Malaria: Description:MalariaMalaria is an infectious disease caused by a parasite, Plasmodium, which infects red blood cells. Malaria is characterized by cycles of chills, fever, pain and sweating. Historical records suggest malaria has infected humans since the beginning of mankind. The name "mal 'aria" (meaning "bad air" in Italian) was first used in English in 1740 by H. Walpole when describing the disease. The term was shortened to "malaria" in the 20th century. C. Laveran in 1880 was the first to identify the parasites in human blood. In 1889, R. Ross discovered that mosquitoes transmitted malaria. Of the four species of malaria, the most serious type is Plasmodium falciparum malaria. It can be life-threatening. The other three species of malaria (P. vivax, P. malariae, and P. ovale) are generally less serious and are not life-threatening.Malaria is a particular problem and a major one in areas of Asia, Africa, and Central and South America. Unless precautions are taken, anyone living in or traveling to a country where malaria is present can get the disease. Malaria occurs in about 100 countries; approximately 40% of the world population is at risk for contracting malaria.Usually, people get malaria by being bitten by an infected female Anopheles mosquito. Only Anopheles mosquitoes can transmit malaria and they must have been infected through a previous blood meal taken on an infected person. When a mosquito bites, a small amount of blood is taken in which contains the microscopic malaria parasites. The parasite grows and matures in the mosquito's gut for a week or more, then travels to the mosquito's salivary glands. When the mosquito next takes a blood meal, these parasites mix with the saliva and are injected into the bite.Once in the blood, the parasites travel to the liver and enter liver cells to grow and multiply. During this "incubation period", the infected person has no symptoms. After as few as 8 days or as long as several months, the parasites leave the liver cells and enter red blood cells. Once in the cells, they continue to grow and multiply. After they mature, the infected red blood cells rupture, freeing the parasites to attack and enter other red blood cells. Toxins released when the red cells burst are what cause the typical fever, chills, and flu-like malaria symptoms.If a mosquito bites this infected person and ingests certain types of malaria parasites ("gametocytes"), the cycle of transmission continues.Because the malaria parasite is found in red blood cells, malaria can also be transmitted through blood transfusion, organ transplant, or the shared use of needles or syringes contaminated with blood. Malaria may also be transmitted from a mother to her fetus before or during delivery ("congenital" malaria).Malaria is not transmitted from person to person like a cold or the flu. You cannot get malaria from casual contact with malaria-infected people.Symptoms:The symptoms characteristic of malaria include flu-like illness with fever, chills, muscle aches, and headache. Some patients develop nausea, vomiting, cough, and diarrhea. Cycles of chills, fever, and sweating that repeat every one, two, or three days are typical. There can sometimes be vomiting, diarrhea, coughing, and yellowing (jaundice) of the skin and whites of the eyes due to destruction of red blood cells and liver cells.People with severe P. falciparum malaria can develop bleeding problems, shock, liver or kidney failure, central nervous system problems, coma, and can die from the infection or its complications. Cerebral malaria (coma, or altered mental status or seizures) can occur with severe P. falciparum infection. It is lethal if not treated quickly; even with treatment, about 15%-20% die.Treatment:Three main factors determine treatments: the infecting species of Plasmodium parasite, the clinical situation of the patient (for example, adult, child, or pregnant female with either mild or severe malaria), and the drug susceptibility of the infecting parasites. Drug susceptibility is determined by the geographic area where the infection was acquired. Different areas of the world have malaria types that are resistant to certain medications. The correct drugs for each type of malaria must be prescribed by a doctor who is familiar with malaria treatment protocols. Since people infected with P. falciparum malaria can die (often because of delayed treatment), immediate treatment for P. falciparum malaria is necessary.Mild malaria can be treated with oral medication; severe malaria (one or more symptoms of either impaired consciousness/coma, severe