Malaria, Falciparum

Falciparum malaria must be considered a life-threatening medical emergency. 

Complications of falciparum malaria include hypoglycemia, acute renal failure, pulmonary edema, seizure, and coma. 

Malaria is transmitted by the bites of the Anopheles mosquitoes which introduce into the bloodstream one of four species of sporozoites of the plasmodia (Plasmodium falciparum, P. ovale, P. vivax or P. malariae). Initial symptoms of malaria are nonspecific and may resemble influenza and include chills, headache, fatigue, muscle pain, rigors, and nausea. The onset of the symptoms is between 1 to 3 weeks following exposure. Fever may appear 2 to 3 days after initial symptoms and may follow a pattern and occur every 2 or 3 days (P. vivax, P. ovale and P. malariae). Fever with P. falciparum can be erratic and may not follow specific patterns. It is not unusual for patients to have concomitant infections with P. vivax and P. falciparum. Falciparum malaria must always be regarded as a life-threatening medical emergency. 

P. falciparum malaria is a life-threatening emergency. Complications include hypoglycemia, acute renal failure, pulmonary edema, severe anemia (high parasitism), thrombocytopenia, heart failure, cerebral congestion, seizures, coma, and adult respiratory distress syndrome. 

In an uncomplicated attack of malaria (for all plasmodia except chloroquine-resistant P. falciparum and P. vivax), the recommended regimen is chloroquine 600 mg (base) initially, followed by 300 mg (base) 6 hours later, and then 300 mg (base) daily for 2 days.3 In severe illness or falciparum malaria, patients should be admitted to an acute care unit and quinidine gluconate 10 mgsalt/kg... 

Following treatment of falciparum malaria, TW has remained well for 2 months. However, 2 days ago, he started developing fever and chills, nausea, and abdominal pain. When seen in the emergency department he has a fever of 38.4°C and complains of severe headache. Examinations of a thick and thin blood smear of the patient s blood identified P. vivax infection. TW received a course of chloroquine and primaquine. In a follow-up 2 weeks later, a repeat blood smear was negative for parasites and the patient was asymptomatic. 

Exchange transfusion that may be required in patients with P. falciparum malaria in whom parasitemia may be between 5% and 15% remains a questionable modality. Either peritoneal or hemodialysis may be indicated in renal failure. 

When advising potential travelers on prophylaxis for malaria, be aware of the incidence of chloroquine-resistant P. falciparum malaria and the countries where it is prevalent. In patients who have P. vivax or P. ovale malaria (note that some patients can have P. falciparum and one of these species), following the treatment of the acute phase of malaria and screening for glucose-6-phosphate dehydrogenase deficiency, patients should receive a regimen of primaquine for 14 days to ensure eradication of the hypnozoite stage of P. vivax or P. ovale. For detailed recommendations for prevention of malaria go to www.cdc.gov/travel/. 

Acute P. falciparum malaria resistant to chloroquine should be treated with intravenous quinidine via central venous catheter and fluid status and the electrocardiogram (ECG) should be monitored closely. 

Primaquine is also gametocytocidal and a single dose of 30-45 mg has been suggested to prevent transmission of falciparum malaria particularly in areas where there is a potential for reintroduction of malaria. Primaquine is also used in the treatment of Pneumocystis carinii pneumonia in AIDS patients in combinations with clindamycin [3]. 

The mechanism of action of chloroquine in Plasmodium falciparum malaria is elimination of... 

The Plasmodium falciparum malaria PD model successfully described the antimalarial effect of artemisinin, mefloquine, and a combination of the two drugs... 

Svensson, U.S., Alin, H., Karlsson, M.O., Bergqvist, Y., and Ashton, M., Population pharmacokinetic and pharmacodjmamic modeling of artemisinin and mefloquine enantiomers in patients with falciparum malaria, Eur.. Clin. Pharmacol, 58, 339-351, 2002. 

It turns out female Anopheles mosquitoes, the most important vectors for Plasmodium falciparum malaria, possess odorant receptors for these molecules. This permits the mosquito to home in on humans, at least those that sweat. Malaria is responsible for more than a million deaths per year. This finding suggests novel ways of creating mosquito repellants and/or traps. ... 

