric
Pediatric
Standard Primary
Duration
Vaccines
Dose (Volume)
Dose (Volume)
Schedule
of Protection
Hepatitis A
Hepatitis B
Hepatitis A/B
Japanese encephalitis
single booster isusually given after24 months ifongoing risk Meningococcal
activities (cavers,veterinarians, lab-oratory workers),serologic testing is recommended every 2 yrs withbooster doses iflow levels5 Yellow Fever
1. Protection likely lasts at least 12 months after a single dose.
2. According to the CDC it is safe for children < 2 years old who require vaccination for the Hajj.
3. Repeat after three years for children vaccinated at 2-6 years of age.
4. Regimen for pre-exposure prophylaxis. If a previously vaccinated traveler is exposed to a potentially rabid animal, post-exposure prophylaxis with 2 additional vaccine doses separated by 3 days should be initiated as soon as possible.
5. Minimal acceptable antibody level is complete virus neutralization at a 1:5 serum dilution by the rapid fluorescent focus inhibition test.
Treatment Guidelines from The Medical Letter • Vol. 7 ( Issue 87) • November 2009
Advice for Travelers
accelerated schedule of 0, 7 and 14 days, followed by a season or to the tropics at any season, or when travel- booster dose at 6 months, can also be used with either ing in a group with persons from the Southern Hemisphere during their influenza season (April-September).11 In some years, the vaccine strains are the An interrupted hepatitis B vaccination series can be same in both hemispheres. If the vaccine strains are completed without being restarted. A 3-dose series different, high-risk patients from the Northern started with one vaccine may be completed with the Hemisphere who travel to the Southern Hemisphere other. Post-vaccination serologic testing is recommend- during that region’s influenza season could also con- ed for healthcare workers, infants born to HBsAg-pos- sider being immunized on arrival because the vaccine itive mothers, hemodialysis patients, HIV-infected and active against strains in the Southern Hemisphere is other immunocompromised patients, and sex- and nee- rarely available in the Northern Hemisphere.
dle-sharing partners of HBsAg-positive patients.
A monovalent vaccine is available to protect against HEPATITIS A/B — A combination vaccine (Twinrix)
the currently (2009) circulating pandemic influenza A containing the same antigenic components as pediatric (H1N1) virus.12 It can be given at the same time as the Havrix and Engerix-B is available for patients >18 seasonal vaccine, except not the 2 live attenuated for- years old. It is given in 3 doses at 0, 1 and 6 months.
mulations together. Both the seasonal and monovalent An accelerated schedule of 0, 7 and 21-30 days with a influenza vaccines are prepared in eggs.
booster dose at 12 months is also approved.8 Hypersensitivity reactions could occur.
The combination vaccine can be used to complete an There is no commercial influenza vaccine available for immunization series started with monovalent hepatitis pathogenic strains of avian influenza (H5N1, H7N2, A and B vaccines. Twinrix Junior is available outside H9N2, H7N3, H7N7), but an inactivated vaccine against avian H5N1 is FDA-approved and is beingincluded in the US Strategic National Stockpile.
Table 2. Low-Risk Areas For Hepatitis A & B*
Hepatitis A
Hepatitis B
JAPANESE ENCEPHALITIS
encephalitis is an uncommon but potentially fatal mos- quito-borne viral disease that occurs in rural Asia, especially near pig farms and rice paddies. It is usual- ly seasonal (May-October), but may occur year-round in equatorial regions. The attack rate in travelers has Vaccination is recommended for travelers >1 year old who expect a long stay (>1 month) in endemic areas or heavy exposure to mosquitoes (such as adventure trav- elers) during the transmission season. Vaccination also should be considered for travelers spending less than a * All other areas are intermediate to high risk; vaccine is indicated.
month in endemic areas during the transmission season 1. Risk is intermediate in Alaska natives and is high in indigenous popula- if they will be sleeping without air conditioning, screens 2. Risk is intermediate in Greece, Portugal and Spain.
or bed nets, or spending considerable time outside inrural or agricultural areas, especially in the evening or at INFLUENZA — Influenza may be a risk in the trop-
night.14 Some Medical Letter consultants suggest that, ics year-round and in temperate areas of the Southern given the rarity of the disease in US residents, compul- Hemisphere from April to September. Outbreaks have sive use of insect repellents and judicious avoidance of occurred on cruise ships and on organized group tours exposure to mosquitoes might be reasonable alternatives to vaccination for short-term travelers.
