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Therapeutic Technologies: Selected Tropical Diseases Contents 9 ■ Therapeutic Technologies: Selected Tropical Diseases Contents . Page Introduction . 181 Therapies: Current status for “Selected Tropical Diseases . 182 Malaria . 182 Schistosomiasis . 185 Trypanosomiasis . 186 Leishmaniasis . ,.. 187 Filariasis . ... 188 Leprosy . .$, . 188 Tuberculosis. 189 Diarrheal and Enteric Diseases . 190 Acute Respiratory Infections . , 193 Arboviral and Related Viral Infections . 196 Summary . .,,... 197 9. Therapeutic Technologies: Selected Tropical Diseases INTRODUCTION The purpose of therapy is to alter the course of therapy, while for others, there is no adequate of disease so that its consequences are less severe, therapy. The treatment for diseases caused by pro- or to make being ill more tolerable for the patient. tozoa is similar. The development of antiviral Therapy for infections may treat symptoms, drugs is still in its infancy. which themselves can be dangerous, or may The mere existence of adequate therapy does directly attack the responsible organism. not guarantee that it will be used. The availabil- Symptomatic treatment is quite common. Thus, ity and quality of health care varies from coun- for instance, it is usual to take measures against try to country and from one region of a country high fevers, regardless of the cause, because very to another. Some areas in developing countries, high body temperatures can result in brain dam- principally the cities, have quite modern health age. There may or may not be treatment to elim- facilities; other areas have only dispensaries or inate the organism causing the infection, and the often nothing at all. This variability results in a organism may not even be identified; neverthe- marked inconsistency in the ability to make specif- less, controlling fever is important. Another symp- ic diagnoses and administer pathogen-directed tomatic treatment that has quickly become one treatments. In most developing countries, anti- of the most potent tools in the tropics is oral de- microbial are readily available over-the-counter. hydration therapy (ORT) for the dehydration that The result is two common abuses of these drugs: accompanies diarrheal diseases (see Case Study use for conditions in which they are ineffective A: Oral Dehydration Therapy for Diarrheal and use in inadequate doses. Both extensive use Diseases). and underdosing promote drug resistance in the pathogens. The prevalence of organisms resistant Symptomatic treatment is adequate for some to the antimicrobial most commonly available infections that are self-limited. For infections that is high and thus poses significant therapeutic the body cannot eliminate, however, the goal of problems. therapy is the eradication of the disease-producing organisms, not simply alleviation of symptoms, The antimicrobial that are generally available although this goal is difficult if not impossible to in developing countries are penicillin, chloram- achieve for many tropical diseases. phenicol, various sulfonamides, tetracycline, streptomycin, isoniazid (INH), chloroquine, pyri- In general, therapy against bacterial infections methamine-sulfadoxine (P/S), and some antihel- is safe, effective, and usually lasts about 1 week. minthic drugs. These are relatively inexpensive Some bacterial infections (e.g., urinary tract in- compared to other, newer agents, but have sig- fections) can be treated with one dose; others nificant drawbacks. It is to these agents that (e.g., those causing enlargement of the heart, en- resistance in some areas is widespread and grow- docarditis) may require 6 weeks of therapy. ing. Alternatives are usually marketed, but fre- Prolonged treatment, usually 6 months or more, quently not available where they are needed, often is the norm for tuberculosis, and lifetime treat- because they are too expensive. Many of the older ment is necessary in the case of lepromatous lepro- drugs, particularly the antihelminthics, are toxic sy. Many tropical diseases caused by helminths to the patient. Drugs for chronic infections often can now be adequately treated with 1 to 6 days require months or years of treatment, so their ef- 181 182 • Status of Biomedical Research and Related Technology for Tropical Diseases fective use in developing countries, particularly cal diseases. Alternatives to the present toxic in rural areas, is unlikely. agents and alternatives for use against drug- resistant organisms are particularly pressing Some progress is being made. Older chemother- needs. A major problem with new drug develop- apeutic agents are being reexamined; newer ones ment for important pathogens in developing coun- are being screened in the laboratory and in tries is that some diseases at-e relatively rare and animals. The process of drug development is