Dengue

Key Points

Mosquito Borne Illnesses

� Dengue is a viral infection acquired through the bites of mosquitoes carrying the dengue virus.� Travelers are at highest risk in populated urban and residential areas in most tropical countries.� Symptoms range from a mild flu-like illness to high fever and rash associated with severe headache

and muscle, joint, and back pain.� Classic dengue is self-limited (average duration: 6 days), but severe fatigue that lasts for weeks or

months may ensue. Rarely, severe cases progress to significant hemorrhage and organ damage.� No vaccine for travelers is available. Prevention includes personal protective measures against

mosquito bites.

Introduction Dengue is a viral infection acquired through the bites of mosquitoes carrying the dengue virus. Four

different types of dengue virus (called serotypes) can cause the disease. Travelers can become

infected by any of the serotypes that they have not previously encountered. Infection with one serotype

confers protection against that virus for life but does not give protection against subsequent infection

with the other serotypes.

Risk Areas Dengue infection is the most common cause of systemic febrile illness in travelers returning from the

Caribbean, Latin America, and Southeast Asia. The incidence of dengue is usually higher during warm

and humid seasons.

Travelers are at highest risk in populated urban and residential areas in most tropical countries. Infection rates range from 2.9 to 8.0% among travelers with fever who are returning from dengue areas in the tropics.

Transmission

Humans become infected when bitten by the mosquitoes that carry the dengue virus.

These mosquitoes are associated with the living spaces of humans. Larvae are most frequently found in containers with stagnant water, such as discarded tires, flowerpots, and blocked rain gutters. These mosquitoes will interrupt their feeding at the slightest movement but return quickly to feed on the same or a different human host in the same location.

Unlike malaria-transmitting mosquitoes, dengue-transmitting mosquitoes are daytime feeders with 2 peak times of biting activity: 2-3 hours after dawn and mid-to-late afternoon. This pattern, however, changes to an all-day activity when the mosquitoes are indoors or during overcast days.

Risk Factors All persons in an endemic area who previously have not been exposed to the currently circulating

serotype are at risk of acquiring dengue. The risk is higher for those staying in places near stagnant

water.

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Symptoms Symptoms of dengue most often appear 2-5 days after exposure (uncommonly, more than 7 days

and, rarely, up to 14 days after exposure). Fever that presents more than 14 days after last exposure

is not due to dengue. Although mild cases with only flu-like symptoms occur, classic dengue cases

present with the sudden onset of high-grade fever, severe muscle, joint, and lower back pain, severe

pain behind the bony socket of the eye, nausea, vomiting, and generalized weakness. A subtle

diffuse red rash appears in most patients during the initial fever phase, and in some cases, a diffuse

bright red rash with scattered clear spots is observed 4-6 days into the recovery phase. In many

cases, the fever subsides for a day and then returns. Mild bleeding from the nose, mouth, or under

the skin (seen as bruising) may also occur.

Dengue has symptoms in common with chikungunya and Zika virus infections, which usually co-exist in the same areas because they are all transmitted by the same mosquitoes.

Consequences of Infection Classic dengue is self-limited, with an average total duration of 6 days, but severe fatigue that lasts

for weeks or months may ensue.

Severe dengue is indistinguishable from classic dengue in its initial stages. In the period when fever has subsided, severe cases may infrequently progress to significant hemorrhage and organ (kidney, liver, brain) damage. Rarely, hemorrhagic fever or shock may ensue.

Experts have debated whether the risk of developing severe dengue is higher in persons who have been previously infected with a different viral serotype of dengue. The residual immune response from a previous infection is thought to be a contributor in a small percentage (less than 2%) of those who develop severe dengue. Thus, travelers who have already had an episode of dengue fever do not need to avoid future travel.

Need for Medical Assistance Travelers with persistent fever should be seen by a health care professional when possible to ensure

that another serious disease (e.g., malaria) is not present.

Travelers with severe abdominal pain, persistent vomiting, an abrupt change from fever to hypothermia (subnormal body temperature) with profuse sweating, extreme exhaustion, lack of energy, or mental status changes should seek immediate medical attention.

Travelers should avoid using aspirin and other nonsteroidal anti-inflammatory drugs for fever because they prevent formation of blood clots.

Prevention There is no dengue vaccine available for travelers. Prevention includes personal protective measures

against mosquito bites (see Insect Precautions).