Seasonal influenza vaccine directed against strains in Two formulations are FDA-approved in the United the Northern Hemisphere is sometimes available in States: JE-Vax, which is a mouse-brain preparation, and the US until the end of June and the US Advisory the recently approved Ixiaro, a non-mouse-brain vac- Committee on Immunization Practices (ACIP) recom- cine, which is preferred for use in adults, but has not mends that persons for whom seasonal influenza vac- been approved for use in children in the US.15 In clini- cine is indicated10 consider being vaccinated before cal trials, 2 doses of Ixiaro (one is not enough) appeared travel to the Southern Hemisphere during influenza to be as effective as JE-Vax, and considerably safer.16 Treatment Guidelines from The Medical Letter • Vol. 7 ( Issue 87) • November 2009
Advice for Travelers
MEASLES — The measles vaccine is no longer avail-
series of inactivated polio vaccine (IPV) if traveling to able in a monovalent formulation. It is available as an areas where polio is still endemic (Nigeria, India, attenuated live-virus vaccine in combination with Pakistan, Afghanistan) or to areas with documented mumps and rubella (MMR). Adults born in or after outbreaks or circulating vaccine-derived strains (see 1957 (1970 in Canada) and healthcare workers of any Table 3).22 Previously unimmunized children should age who have not received 2 doses of live measles vac- also receive a primary series of IPV.
cine (not the killed vaccine that was commonly used inthe 1960s) after their first birthday and do not have a If protection is needed within 4 weeks, a single dose physician-documented history of infection or laborato- of IPV is recommended, but provides only partial pro- ry evidence of immunity should receive two doses of tection. Adult travelers to risk areas who have previ- MMR vaccine, separated by at least 28 days.17 ously completed a primary series and have never hada booster should receive a single booster dose of IPV.
Previously unvaccinated children >12 months oldshould receive 2 doses of MMR vaccine at least 28 Table 3. Countries with a Risk of Polio1
days apart before traveling outside the US. Children6-11 months old should receive 1 dose before travel- ing, but will still need two subsequent doses for rou- tine immunization, one at 12-15 months and one at 4- MENINGOCOCCAL — A single dose of meningo-
coccal vaccine is recommended for adults and children >2 years old who are traveling to areas where epi- demics are occurring, or to anywhere in the “meningi- tis belt” (semi-arid areas of sub-Saharan Africa extend- ing from Senegal and Guinea eastward to Ethiopia) from December to June. Saudi Arabia requires a cer- tificate of immunization for pilgrims during the Hajj.
1. Centers for Disease Control and Prevention. Update on the Global Status Immunization should also be considered for travelers of Polio. October 1, 2009. Available at: http://wwwnc.cdc.gov/travel/con- to other areas where Neisseria meningitidis is hyper- tent/in-the news/polio-outbreaks.aspx.
endemic or epidemic, particularly for those who willhave prolonged contact with the local population, such RABIES — Rabies is highly endemic in parts of
as those living in a dormitory or refugee camp, or Africa, Asia (particularly India) and Central and South America, but the risk to travelers is generally low. Pre-exposure immunization against rabies is recommended Two quadrivalent vaccines are available against N. for travelers with an occupational risk of exposure, for meningitidis serogroups A, C, Y and W135. Menomune those (especially children) visiting endemic areas contains meningococcal capsular polysaccharides. where immediate access to medical treatment, particu- Menactra, which contains capsular polysaccharides larly rabies immune globulin, tends to be limited, and conjugated to diphtheria toxoid, is preferred, but for outdoor-adventure travelers.23,24 The 2 vaccines Menomune is an acceptable alternative. Neither vac- available in the US (Imovax, RabAvert) are similar; cine provides protection against serogroup B, which both are given in the deltoid (not gluteal) muscle at 0, does not have an immunogenic polysaccharide capsule.
Group B infections are rare in sub-Saharan Africa.
After a bite or scratch from a potentially rabid animal, The most common adverse reactions to Menactra have patients who received pre-exposure prophylaxis been headache, fatigue and malaise in addition to pain, should promptly receive 2 additional doses of vaccine redness and induration at the site of injection. The rates at days 0 and 3. Without pre-exposure immunization, of these reactions are higher than with Menomune, but the ACIP recommends rabies immune globulin (RIG) similar to those with tetanus toxoid. Guillain-Barré and is now recommending 4 doses (over 14 days) of syndrome has been reported rarely in adolescents who vaccine instead of 5 doses (over 28 days). Patients with received Menactra, but cause and effect have not been immunosuppression should still receive 5 doses of vaccine.25 The reduced vaccine dosing schedule maynot be included in the prescribing information from the POLIO — Adults who have not previously been
manufacturers of the approved vaccines. According to immunized against polio should receive a primary the CDC, cell culture rabies vaccines available outside Treatment Guidelines from The Medical Letter • Vol. 7 ( Issue 87) • November 2009
Advice for Travelers
the US are acceptable alternatives to FDA-approved Encepur, it may be only 12-18 months. Boosters give vaccines; neural tissue vaccines have high rates of seri- 5 years of protection for patients <50 years old and 3 ous adverse effects.26 RIG is a blood product, and its purity and potency may be less reliable, if it is avail-able at all, in developing countries.
TYPHOID — Typhoid vaccine is recommended for
travelers to South Asia and other developing countries
TETANUS, DIPHTHERIA AND PERTUSSIS —
in East and Southeast Asia, Central and South Previously unimmunized children should receive 3 or America, the Caribbean and Africa, especially if they (preferably) 4 doses of pediatric diphtheria, tetanus will be visiting friends or relatives or traveling outside and acellular pertussis vaccine (DTaP) before travel.
