Outline # 13: Anne McCarthy
Chemoprophylaxis (e.g. malaria, traveler’s diarrhea, filariasis, leptospirosis )
Self treatment (e.g. diarrhea, malaria)
CHEMOPROPHYLAXIS
Indications
The travel itinerary should be reviewed in detail and compared with information on risk areas within a given country to determine whether the traveler will actually be at risk of acquiring malaria. Because Anopheles mosquitoes bite from dusk to dawn, antimalarial drugs are only recommended for travelers who will have exposure during those hours in malaria risk areas. Additional factors should be considered, including whether the traveler has previously experienced an allergic or other reaction to the antimalarial drug of choice and whether medical care will be readily accessible during travel.
Malaria chemoprophylaxis should begin 1 week before travel to malarious areas (except for doxycycline, primaquine, and atovaquone/proguanil, which should begin 1 day before travel). In addition to helping build up adequate blood levels of the drug, this regimen allows any potential side effects to be evaluated and treated by the traveler's health care provider and an alternative drug to be prescribed. As a rule, malaria chemoprophylaxis should be continued as long as exposure occurs, even for many years if necessary, and for 4 weeks after leaving the area of exposure (except for atovaquone/proguanil and primaquine, which must be continued for 1 week after leaving the area of risk).
Drug Resistance
Resistance of P. falciparum to chloroquine has been confirmed or is probable in all malarious areas except for the following: North Africa, most countries in the Middle East, the Newly Independent States (former USSR) in Asia, portions of China, Haiti and the Dominican Republic, Central America west of the Panama Canal, and temperate South America. Resistance to both chloroquine and Fansidar is widespread in Thailand, Myanmar (formerly called Burma), Cambodia, the Amazon basin area of South America, and many areas in sub-Saharan Africa. Mefloquine (Lariam) resistance has been confirmed along the eastern and western borders of Thailand. Resistance of P. vivax to chloroquine has been confirmed in Papua New Guinea, Indonesia, India, Colombia, and Brazil; however, this has little clinical significance since chloroquine is not recommended for these countries.
CHEMOPROPHYLACTIC REGIMENS FOR ADULTS
See dosage chart, "Drugs Used in Malaria Prophylaxis." Also see "Prophylaxis During Pregnancy" and "Prophylaxis While Breast-feeding."
General
Using chemoprophylaxis in addition to personal protection measures against mosquito bites is an equally important safeguard for persons traveling to malarious areas. Travelers should be reminded that no matter which medication is used to prevent malaria there is always the risk of side effects. However, the risk of side effects must be weighed against the risk of a potentially fatal infection with Plasmodium falciparum.
It is important to note that there is no consensus globally, even among physicians within one's own country, as to the optimal drug to prevent malaria. For example, in some countries, notably the United Kingdom, unwarranted and exaggerated media reports concerning mefloquine side effects have led to decreased use of the drug. However, in North America, mefloquine has remained an important drug for the prevention of malaria. Therefore, travelers should be instructed that when they are confronted with conflicting views concerning their chemoprophylactic agent, they should smile politely and ignore the advice of fellow travelers and overseas health care providers.
Antimalarials such as chloroquine, mefloquine, doxycycline, and azithromycin act in the blood after the liver phase of parasite development and therefore must be continued for 4 weeks after exposure to eradicate any parasites that may have been released from the liver. However, newer antimalarials such as primaquine and the atovaquone/proguanil combination prevent parasite development in the liver and therefore can be discontinued 1 week after exposure. The current drugs of choice to prevent chloroquine-resistant falciparum malaria include atovaquone/proguanil, mefloquine, primaquine, and doxycycline. Although limited data are available concerning atovaquone/proguanil, it appears to be as effective as the alternatives and has fewer side effects. However, for the longer-stay traveler (1 month or more) it is considerably more expensive. The choice of drug will be determined by its efficacy, the traveler's willingness to accept potential side effects, the convenience of the regimen (weekly vs. daily), the cost, and, of course, whether or not there are any contraindications to the drug.
Because product recommendations (particularly for scheduling, compatibility, adverse reactions, contraindications, and precautions) are subject to change, always check information provided on the package insert of the lot currently in use (check with manufacturer if product has been stored for a prolonged period).