The mosquitoes that transmit dengue are generally day biters. In risk areas, travelers should be especially vigilant in applying repellent during daytime hours, especially during peak biting times during the early morning and late afternoon hours. Travelers should also consider treating outer clothing, tents, and sleeping bag liners with permethrin (or another pyrethroid) when traveling in very high risk areas for dengue or other mosquito-borne diseases.

In addition, containers with stagnant water that can serve as breeding sites for mosquitoes should be removed from the proximity of human habitation whenever possible.

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Japanese Encephalitis

Key Points

� Japanese encephalitis (JE) is a viral infection acquired through the bite of an infected mosquito inmany areas of south-central, southeastern, and eastern Asia.

� Risk is high for long-stay travelers (with extensive unprotected outdoor, evening/nighttimeexposure) going to rural areas in affected countries, especially during JE virus (JEV) transmissionseason (May to October in most affected countries). Risk is negligible for short-stay travelers andpersons who confine their travel to urbanized areas.

� Symptoms include sudden high fever, nausea, headache, and altered mental status.� Consequences of infection may include convulsions, muscular paralysis, difficulty breathing, and

coma.� Prevention includes wearing long sleeves and long pants and observing personal protective

measures against mosquito bites.� JE vaccine (Ixiaro) is given as 2 doses, 28 days apart and at least 1 week prior to potential

exposure. For imminent departures, the 2 doses can be administered 7 days apart in adults.� Vaccine side effects are most commonly injection-site reactions, fever, headache, and muscle

aches.� Duration of vaccine protection is 10 years or longer following an initial booster (given at least 11

months after the initial 2 doses). No further booster dose is recommended.

Introduction JE is a viral infection acquired by the bite of infected mosquitos, resulting in fever, nausea, headache,

and altered mental status. In local people, JE is a relatively common vaccine-preventable cause of

encephalitis (brain inflammation) in Asia and parts of the western Pacific.

Risk Areas JE occurs in a wide belt from Japan and northern coastal China, throughout Southeast Asia, and

across India to Pakistan and is present through the Western Pacific islands from Indonesia to Papua

New Guinea and as far north as the Philippines.

Risk is highest in rural agricultural areas that are often associated with rice cultivation and flood irrigation. However, in some areas, these ecological conditions may occur near (or occasionally within) urban centers.

Altitude and local variations in rainfall and temperature affect mosquito breeding and seasonality of transmission. In temperate areas of Asia, the prevalence of human JEV infection increases toward the end of the summer rains and usually peaks in the summer and fall. In the subtropics and tropics (including Indonesia, the Philippines, southern Thailand, and southern Vietnam), seasonality varies with monsoon rains and irrigation practices and may be prolonged or even occur throughout the year.

Fewer than 100 cases of JE have been reported in travelers going to risk areas of Asia since the 1970s. No travel-related cases have been reported among exclusively urban travelers.

Transmission JEV is transmitted to humans through the bite of infected evening-biting and night-biting mosquitoes

that breed in rice fields. Mosquitoes acquire the virus when they bite wading birds or pigs (in rural

farms) that carry JEV.

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Risk Factors Risk is very low for short-stay travelers and persons who confine their travel to urbanized areas or who

have brief daytime exposures during common tourist excursions. However, cases may be sporadic and

have been reported (albeit rarely) in short-stay visitors traveling out of season whose only rural travel

had been to beach resorts.

Risk is highest for expatriates and long-stay travelers (more than 1 month) in rural areas where JE is prevalent. Persons with extensive unprotected outdoor, evening, or nighttime exposure (e.g., biking, hiking, camping, and certain occupational activities) in rural areas might be at high risk even if their trip is brief.

For U.S. travelers, all age groups are equally susceptible to JEV infection due to lack of prior exposure.

Symptoms Symptoms most commonly appear 5 to 15 days following exposure and include sudden high fever,

abdominal pain, nausea, vomiting, headache, and altered mental status.

Consequences of Infection JEV infection can lead to convulsions, muscular paralysis, breathing difficulties, seizures, mild tremors,

poor concentration, memory problems, and coma. Death occurs in about 30% of symptomatic cases.

Need for Medical Assistance Travelers who develop symptoms (especially altered mental status) within 15 days of leaving a risk area

should seek urgent medical attention.

