Malaria is caused by 4 different species of Plasmodia: Plasmodium vivax, plasmodium ovale, Plasmodium malariae, and Plasmodium falciparum. Simultaneous infections with more than one species are not uncommon.

Malaria is caused by a parasite that is transmitted from person to person by the bite of an infected Anopheles mosquito. Human malaria is transmitted by 60 species (of 200) of the Anopheles mosquito. These mo squitoes are present in almost all countries in the tropics and subtropics. Anopheles mosquitoes bite during nighttime hours, from dusk to dawn. Congenital infections occur in 1% of patients who have patent infection during pregnancy. Mechanical tr ansmission can also occur during blood transfusion, by contaminated needles, or the mouth parts of biting or bloodsucking insects (e.g., Culex mosquitoes).

Sporozoites, injected by the mosquito, quickly become intracellular parasites of the liver parenchyma. After about a week of asexual reproduction in liver cells, the parasite invades erythrocytes, with P. vivax pre ferring reticulocytes, P. malariae preferring older red blood cells, and P. falciparum having no preference. The parasites go through several developmental stages (ring stage, ameboid trophzite, and schizont or gametocyte) and asexual divisi on, eventually lysing the erythrocyte. The asexual cycle is called schzogony because schizonts are made. Merozoites invade other red blood cells to continue the cycle. Gametocytes consumed by the mosquito undergo sexual cycle which called sporogony becau se sporozoites are produced.

Malaria presents with abrupt onset of fever, chills, accompanied by headache, mylagias, arthralgias, and malaise, about 2 weeks after mosquito bite. Early stages of malaria may resemble the onset of the flu. Fever may be continuous early in the disease; the typical periodic cycle does not develop for several days after onset. The fever spike, which can reach 41 C, is frequently accompanied by nusea, vomiting, and abdominal pain. The fever is followed by drenching sweats. Splenomegaly is seen in most patients, and hepatomegaly occurs in roughly one-third. anemia is prominent. Extensive brain and kidney damage is occur from untreated malaria caused by P flaciparum. Malaria caused by other 3 Plasmodia is usually self-limited , with a low mortality rate. However, relapses of P vivax and p ovale malaria can occur up to several years after the initial illness as a result of hypnozoites latent in the liver.

Travelers can still get malaria, despite use of prevention measures. Malaria symptoms can develop as early as 6-8 days after being bitten by an infected mosquito or as late as several months after departure from a malarious area, after antimalarial drugs are discontinued.

Pathogenesis

Most of the pathologic findings of malaria are due to the destruction of red blood cells. Not only does the parasite rupture erythrocytes upon release of the merozites, but the spleen sequesters and destroys many red cells also. The e nlarged spleen characteristic of malaria is due to congestion of sinusoids with erythrocytes, coupled with hyperplasia of lymphocytes and macrophages. malaria caused by p falciparum can lead to a life-threatening hemorrhage necrosis particularly in the brain and can damage the kidney, with resulting hemoglobinuria. the dark color of the patient’s urine has given rise to the term "blackwater fever". The fever cycle for p malariae is 72 hours and 48 hours for the other psalmodies. Quartan m alaria is the disease caused by p malariae because the fever recurs every fourth day. Whereas Tertian malaria is the term used to describe the fever caused by other plasmodiums when it recurs every third day. Tertian malaria is subdivided into mali gnant malaria, caused by p. falciparum and benign malaria, caused by p. viviax and p. ovale.

Epidemiology

More than 200 million people worldwide have malaria, and more than 1 million die from it each year, making it the most common lethal disease. It occurs primarily in tropical and subtropical areas, especially in Asia, Africa , and Central south America. Malaria in USA in the American who travel to endemic areas without adequate chemoprophylaxis and immigrants from endemic areas. Malaria occurs in most of sub-Saharan Africa, southern and southeast Asia, Mexico, Haiti, the Domi nican Republic, Central and South America, Papua New Guinea, Vanuatu, and the Solomon Islands. Major cities in Asia and South America are nearly malaria free; cities in Africa, India, and Pakistan are not. There is generally less risk of malaria at altitu des above 1500 meters (4500 feet). Certain region regions in southeast Asia, South America, and east Africa are particularly affected by chloroquine-resistant strains of p. falciparum.

Partial immunity based on humoral antibodies that block merozoites from invading the red cells occurs in infected individuals. A low level of parasitemia and low-grade symptoms result; this condition is known as premunition . No vaccine against malaria is available, but travelers can protect themselves by using anti-mosquito measures and by taking drugs to prevent malaria. Individuals with sickle cell trait (hetero-zygotes) are protected against malaria because their red ce lls have too little ATPase activity and cannot produce sufficient energy to support the growth of the parasite. People with homozygous sickle cell anemia are also protected but rarely live long enough to obtain much benefit.