A known or suspected allergy to an antimalarial is a contraindication to its use, and concomitant or chronic illness should be a consideration in the use of antimalarials as it would be in the use of any medication.
Chloroquine
Chloroquine is still effective in specific regions, as noted in "Drug Resistance" above. Chloroquine prophylaxis should be started 1 week before travel to malarious areas, continued weekly while there, and continued for 4 weeks after leaving the malarious area (see "Drugs Used in Malaria Prophylaxis" for dose). Limited data indicate that the combination of chloroquine with daily proguanil (Paludrine) is more effective than chloroquine alone in sub-Saharan Africa; however, this combination has considerably lower efficacy than the drugs recommended above for the prevention of chloroquine-resistant malaria. (Editor's note: proguanil is not available in the United States.) Adult travelers to Africa who use chloroquine for prophylaxis should also simultaneously take 200 mg of proguanil daily. Travelers who elect to use chloroquine or chloroquine/proguanil in chloroquine-resistant areas should be given a treatment dose of Malarone or, if that is not possible, Fansidar to be carried along. (See "Self-Treatment.")
Precautions and Contraindications
Chloroquine is contraindicated for persons with an allergy to chloroquine or related compounds.
Adverse Effects
Chloroquine rarely causes serious adverse reactions when taken at prophylactic doses for malaria. Minor side effects may occur, such as gastrointestinal disturbance, headache, dizziness, blurred vision, and pruritus (especially in African Americans), but generally these effects do not require discontinuation of the drug. The few people who experience uncomfortable side effects may tolerate the drug better by taking it with meals or in divided, twice-weekly doses. Also, chloroquine may exacerbate psoriasis.
High doses of chloroquine, as used in the treatment of rheumatoid arthritis, have been linked with retinopathy, but this side effect does not appear to be associated with routine weekly malaria prophylaxis. If long-term chloroquine therapy is being considered, refer to the package insert for recommendations regarding the need for periodic ophthalmologic examinations. See also "Compatibility."
Atovaquone/Proguanil (Malarone)
Malarone, a fixed combination of atovaquone (250 mg) and proguanil (100 mg) in 1 tablet (adult tablet), is licensed in North America for the treatment and prevention of chloroquine-resistant P. falciparum malaria. The drug has equal efficacy to mefloquine, doxycycline, and primaquine and appears to be very safe (but expensive for the long-stay traveler). Cost considerations aside, for many practitioners it has become the drug of choice both for the prevention of malaria among short-term travelers and for self-treatment of malaria. (See "Self-Treatment.") Atovaquone/proguanil is also effective along the borders of Thailand where chloroquine resistance and mefloquine resistance are well documented. (Doxycycline is an equally effective option.)
Atovaquone/proguanil should be started 1 day before travel to malarious areas, continued daily while there, and continued for only 1 week after departure from a malarious area. (See "Drugs Used in Malaria Prophylaxis.") In the United States, a pediatric formulation contains one-fourth of the adult dose.
Precautions and Contraindications
Atovaquone/proguanil is contraindicated for pregnant women and for persons with allergy to the drugs in the combination.
Adverse effects
Since side effects from the atovaquone/proguanil drug were no different from the placebo in several prophylaxis studies, it appears to be very safe. However, when the drug is used for treatment, symptoms such as nausea, vomiting, diarrhea, and abdominal pain occur occasionally; seizures and rash are rare.
Doxycycline
Travelers to risk areas where chloroquine-resistant or mefloquine-resistant malaria is endemic may use doxycycline or atovaquone/proguanil. Doxycycline and atovaquone/proguanil are equally effective prophylactic drugs for travelers visiting the Thai/Myanmar and Thai/Cambodian borders. Doxycycline prophylaxis should begin on the day before entering a malarious area, be continued daily while there, and continue for 4 weeks after departure. If doxycycline is used, there is no need to take other preventive drugs.