Prevention

Nonvaccine

Mosquito precautions in the evening and nighttime are recommended when in risk areas, regardless of vaccination status. Travelers should be especially vigilant in applying repellent at dusk and again at dawn, when the mosquitoes that transmit JEV are most active. See Insect Precautions.

Vaccine

An injectable vaccine (Ixiaro) is available in the U.S. and is approved for persons 2 months and older. Several vaccines are available outside the U.S.

Persons with underlying medical conditions or those who have concerns about the vaccine should speak to their health care provider before vaccine administration.

Side Effects

The most common vaccine side effects are injection-site reactions, fever, headache, and muscle aches. Fever, irritability, and diarrhea are most common in infants and children younger than 12 years. Allergic reactions (both immediate and delayed) to the vaccine have occurred. Timing

The primary series consists of 2 doses, given 28 days apart and at least 1 week before potential exposure. An accelerated schedule for travelers aged 18-65 years consists of 2 doses given 7 days

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apart.

A booster dose may be given at least 11 months after completion of the primary immunization series if ongoing exposure or re-exposure to JEV is expected. Duration of protection is 10 years or longer.

Malaria

Key Points

� Malaria is an infection caused by a parasite that lives within the red blood cells and is acquiredthrough the bite of mosquitoes which generally feed at night.

� This infection occurs in tropical and subtropical countries, mostly in sub-Saharan Africa where risk isconsiderably higher than anywhere else.

� Travelers who visit or live in rural areas of tropical countries where the disease is common are at highrisk.

� Symptoms always include fever and influenza-like symptoms (chills, sweats, muscle aches, headache).Vomiting, abdominal pain, diarrhea, cough, and jaundice (yellow skin and eyes) may occur.

� Without immediate and proper treatment, severe malaria can progress to shock, lung and kidneyfailure, coma, and death. Some forms of malaria can persist for many months and can cause relapses.

� Prevention includes medications taken during the trip and for a short period thereafter, as well aspersonal protective measures against mosquito bites.

� Atovaquone-proguanil (Malarone or generic), doxycycline, and mefloquine are equally effectiveantimalarial drugs when taken as instructed.

� For short-term travel (less than 2-3 weeks), atovaquone-proguanil may be preferable becausetravelers can stop taking the drug just 7 days after leaving the malarious area. Longer courses ofatovaquone-proguanil appear safe but are more costly than mefloquine or doxycycline.

� For long-term travel, mefloquine is preferable (if it is tolerated and if there is no resistance to the drug)due to the lower cost and once-weekly doses (rather than daily doses).

� Chloroquine, an older drug, is the drug of choice in limited chloroquine-sensitive areas. Atovaquone-proguanil, doxycycline, and mefloquine are also completely effective in these areas and may be usedwhen more convenient.

� Mefloquine should not be used in areas of mefloquine resistance (i.e., Southeast Asia).

Introduction Malaria is an infection caused by a parasite that lives within the red blood cells and is acquired through

the bite of Anopheles mosquitoes which generally feed at night.

Malaria remains the most frequent infectious cause of death for persons traveling to tropical and subtropical countries.

There is no malaria vaccine available; however, malaria usually (but not always) can be prevented by the use of antimalarial drugs and personal protective measures against mosquito bites. (See Insect Precautions.)

Risk Areas Malaria occurs in approximately 100 countries in Africa, Central and South America, South Asia,

Southeast Asia, the Middle East, and South Pacific islands. Most of the world's malaria occurs in sub-

Saharan Africa where risk is considerably higher than anywhere else.

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In most parts of the world, malaria is a rural disease with minimal or no risk in urban areas. However, malaria risk occurs in both rural and urban areas of sub-Saharan Africa and South Asia. Malaria is less common above a certain altitude (usually around 8,200 ft / 2,500 m), during dry seasons, and among persons who stay in air-conditioned and/or screened accommodations.

The risk of getting malaria can vary greatly within a country depending on the intensity of transmission, the traveler's itinerary, season, duration and type of travel, the location (e.g., urban vs. rural), and where an individual spends the evening and nighttime hours. For example, short-term travelers living in urban centers and staying in air-conditioned hotels will be at much lower risk than long-stay, adventurous travelers living in rural areas. However, brief exposure, such as a 1-night stay in a malarious area or a night-time train trip through a malarious area, requires that protective measures be taken, including insect precautions and possibly a full course of prescription anti-malarial drugs. It is also possible to contract malaria during brief stopovers at airports in malarious zones if health officials have not taken proper measures to rid the area of mosquitoes. Airports off the main circuit of international travel are particularly suspect. Country-specific malaria risk information is available from health care providers in the form of a Travax country report malaria recommendation map (where available).