An accelerated schedule can be used beginning at age6 weeks, with the second and third doses given 4 A live attenuated oral vaccine (Vivotif) is available for weeks after the previous dose, and the fourth dose 6 adults and children >6 years old. It is taken every other day as a single capsule (at least 1 hour before eating)for a total of 4 capsules, beginning no later than 2 Adults with an uncertain history of primary vaccina- weeks before departure; it protects for about 5 years.
tion should receive 3 doses of a tetanus and diphtheria The capsules must be refrigerated. Antibiotics should toxoid vaccine. Two vaccines (Adacel; Boostrix) con- be avoided for at least 72 hours before the first cap- taining protein components of acellular pertussis com- sule. A purified capsular polysaccharide parenteral bined with diphtheria and tetanus toxoids (Tdap) are vaccine (Typhim Vi) for adults and children >2 years available for adults <64 years of age.27 One of the 3 old is given as a single IM dose at least 2 weeks before doses (preferably the first) should be Tdap. The first 2 departure. Re-vaccination is recommended every 2 doses should be administered at least 4 weeks apart and the third 6-12 months after the second. DTaP con-tains larger amounts of diphtheria and pertussis anti- A combined hepatitis A/typhoid vaccine (Vivaxim – gens than Tdap and is not licensed for use in adults.
Sanofi Pasteur) is available in Canada.
Inactivated adsorbed (aluminum-salt-precipitated) YELLOW FEVER — Yellow fever vaccine (YF-
tetanus and diphtheria toxoid (Td) has been the stan- Vax), a single-dose attenuated live virus vaccine pre- dard booster vaccine for adults. A booster dose of Td is pared in eggs, should be given at least 10 days before recommended every 10 years. Persons 11-64 years old travel to endemic areas, which include much of tropi- who have completed a primary childhood series and cal South America and sub-Saharan Africa between have not yet received Tdap should receive a single dose 15°N and 15°S.32 Some countries in Africa require an of Tdap at the time of their next scheduled routine Td International Certificate of Vaccination against yellow booster. Tdap can be given less than 10 years after the fever, or a physician’s waiver letter, from all entering last Td to provide pertussis protection before travel.
travelers; other countries in Africa, South Americaand Asia require evidence of vaccination from travel- TICK-BORNE ENCEPHALITIS (TBE) — TBE
ers coming from or traveling through endemic or occurs in temperate areas of Europe and Asia, from infected areas. The vaccine is available in the US only eastern France to northern Japan, and from northern from providers certified by state health departments.33 Russia to Albania.28,29 The risk is greatest from April Boosters are given every 10 years, but immunity to November. Humans acquire the disease through the probably lasts much longer. If other injectable or bite of a tick or, rarely, from eating unpasteurized dairy intranasal live vaccines are not administered simulta- (mostly goat) products. Immunization is recommended neously with yellow fever vaccine, administration only for travelers who will spend extensive time out- should be separated by one month to avoid a dimin- doors in rural areas. The vaccine, which is not ished immune response to the vaccines.
approved in the US but is available in Canada andEurope (Encepur – Novartis; FSME-Immun – Baxter Yellow fever vaccine is contraindicated in travelers AG), is usually given in 3 doses over 9-12 months, but who have symptomatic HIV infection (and possibly in can be given (Encepur) over 3 weeks (0, 7 and 21 those with CD4 counts <200 cells/mm3), are immuno- days). FSME-Immun can be obtained in Canada by compromised or have egg allergy. Yellow fever vac- contacting the Special Access Programme, Health cine-associated viscerotropic disease, a severe sys- temic illness that can cause fatal organ failure, hasbeen reported rarely. It has occurred only in first-time The usual duration of protection after the primary recipients, especially those with thymus disorders.
series is 3 years; with the accelerated schedule of Vaccine-associated neurologic disease (encephalitis, Treatment Guidelines from The Medical Letter • Vol. 7 ( Issue 87) • November 2009
Revised 11/25/09: In the oral rehydration salts paragraph, the first sentence has been changed from “.can help
maintain electrolyte balance.” to “.can prevent and treat dehydration.”
Advice for Travelers
Guillain-Barré, Bell’s palsy) has also occurred. The mg daily for 1-3 days, is an alternative37,38 and is the vaccine should be avoided if possible in infants <9 drug of choice for travelers to areas with a high preva- months old and it is contraindicated in infants <6 lence of fluoroquinolone-resistant Campylobacter, months old.34 Travelers >60 years of age also have a such as Thailand and India.39,40 Azithromycin can be relatively high risk of systemic adverse effects.35 used in pregnant women and children (10 mg/kg/d x3d), and in patients who do not respond to a fluoro- Table 4. Antimicrobial Drugs for Treatment of
Travelers’ Diarrhea
Dosage Cost1
A non-absorbed oral antibiotic derived from rifampin, rifaximin is approved for treatment of travelers’ diar- rhea caused by noninvasive strains of E. coli in travel- ers >12 years of age. In clinical trials in patients with diarrhea mostly caused by E. coli, it has been similar in efficacy to ciprofloxacin, with fewer adverse effects.41 It should not be used in infections associated with fever or blood in the stool or those caused by C. jeju- ni, Salmonella, Shigella or other invasive pathogens, One meta-analysis found that combinations of an anti- bacterial plus loperamide were more effective than anantibacterial alone in decreasing the duration of illness.42 1. Cost of 3 days’ treatment based on August 2009 data from retail phar- macies nationwide available from Wolters Kluwer Health.