Laboratory Diagnosis

is based on microscopic examination of blood, using both thick and thin Giemsa-stained smears. The thick smear is used to screen for the presence of organisms, and the thin smear is used for species identification. It is importan t to identify the species, because the treatment of different species can differ. Ring-shaped trophozoites is identical in the infected red blood cells. The gametocytes of p falcipartum are crescent-shaped ("banana-shaped"), whereas those of the other plasmodia are spherical. There is a new dip-sti9ck method for rapid diagnosis of Plasmodium vivax and Plasmodium falciparum malaria. which is rapid and provides a specific diagnostic

Malaria can be treated effectively in its early stages, but delaying treatment can have serious consequences.

Chloroquine is the drug of choice for acute malaria caused by sensitive strains. Chloroquine kills the merozoites, thereby reducing the parasitemia, but does not affect the hypnozoites of p. vivax and p. ovale in the liver. These are killed by primaqune, which must be used to prevent relapses.

This is for the chloroquine-resistant strain of p. falciparum, either mefloquine or a combination of quinine and fansidar (sulfadoxine and pyrimethamine) is used. Over dosage of antimalarial dru gs can be fatal and should be stored in childproof containers.

Malaria can often be prevented by the use of antimalarial drugs and use of personal protection measures against mosquito bites. The risk of malaria depends on the traveler's itinerary, the duration of travel, and the place where the traveler will spend the evenings and nights. Travelers who become ill with a fever during or after travel in a malaria risk area should seek prompt medical attention and should inform their physician of their recent travel history. Neither the traveler nor the physician should assume that the traveler has the flu or some other disease without doing a laboratory test to determine if the symptoms are caused by malaria. antimalarial drugs are only recommended for travelers who will have exposure d uring evening and nighttime hours in malaria risk areas. All travelers to areas of the world where malaria is present are advised to use the appropriate drug regimen and personal protection measures to prevent malaria.

In short During travel to areas in which malaria is present,

- Travelers should use anti-mosquito measures

- Travelers should take a drug to prevent malaria

- Travelers should consult a physician if they get sick and physicians have to report all cases.

In addition to using drugs to prevent malaria, travelers should use measures to reduce exposure to malaria-carrying mosquitoes, which bite during the evening and night. To reduce mosquito bites travelers should remain in w ell-screened areas, use mosquito nets, and wear clothes that cover most of the body. Travelers should also take insect repellent with them to use on any exposed areas of the skin. The most effective repellent is DEET (N,N-diethyl meta-toluamide) an ingred ient in most insect repellents. DEET containing insect repellents should always be used according to label directions and sparingly on children. Adults should use 30-35% DEET on exposed areas of the skin. Avoid applying higher-concentration (greater than 35%) products to the skin. Pediatric insect repellents with 6-10% DEET are available. Rarely toxic reactions or other problems have developed after contact with DEET. Travelers should also purchase a flying insect-killing spray to use in living and sleepi ng areas during the evening and night. For greater protection, clothing and bed-nets can be soaked in or sprayed with PERMETHRIN, which is an insect repellent licensed for use on clothing. If applied according to the directions, permethrin will repel inse cts from clothing for several weeks. Portable mosquito bed-nets, DEET containing repellents, and permethrin can be purchased in hardware, back-packing, or military surplus stores.

Avoiding the bites of Anopheles mosquitoes (which usually bite only between dusk and dawn) is the best way to prevent infection.

Malaria infection in pregnant women may be more severe than in nonpregnant women. In addition, there may be increased risk of adverse pregnancy outcomes including prematurity, abortion, and stillbirth. For these reasons, and because chloroquine has not been found to have any harmful effects on the fetus when used in the recommended doses for malaria prophylaxis, pregnancy is not a contraindication to malaria prophylaxis with chloroquine. However, because no chemoprophylactic regimen is completely effective in areas with chloroquine-resistant P. falciparum, women who are pregnant or likely to become so should avoid travel to such areas.