Transmission Malaria is usually transmitted between dusk and dawn, the time that Anopheles mosquitoes generally feed

on humans. Occasionally, malaria is transmitted through blood transfusion, transferal from mother to fetus,

or contaminated needles and syringes.

Risk Factors Travelers who visit or live in rural areas of tropical countries where the disease is common have greater

risk of acquiring malaria. Very young and very old persons are at high risk, as are pregnant women.

Adults who grew up in malarious areas should be aware that immunity to malaria disappears within 6 months of the last exposure to malaria. Preventive medications are indicated for these individuals just as they are for first-time travelers to a malarious region.

Symptoms

Malaria symptoms usually develop within days after being exposed. Less commonly, symptoms can appear

weeks, months, or even a few years after leaving a malarious area (when use of preventive drugs has

been stopped).

Symptoms always include fever and influenza-like symptoms (chills, sweats, muscle aches, headache) that may come and go. Vomiting, abdominal pain, diarrhea, cough, and jaundice (yellow skin and eyes) can occur. The symptoms of malaria can mimic almost any other infection that causes fever.

Malaria caused by the P. falciparum strain usually occurs about 10 to 12 days after infection and is a medical emergency. If falciparum malaria is not treated immediately and properly, it can proceed to shock, lung and kidney failure, coma, and death.

Malaria caused by milder strains (P. vivax, P. ovale, and P. malariae) is not usually life-threatening, but there may be serious health risks to very young or very old persons and to those with underlying illness. Malaria due to P. vivax and P. ovale may eventually resolve without treatment, but can relapse periodically until properly treated.

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Malaria is always completely curable when the appropriate drug is used.

Consequences of Infection Without immediate and proper treatment, severe malaria can progress to shock, lung and kidney failure,

coma, and death. Some forms of malaria can persist for many months and can cause relapses.

Need for Medical Assistance Individuals who think they might have symptoms of malaria (especially fever and/or influenza-like

symptoms) should seek medical attention immediately because delay of appropriate treatment can lead to

serious or fatal consequences. Inform the health care provider that risk of malaria exists and where travel

occurred. Request "thick and thin blood films" or a malaria rapid diagnostic card test for diagnosis. One

negative blood film does not rule out malaria; if symptoms persist, 2 additional films should be performed

12 to 24 hours apart. Similarly, a negative rapid malaria test should be followed with up to 3

thick/thin blood films.

� Certain strains of malaria can lie dormant in the liver and cause malaria symptoms months or even years after leaving the malaria risk area and discontinuing malaria drugs. The development of fever or influenza-like symptoms is cause to seek medical attention and to advise the health care provider of previous travel to a malarious area.

Travelers should be aware that the medical management of malaria in countries where the disease routinely occurs may differ from their country of origin. However, in many countries where malaria is endemic, there may be a limited number of effective medications available for treatment. In fact, some of the drugs used may be ineffective for persons, such as travelers, without partial immunity to malaria or may be associated with unacceptable adverse effects.

Prevention The use of preventive medications such as atovaquone-proguanil, doxycycline, or mefloquine (taken during

the trip and for a short period thereafter), as well as personal protective measures against mosquito bites,

are important safeguards for travelers to malarious areas. (See Insect Precautions.)

Drugs that are used for malaria prevention are listed below. The choice of drug depends on patient, itinerary, and economic factors; each drug has advantages and disadvantages.

There is always the risk of potential side effects no matter which medication is used to prevent malaria. However, any possible minor side effects of antimalarial medications must always be weighed against the risk of severe and potentially fatal infection with P. falciparum. Disabling side effects are uncommon with most antimalarial drugs. If intolerable side effects arise, if at all possible, contact the original prescribing health care provider for advice. Should medications need to be changed mid-course due to side effects (or any desire to take a different medication for the next portion of the trip), special considerations apply with respect to duration of therapy. Travelers should obtain instruction on how to do this from a knowledgeable physician.