Packets of oral rehydration salts (Ceralyte, ORS, and 2. 20 500-mg tablets cost $4 at some discount pharmacies.
others) mixed in potable water can prevent and treatdehydration, particularly in children and the elderly.
TRAVELERS’ DIARRHEA
They are available from suppliers of travel-relatedproducts and some pharmacies in the US, and from The most common cause of travelers’ diarrhea, usual- ly a self-limited illness lasting several days, is infec-tion with noninvasive enterotoxigenic (ETEC) or Prophylaxis – Medical Letter consultants generally do
enteroaggregative (EAEC) strains of Escherichia coli.
not prescribe antibiotic prophylaxis for travelers’ diar- Infections with Campylobacter, Shigella, Salmonella, rhea, but rather instruct the patient to begin self-treat- Aeromonas, viruses and parasites are less common.
ment when symptoms are distressing or persistent.
Children tend to have more severe illness and are par- Some travelers, however, such as immunocompro- ticularly susceptible to dehydration. Travelers to areas mised patients or those with time-dependent activities where hygiene is poor should avoid raw vegetables, who cannot risk the temporary incapacitation associat- fruit they have not peeled themselves, unpasteurized ed with diarrhea, might benefit from prophylaxis.43 In dairy products, cooked food not served steaming hot, such patients, ciprofloxacin 500 mg, levofloxacin 500 mg, ofloxacin 300 mg or norfloxacin 400 mg can begiven once daily during travel and for 2 days after Treatment – For mild diarrhea, loperamide
return and are generally well tolerated. In one 2-week (Imodium, and others), an over-the-counter syn- study among travelers to Mexico, rifaximin (200 mg thetic opioid (4-mg loading dose, then 2 mg orally 1-3x/d) was effective in preventing travelers’ diar- after each loose stool to a maximum of 16 mg/d for rhea.44 Bismuth subsalicylate (Pepto-Bismol, and oth- adults), often relieves symptoms in <24 hours. It ers) can prevent diarrhea in travelers who take 2 tablets should not be used if fever or bloody diarrhea are 4 times a day for the duration of travel, but it is less present, and some patients complain of constipa- effective than antibiotics. It is not recommended for tion after use. Loperamide is approved for use in If diarrhea is moderate to severe, persists >3 days or isassociated with high fever or bloody stools, self-treat- No drug is 100% effective for prevention of malaria; ment for 1-3 days with ciprofloxacin, levofloxacin, travelers should be told to take protective measures norfloxacin or ofloxacin is usually recommended.36 against mosquito bites in addition to medication.45 Azithromycin, taken as a single 1000-mg dose or 500 Countries with a risk of malaria are listed in Table 5.
Treatment Guidelines from The Medical Letter • Vol. 7 ( Issue 87) • November 2009
Advice for Travelers
CHLOROQUINE-SENSITIVE MALARIA
Table 5. Countries with a Risk of Malaria1
Chloroquine is the drug of choice for prevention of
malaria in the few areas that still have chloroquine- sensitive malaria (see Table 5, footnotes 4, 6 and 7).
Patients who cannot tolerate chloroquine should take atovaquone/proguanil, doxycycline, mefloquine or, in some circumstances, primaquine in the same doses used for chloroquine-resistant malaria (see Table 6).
CHLOROQUINE-RESISTANT MALARIA —
Three drugs of choice with similar efficacy, listed with their dosages in Table 6, are available in the US for prevention of chloroquine-resistant malaria.
A fixed-dose combination of atovaquone and
proguanil (Malarone) taken once daily is generally
the best tolerated prophylactic,46 but it can cause
AMERICAS
Argentina3,4
headache, insomnia, GI disturbances and mouth ulcers.
Single case reports of Stevens-Johnson syndrome and hepatitis have been published. Atovaquone/proguanil should not be given to patients with severe renal impairment (CrCl <30 mL/min). There have been iso- lated case reports of treatment-related resistance to ato- vaquone/proguanil in Plasmodium falciparum inAfrica, but Medical Letter consultants do not believe there is a high risk for acquisition of resistant dis- ease.47-50 In one study of malaria prophylaxis, ato- vaquone/proguanil was as effective and better tolerat- ed than mefloquine in nonimmune travelers.51 The pro- tective efficacy of atovaquone/proguanil against P. vivax is variable ranging from 84% in Indonesian New Guinea52 to 100% in Colombia.53 Some Medical Letter consultants prefer other drugs if traveling to areas OCEANIA
Papua New
Mefloquine has the advantage of once-a-week dosing,
but is contraindicated in patients with a history of any
1. Only includes countries for which prophylaxis is recommended. Regional variation in risk may exist within a country. More detailed information is psychiatric disorder (including severe anxiety and available at www.cdc.gov/malaria and by phone for medical personnel depression), and also in those with a history of from the Malaria Branch of the CDC at 770-488-7788.
seizures or cardiac conduction abnormalities.54 2. Limited to Island of Saõ Tiago.