anemia, renal failure, pulmonary edema, acute respiratory distress syndrome, shock, disseminated intravascular coagulation, spontaneous bleeding, acidosis, hemoglobinuria [hemoglobin in the urine], jaundice, repeated generalized convulsions, and/or parasitemia [parasites in the blood] of > 5%) requires intravenous (IV) drug treatment and fluids.Drug treatment of malaria is not always easy. Chloroquine phosphate is the drug of choice for all malarial parasites except for chloroquine-resistant Plasmodium strains. Although almost all strains of P. malariae are susceptible to chloroquine, P. falciparum, P. vivax and even some P. ovale strains have been reported as resistant to chloroquine. Unfortunately, resistance is usually noted by drug-treatment failure in the individual patient. There are, however, multiple drug-treatment protocols for treatment of drug resistant Plasmodium strains (for example, quinine sulfate plus doxycycline [Vibramycin, Oracea, Adoxa, Atridox] or tetracycline [Achromycin], or clindamycin [Cleocin], or atovaquone-proguanil [Malarone]). There are specialized labs that can test the patient's parasites for resistance, but this is not done frequently. Consequently, treatment is usually based on the majority of Plasmodium species diagnosed and its general drug-resistance pattern for the country or world region where the patient became infested. For example, P. falciparum acquired in the Middle East countries is usually susceptible to chloroquine, but if acquired in sub-Sahara African countries, is usually resistant to chloroquine.Causes and Risk factors:Malaria is caused by a parasite that is transmitted from one human to another by the bite of infected Anopheles mosquitoes. In humans, the parasites (called sporozoites) migrate to the liver where they mature and release another form, the merozoites. These enter the bloodstream and infect the red blood cells.The parasites multiply inside the red blood cells, which then rupture within 48 to 72 hours, infecting more red blood cells. The first symptoms usually occur 10 days to 4 weeks after infection, though they can appear as early as 8 days or as long as a year later. Then the symptoms occur in cycles of 48 to 72 hours.The majority of symptoms are caused by the massive release of merozoites into the bloodstream, the anemia resulting from the destruction of the red blood cells, and the problems caused by large amounts of free hemoglobin released into the circulation after red blood cells rupture.Malaria can also be transmitted congenitally (from a mother to her unborn baby) and by blood transfusions. Malaria can be carried by mosquitoes in temperate climates, but the parasite disappears over the winter.The disease is a major health problem in much of the tropics and subtropics. The CDC estimates that there are 300-500 million cases of malaria each year, and more than 1 million people die. It presents a major disease hazard for travelers to warm climates.In some areas of the world, mosquitoes that carry malaria have developed resistance to insecticides, while the parasites have developed resistance to antibiotics. This has led to difficulty in controlling both the rate of infection and spread of this disease.Falciparum malaria, one of four different types of malaria, affects a greater proportion of the red blood cells than the other types and is much more serious. It can be fatal within a few hours of the first symptoms.Risk Factors: People who have little or no immunity to malaria are most at risk for serious illness. Residents of a malaria region may acquire some immunity to the disease during their lifetime, but those who haven't yet acquired immunity are at risk. People at increased risk for serious disease include:1. Young children and infants.2. Travelers coming from areas with no malaria.3. Pregnant women and their unborn children.4. Poverty, lack of knowledge, and little or no access to health care also contribute to malaria deaths worldwide.It's also possible to lose your immunity if you're no longer frequently exposed to the parasite. So even if you've previously lived in a region where malaria exists, take antimalarial precautions if you return to such an area after an extended period away.Diagnosis:Diagnosis of malaria involves identification of malaria parasite or its antigens/products in the blood of the patient. Although this seems simple, the efficacy of the diagnosis is subject to many factors. The different forms of the four malaria species; the different stages of erythrocytic schizogony; the endemicity of different species; the population movements; the