Although the use of preventive drugs and insect precautions will decrease the chance of getting malaria, such measures do not guarantee protection.

Travelers may encounter fellow travelers who have been prescribed regimens different from their own, some highly effective but many others much less so. They may include drugs that are not available in the U.S. Travelers should adhere to their own drug regimen at all times.

Timing of Antimalarial Drugs Different drugs must be started at different times with respect to the beginning of travel. This has to do with

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the time it takes to build up effective blood levels as well as the need to assess for any serious side effects

prior to departure.

Malarious countries may not have malaria in all areas. In determining antimalarial regimens, it is important to note that the first day in a malarious area may not correspond to the first day in that country, as many itineraries may begin in a nonmalarious area. An individual who will be in a nonmalarious area of the country for several days or weeks before entering a malarious area does not need to start taking the drug until the appropriate time before the actual malaria exposure starts. The traveler will need to continue to take antimalarials for as long as malaria risk occurs, in some cases months or even years, and then continue taking the antimalarial drugs for a specified period of time after leaving the malaria risk area. See below for information on the drugs that may be prescribed. Some long-term travelers or expatriatesmay travel into malarious areas only periodically and may need to take antimalarials only periodically. A health care provider can determine the best strategy.

Antimalarial Drugs

Atovaquone-Proguanil (Malarone and Generics)

Atovaquone-proguanil (Malarone or a generic version of the drug) is available in a single tablet. The adult dose is a 250 mg/100 mg tablet, taken orally once a day. Start taking atovaquone-proguanil 1 day before arrival in a malaria risk area, take it daily while in the risk area, and continue taking it daily for 1 week after leaving the malarious area. Atovaquone-proguanil should be taken with a meal or milk at the same time each day.

A missed dose can be taken later the same day, but individuals should not double the next day's dose if a dose is missed completely. In the event of a missed dose occurring at a time when exposure to malaria is possible, atovaquone-proguanil must be continued for a minimum of 4 more weeks after resuming the medication and for a minimum of 1 week after the last day of exposure. In the event of a missed dose during the week after exposure, atovaquone-proguanil must be continued for a minimum of 4 weeks after the last day of exposure.

When atovaquone-proguanil is used for malaria prevention, side effects are uncommon. However, nausea, vomiting, stomach pain, and diarrhea may occur.

Chloroquine (Aralen and Generics)

Chloroquine (Aralen) is a safe and effective medication that may be used to prevent malaria in the very few areas where chloroquine resistance has not occurred. The adult dose of chloroquine is 500 mg taken orally once a week. Start taking chloroquine 1 week before arrival in a malaria risk area, take it weekly while in the risk area, and continue taking it weekly for 4 weeks after leaving the malarious area. A missed dose should be taken as soon as possible that same week (but not the day before the next regularly scheduled dose), resuming the schedule on the next normally scheduled day. Do not take a double dose if a dose is completely missed one week. Most people find Sunday the most convenient and easy day to remember for weekly medication. Serious side effects of chloroquine are uncommon. Minor side effects may occur, such as upset stomach, headache, dizziness, blurred vision, and itching (the latter most often in African Americans). Persons with epilepsy may be at risk for seizures.

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Doxycycline

The adult dose of doxycycline is a 100 mg tablet, taken orally once daily. Start taking doxycycline 1 day before arrival in a malaria risk area, take it daily while in the risk area, and continue taking it daily for 4 weeks after leaving the malarious area. Late doses can be made up on the same day, resuming the normal schedule the following day. Do not double the dose the next day if a dose is completely missed one day. Doxycycline should be taken while sitting or standing in an upright position, and it should be taken with food or a liberal amount of fluid. Do not lie down for 30 minutes after taking this drug. Do not take Pepto Bismol or antacids while taking doxycycline, as they can interfere with absorption of the drug.

Skin sensitivity to sunlight is an uncommon side effect but can lead to severe sunburn. Risk of this complication can be lowered by using a sunscreen that blocks both UVA and UVB rays, avoiding prolonged exposure to sunlight, and wearing protective clothing, including a hat. Women who take doxycycline may develop vaginal yeast infections and should carry an antifungal drug for self-treatment.