3. No malaria in major urban areas.
Dizziness, headache, insomnia and disturbing dreams 4. Chloroquine is the drug of choice for prophylaxis.
are the most common CNS adverse effects. The drug’s 5. Only Great Exuma Island.
6. Chloroquine is recommended in Bocas del Toro province.
adverse effects in children are similar to those in 7. Chloroquine is recommended except in Hainan and Yunnan provinces.
adults. If a patient develops psychological or behav-ioral abnormalities such as depression, restlessness orconfusion while taking mefloquine, another drug Some countries with endemic malaria transmission should be substituted. Mefloquine should not be given may not have malaria in the most frequently visited together with quinine, quinidine or halofantrine due to major cities and rural tourist resorts. Travelers to potential prolongation of the QT interval; caution is malarious areas should be reminded to seek medical required when using these drugs to treat patients who attention if they have fever either during their trip or up to a year (especially during the first 2 months) afterthey return. Travelers to developing countries, where Doxycycline (Vibramycin, and others), which fre-
counterfeit and poor quality drugs are common, quently causes GI disturbances and can cause photo- should consider buying antimalarials before travel.
sensitivity and vaginitis, offers an inexpensive once- Treatment Guidelines from The Medical Letter • Vol. 7 ( Issue 87) • November 2009
Advice for Travelers
Table 6. Drugs of Choice for Prevention of Malaria1
Adult dosage
Pediatric dosage
Duration
All Plasmodium species in chloroquine-sensitive areas2
Drug of Choice3,4:
All Plasmodium species in chloroquine-resistant areas2
Drug of Choice3:
21-30 kg: 2 peds tabs/d31-40 kg: 3 peds tabs/d>40 kg: 1 adult tab/d 31-45 kg: ¾ tab once/wk9>45 kg: 1 tab once/wk9 Start: 1d before travelStop: 1 wk after leaving No drug guarantees protection against malaria. Travelers should be advised to seek medical attention if fever develops after they return. Insect repellents, insec-ticide-impregnated bed nets and proper clothing are important adjuncts for malaria prophylaxis.
Chloroquine-resistant P. falciparum occurs in all malarious areas except Central America (including Panama north and west of the Canal Zone), Mexico, Haiti,the Dominican Republic, Paraguay, northern Argentina, North and South Korea, Georgia, Armenia, most of rural China and some countries in the Middle East(chloroquine resistance has been reported in Yemen, Saudi Arabia and Iran). P. vivax with decreased susceptibility to chloroquine is a significant problem inPapua New Guinea and Indonesia. There are also a few reports of resistance from Myanmar, India, the Solomon Islands, Vanuatu, Guyana, Brazil, Colombiaand Peru (JK Baird et al, Curr Infect Dis Rep 2007; 9:39). Chloroquine-resistant P. malariae has been reported from Sumatra (JD Maguire et al, Lancet 2002;360:58).
Primaquine is given for prevention of relapse after infection with P. vivax or P. ovale. Some experts also prescribe primaquine phosphate 30 mg base/d (0.6 mgbase/kg/d for children) for 14d after departure from areas where these species are endemic (Presumptive Anti-Relapse Therapy [PART], “terminal prophylax-is”). Since this is not always effective as prophylaxis (E Schwartz et al, N Engl J Med 2003; 349:1510), others prefer to rely on surveillance to detect caseswhen they occur, particularly when exposure was limited or doubtful. See also footnote 11.
Alternatives for patients who are unable to take chloroquine include atovaquone/proguanil, mefloquine, doxycycline or primaquine dosed as for chloroquine-resistant areas.
Chloroquine should be taken with food to decrease gastrointestinal adverse effects. If chloroquine phosphate is not available, hydroxychloroquine sulfate is aseffective; 400 mg of hydroxychloroquine sulfate is equivalent to 500 mg of chloroquine phosphate.
Atovaquone/proguanil is available as a fixed-dose combination tablet: adult tablets (Malarone; 250 mg atovaquone/100 mg proguanil) and pediatric tablets(Malarone Pediatric; 62.5 mg atovaquone/25 mg proguanil). To enhance absorption and reduce nausea and vomiting, it should be taken with food or a milkydrink. The drug should not be given to patients with severe renal impairment (creatinine clearance <30 mL/min).
Doxycycline should be taken with adequate water to avoid esophageal irritation. It can be taken with food to minimize gastrointestinal adverse effects. It is con-traindicated in children <8 years old.