Precautions and Contraindications
This drug is contraindicated for:
· persons with an allergy to doxycycline or tetracycline
· women during their entire pregnancy
· children less than 8 years old
Adverse Effects
Doxycycline may cause photosensitivity, usually manifested as an exaggerated sunburn reaction. Risk of such reaction can be minimized by avoiding prolonged, direct exposure to the sun, using sunscreens that absorb long-wave ultraviolet (UVA) radiation, and wearing a hat. Doxycycline use is associated with an increased frequency of candida vaginitis. This complication should be discussed with female patients before prescribing the drug; an antifungal agent should be carried for self-treatment. Gastrointestinal side effects (nausea or vomiting) may be minimized by taking the drug with a meal, in an upright position, and with a liberal amount of fluids. See also "Compatibility."
Mefloquine
For travel to areas of risk where chloroquine-resistant malaria exists, use of mefloquine alone is recommended. Mefloquine is usually well tolerated and can be used for long-term prophylaxis. (See "Adverse Effects," below.) Mefloquine prophylaxis should be started 1-2 weeks before travel to malarious areas, be continued weekly while remaining in those areas, and continue for 4 weeks after departure (see "Drugs Used in Malaria Prophylaxis" for dose).
Note: In some foreign countries a fixed combination of mefloquine and Fansidar is marketed under the name Fansimef. Fansimef should not be confused with mefloquine and, because of serious adverse reactions associated with its prophylactic use, it is not recommended for malaria prophylaxis.
Recent studies suggest that adverse events of mefloquine can be predicted by using a loading dose (off-label use) of 1 tablet daily for 3 days and then weekly thereafter. The adverse events of mefloquine will occur within the first week of a loading dose compared with the third to seventh weeks when weekly dosing is initiated. If adverse events occur, the drug can be stopped and an alternative can be initiated prior to departure. Adverse events associated with a loading dose are similar to those with the weekly regimen. Alternatively, weekly dosing of mefloquine can be started 3 weeks prior to departure, and if adverse events occur, an alternative can be initiated prior to departure.
Precautions and Contraindications
Mefloquine generally is not recommended for self-treatment because of the increased frequency of side effects (hallucinations, psychosis, convulsions) that have been associated with high dosages used for treatment. These occur in the order of 1:100 to 1:1500 users, 10-fold higher than when the drug is used for prophylaxis. Mefloquine is not recommended for persons with:
· an allergy to mefloquine or related compounds
· a history of epilepsy
· active depression or recent history of depression, generalized anxiety disorder, psychosis, schizophrenia, or other major psychiatric disorder
Mefloquine should be used with caution in patients with previous history of depression. If psychiatric symptoms occur during prophylactic use, they may be prodromal to a more serious event and the drug should be discontinued and an alternative medication substituted.
Mefloquine may be given to individuals concurrently using calcium channel or beta-blockers or to those with a rhythm disturbance if they do not have a cardiac conduction defect. Per the manufacturer's insert, risks and benefits of administering mefloquine should be weighed against the possibility of adverse effects when used concurrently with quinine, quinidine, or other drugs that alter cardiac conduction. Persons planning to drive, pilot aircraft, or operate machines while using mefloquine should be informed that mild dizziness is among the possible short-term side effects. Persons on mefloquine prophylaxis should not use halofantrine (Halfan), an antimalarial drug licensed in the United States but not commercially available there, although it is available in many other countries for the treatment of malaria. (See "Self-Treatment.")
Adverse Effects
The side effects of mefloquine have been greatly exaggerated in the media. Nine prospective, randomized, placebo-controlled trials show that the risk of disabling neuropsychological problems (such as insomnia, nightmares, irritability, and depression) occurs in the order of 1:200 to 1:500 users. On the other hand, severe side effects such as seizures and psychosis occur rarely, in the order of 1:10,000 to 1:13,000 users. Approximately 97% of mefloquine users are able to tolerate the drug without discontinuing it.
Minor side effects (such as gastrointestinal disturbance and dizziness) observed with prophylactic doses tend to be mild and temporary. There have been occasional reports of more severe neuropsychiatric disorders such as tremor, ataxia, mood changes, or panic attack, and infrequent reports of chest pain, edema, and dyspnea. Rare cases of suicide have been reported although no relationship to the administration of mefloquine has been confirmed.
Per the manufacturer, unexplained acute anxiety, depression, restlessness, or confusion may be prodromal to a more serious event and therefore the drug should be discontinued and an alternative medication substituted. See also "Compatibility."