inter-relation between the levels of transmission, immunity, parasitemia, and the symptoms; the problems of recurrent malaria, drug resistance, persisting viable or non-viable parasitemia, and sequestration of the parasites in the deeper tissues; and the use of chemoprophylaxis or even presumptive treatment on the basis of clinical diagnosis can all have a bearing on the identification and interpretation of malaria parasitemia on a diagnostic test.The diagnosis of malaria is confirmed by blood tests and can be divided into microscopic and non-microscopic tests.Microscopic TestsFor nearly a hundred years, the direct microscopic visualization of the parasite on the thick and/or thin blood smears has been the accepted method for the diagnosis of malaria in most settings, from the clinical laboratory to the field surveys. The careful examination of a well-prepared and well-stained blood film currently remains the "gold standard" for malaria diagnosis.The microscopic tests involve staining and direct visualization of the parasite under the microscope.Peripheral Smear Study: Peripheral smear study for malarial parasites is the gold standard in diagnosing malarial infection. It involves collection of a blood smear, its staining with Romanowsky stains and examination of the Red Blood Cells for intracellular malarial parasites.The smear can be prepared from blood collected by venipuncture, finger prick and ear lobe stab. In obstetric practice, cord blood and placental impression smears can be used. In fatal cases, post-mortem smears of cerebral grey matter obtained by needle necropsy through the foramen magnum, superior orbital fissure, ethmoid sinus via the nose or through fontanelle in young children can be used.Sometimes no parasites can be found in peripheral blood smears from patients with malaria, even in severe infections. This may be explained by partial antimalarial treatment or by sequestration of parasitized cells in deep vascular beds. In these cases, parasites, or malarial pigment may be found in the bone marrow aspirates. Presence of malarial pigment in circulating neutrophils and monocytes may also suggest the possibility of malaria.Thick and thin smears are usually prepared. Thick smears are used to identify the parasites and thin smears for identifying the species.Quantitative Buffy Coat (QBC) test: The QBC Test, developed by Becton and Dickenson Inc., is a new method for identifying the malarial parasite in the peripheral blood. It involves staining of the centrifuged and compressed red cell layer with acridine orange and its examination under UV light source. It is fast, easy and claimed to be more sensitive than the traditional thick smear examination.Method: The QBC tube is a high-precision glass hematocrit tube, pre-coated internally with acridine orange stain and potassium oxalate. It is filled with 55-65 microliters of blood from a finger, ear or heel puncture. A clear plastic closure is then attached. A precisely made cylindrical float, designed to be suspended in the packed red blood cells, is inserted. The tube is centrifuged at 12,000 rpm for 5 minutes. The components of the buffy coat separate according to their densities, forming discrete bands. Because the float occupies 90% of the internal lumen of the tube, the leukocyte and the thrombocyte cell band widths and the top-most area of red cells are enlarged to 10 times normal. The QBC tube is placed on the tube holder and examined using a standard white light microscope equipped with the UV microscope adapter, an epi-illuminated microscope objective. Fluorescing parasites are then observed at the red blood cell/white blood cell interface.The key feature of the method is centrifugation and thereby concentration of the red blood cells in a predictable area of the QBC tube, making detection easy and fast. Red cells containing Plasmodia are less dense than normal ones and concentrate just below the leukocytes, at the top of the erythrocyte column. The float forces all the surrounding red cells into the 40 micron space between its outside circumference and the inside of the tube. Since the parasites contain DNA which takes up the acridine orange stain, they appear as bright specks of light among the non-fluorescing red cells. Virtually all of the parasites found in the 60 microliter of blood can be visualized by rotating the tube under the microscope. A negative test can be reported within one minute and positive result within minutes.Non-Microscopic Tests:Several attempts have been made to take the malaria diagnosis out of the realm of the microscope and the microscopist. These