Mefloquine (Lariam and Generics)

The adult dose of mefloquine is 1 tablet containing 250 mg taken orally once a week. Start taking mefloquine 2-3 weeks before arrival in a malaria risk area, take it weekly while in the risk area, and continue taking it weekly for 4 weeks after leaving the malarious area. A missed dose should be taken as soon as possible that same week (but not the day before the next regularly scheduled dose), resuming the schedule on the next normally scheduled day. Do not double the dose the next week if a dose is completely missed one week.

Mefloquine usually is well tolerated but may cause side effects affecting the gastrointestinal tract, nerves, and emotional and mental processes.

Minor side effects include headache, stomach upset, dizziness, and bad dreams, which tend to be mild or temporary. Individuals who plan to drive, pilot a plane, or operate machinery should be aware that mild dizziness is a possible side effect.

The FDA has added a warning to the packaging label for mefloquine, stating that it can cause serious neurological and psychiatric side effects. These reactions can persist for months, years, or permanently, even after discontinuation of mefloquine.

About 5% of users develop disabling anxiety, dizziness, depression, insomnia, or irritability that is bad enough to make them stop taking the drug. However, it is important to remember that about 95% of mefloquine users tolerate the drug without discontinuing it, and for long-stay travelers to chloroquine-resistant areas, this weekly medication is the most convenient regimen.

Severe adverse events, such as symptoms of insanity, seizures, and brain dysfunction may occur in about 1 out of 6,000 to 10,000 users. Adverse reactions affecting the nerves, emotional and mental processes, and the inner ear which helps control balance, can persist for months, years, or permanently, even after discontinuation of mefloquine.

Individuals should not take mefloquine if they have an allergy to the drug; a history of convulsions or epilepsy; conduction abnormalities of the heart; or current or recent history of depression, anxiety disorder, insanity (psychosis), schizophrenia, or any other major psychiatric disorder. Stop taking the drug if the following symptoms occur while taking the drug for malaria prevention: acute anxiety, depression, restlessness, or confusion. In this case, an alternative medication should be obtained from a health care provider.

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Infants and Children All children (including young infants) who travel to malaria risk areas should be protected against

insects and should take drugs to prevent malaria. The dosage will depend on the child's age and/or

weight.

Young children should avoid travel to areas of chloroquine-resistant falciparum malaria unless they can take an effective drug such as mefloquine, doxycycline, or atovaquone-proguanil.

� Doxycycline should not be given to infants and children younger than 8 years in the U.S. or younger than 12 years in the U.K.

� If a physician prescribes chloroquine or mefloquine for a child, the pharmacist can crush the tablets (which have a bitter flavor) and place the powder in gelatin capsules with calculated pediatric doses. Children may tolerate antimalarial medications more readily if the crushed powder is mixed in food (for example, honey or chocolate sauce) or drink.

� Atovaquone-proguanil is available (in the U.S. and Canada) in a pediatric formulation that can be crushed and mixed with condensed milk for children who have difficulty swallowing tablets.

� Medications should be stored in child-proof containers out of children's reach.� The dosage will need to be adjusted according to the increasing weight of a growing child if he or she

is a long-term traveler or expatriate. A travel medicine provider can advise parents or guardians on adjusting the child's dosage before departing for long-term travel.

Travelers Taking Anticoagulants Travelers taking warfarin or other coumarin derivatives should start the antimalarial drug 2-3 weeks

before travel to a malaria risk area so that the health care provider can determine whether the warfarin

dosage needs to be adjusted. A baseline international normalized ratio (INR) should be checked prior to

starting the drug and rechecked 1 week after starting the drug to determine whether the warfarin dosage

needs to be adjusted. Once the preventive medication has been completed, the INR should be checked

again to restabilize anticoagulant therapy.

New oral anticoagulants such as dabigatran etexilate, rivaroxaban, and apixaban have a lower potential for drug interactions than do the coumarins, and no clinically significant interactions have occurred.

Travelers on extended trips should monitor their INR with periodic checks at the destination; however, the sensitivity of thromboplastin reagents used in different countries may vary. INR self-testing devices are readily available and can be used safely by experienced patients who may wish to stay in contact with their home anticoagulant clinic for dosage recommendations.

Self-Treatment of Presumptive Malaria In most cases, travelers will not need to carry self-treatment drugs when using the recommended

medication to prevent malaria. However, in rare situations in which a less effective medication must be

used and access to medical care within 24 hours of developing a fever while in a malarious area may

not be possible, it may be prudent to carry a drug for self-treatment. The treatment drug should not be

the same as the prevention drug.