Azithromycin (Zithromax)
Azithromycin, a macrolide antibiotic, has shown some efficacy in the prevention of chloroquine-resistant falciparum malaria (an off-label use); however, the drug is a suboptimal antimalarial because it is less effective than other antimalarials (mefloquine, atovaquone/proguanil, doxycycline, primaquine) used for the prevention of chloroquine-resistant falciparum malaria and is very, very expensive. Azithromycin has been shown to be safe in pregnant women and young children, the precise populations for whom a suboptimal drug should not be used. However, it might be considered for a pregnant woman who must travel in a chloroquine-resistant area but who cannot take mefloquine
Azithromycin should be started 1 week prior to entry to malarious areas, continued daily during exposure, and continued for 4 weeks after departure.
Precautions and Contraindications
Azithromycin is contraindicated for those with an allergy to the drug.
Adverse Effects
Gastrointestinal side effects (nausea, vomiting, abdominal pain, diarrhea) are infrequent. Liver dysfunction and hematological abnormalities (leukopenia, pancytopenia) are rare.
Primaquine
Primaquine is used in 2 different ways to prevent malaria.
Precautions and Contraindications
Primaquine is a potent oxidizing agent and therefore should not be given to those with a G6PD (Glucose-6-phosphate dehydrogenase) deficiency. G6PD deficiency is most frequently found among African Americans, Mediterraneans, South Asians, and Orientals. Before primaquine is recommended, a G6PD level is mandatory to ensure that the enzyme level is normal. In persons with a genetic deficiency of methemoglobin reductase, methemoglobinemia may occur at 30 mg/day and more rarely at 15 mg/day of primaquine.
Primaquine is contraindicated in those with low levels of G6PD and in pregnant women.
Primaquine should be administered with food to reduce gastrointestinal upset.
Adverse Effects
Nausea, vomiting, and abdominal pain are frequent unless the drug is given with food. In those with G6PD deficiency, hemolytic anemia may occur. In those with a genetic deficiency of methemoglobin reductase, methemoglobinemia may occur at 30 mg/day and more rarely at 15 mg/day of primaquine.
Prophylaxis During Pregnancy
Malaria infection in pregnant women may be more severe than in nonpregnant women, and it may increase the risk of adverse pregnancy outcomes, including prematurity, miscarriage, and stillbirth. Pregnant women planning to travel to a malaria risk area may need to consult with a travel medicine expert, should maximize personal protection measures to avoid mosquito bites (see "Insect Precautions"), and should take appropriate prescription drugs to prevent malaria. Neither mefloquine nor chloroquine has been found to have any harmful effects on the fetus when used in the recommended doses for malaria prophylaxis. Mefloquine can be used during all trimesters of pregnancy and is the drug of choice for women traveling to areas with chloroquine-resistant P. falciparum. In chloroquine-sensitive areas, pregnant women should take chloroquine for malaria prevention.
Doxycycline is contraindicated for malaria prophylaxis during pregnancy. Adverse effects of tetracyclines on the fetus include discoloration and dysplasia of the teeth and inhibition of bone growth. Tetracyclines would be indicated in pregnancy only if required to treat life-threatening infections due to multi-drug-resistant P. falciparum.
Primaquine (see "Prevention of Relapses of P. vivax and P. ovale") should not be used during pregnancy because the drug may be passed transplacentally to a G6PD-deficient fetus and cause hemolytic anemia in utero. Whenever radical cure or terminal prophylaxis with primaquine is indicated during pregnancy, chloroquine should be given once a week until delivery, at which time primaquine may be given.
Atovaquone/proguanil is contraindicated during pregnancy.
Proguanil (not available in the United States) has been used widely for several decades, and no adverse effects on pregnancy or fetus have been established. However, the combination of chloroquine/proguanil has lower efficacy than other drugs of choice. Similarly, azithromycin is safe during pregnancy but also has lower efficacy than drugs of choice indicated above.
Prophylaxis While Breast-feeding
Very small amounts of antimalarial drugs are secreted in breast milk, but the amount of drug transferred is not thought to be harmful to the nursing infant. Because the quantity of antimalarials transferred in breast milk is insufficient to provide adequate protection against malaria, infants who require chemoprophylaxis should receive the recommended dosages of antimalarials (see "Antimalarial Chemoprophylaxis for Children").
