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FansidarR taken once weekly in combination with chloroquine may be considered in exceptional circumstances involving prolonged exposure in areas with intense transmission of CRPF and where medical care is not available. If weekly use of Fansidar® is prescribed, the traveler should be cautioned about the possible side effects as described in the section on adverse reactions.

Proguanil (Paludrine®) is, like pyrimethamine, a dihydrofolate reductase (DHFR) inhibitor. Resistance of P. falciparum to DHFR inhibitors is present in some endemic regions, but its distribution is not well delineated. Proguanil is not available commercially in the United States. Limited data suggest that it may be effective in Kenya, but not in Thailand and Papua New Guinea. No current data are available on the efficacy of proguanil in other areas of CRPF, especially West Africa. Travelers using proguanil should take a daily 200-mg dose (adult) in combination with a weekly regimen of chloroquine.

Mefloquine (Lariam®), a new antimalarial similar in structure to quinine, is highly effective against both chloroquine- and Fansidar®-resistant P. falciparum infections. Approval for use in the United States is pending; currently the drug is available in France and Switzerland. Mefloquine may be considered for use by travelers to areas where there is risk of CRPF infection and by travelers to areas where P. falciparum is resistant to both chloroquine and FansidarR. Currently available information suggests the adult prophylactic dose is 250 mg weekly. Mefloquine prophylaxis should begin 1 week before entry into the malarious area and should continue weekly while the traveler is there. Adverse reactions are infrequent at prophylactic dosage but may become more common with the higher doses used in treatment. Minor side effects observed with prophylactic doses, such as gastrointestinal disturbance and dizziness, tend to be transient and self-limited. Because mefloquine has occasionally been associated with asymptomatic sinus bradycardia and a prolonged QT interval, it should not be used by those receiving beta-blockers, calcium channel antagonists, or other drugs that may prolong or alter cardiac conduction.

Primaquine: Prevention of Relapses of P. vivax and P. ovale

Unlike P. falciparum and P. malariae, P. vivax and P. ovale have forms that can persist in the liver and cause relapses for as long as 4 years after routine chemoprophylaxis is discontinued. Travelers to malarious areas should be alerted to this risk; if they develop malaria symptoms after they return home, they should report their travel history and the possibility of malaria to a physician as soon as possible. Primaquine prevents relapses by acting against the liver stages of P. vivax and P. ovale; however, its use is not indicated for all travelers. Primaquine is administered after the traveler leaves an endemic area and usually in conjunction with chloroquine during the last 2 weeks of the 4-week period of prophylaxis after exposure in an endemic area has ended.

Since most malarious areas of the world (except Haiti) have at least one species of relapsing malaria, travelers to these areas have some risk of acquiring either P. vivax or P. ovale. However, this risk is extremely difficult to quantify. Prophylaxis with primaquine is generally indicated for persons who have had prolonged exposure in malaria-endemic areas, e.g., missionaries and Peace Corps volunteers. While the actual risk to the traveler with less intense exposure is difficult to define, with the exception of individuals deficient in glucose-6-phosphate dehydrogenase (G6PD) (see Adverse Reactions, page 282), most individuals can tolerate the standard regimen of primaquine.

Malaria - Continued

Adverse Reactions and Contraindications to Antimalarials

The frequent or serious side effects of recommended antimalarials are discussed below. However, physicians should review the prescribing information in standard pharmaceutical reference texts and in the manufacturers' package inserts.

Chloroquine and hydroxychloroquine rarely have serious adverse reactions when taken at prophylactic doses for malaria. Occasionally, minor side effects such as gastrointestinal disturbance, headache, dizziness, blurred vision, and pruritus occur, but generally these do not require discontinuing the drug. While high doses of chloroquine, such as those used to treat rheumatoid arthritis, have been associated with retinopathy, this serious side effect has not been associated with routine weekly malaria prophylaxis. However, periodic ophthalmologic examinations for persons using chloroquine for extended periods (more than 6 years of cumulative weekly prophylaxis) are recommended. Chloroquine and related compounds may exacerbate psoriasis and may interfere with the antibody response to human diploid cell rabies vaccine.

Amodiaquine, a 4-aminoquinoline similar to chloroquine in structure and activity, has been used as an alternative prophylactic drug in areas where CRPF is endemic. It is not commercially available in the United States. Amodiaquine-associated agranulocytosis has been reported among travelers from the United Kingdom and Switzerland, countries where the drug has been commercially available. Therefore, amodiaquine is not recommended for malaria prophylaxis (1).

