Diabetes

Diabetes and a little about Anti-Infectives

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PREVENTION OF MALARIA: CHEMOPROPHYLAXIS

A number of medications have been shown to have efficacy in preventing malaria infection. As with all treatments, the use of an antimalarial regimen should weigh the potential adverse effects against the risk of acquiring malaria. The clinician must review the travel itinerary to assess the risk of malaria exposure and recognize areas of travel within drug-resistant zones. Contraindications to the use of specific antimalarials for that patient should be identified.

Drug Resistance

Chloroquine-resistant P. falciparum exists throughout the entire malaria endemic world except for Mexico, Central America west of Panama, Argentina, the Caribbean, parts of China, and parts of the Middle East. P. falciparum in any other part of the world must be assumed to be chloroquine-resistant. P. falciparum that is resistant to both mefloquine and chloroquine can be found in Southeast Asia along the Thailand-Myanmar (formerly Burma) and the Thailand-Cambodia borders. Chloroquine-resistant P. vivax is also becoming an important problem, particularly in Papua New Guinea, Irian Jaya, Vanuatu, Myanmar, and Guyana.

Chloroquine

Because of the emergence of drug-resistant P. falciparum strains, chloroquine (Aralen, Sanofi-Synthelabo) is no longer the recommended chemoprophylaxis medication for most parts of the world. Chloroquine is still recommended for prophylaxis for travel to Central America west of the Panama Canal, Hispaniola (Haiti and the Dominican Republic), Argentina, parts of China, and parts of the Middle East (primarily Syria, Jordan, and Iraq). The antimalarial dosage for a traveler to these areas is one 500 mg tablet (300 mg base) per week beginning 2 weeks before departure, one tablet weekly during exposure, and one tablet per week for 4 weeks after the trip. The most common side effect is dyspepsia, but it can also cause pruritus (especially in dark-skinned individuals), exacerbations of psoriasis, agranulocytosis, photosensitivity, and, rarely, neuropsychiatric disturbances such as vertigo or insomnia. The drug is a safe option during pregnancy. Concurrent use of chloroquine interferes with antibody response to the intradermal administration of the human rabies vaccine.

Mefloquine

Mefloquine (Lariam, Hoffman-LaRoche) is the drug of choice for most travelers to chloroquine-resistant regions. The traveler takes a 250 mg tablet once a week for 2 weeks before departure, then takes a dose weekly during travel, followed by one dose per week for 4 weeks after returning home. In the past decade, many anecdotal reports of neuropsychological adverse effects have raised major concerns about this drug. However, adverse effects are similar in frequency and severity to those reported with weekly chloroquine use. The most commonly reported side effects include nausea, dizziness, headaches, and vivid dreams. Mefloquine should be used with caution in patients with a history of psychosis, seizure disorder, or cardiac conduction defects. It is the most efficacious and safe option for the prevention of malaria in pregnant women traveling to areas with chloroquine-resistant P. falciparum.
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ANTI-INFECTIVES

MALARIA PREVENTION: PROTECTION AGAINST MOSQUITOES

The most effective protection against malaria is to avoid exposure to the Anopheles mosquito that carries the disease. All travelers to malaria-endemic areas need to be instructed on how best to avoid bites from these mosquitoes. A significant reduction in the risk of acquiring the disease can be achieved by simply limiting evening exposure to mosquitoes.

Travelers in endemic areas can substantially reduce the probability of infection with certain behavioral adaptations. Wearing clothes that minimize the amount of exposed skin is helpful. The use of insect repellent on exposed skin should also be encouraged. Repellents containing N, N-diethyl-3-methylbenzamide (DEET) in concentrations of approximately 30% are effective and safe. DEET has been used safely by millions of people worldwide and is clearly superior to all alternative insect repellants. It is generally well tolerated but has been noted to cause urticaria, irritation of the eyes, or headaches on rare occasion. When in small, enclosed spaces such as a typical hotel room or tent, spraying with an ordinary household insecticide can “knock down” mosquitoes already in the room. Finally, since mosquitoes are not strong fliers, utilizing a fan can keep them out of the air.

Persons who will not be staying in rooms that are well screened or air-conditioned should consider sleeping under a mosquito bed net. The use of bed nets has been reported to reduce the mosquito attack rate by 97 %. Bed nets and sleeping bags impregnated with an insecticide such as permethrin are preferred, since they are effective barriers to vectors even when wholes or tears are present.

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OVERALL APPROACH TO MALARIA PREVENTION

The risk of malaria can be reduced by regular use of measures that limit contact with mosquitoes and by strict adherence to chemoprophylaxis. To help travelers adhere to these recommendations, thorough pre-travel advice must be provided by their health care providers. Even a brief exposure in an endemic area puts the unprotected traveler at risk. All travelers to endemic areas need to be aware of the threat of malaria in their destination and understand how to prevent it. Since no preventive regimen is completely effective, travelers should also know to seek medical attention urgently should they become febrile during or after their trip.

In summary, the overall approach to malaria prevention should consist of the following four principles:

-    Assess the risk of malaria infection on the basis of itinerary.
-    Discuss the available methods to reduce contact with Anopheles mosquitoes.
-    Identify the most appropriate antimalarials for chemoprophylaxis.

-    Alert the traveler to seek early diagnosis and treatment if fever develops during or after travel.

These principles provide a framework for the clinician to follow when counseling on malaria prevention during any pre-travel patient visit.
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LIFE CYCLE OF PLASMODIUM

The prevention of malaria has always been a “hot topic” among travelers to tropical locales. In 1998, the World Health Organization indicated that there were more than 270 million cases of malaria with more than one million deaths due to the disease. In the United States, approximately 1400 cases are reported annually to the Centers for Disease Control and Prevention. The evolving pattern of drug resistance by malaria parasites as well as the changes in the recommendations for chemoprophylaxis present a challenge to physicians who advise travelers on the prevention of this disease. Improving adherence to antimosquito measures and antimalarial medications could prevent many cases of malaria in travelers.
To better appreciate the methods of malaria prevention, it is necessary to understand the parasite’s life cycle. Malaria is transmitted by the bite of an infected female Anopheles mosquito and is caused by infection with one of four species of the protozoa Plasmodium (Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, and Plasmodium ovale). When an infected mosquito takes a blood meal during its feeding period between dusk and dawn, it injects sporozoites of Plasmodium from its salivary glands into the bloodstream of the host. The sporozoites circulate to the liver and invade hepatocytes, where they divide to form tissue schizonts and then merozoites, which escape into the bloodstream. Merozoites invade erythrocytes, they differentiate into trophozoites, and the trophozoites then divide to become blood schizonts. These then mature into merozoites, which, when released from red blood cells, can continue the cycle in the blood. A proportion of the sporozoites of P. vivax and P. ovale develop into dormant forms within the liver, called hypnozoites, that can activate months to years later to release more merozoites into the bloodstream, causing a symptomatic relapse. The life cycle is completed when merozoites differentiate into sexual forms called gametocytes. The female Anopheles mosquito ingests gametocytes during a blood meal, and sexual stages result in sporozoites that can be transmitted to the next susceptible human host.
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