P. malariae

Four different protozoa of the genus Plasmodium -P. falciparum, P. vivax, P. ovale and P malariae - can cause malaria. P. falciparum is the most virulent, being responsible for virtually all fatal malaria cases. Humans are infected by a feeding female Anopheles mosquito (Fig. 2). The clinical symptoms of malaria are associated with the development of the parasite within human red blood cells, while the liver stages remain asymptomatic. The following dtugs (in alphabetical order) are currently in use for the treatment of malaria [5]. 

P. malariae), P. falciparum is responsible for the most severe form. At particular risk of developing severe malaria-associated pathology are the non-immune, including tourists and, in endemic areas, children and pregnant women during first pregnancy. 

Malaria is transmitted from person to person by a certain species of the Anopheles mosquito. The four different protozoans causing malaria are Plasmodium falciparum, P. malariae, P. ovale, and P. vivax. Drugp used to treat or prevent malaria are called anti malarial drags. Three antimalarial drugs are discussed in the chapter chloroquine, doxycycline, and quinine sulfate. Other examples of antimalarial drugs in use today are listed in the Summary Drug Table Antimalarial Drugs. 

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. 

The distribution of the various species of malaria is not well defined but P. vivax is reported to be prevalent in the Indian subcontinent, Central America, North Africa, and the Middle East, whereas P. falciparum is predominantly in Africa (including sub-Saharan Africa), both East and West Africa, Haiti, the Dominican Republic, the Amazon region of South America, Southeast Asia, and New Guinea. Most P. ovale infections occur in Africa, while the distribution of P. malariae is worldwide.7 Most infections in the United States are reported in American travelers, recent immigrants, or immigrants who have visited... 

Chloroquine is the drug of choice for preventing and treating acute forms of malaria caused by P. vivax, P. malariae, P ovale, as well as sensitive forms of P. falciparum. The mechanism of its action is not completely clear, although there are several hypotheses explaining its antimalarial activity. Chloroquine and its analogs inhibit synthesis of nucleic acids of the parasite by affecting the matrix function of DNA. This happens by preliminary... 

Hydroxychloroquine, like chloroquine, is also used for treating acute forms of malaria caused by P vivax, P. malariae, P. ovale, and also sensitive forms of P. falciparum. It is also effective and safe like chloroquine, although it does not have obvious advantages. The only advantage is that it is somewhat better tolerated. Its use is somewhat more limited than chloroquine. Synonyms of this drug are plaquenil, quensyl, toremonil, and others. 

This powerful inhibitor of dihydrofolate reductase is used for preventing and treating malaria caused by plasmodia P. vivax, P. malariae, P. ovale, including P. falciparum. 

In individuals infected with either P. vivax or P ovale, the exoerythrocytic tissue (e.g., liver) forms can persist after a latent period and give rise to relapses. In P. falciparum and P. malariae malaria, however, there do not appear to be any persistent secondary liver forms. Thus, in both of these forms of malaria, the physician must contend only with the asexual erythrocytic forms and the gametes, not with the latent liver forms found in P. vivax and P. ovale. 

The drug is effective against all four types of malaria with the exception of chloroquine-resistant P. falciparum Chloroquine destroys the blood stages of the infection and therefore ameliorates the clinical symptoms seen in P. malariae, P. vivax, P. ovale, and sensitive P. falciparum forms of malaria. The disease will return in P. vivax and P. ovale malaria, however, unless the liver stages are sequentially treated with primaquine after the administration of chloroquine. Chloroquine also can be used prophylactically in areas where resistance does not exist. In addition to its use as an antimalarial, chloroquine has been used in the treatment of rheumatoid arthritis and lupus erythematosus (see Chapter 36), extraintestinal amebiasis, and photoallergic reactions. 

Mecfianism of Action A quinolone-methanol compound structurally similar to quinine that destroys the asexual blood forms of malarial pafhogens, Plasmodium falciparum, P. vivax, P. malariae, P. ovale. Therapeutic Effect Inhibifs parasite growth. Pharmacokinetics Well absorbed from fhe gasfroinfesfinal (GI) tract. Protein binding 98%. Widely distributed, including cerebrospinal fluid (CSF). Metabolized in liver. Primarily excreted in urine. Half-life 21-22 days. 

Human malaria is caused by four species of Plasmodium namely Plasmodium falciparum, P. vivax, P. malariae and P. ovale. P. vivax is mainly responsible for most of the infections (70%) which results in benign tertian malaria. In P. falciparum and P. vivax infections, the patient has fever with rigors every third day and termed as tertian. The other two, P. ovale and P. malariae are mild in nature in which fever develops every fourth day and termed as benign quartan. Symptoms and complications in P. falciparum malaria are more severe than P. vivax malaria. 