The traveler should stop taking the antimalarial drug for prevention while taking the antimalarial drug for

treatment.

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� Resume the preventive medication immediately upon completion of self-treatment if atovaquone-proguanil will be used for ongoing prevention.

� Resume the preventive medication 1 week after initiating self-treatment if another antimalarial (except atovaquone-proguanil) will be used for ongoing prevention.

Atovaquone-proguanil or co-artemether (artemether-lumefantrine combination; called Coartem in the U.S. and Riamet in Europe) can be used for emergency self-treatment as long as the same drug was not used for prevention.

Adult self-treatment using Coartem consists of 6 doses (a total of 24 tablets) taken over 3 days. On the first day, 4 tablets are taken, followed by 4 more tablets 8 hours later. On the second and third days, 4 tablets are taken every 12 hours.

� Coartem needs to be taken with food. Do not take with grapefruit juice.� Coartem should not be used by persons with a heart condition called QTc prolongation, or those with

an allergy to either component of the drug (artemether or lumefantrine).� The most frequently reported side effects in adults include loss of appetite, muscle aches, and joint

pain. The most common side effects in children are fever, cough, vomiting, loss of appetite, and headache.

The adult self-treatment dose for atovaquone-proguanil consists of 4 tablets taken once daily for 3 days.

� Atovaquone-proguanil should be taken with food.� Atovaquone-proguanil should not be used by pregnant women or persons who are allergic to either

component of the drug.

The self-treatment drug should be taken promptly (according to a health care provider's instructions) if fever and illness occur

during travel and medical care is not available within 24 hours. Remember that self-treatment is only a temporary measure and medical attention should be sought as soon as possible.

An alternative to Coartem or atovaquone-proguanil for self-treatment is quinine plus doxycycline, but this drug has a much more complex schedule of doses and is frequently associated with adverse effects.

Mefloquine should not be used for self-treatment unless there is no other alternative.

Yellow Fever

Key Points

� Yellow fever (YF) is a viral infection that is acquired through the bite of an infected mosquito in tropical sub-Saharan Africa and forested areas of tropical South America.

� Risk is low to very low in travelers and depends on the time of year and itinerary. The risk is 10 times greater in Africa than it is in South America.

� Symptoms are of an influenza-like illness with fever, which may progress to black vomiting, upper abdominal pain, and bleeding.

� Consequences of infection in unimmunized travelers include jaundice, coma, shock, organ failure, and death in up to 90%of those infected.

� Prevention includes wearing long sleeves and long pants and observing personal protective

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measures against mosquito bites.� YF vaccine is a live virus given as a single dose at least 10 days prior to travel (for personal

protection or to meet an entry requirement). Some YF-free countries may require vaccination only for travelers coming from another country with risk of YF transmission.

� Vaccine side effects are most commonly local reactions. Serious side effects are rare but include brain inflammation in young children, neurological reactions, and multiple organ dysfunction (first time vaccinees only, especially those 60 years and older).

� Duration of vaccine protection is long term; a booster dose for personal protection is recommended every 10 years only for persons who will be visiting high-risk areas, travel frequently to risk areas, or may have had an inadequate response to a previous YF vaccination.

Introduction YF is a viral infection that causes fever, death of liver and kidney tissue, bleeding, shock, and results in

death in up to 90% of unimmunized travelers.

Risk Areas YF occurs in tropical sub-Saharan Africa and in the rainforests of tropical South America, where it is

endemic in monkeys. On both continents, YF can be transmitted in jungle and savannah areas.

Transmission in urban areas occurs periodically in Africa but almost never in South America.

Transmission Yellow fever virus (YFV) is transmitted to humans through the bite of mosquitoes that become infected

when they acquire the virus from infected monkeys or infected humans. These mosquitoes remain

infectious for life (2-4 months) and are aggressive biters. Infected humans then transmit the virus back

to mosquitoes that bite them.

YFV may be transmitted from mother to infant through breastfeeding. Theoretically, transmission may occur through blood transfusions or needle sticks.

Risk Factors

From 1970 through 2017, 14 cases of YF were reported in unvaccinated travelers from the U.S. and Europe who had traveled to West Africa (5 cases) or South America (9 cases); 9 of the 14 travelers died. More than 15 unvaccinated long-stay travelers from Africa and Asia developed YF after visiting Angola during a large urban outbreak in 2016.