slow, others are prevalent only in areas with limited eco- however, and a decade can easily elapse before nomical resources. Thus, financial incentives for a promising chemical is marketed as an approved the pharmaceutical companies best equipped to drug. There is a great need for safe, effective, in- develop new agents are lacking. expensive, oral, single dose therapies for tropi- THERAPIES: CURRENT STATUS FOR SELECTED TROPICAL DISEASES Malaria Uganda, Rwanda, Malawi, Zambia, northern Su- clan, Madagascar, and the Comoro Islands (377). Human malaria is caused by four species of the genus Plasm odium: P, falciparum, P. malariae, In some areas, P. falciparum strains are also P. vivax, and P. ovale. There are many groups resistant to drugs other than chloroquine, such of drugs available for the prevention and treat- as P/S, quinine, and mefloquine (see below). ment of this disease. Their use is determined by Strains resistant to P/S were thought originally the stage of disease, the immunologic status of the to be present only in Southeast Asia. Now there patient, and the probability that the parasite is appear to be some resistance in Kenya, Tanza- susceptible to a particular drug (usually geo- nia, and the Amazon basin. Most of these are graphically determined). Some drugs are effective resistant to both chloroquine and P/S. Some against sporozoites (the invasive stage of Plasmo- strains in Southeast Asia are resistant to chloro- dium), some against hypnozoites (the latent stage quine, P/S, and mefloquine, and relatively resis- of P, vivax and P. ovale in the liver), some against tant to quinine. These multiply resistant strains the merozoites (the erythrocytic or red blood cell are mostly limited to the Thailand-Kampuchean stage), and still others against gametocytes (the border. sexual form which is picked up by the mosquito during feeding and perpetuates malaria transmis- Agents for Treatment of Acute Malaria sion after further development in the mosquito). Specific chemotherapy for acute malaria is at Some of the drugs affect more than one stage of least 400 years old. During the 1600s, it was the parasite. known that the bark of a Peruvian tree, the cin- Resistance of P. falciparum to most agents is chona tree, was effective in the treatment of in- growing. Resistance of P. falciparum to chloro- termittent fever. The active ingredient, quinine, quine has been present for some years in Panama, was isolated in 1820 by two French chemists, parts of some South American countries, India, Pelletier and Caventou. Since then, new com- Southeast Asia, Indonesia, China, the Republic pounds have been discovered that are useful in of the Philippines, and other Pacific islands. It has the treatment of malaria; however, the ideal drug spread from some parts of South America to in- is yet to be discovered. The treatment of malaria clude most parts of Bolivia, Venezuela, French becomes less satisfactory almost every year, Guyana, and northern Peru. There is growing mainly because more areas of the world report prevalence of resistance in east Africa, which in- P. falciparum resistant to currently available cludes Kenya, Tanzania, eastern Zaire, Burundi, drugs and drugs in clinical trials. Ch. 9—Therapeutic Technologies: Selected Tropical Diseases ● 183 Quinine. -Quinine was the first medication for choice for treatment of acute malaria in “nonaller- the treatment of malaria, and it continues to play gic” persons with chloroquine-susceptible strains a key role. Quinine is effective mainly against the of the malaria parasite and for prophylaxis for merozoite stage of Plasmodium and therefore is travelers in areas without chloroquine-resistant effective in the treatment of acute malaria of all strains. Chloroquine can be given orally, intra- species. It was the sole specific chemotherapeu- muscularly, or intravenously and is generally tic agent for the treatment of acute malaria until available in the geographical areas where it is World War I. As new drugs such as quinacrine needed. It is well tolerated in the usual treatment (1930) and chloroquine (1934) were discovered, and prophylactic dosages. Occasional side effects the importance and use of quinine diminished, include mild transient headaches, nausea, diar- With the emergence of chloroquine-resistant, rhea, visual disturbances, and pruritus (itching). quinine-sensitive strains of malaria parasites in Pruritis may occur in anyone, but more com- 1959 in Venezuela (274), however, quinine has monly in blacks. It probably does not cause birth again become invaluable, and recent research has defects, and is therefore presumed to be safe dur- helped clarify its proper use. ing pregnancy. Quinine is used parenterally (by injection) or Amodiaquine, —Amodiaquine, another 4- orally as the drug of first choice
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