CHEMOPROPHYLAXIS FOR CHILDREN
All children traveling to malaria risk areas, including young infants, should use personal protection methods to avoid mosquito bites (see "Insect Precautions") and should take antimalarial drugs. The indications for most preventive drugs are the same as for adults; however, it is essential that the correct dosage be used, based on the child's age and/or weight. (See "Pediatric Dose" in "Drugs Used in Malaria Prophylaxis" for prophylaxis.) Do not give doxycycline to children younger than 8 years of age. Young children should avoid travel to areas with chloroquine-resistant P. falciparum unless they can take a drug that is highly effective, such as mefloquine, atovaquone/proguanil, primaquine, or doxycycline.
Pediatric doses should be calculated carefully according to body weight. Pharmacists can pulverize tablets and prepare gelatin capsules with calculated pediatric doses. Chloroquine and mefloquine may be mixed in juice, jelly, ice cream, or chocolate sauce to hide the extremely bitter taste. Alternatively, chloroquine is widely available overseas as suspensions that generally contain 10 mg of chloroquine base in each mL; the dosage is usually indicated on the bottle or package. Parents should calculate the dose and volume to be administered based on body weight, because the concentration of chloroquine base varies in different suspensions.
For treatment with atovaquone/proguanil or Fansidar, see "Self-Treatment" and the "Pediatric Dose" column on the self-treatment chart ("Prescription Drugs for Self-Treatment of Malaria").
Overdose of antimalarial drugs can be fatal. Medication should be stored in childproof containers out of children's reach.
CHEMOPROPHYLAXIS FOR DIARRHEA – see also outline on traveller’s diarrhea
ANTIBIOTICS
Some travelers wish to be given prophylactic antibiotics that would eliminate much of their risk of acquiring TD. Although several antibiotics have been tested as prophylaxis, their use is not routinely recommended for travelers, mostly due to the risk of complications from the antibiotic, which might be severe or would at least panic many patients worried about acquisition of exotic diseases while traveling and not having easy access to medical care for reassurance. Antibiotics have no effect on the acquisition of various viral and parasitic diseases, and the use of these drugs for prophylaxis may give travelers a false sense of security about the risk associated with consuming certain local foods and beverages.
The most effective antibiotics for prophylaxis are the flouroquinolones (ciprofloxacin, norfloxacin, ofloxacin, and levofloxacin). Older antibiotics (doxycycline, TMP/SMX) are no longer effective. Thus, although potentially beneficial, antibiotic prophylaxis is not routinely recommended except for individuals who have a particularly high risk of acquiring diarrhea, who face serious consequences if they do (underlying illnesses), or who have a short-term work assignment that would make diarrhea a disaster. If special circumstances warrant antibiotic use for TD prevention, such prophylaxis should generally be restricted to periods of less than a week. Individuals who inquire about prophylactic antibiotics for TD can be taught how to self-diagnose and treat TD. Treating TD early with the appropriate antibiotic can limit the illness to a single day, and informing patients of this fact usually satisfies their pre-conceived desire to go on prophylactic medications.
If a social situation arises in which food may have to be accepted that may not be safe to eat, the traveler may consider selective use of a single dose of prophylactic or pre-emptive antibiotic (after the offending incident), but only when the risks and benefits are clearly understood by the traveler.
NON-ANTIBIOTIC METHODS
For TD prevention, bismuth subsalicylate can be taken as an ingredient of Pepto-Bismol in liquid form (2 oz., 4 times per day) or as tablets (2 tablets, 4 times per day). Its use has decreased the incidence of TD by about 60% in several studies, but it is not recommended for more than 3 weeks when used for prophylaxis. Side effects are minimal, although travelers may be alarmed by temporary black stools or a black tongue. Nausea and constipation may occur occasionally, and, rarely, there is tinnitus. Bismuth subsalicylate should not be used by individuals with an allergy to aspirin; by those with renal insufficiency or gout; or by persons taking anticoagulants, probenecid, or methotrexate. Because bismuth subsalicylate can prevent absorption of doxycycline, the two should not be taken concurrently. Bismuth subsalicylate is not approved for use in children under 3 years old. Taking live lactobacillus strains has been shown in some controlled studies to produce a mild decrease in the rate of TD. These strains appear to have little in the way of side effects.