Risk depends on the time of year, the traveler's itinerary and activities, mosquito density, presence of YFV, and vaccination status. The rate of disease for unimmunized travelers is 10 times greater in Africa than it is in South America.

Symptoms Symptoms are of an influenza-like illness with fever, which may progress to black vomiting, upper

abdominal pain, and bleeding. The disease is mild in the local population but almost always progresses

to complications in nonimmune travelers.

Consequences of Infection Consequences of infection in unimmunized travelers include jaundice, coma, shock, organ failure, and death in up

to 90% of those infected.

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Need for Medical Assistance Medical assistance should be sought if fever and symptoms of YF disease (described above) occur

during travel or after returning from an endemic country. Treatment is supportive and frequently

ineffective. Avoid the use of aspirin or nonsteroidal anti-inflammatory drugs, which may increase the risk

for bleeding.

Prevention

Nonvaccine: Unvaccinated travelers should avoid areas where an ongoing outbreak of YF in humans is occurring. Mosquito precautions in daytime and nighttime are recommended when in risk areas, regardless of vaccination status, because the risk of other mosquito-borne illnesses may exist. See Insect Precautions.

Vaccine: YF vaccination is given for 2 distinctly different purposes: to prevent the spread of the disease in a country and to protect the individual traveler from infection. Vaccination is 100% protective in healthy travelers, and, in principle, every traveler going to an area in which a risk of YF transmission exists should be vaccinated.

All travelers going to YF-risk areas of affected countries should be vaccinated. Travelers going to nonrisk areas of countries where risk of YF transmission exists only in other regions of that country but who do not have assuredly fixed travel plans and long-stay travelers going to any country, any part of which has risk of YF transmission should also be vaccinated.

Some countries require YF vaccination for all travelers. Some YF-free countries may require vaccination only for travelers coming from another country with risk of YF transmission to prevent the importation of YFV into that country. Travelers who do not know all their flight details at the time of their clinic visit should re-contact the clinic when flight details become available, in the event that transit stops trigger a YF vaccination requirement for their itineraries.

� For entry requirements, the vaccine must be given at least 10 days before entry into the country anddocumented in the International Certificate of Vaccination or Prophylaxis (ICVP).

� Travelers with an ICVP that is not yet valid (e.g., issued less than 10 days earlier) may be deniedentry and quarantined until the ICVP becomes valid or until a period of not more than 6 days havepassed since the last possible exposure to infection, whichever is shorter. Travelers may be not bevaccinated at the port of entry of entry against their will but may do so voluntarily in lieu ofquarantine.

� Any ICVP for YF vaccination, no matter when issued, is valid for life for the purposes of meeting acountry's entry requirement. However, uncertainty exists regarding recognition of this lifetime validityby all countries.

Persons with underlying medical conditions or those who have concerns about the vaccine should speak to their health care provider before vaccine administration.

Side Effects: The most common side effects with this live virus vaccine are injection-site reactions, such as fever, headache, and muscle aches. Most of these occur within the first 2 to 3 days after vaccination and last 5 to 10 days. Serious side effects are rare but can include severe allergic reaction, brain inflammation in children younger than 6 months, neurological reactions, and multiple organ dysfunction (which is life threatening but, to date, has occurred only in first-time vaccinees, especially those 60 years and older).

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booster can be assured of the general durability of immunity if they were previously immunized when healthy.

Medical Waivers

A medical waiver letter may be given if the only reason for vaccination is to meet an entry requirement and if travel to a risk area of the country is not planned. A medical waiver letter is valid only for the current trip. Acceptance of a waiver letter is at the discretion of the destination country, which may quarantine the traveler for up to 6 days or request that the traveler be placed under surveillance.

Timing: YF vaccine is given as a single injection and provides long-term immunity for most persons. A booster dose is recommended at intervals of 10 years (or less) only for persons who will be visiting high-risk areas or who may have had an inadequate response to a previous YF vaccination due to a health condition. Frequent travelers who might be at risk should consider a booster every 10 years.

Unvaccinated travelers who cannot receive the vaccine (e.g., due to an egg allergy or immunosuppression) should not travel to areas with significant ongoing transmission of YF. Previously vaccinated persons who cannot receive an indicated vaccine

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