FansidarR can cause severe adverse cutaneous reactions. Between 1982 and 1985, 24 cases of erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis were documented among American travelers using Fansidar®. Seven of these reactions were fatal. Available data indicate that the incidence of fatal cutaneous reactions associated with the use of FansidarR among American travelers ranges from 1/11,000 to 1/25,000 users. These severe cutaneous reactions were associated with FansidarR when used as once-weekly prophylaxis. Fansidar® has also been associated with serum-sickness-type reactions, urticaria, exfoliative dermatitis, and hepatitis. IF ONCE-WEEKLY USE OF FANSIDAR IS PRESCRIBED, THE TRAVELER SHOULD BE ADVISED TO DISCONTINUE IT IMMEDIATELY IF HE/SHE DEVELOPS A POSSIBLE ILL EFFECT, ESPECIALLY ANY SKIN OR MUCOUS MEMBRANE SIGNS OR SYMPTOMS, SUCH AS ITCHING, REDNESS, RASH, MOUTH OR GENITAL LESIONS, OR SORE THROAT. Use of FansidarR is contraindicated for persons with histories of sulfonamide intolerance and for infants under 2 months of age.

Doxycycline is a tetracycline and may cause side effects associated with this group of drugs. Travelers to tropical climates who use doxycycline should be made aware of the possibility of photosensitivity, usually manifested as an exaggerated sunburn reaction. The risk of such a reaction can be minimized by avoiding prolonged, direct exposure to the sun. In addition, doxycycline use may be associated with an increased frequency of monilial vaginitis. Doxycycline is contraindicated in pregnancy (see Prophylaxis During Pregnancy, this page) and for children under 8 years of age. Primaquine may cause severe hemolysis in G6PD-deficient individuals. Before using primaquine, G6PD deficiency should be ruled out by appropriate laboratory testing.

Prophylaxis During Pregnancy

Malaria infection in pregnant women may be more severe than in nonpregnant women. In addition, the risk of adverse pregnancy outcomes, including prematurity,

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abortion, and stillbirth, may be increased. For these reasons, and because chloroquine has not been found to have any harmful effects on the fetus when used in the recommended doses for malaria prophylaxis, pregnancy is not a contraindication to malaria prophylaxis with chloroquine or hydroxychloroquine. However, because no chemoprophylactic regimen is completely effective in areas with CRPF, women who are pregnant or likely to become so should avoid travel to such areas.

The safety of FansidarR during pregnancy has not been completely established. Experimental data demonstrating the teratogenic effect of pyrimethamine in laboratory animals has resulted in restrictions in the licensing of compounds containing pyrimethamine. However, pyrimethamine, alone and in combination with sulfonamides, has been used for nearly 30 years to treat pregnant women with toxoplasmosis (another protozoal parasitic infection). While caution must be exercised when extrapolating from accumulated case reports of women treated for this infection, it is difficult to implicate pyrimethamine as a cause of fetal abnormalities. Thus, while the teratogenic effect in animals cannot be ignored, published data do not substantiate the inference that pyrimethamine is a human teratogen.

Sulfadoxine is a sulfonamide antimicrobial that, when administered during the last trimester of pregnancy, theoretically could compete with bilirubin for plasma proteins and exacerbate neonatal jaundice. It is unclear, however, whether this specific sulfa congener poses any risk to the newborn.

Doxycycline, a tetracycline, is generally contraindicated for malaria prophylaxis during pregnancy. Adverse effects of tetracyclines on the fetus include discoloration and severe dysplasia of the teeth and inhibition of bone growth. In pregnancy, therefore, tetracyclines would be indicated only if required to treat life-threatening infections due to multidrug-resistant P. falciparum.

Primaquine should not be used during pregnancy because the drug may be passed transplacentally to a G6PD-deficient fetus and cause life-threatening hemolytic anemia in utero. Whenever radical cure or terminal prophylaxis with primaquine is indicated, chloroquine should be given once a week until delivery, at which time the decision to give primaquine may be made.

Prophylaxis While Breastfeeding

Very small amounts of antimalarial drugs are secreted in the breast milk of lactating women. The amount of drug transferred is not thought to be harmful to the nursing infant; however, more information is needed. 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 (Table 1).