CHEMOPROPHYLAXIS FOR FILARIA – see also filarial outline.
In the endemic areas, filarial infections are controlled by the use of insecticides or mass chemotherapy. For long-term visitors to endemic areas working in at-risk situations, chemoprophylaxis with diethylcarbamazine 300 mg weekly has been shown to prevent loiasis but is not suitable for short-term travelers. Therefore the best prevention is to avoid travel to at-risk places during seasons of transmission; if that is not possible, stay there as short a time as possible and avoid being bitten by the vectors especially during peak biting times, if possible. Use of long sleeves, trousers, and insect repellents, if practicable and tolerable, will reduce bites by Simulium and Chrysops to some extent, and sleeping under permethrin-impregnated bednets in filariasis areas will reduce bites by mosquitoes.
CHEMOPROPHYLAXIS FOR LEPTOSPIROSIS.
The main prevention strategy against leptospirosis is to avoid exposure to potentially contaminated water, soil, and mud, as well as animal tissues or urine. Bodies of water that represent the highest risk are those around which there are extensive populations of such animals as rodents, opossums, raccoons, skunks and foxes, which are known to be frequently infected. Although a vaccine exists for animal use that can be useful in reducing transmission to other animals and humans, especially in epidemic situations, limited experience with vaccination of humans suggests that the limited number of serovars in the vaccine elicits only a partially protective response.
Additionally, chemoprophylaxis with doxycycline, 200 mg PO weekly, can drastically reduce the risk of acquiring leptospirosis in individuals at high risk due to unavoidable contact with contaminated water or soil. Although the trials supporting the efficacy of this regimen were done among military personnel destined to training exercises in the Central American jungle, it is currently recommended for outdoor adventure travelers who plan to engage in high-risk activities such as prolonged hiking, biking, or water sports in endemic areas, as well as for persons in areas of recent flooding. An alternative regimen of doxycycline, 100 mg PO daily for 7 days, is recommended only for individuals with documented high-risk exposures.
CHEMOPROPHYLAXIS FOR SCHISTOSOMIASIS (prevention also)
Local control measures include decreasing snail vectors, preventing contamination of local water sources by human excreta (urine and feces), and providing safe freshwater supplies. A vaccine to protect against schistosomiasis does not exist and is not expected in the near future.
Travelers should be warned that one should never assume freshwater to be free of schistosomes in an endemic area; in fact, even deep lake water far offshore cannot reliably be regarded as safe. If water exposure cannot be avoided then travelers can utilize methods to prevent cercariae from reaching the skin by wearing protective footwear or clothing and by the application of N,N-diethyl-m-toluamide (DEET)-containing insect repellent. Cercariae die quickly on removal from water and cannot survive drying; therefore, quick drying of exposed skin and clothing provides some protection. Rubber boots and wetsuits are protective. Chlorinated water, such as a properly maintained swimming pool, or water stored in a snail-free container for 48 hours is safe.
Prevention is the key defense against illness with schistosomiasis. Some rafting companies with trips along infested rivers advocate preemptive treatment with praziquantel (Biltricide). There is no data to support the immediate use of praziquantel since it is not effective against immature worms. However, it can be used 2 or more months after infection as a single dose. In general, self-treatment following possible exposure is not advocated.
Cercarial dermatitis requires no treatment, but if symptoms are severe they can usually be controlled with antihistamines. Immediate medical assistance should be sought in the event of a febrile/flu-like illness with malaise or urticaria. Any acute neurological event such as limb weakness or paralysis requires immediate medical evaluation. Hematuria or bloody diarrhea should also alert the traveler to seek medical assistance.
A medical evaluation may be prudent upon return from high-risk travel and should include urine and stool exams for schistosome eggs; however, eggs may not appear in the urine (S. haematobium) or feces (S. mansoni, S. japonicum, S. mekongi, S. intercalatum) for up to 3 months after exposure. A reliable ELISA test is available for schistosomiasis.