Four species of plasmodium typically cause human malaria Plasmodium falciparum, P vivax, P malariae, and P ovale. A fifth species, P knowlesi, is primarily a pathogen of monkeys, but has recently been recognized to cause illness, including severe disease, in humans in Asia. Although all of the latter species may cause significant illness, P falciparum is responsible for the majority of serious complications and deaths. Drug resistance is an important therapeutic problem, most notably with P... 

In P falciparum and P malariae infection, only one cycle of liver cell invasion and multiplication occurs, and liver infection ceases spontaneously in less than 4 weeks. Thus, treatment that eliminates erythrocytic parasites will cure these infections. In P vivax and P ovale infections, a dormant hepatic stage, the hypnozoite, is not eradicated by most drugs, and subsequent relapses can therefore occur after therapy directed against erythrocytic parasites. Eradication of both erythrocytic and hepatic parasites is... 

When not limited by resistance, chloroquine is a highly effective blood schizonticide. It is also moderately effective against gametocytes of P vivax, P ovale, and P malariae but not against those of P falciparum. Chloroquine is not active against liver stage parasites. 

In/ falciparum and P malariae infection, only one cycle of liver cell invasion and multiplication occurs, and liver infection ceases spontaneously in less than 4 weeks. Thus, treatment that... 

Over 100 Plasmodium species contribute to the spread of malaria, but only four of these (P. falciparum, P. vivax, P. ovale, and P. malariae) account for human infection, the deadliest being P. falciparum. The malaria life cycle exists first in a mosquito, and then it passes to a human host. An infected female Anopholes mosquito is the host of the parasite s sporogonic hfe cycle. Mature P. falciparum sporozoites reach the salivary glands of the mosquito, and the parasite is transmitted to a human host when the mosquito feeds. During this blood meal, sporozoites are released into the bloodstream where they penetrate hepatic cells and mature into schizonts. The liver cells rupture after approximately two weeks, discharging merozoites into the bloodstream whereupon they infect red blood cells (RBCs). Every 48 to 78 hours, mature merozoites rupture from... 

Pagola S, Stephens P, Bohle D, Kosar A, Madsen S. The structure of malaria pigment beta-hematin. Nature 2000 404 307-310. Schwarzer E, Kuhn H, Valente E, Arese P. Malaria-parasitized erythrocytes and hemozoin nonenzymatically generate large amounts of hydroxy fatty acids that inhibit monocyte functions. Blood 2003 101 722-728. 

Alphonse Laveran, a French Army physician working in North Africa in the 1880s, was the first to observe malarial parasites in human blood. Their mode of transmission was not understood, however, until Ronald Ross, a British medical officer in India, found the organisms within the bodies of Anopheles mosquitoes. Malaria is caused by four species of parasitic protozoa Plasmodium vivax, P. ovale, P. malariae, satid P. falciparum. These organisms have complex life cycles involving several different developmental stages in both human and mos-... 

P. malariae While causing only 10% of all malarial coses, relapses arc very common. 

The most common symptom of malaria is fever, although chills, headache, myalgia and nausea are frequently seen and other symptoms such as vomiting, diarrhoea, abdominal pain and cough occasionally appear. In all types of malaria, the periodic febrile response (fever) is caused by rupture of mature schizonts (one of the cell forms arising as part of the life cycle). In P. vivax and P. ovale malaria fever occurs every 48 hours, whereas in P. malariae, maturation occurs every 72 hours. In falciparum malaria fever may occur every 48 hours, but is usually irregular, showing no distinct periodicity. Apart... 

Malaria is a vector-borne infectious disease caused by protozoan parasites. Human malaria is usually caused by the infection of Plasmodium falciparum, P. malariae, P. ovale, and P. vivax (Mendis et al, 2001). It is widespread in tropical and subtropical regions, including Asia, Africa, and parts of the Americas. Each year there are about 350-500 million cases of malaria, and more than 1 million people die (CDC, 2009). A series of gossypol derivatives with modified aldehydic groups and hydroxyl groups (Figs. 6.10 and 6.11) have been shown to inhibit the growth of P. falciparum (Razakantoanina et al, 2000 Royer et al, 1986). Table 6.3... 

A number of species of Plasmodium invade the blood and liver causing malaria in man and animals. The important pathogens of malaria in man are Plasmodium falciparum, P. vivax, P. ovale and P. malariae. The disease is transmitted to man by female mosquitoes belonging to the genus Anopheles and is endemic in several parts of Asia, Africa and South America. 

---