Chemoprophylaxis for Children

Children of any age can contract malaria. Consequently, the indications for prophylaxis are identical to those described for adults. Doxycycline is contraindicated for children less than 8 years of age, and Fansidar® is contraindicated for infants less than 2 months of age.

Chloroquine phosphate, which is manufactured in the United States in tablet form only, tastes quite bitter. Pediatric doses should be calculated carefully according to body weight. Pharmacists can pulverize tablets and prepare gelatin capsules with calculated pediatric doses. Mixing the powder in food or drink may facilitate the weekly administration of chloroquine to children. Alternatively, chloroquine in suspension is widely available overseas.

Malaria - Continued

OVERDOSE OF ANTIMALARIAL DRUGS CAN BE FATAL. THE MEDICATION SHOULD BE STORED IN CHILDPROOF CONTAINERS OUT OF THE REACH OF CHILDREN.

Health Information for International Travel 1988 will soon be published by the Center for Prevention Services, CDC. This document includes the above recommendations for the prevention and presumptive treatment of malaria in travelers. In addition, it includes the chemoprophylactic regimen recommended for each country and the risk of malaria in each country. It will be a useful reference to health professionals, travel agencies, international businesses, and other agencies that advise international travelers concerning malaria and other health risks they may encounter when visiting foreign countries. This publication will be available from the Superintendent of Documents, U.S. Government Printing Office, Washington, D.C. 20402, telephone (202)783-3238, as DHHS publication no. (CDC)88-8280.

Reported by: Malaria Br, Div of Parasitic Diseases, Center for Infectious Diseases; Div of Quarantine, Center for Prevention Svcs, CDC.

Reference

1. Centers for Disease Control. Agranulocytosis associated with the use of amodiaquine for malaria prophylaxis. MMWR 1986;35:165-6.

✩U.S. Government Printing Office: 1988-530-111/81500 Region IV

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In 1987, the Council of State and Territorial Epidemiologists (CSTE) recommended designating traumatic spinal cord injuries (SCIs) as the first injury condition reportable to state health agencies and to CDC. In that same year, two surveys were conducted to identify existing registries for SCls in the United States. One survey, which was conducted by the Spinal Cord Injury Program in Florida, used a computerbased information exchange system to gather information from vocational rehabilitation agencies. Agencies in 82% (42 of 51) of the states and the District of Columbia replied. The second, a telephone survey, was conducted independently by the National Spinal Cord Injury Association (NSCIA).* State health departments in all 50 states were contacted.

Each survey identified eight states as having SCI registries; however, the results of the surveys differed. These results and information obtained by personal communication indicate that the following 14 states have registries for traumatic SCI: Alabama, Arkansas, Colorado, Florida, Georgia, lowa, Louisiana, Maryland, Missouri, Oklahoma, New Jersey, North Dakota, Virginia, and West Virginia. In ten states, reporting is mandated by law; it is voluntary in the remaining four states. In most states, SCI data are collected to aid in planning for rehabilitative services.

Reported by: the Spinal Cord Injury Program, Div of Vocational Rehabilitation, Dept of Labor and Employment Security, Tallahassee, Florida. J Spack, JD, National Spinal Cord Injury Assoc, Woburn, Massachusetts. GR Istre, MD, State Epidemiologist, Oklahoma State Dept of Health. Div of Injury Epidemiology and Control, Center for Environmental Health and Injury Control, CDC. Editorial Note: CSTE's recommendation to designate SCIs as reportable was based on the magnitude of the morbidity and mortality due to traumatic SCIs, the cost associated with these injuries, and the potential for their prevention. It is a practical choice because the number of cases is manageable and consensus can be reached on the case definition.

Estimates of the incidence of acute traumatic SCI in the United States range between 28 and 50 injuries per million persons per year (1). At present, there are over 200,000 cases of SCI in the United States (2). Older adolescent and young adult males are at high risk for SCI. The consequences of injury for persons in these age groups include reduced lifetime employment, limited productivity, and decreased quality of life. Injured individuals may also need special services throughout life (1). The direct medical costs of these injuries to the federal government exceed $4 billion per *NSCIA is a private, nonprofit national health agency that serves as a resource and clearinghouse for information on SCls, including prevention and rehabilitation. *The District of Columbia was not contacted.

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES/PUBLIC HEALTH SERVICE

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