DIARRHEA SELF-DIAGNOSIS AND SELF-TREATMENT
Because the majority of all enteric bacterial pathogens are currently sensitive to quinolones (with the exception of some Campylobacter species), it is not necessary to make a specific bacterial diagnosis in a traveler. Therefore, it is sufficient to subclassify treatable TD into two major categories: bacterial and protozoal. And because the majority of cases are due to bacteria, the empiric diagnosis of TD is heavily slanted toward bacterial etiologies.
Oral Rehydration
Traveler’s diarrhea in adults is not typically associated with clinically significant dehydration, but replacement of fluids that are lost remains a cornerstone of self-treatment. At the same time, any diarrhea that is severe enough to pose a risk of dehydration should be considered for antibiotic treatment (see below). Dehydration can be corrected with any fluid, and a patient should drink any available appropriate fluid while oral rehydration fluid is sought. In cases of TD where vomiting is also prominent, oral rehydration solutions (ORS) were designed to be rapidly absorbed from the intestine. If ORS is thought to be indicated, many stores and pharmacies in developing countries carry ORS packets. Travelers to remote areas should carry their own ORS packets. The packet is added to boiled or treated water; package instructions should be checked carefully to be sure the correct amount of water is used.
Standard WHO ORS tastes salty and is often unpalatable to travelers. (In the United States, WHO ORS packets are available from the major travel medicine supply houses.) Flavored rice-based ORS (Ceralyte) is also available in the U.S. and may be more palatable. Solution held at room temperature should be consumed or thrown away within 12 hours; if it has been kept refrigerated, it must be discarded after 24 hours. If commercial ORS is not readily available, the traveler can make his own replacement solution by drinking alternating glasses of fluid. Glass #1: drink 8 oz. fruit juice plus ½ tsp corn syrup or honey or sugar plus a pinch of salt. Glass #2: drink 8 oz. boiled water plus ¼ tsp baking soda.
Dietary Management of TD
The dietary advice routinely given to sufferers of TD (i.e., advice to fast in the first 24 hours or to eat only bananas, boiled rice, dry toast, chicken soup, etc.) has virtually no scientific basis. What's known from studies of oral rehydration solutions suggests that balanced salt and carbohydrate solutions may be easier to absorb during diarrhea and may even diminish fluid loss into the intestines.
The following guidelines appear to be reasonable: If the person with diarrhea is not hungry, push fluids but don't encourage eating. If hungry, the person can be allowed to eat, avoiding known intestinal irritants such as alcohol, coffee, strong tea, spicy food, and greasy food. Dairy products should be avoided.
Drug Treatment
Travelers are often in areas where prompt, effective medical care is unavailable due to remoteness, the difficulty of finding a doctor, or lack of confidence in the abilities of local practitioners and lab personnel. Therefore, it is often more practical to utilize empiric self-treatment with antibiotics purchased prior to leaving for the trip. The usual effect of antibiotics is to turn a 3- or 4-day illness into a 1-day illness, especially in areas that have a proven high incidence of bacterial pathogens.
For empiric treatment of suspected bacterial diarrhea, the traveler can use any of the quinolone antibiotics shown in the table below. Single-dose therapy is likely adequate for very susceptible pathogens such as enterotoxigenic E. coli, but since the traveler cannot know what he/she is infected with, most clinicians recommend 3 days of therapy to cover for more invasive bacteria.
Azithromycin has been shown to be very effective in TD and should be considered as an alternative to the quinolones. Because of the increasing incidence of quinolone-resistant campylobacter in many countries, azithromycin should be started in all patients who have no response at all to a quinolone in 36-48 hours. In Thailand and any other country with known high rates of quinolone resistance, azithromycin should be the first line therapy. Azithromycin is also the drug of choice for children and pregnant women. (See "Children and Travel: Diarrhea and Dehydration" and "Pregnant Travelers: Food and Water Precautions.")
Bowel immobilizers such as loperamide are often utilized to manage the symptoms of TD. Although there is still some controversy, studies have demonstrated the safety of bowel immobilizers even in travelers with fever or blood in the stool, if they are used along with an appropriate antibiotic. Loperamide appears to be safer than diphenoxylate in this regard. Bowel immobilizers sometimes induce prolonged constipation even at low doses, and they can lead to a bloated, uncomfortable feeling if taken for moderately severe infections without taking an antibiotic as well. Their use should be discontinued if symptoms last more than 48 hours.