Snow RW, Guerra CA, Noor AM, Myint HY, Hay SI. (2005) The global distribution of clinical episodes of Plasmodium falciparum malaria. Nature 434 214-217. 

Price R, Van Vugt M, Phaipun F, Fuxemburger C, Simpson J, McGready R, Kuile FT, Khan A, Chongsuphajasiddhi T, White NJ, Nosten F. (1999) Adverse effects in patients with acute falciparum malaria treated with artemisinin derivatives. Am J Trop Med Hyg 60 547-555. 

Artemisinin, a tetracyclic 1,2,4-trioxane isolated from Artemisia annua L., is currently recommended as a first-line agent against Plasmodium falciparum malaria. Artemisinin and its synthetic derivatives have also been shown to be promising prototypes for the development of new antiproliferative agents. This chapter presents the recent advances on the analytic methods for extraction and quantification of artemisinin from A. annua plants as well as the biological properties of this natural product. 

Chadwick J, Mercer AE, Park BK, Cosstick R, O Neill PM. (2009) Synthesis and biological evaluation of extraordinarily potent C-10 carba artemisinin dimers against P. falciparum malaria parasites and HL-60 cancer cells. Bioorg Med Chem 17 1325-1338. 

T3. Targett, G. A. T., Antibody response to Plasmodium falciparum malaria comparisons of immunoglobulin concentrations. Antibody litres and the antigenicity of different asexual forms of the parasite. Clin. Exp. Immunol. 7, 501-517 (1970). 

Quinidine gluconate - Life-threatening Plasmodium falciparum malaria. 

QUINIDINE GLUCONATE - P. falciparum malaria The following 2 regimens are effective empirically. As soon as practical, institute standard oral antiplasmodial therapy. 

Many pathogenic protozoa. Including Trypanosoma brucei (trypanosomiasis or African sleeping sickness), Plasmodium falciparum (malaria), Leishmania species (leishmaniasis), and the intestinal parasites Giardia lamblia and Entamoeba histolytica, depend on farnesylated proteins for growth... 

The use of the long-acting sulfonamides such as sulfadimethoxine and sulfadoxine is limited because of a high rate of hypersensitivity reactions. Sulfadoxine in combination with pyrimethamine is indicated for chloroquine-resistant falciparum malaria. 

Quinine is the principal alkaloid derived from the bark of the cinchona tree. It has been used for malaria suppression for over 300 years. By 1959 it was superseded by other drugs, especially chloroquine. After widespread resistance to chloroquine became manifest quinine again became an important antimalarial. Its main uses are for the oral treatment of chloroquine-resistant falciparum malaria and for parenteral treatment of severe attacks of falciparum malaria. Quinine is a blood schizonticide with some gametocytocidal activity. It has no exoerythrocytic activity. Its mechanism of action is not well understood. It can interact with DNA, inhibiting strand separation and ultimately protein synthesis. Resistance of quinine has been increasing in South-East Asia. 

VI.a.2.4. Diaminopyrimidines. Pyrimethamine is a dihydrofolate reductase inhibitor, like the biguanides, and is structurally related to trimethoprim. It is seldom used alone. Pyrimethamine in fixed combinations with dapsone or sulfadoxine is used for treatment and prophylaxis of chloroquine-resistant falciparum malaria. The synergistic activities of pyrimethamine and sulfonamides are similar to those of trimethoprim/sulfonamide combinations. Resistant strains of Plasmodium falciparum have appeared world wide. Prophylaxis against falciparum... 

For uncomplicated falciparum malaria there are several options (with the major drawback in brackets) halofantrine (arrhytmia), mefloquine (neurotoxicity), quinine (vomiting, tinnitus), artemether (recrudescence), atovaquone-proguanil (possible fast development of resistance). 

In complicated falciparum malaria exchange transfusion can be considered if high parasitemia s (>5%) is present, although the benefit has not been proven with a randomised controlled trial. In these severe cases i.v. quinine (with loading dose) is gradually being replaced by artesunate, wich has proven less mortality and less side effects than good old ... 

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