In the US, a 250-mg tablet of mefloquine contains 228 mg mefloquine base. Outside the US, each 275-mg tablet contains 250 mg base. Mefloquine can begiven to patients taking ß-blockers if they do not have an underlying arrhythmia; it should not be used in patients with conduction abnormalities. Mefloquine shouldnot be taken on an empty stomach; it should be taken with at least 8 oz. of water.
Most adverse events occur within 3 doses. Some Medical Letter consultants favor starting mefloquine 3 weeks prior to travel and monitoring the patient foradverse events; this allows time to change to an alternative regimen if mefloquine is not tolerated.
10. For pediatric doses <½ tablet, it is advisable to have a pharmacist crush the tablet, estimate doses by weighing, and package them in gelatin capsules. There is no data for use in children <5 kg, but based on dosages in other weight groups, a dose of 5 mg/kg can be used.
11. Patients should be screened for G-6-PD deficiency before treatment with primaquine. It should be taken with food to minimize nausea and abdominal pain.
12. Not FDA-approved for this indication.
daily alternative. Doxycycline should not be taken that daily primaquine can provide effective prophylax- concurrently with antacids, oral iron or bismuth salts is against chloroquine-resistant P. falciparum and P. vivax.55 Some experts also prescribe primaquine for A fourth drug, primaquine phosphate, can also be
prophylaxis after departure from areas where P. vivax used for prophylaxis, especially in areas where P. vivax and P. ovale are endemic (see Table 6, footnote 3).
is the predominant species, but in other areas should bereserved for travelers unable to take any other drug; it Primaquine can cause hemolytic anemia in patients is somewhat less effective than the alternatives against with glucose-6-phosphate dehydrogenase (G-6-PD) P. falciparum. However, several studies have shown deficiency, which is most common in African, Asian, Treatment Guidelines from The Medical Letter • Vol. 7 ( Issue 87) • November 2009
Advice for Travelers
and Mediterranean peoples. Travelers should be also available and can provide longer protection than screened for G-6-PD deficiency before treatment with similar concentrations of other DEET formulations.
the drug. Primaquine should be taken with food toreduce GI effects.
According to the CDC, DEET is probably safe in chil-dren and infants >2 months old; the American MEFLOQUINE-RESISTANT MALARIA — Doxy-
Academy of Pediatrics recommends use of concentra- cycline or atovaquone/proguanil is recommended for tions containing no more than 30%. One study found prophylaxis against mefloquine-resistant malaria, that applying DEET regularly during the second and which occurs in the malarious areas of Thailand and in third trimesters of pregnancy did not result in any the areas of Myanmar and Cambodia that border on adverse effects on the fetus.61 DEET has been shown Thailand. It has also been reported on the borders to decrease the effectiveness of sunscreens when it is between Myanmar and China, and Laos and Myanmar, applied after the sunscreen; nevertheless, sunscreen should be applied first because it may increase theabsorption of DEET when DEET is applied first.62 PREGNANCY — Malaria in pregnancy is particular-
ly serious for both mother and fetus; prophylaxis is
PICARIDIN — Picaridin has been available in
indicated if travel cannot be avoided. Chloroquine has Europe and Australia for many years. Data on the 7% been used extensively and safely for prophylaxis of and 15% formulations (Cutter Advanced) currently chloroquine-sensitive malaria during pregnancy.
sold in the US are limited. The 20% formulation Mefloquine is not approved for use during pregnancy.
(Natrapel 8 Hour; GoReady) has been shown to pro- It has, however, been reported to be safe for prophy- tect for up to 8 hours; in clinical trials it has been about lactic use during the second or third trimester of preg- nancy and possibly during early pregnancy as well.56,57The safety of atovaquone/proguanil in pregnancy has PERMETHRIN — An insecticide available in liquid
not been established, and its use is not recommended.
and spray form, permethrin (Duranon, Permanone, However, outcomes were normal in 24 women treated and others) can be used on clothing, mosquito nets, with the combination in the second and third tents and sleeping bags for protection against mosqui- trimester,58 and proguanil alone has been used in preg- toes and ticks. After application to clothing, it remains nancy without evidence of toxicity. Doxycycline and active for several weeks through multiple launderings.
primaquine are contraindicated in pregnancy.
Using permethrin-impregnated mosquito nets whilesleeping is helpful when rooms are not screened or air- PREVENTION OF INSECT BITES
conditioned. If bednets or tents are immersed in theliquid, the effect can last for about 6 months. The com- To minimize insect bites, travelers should wear light- bination of DEET on exposed skin and permethrin on colored, long-sleeved shirts, pants, socks and covered clothing provides increased protection.
shoes. They should sleep in air conditioned or screenedareas and use insecticide-impregnated bed nets.