It may be reasonable to suggest the use of antibiotics and other drugs as follows:
Mild loose stools without constitutional symptoms:
Moderately loose or frequent stools with cramps or nausea:
Severe diarrhea with intense cramps, nausea, bloody stools, dehydration, or fever and chills:
Protozoal infections such as giardiasis and Entamoeba histolytica more often cause diarrhea and prolonged problems of intestinal motility in the returned or long-term traveler. Giardia lamblia is the most common protozoal infection of travelers. It can be suspected, empirically, when the traveler has the gradual onset of loose stools, increased intestinal gas and bloating, upper abdominal discomfort, and gradually increasing fatigue. Vomiting is very rare and fever almost never occurs in G. lamblia infections. The standard therapy at present is metronidazole. Metronidazole has predictable side effects of nausea and malaise, and a metallic taste in the mouth. In many countries around the world, the closely related drug, tinidazole, is preferred. In general, patients should not carry these drugs for self-treatment. A proper diagnosis should be made and the drugs administered under supervision. Travelers going to extremely remote locations can be given these drugs to carry on a case-by-case basis.
General
Given the high degree of efficacy of current antimalarials, the need for travelers to carry medication for self-treatment is limited to those who will travel in remote areas where they will not have access to medical care for 48 hours or more, especially those who are using suboptimal antimalarials in drug-resistant areas (e.g., use of chloroquine/proguanil, or azithromycin in chloroquine-resistant areas). Travelers who elect to carry self-treatment should be given a treatment dose(s) of the medication that is to be carried along; the medication should be taken promptly if they have a febrile illness during travel and medical care is not readily available within 24 hours. Travelers should be aware that self-treatment of a possible malarial infection is only a temporary measure, that prompt medical evaluation is imperative, and that malaria can be fatal if treatment is delayed. The drug used for self-treatment should not be the same as the one being used to prevent malaria. After self-treatment, travelers should continue their preventive medication. Travelers to underdeveloped countries where antimalarial drugs may not be available at all should also consider carrying a treatment dose of antimalarials to deal with physician-diagnosed chemoprophylaxis breakthroughs.
Atovaquone/proguanil (Malarone)
Atovaquone/proguanil is licensed in the United States for treatment and prevention of malaria. The atovaquone/proguanil combination is the drug of choice for self-treatment of malaria. Treatment doses are associated with nausea, vomiting, abdominal pain, diarrhea, increased transaminases, and, rarely, rash and/or seizures. See "Prescription Drugs for Self-Treatment of Malaria." The drug is contraindicated during pregnancy.
Pyrimethamine-sulfadoxine (Fansidar)
Fansidar resistance is well documented in Southeast Asia, the Amazon basin of Brazil, and parts of East Africa, and therefore Fansidar should be avoided in these areas. The drug appears to be safe during pregnancy. Fansidar is contraindicated for:
In rare instances, use of Fansidar has been associated with severe reactions, including Stevens-Johnson Syndrome and toxic epidermal necrolysis. See "Prescription Drugs for Self-Treatment of Malaria."
Quinine plus doxycycline
The combination of quinine and doxycycline is a standard therapy for the treatment of P. falciparum malaria. As a self-treatment regimen it is very effective but somewhat complicated, involving multiple doses over at least 1 week, and frequently is associated with adverse events. This combination should be reserved for individuals who are likely to be compliant with this complicated regimen. Side effects from quinine are frequent and include tinnitus, dizziness, hearing loss, nausea, headache, and blurred vision. Cardiac conduction disturbances occur occasionally. Gastrointestinal upset is a frequent complication of doxycycline (see "Doxycycline" for preventive therapy).
Mefloquine
Mefloquine should be avoided for self-treatment because of the frequency of side effects (hallucinations, psychosis, convulsions) that have been associated with high dosages used for treatment. These severe symptoms occur in 1:100 to 1:1500 of those who are treated with the drug. Mefloquine may increase the risk of fetal loss when used for treatment during pregnancy, especially during the first trimester.