tests involve identification of the parasitic antigen or the antiplasmodial antibodies or the parasitic metabolic products. Nucleic acid probes and immunofluorescence for the detection of Plasmodia within the erythrocytes; gel diffusion, counter-immunoelectrophoresis, radio immunoassay, and enzyme immunoassay for malaria antigens in the body fluids; and hemagglutination test, indirect immunofluorescence, enzyme immunoassay, immunochromatography, and Western blotting for anti-plasmodial antibodies in the serum have all been developed. These tests have found some limited applications in research, retrograde confirmation of malaria, investigation of cryptic malaria, transfusion blood screening, and investigation of transfusion acquired infections.Rapid Diagnostic Tests (RDTs):1. Para Sight F test2. OptiMal Assay.3. The immuno chromatographic test (ICT Malaria P. f. test).4. Polymerase Chain Reaction.Medicine and medications:Malaria treatment is not always straightforward and may be complex. Contacting the CDC for the latest treatment guidelines and drug regimens is advised. Not all recommended treatment regimens or drugs are included below. Treatment in pregnancy and complicated malaria requires specialized drug regimens. Consult the CDC as below.Treatment regimens are dependent on the geographic derivation of infection.Antipyretics, such as acetaminophen or NSAIDs, are indicated to reduce the level of discomfort caused by the infection and to reduce fever. NSAIDs should be used with caution if bleeding disorder or hemolysis is suspected.No one drug that can eradicate all forms of the parasite's life cycle has been discovered or manufactured yet. Therefore, one or more classes of drugs often are given at the same time to combat malarial infection synergistically.Antiprotozoal: Chloroquine remains the DOC if the patient is infected with a nonresistant strain of Plasmodium species. For chloroquine-resistant strains, a form of quinine is the drug next in line.Chloroquine (Aralen HCl, Aralen Phosphate): Inhibits parasite growth by concentrating within acid vesicles of the parasite and increasing its internal pH. In addition, inhibits hemoglobin utilization and metabolism by the parasite.Clindamycin (Cleocin): Lincosamide useful as treatment against serious skin and soft tissue infections caused by most staphylococci strains. Also effective against aerobic and anaerobic streptococci, except enterococci. Inhibits bacterial protein synthesis by inhibiting peptide chain initiation at the bacterial ribosome where it preferentially binds to the 50S ribosomal subunit, causing bacterial growth inhibition.Doxycycline (Vibramycin, Vibra-Tabs, Doryx): Inhibits protein synthesis and thus bacterial growth by binding with 30S and possibly 50S ribosomal subunits of susceptible bacteria.Primaquine: If uncomplicated infection is caused by P vivax or P ovale, important to treat patient with primaquine to prevent relapse. If species is initially unknown, then identified as P vivax or P ovale, primaquinephosphate treatment should be initiated. Binds to DNA and may disrupt parasite's mitochondria, causing major disruption in metabolic process of the parasite. Exoerythrocytic forms of the parasite are inhibited.Quinine sulfate (Formula Q): Used in chloroquine-resistant or unknown resistant infections. By increasing pH within intracellular organelles and possibly by intercalating into DNA of parasites, may inhibit growth of parasite.Quinidine gluconate: Indicated for severe or complicated malaria and used in conjunction with one of the following: doxycycline, tetracycline, or clindamycin. Increases pH within intracellular organelles and possibly by intercalating into DNA of parasites, may inhibit growth of parasite.Tetracycline (Achromycin V, Sumycin): Treats susceptible bacterial infections of both gram-positive and gram-negative organisms as well as infections caused by Mycoplasma, Chlamydia, and Rickettsia species. Inhibits bacterial protein synthesis by binding with 30S and possibly 50S ribosomal subunits of susceptible bacteria.Antimalarials: These agents inhibit growth of malarial pathogens by interfering with their stages of growth.Mefloquine (Lariam): Not used in complicated malaria. Acts as a blood schizonticide and may act by raising intravesicular pH within the parasite acid vesicles. Structurally similar to quinine.Artemether (Artenam): Used only for severe or complicated malaria. Not FDA approved.DISCLAIMER: This information should not substitute for seeking responsible, professional medical care. 


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