SOME OTHER INFECTIONS
Mosquitoes that transmit malaria are most activebetween dusk and dawn; those that transmit dengue DENGUE — Dengue fever is a viral disease transmit-
fever bite during the day, particularly during early ted by mosquito bites that occurs worldwide in tropical and subtropical areas, including cities. Epidemics haveoccurred in recent years in Southeast Asia (especially DEET — The most effective topical insect repellent is
Thailand), South Central Asia, sub-Saharan Africa, the N, N-diethyl-m-toluamide (DEET).60 Applied on South Pacific and Australia, Central and South exposed skin, DEET repels mosquitoes, as well as America and the Caribbean. It has also been reported ticks, chiggers, fleas, gnats and some flies. DEET is in travelers from the US vacationing at popular tourist available in formulations of 5-100% even though destinations in Puerto Rico, the US Virgin Islands and increasing the concentration above 50% does not seem Mexico.66 Prevention of mosquito bites during the day, to improve efficacy. Medical Letter consultants prefer particularly in early morning and late afternoon, is the concentrations of 30-35%. A long-acting DEET for- primary way to protect against dengue fever; no vac- mulation originally developed for the US Armed Forces (US Army Extended Duration Topical Insectand Arthropod Repellent – EDTIAR) containing 25- LEPTOSPIROSIS — Leptospirosis, a bacterial dis-
33% DEET (Ultrathon) protects for 6-12 hours. A ease that occurs in many domestic and wild animals, is microencapsulated sustained-release formulation con- endemic worldwide, but the highest incidence is in taining 20% DEET (Sawyer Controlled Release) is tropical and subtropical areas. Transmission to humans Treatment Guidelines from The Medical Letter • Vol. 7 ( Issue 87) • November 2009
Advice for Travelers
usually occurs through contact with fresh water or To minimize the risk, travelers should be advised to damp soil contaminated by the urine of infected ani- walk around or, if necessary, exercise while sitting by mals.67 Travelers at increased risk, such as adventure flexing/extending ankles and knees, to drink extra flu- travelers and those who engage in recreational water ids, and to avoid alcohol and caffeine. Compression activities, should consider prophylaxis with doxycy- stockings can decrease the risk of asymptomatic cline 200 mg orally once a week, beginning 1-2 days DVT.72 Giving a single dose of a low-molecular- before and continuing throughout the period of expo- weight heparin as prophylaxis to travelers at high risk sure. No human vaccine is available in the US.
reduced the incidence of DVT in a clinical trial.73 NON-INFECTIOUS RISKS OF TRAVEL
JET LAG — Disturbance of body and environmental
rhythms resulting from a rapid change in time zones
Many non-infectious risks are associated with travel.
gives rise to jet lag, which is characterized by insom- Injuries, particularly traffic accidents and drowning,
nia, decreased quality of sleep, loss of concentration, which account for the majority of travel-related deaths, irritability and GI disturbances. It is usually more and sunburn occur in many travelers.
HIGH ALTITUDE ILLNESS — Rapid exposure to
A variety of interventions have been tried, but none is altitudes >8,000 feet (2500 meters) may cause acute proven to be effective. Shifting daily activities to cor- mountain sickness (headache, fatigue, nausea, anorex- respond to the time zone of the destination country ia, insomnia, dizziness); pulmonary and cerebral before arrival along with taking short naps, remaining edema can occur.68 Sleeping altitude appears to be well hydrated, avoiding alcohol and pursuing activities especially important in determining whether symp- in sunlight on arrival may help. The dietary supple- toms develop. The most effective preventive measure ment melatonin (0.5-5 mg started on the first night of is pre-acclimatization by a 2- to 4-day stay at interme- travel and continued for 1-5 days after arrival) has diate altitude (6000-8000 feet) and gradual ascent to been reported to facilitate the shift of the sleep-wake cycle and decrease symptoms in some patients. A pro-gram of appropriately timed light exposure and avoid- Acetazolamide, a carbonic anhydrase inhibitor taken in ance in the new time zone may adjust the “body clock” a dosage of 125-250 mg twice daily (or 500 mg daily and reduce jet lag.75 In one study, zolpidem (Ambien, with the slow-release formulation Diamox Sequels) and others) started the first night after travel and taken beginning 1-2 days before ascent and continuing at high altitude for 48 hours or longer, decreases the inci-dence and severity of acute mountain sickness.69 The MOTION SICKNESS — Therapeutic options for
recommended dose for children is 5 mg/kg/d in 2 or 3 motion sickness remain limited.77 A transdermal patch divided doses. Although acetazolamide, a sulfone, has or oral formulation of the prescription cholinergic little cross-reactivity with sulfa drugs, hypersensitivity blocker scopolamine can decrease symptoms.
reactions to acetazolamide are more likely to occur in Transderm Scop is applied to the skin behind the ear at those who have had severe (life-threatening) allergic least 4 hours before exposure and changed, alternating ears, every 3 days. The oral 8-hour tablet (Scopace) istaken 1 hour before exposure. Oral promethazine Symptoms can be treated after they occur by descent to (Phenergan, and others) is a highly sedating alterna- a lower altitude or by giving supplemental oxygen, tive. Over-the-counter drugs such as dimenhydrinate especially during sleep. When descent is impossible, (Dramamine, and others) or meclizine (Bonine, and dexamethasone (Decadron, and others) 4 mg q6h, others) are less effective, but may be helpful for milder acetazolamide 250-500 mg q12h, or the two together, may help. Nifedipine (Procardia, and others), 20-30mg twice daily may also be helpful.
VENOUS THROMBOEMBOLISM — Prolonged
immobilization, particularly during air travel, increas- es the risk of lower extremity deep vein thrombosis (DVT). Travelers with risk factors for thrombosis (past history of thrombosis, obesity, malignancy, increased platelets) are at even higher risk. Nevertheless, flight- related symptomatic pulmonary embolism is rare.71 Treatment Guidelines from The Medical Letter • Vol. 7 ( Issue 87) • November 2009
Advice for Travelers
Treatment Guidelines from The Medical Letter • Vol. 7 ( Issue 87) • November 2009
Advice for Travelers
Centers for Disease Control and Prevention. CDC Health Information Coming Soon in Treatment Guidelines:
for International Travel 2010. Atlanta: U.S. Department of Health and Human Services, Public Health Service, 2009, p 469.
EDITOR IN CHIEF: Mark Abramowicz, M.D.
EDITOR IN CHIEF:
EXECUTIVE EDIT Mark Abramo
wicz, M.D
Gianna Zuccotti
, M.D., M.P.H., F.A.C.P., Harvard Medical EXECUTIVE EDIT
OR: Gianna Zuccotti, M.D., M.P.H., Weill Medical College
Jean-Marie Pflomm, Pharm.D.
ASSIST Jean-Marie Pflomm
ANT EDITORS, DR
UG INFORMATION: Susan M. Daron, Pharm.D.,
ASSISTANT EDIT
Blaine M. Houst OR, DR
UG INFORMA
m.D., Corinne E.TION: Susan More
Zanone, Pharm.D. y, Pharm.D.
CONTRIBUTING EDITOR: Eric J. Epstein, M.D. Albert Einstein College of Medicine
CONTRIBUTING EDITORS:
CONTRIBUTING EDITOR, DRUG INTERACTIONS: Philip D. Hansten, Pharm.D.,
Carl W. Bazil, M.D., Ph.D., Columbia University College of Physicians and Surgeons
Vanessa K. Dalton, M.D., M.P.H., University of Michigan Medical School
ADVISORY BOARD:
Eric J. Epstein, M.D., Albert Einstein College of Medicine
Jules Hirsch, M.D., Rockefeller University
David N. Juurlink, BPhm, M.D., PhD, Sunnybrook Health Sciences Centre
David N. Juurlink, BPhm, M.D., PhD, Sunnybrook Health Sciences Centre
Richard B. Kim, M.D., University of Western Ontario
Richard B. Kim, M.D., University of Western Ontario
Hans Meinertz, M.D., University Hospital, Copenhagen
Gerald L. Mandell, M.D., University of Virginia School of Medicine
Sandip K. Mukherjee, M.D., F.A.C.C., Yale School of Medicine
SP Frances et al. Laboratory and field evaluation of commercial repel- Hans Meinertz, M.D., University Hospital, Copenhagen
F. Estelle R. Simons, M.D., University of Manitoba
lent formulations against mosquitoes (diptera: culcidae) in Dan M. Roden, M.D., Vanderbilt University School of Medicine
Jordan W. Smoller, M.D., Sc.D., Harvard Medical School
F. Estelle R. Simons, M.D., University of Manitoba
Queensland, Australia. Aust J Entomol 2005; 44:431.
Neal H. Steigbigel, M.D., New York University School of Medicine
Neal H. Steigbigel, M.D., New York University School of Medicine
SENIOR ASSOCIA
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ORS: Donna Goodstein, Amy Faucard
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Treatment Guidelines from The Medical Letter • Vol. 7 ( Issue 87) • November 2009
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Treatment Guidelines from The Medical Letter • Vol. 7 ( Issue 87) • November 2009
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Issue 87 Questions
1. Hepatitis A vaccine is recommended for travelers going to: 7. A vaccine for tick-borne encephalitis is: 2. For hepatitis B vaccination, an accelerated schedule of 0, 7 and 14 8. Travelers’ diarrhea can be treated with: 3. Off-season use of seasonal influenza vaccine should be consi- 9. Among the most effective drugs used for prevention of chloroquine- resistant malaria, the one generally best tolerated is: c. traveling in a group with persons from the Southern 10. Mosquitoes that transmit malaria are most active: 4. The preferred vaccine for adults against Japanese encephalitis is: 5. The “meningitis belt” where meningococcal meningitis is endemic a. DEET applied after sunscreen can decrease the effective- b. Sunscreen applied after DEET can increase absorption of c. Sunscreen should be applied before DEET.
6. Unimmunized travelers bitten by a potentially rabid animal should 12. The most effective measure to prevent high-altitude illness is: ACPE UPN: 379-000-09-087-H01-P; Release: November 2009, Expire: November 2010
Treatment Guidelines from The Medical Letter • Vol. 7 ( Issue 87) • November 2009

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