1. Failure of Malaria Eradication

2. Antimalarial Drug Resistance

3. Social changes:-

a. Urbanization

b. Economic development and changes in land usage

c. Sociopolitical disturbances and natural disasters

d. International travel and commerce

4. Malaria epidemics due to climatic change

5. Breakdown of public health infrastructure

DDT is used to kill mosquitoes, antimalarial drugs to treat malaria and vaccines to provide immunity and has eradicated malaria from all developed countries and large areas of tropical Asia and Latin America. Now we have a N EW problem: Vector resistance to DDT and of malaria parasites to chloroquine, a safe and affordable drug has resulted in a new epidemic of malaria which threatens to come home to the US and invade our shores. We need to focus on curing malaria as a diseas e rather than rely just on parasite control and use new tools to combat malaria. Already there is a positive impact in several countries, such as Philippines, Vanuatu, Vietnam, Brazil, China, Solomon Islands, and Thailand. Malaria is again being controlle d! But the fight is NOT OVER. Malaria which results from an infection by Plasmodium falciparum is the most important infectious disease in the tropical world. About 2000 million people live in malaria infested areas and 300 million individuals are infecte d every year. In the southern region of Africa over 1 million children die annually as a result of malaria.

There is now a major problem brewing: INCREASED NUMBER OF INSECTS! The impact of global warming will therefore increase the incidence of malaria.. This increase is happening at the borders of endemic malaria areas and at hi gher altitudes within malarial areas. The increase incidence is happening in areas of the United States, Southeast Asia, South America, and parts of Africa where the disease is less endemic; in these regions the numbers of years of healthy life lost wil l now start to increase significantly

Malaria is increasing in many countries where it was once eradicated or under control. In New York City, imported cases of malaria are increasing. This is happening all over the United States. The New York City Department of Health is on alert and warning people of the danger. Laboratory diagnosis of malaria is in full swing now in the city.. The biggest number of cases, 254 (26%), occurred in 1996, Travel outside of the United States was reported by 958 patients, the majorit y to Africa . Plasmodium falciparum was identified in 505 (51%) and P. vivax in 356 (36%) of the cases. Four fatal cases involved infections with P. falciparum.

Malaria was present in the United States before World War II. but recently cases of locally acquired malaria is becoming a problem, especially with El Nino and global warming induced increases in insect numbers. In Texas a 6 2-year-old man at the Houston Veterans Affairs Medical Center had a Plasmodium vivax infection. He had no previous history of malaria and had not been out of the country in 37 years. He mentioned heavy exposure to mosquitoes. Thus, malaria was probably du e to him being bit by mosquitoes.

A human vaccine to induce protective CD8+ T cell responses in against Plasmodium falciparum infected hepatocytes is now being tested. The vaccine stimulate protective CD8+ T cells using DNA and works against falciparum mala ria. Extensive exposure to malaria does not provide sterile immunity but the acquisition of partial immunity allows over 60 per cent of these people carry the parasite in their blood without symptoms. Immunity comprises both antibody-dependent and antibod y-independent mechanisms. T cells are essential for the induction and maintenance of immunity. T cell-derived soluble factors are mediators of cellular effect or mechanisms in malaria immunity. The efficacy of an antigen depends on the T cell recognition sites and to select suitable epitopes in an immunogen the nature of the T cell responses induced in endemic populations is most important.

Malaria has been eradicated from all developed countries and large areas of tropical Asia and Latin America. The WHO Action Plan for Malaria Control (1995-2000) has estimated that approximately US$28 million per annum of externa l investment in malaria control is needed in Africa. Outside Africa, malaria program s cost an estimated US$175-350 million a year. The Malaria Eradication Campaign was only launched in three countries of tropical Africa since it was not considered feasib le in the others.. Despite these achievements, improvements in the malaria situation could not be maintained indefinitely by time-limited, highly prescriptive and centralized programs. Also, vector resistance to DDT and of malaria parasites to chloroquine . More international planing and sport for those programs in the endemic areas are still in great need for help. Four areas of research show promise for the future:

1. Vector Control 2 Chemo-therapy 3. Malaria vaccines 4. Genome molecular epidemiology studies

Dr. Stephen Hoffman at the Naval Medical Research Center has tested a human DNA malaria vaccine. This PLASMID MALARIA DNA vaccine stimulated immune response to malaria. A more potent vaccine will be tested next year and it will protection against malaria. The article appeared in Science on October 15, 1998. The plasmid DNA was injected into muscle tissue and the muscles cells started to produce a protein for malaria. New Malaria Vaccine Being Developed Using PLASMID DNA: Ready by 2005??

The world’s experience with malaria and the lessons of the past tell us that no single approach to control of malaria will provide a long term solution. Social change, as well as natural and man-made changes to the environment will all contribute to create complex global patterns of malaria transmission. Adequate resources to fund the basic and the applied research are in desperate need.

A. Text books: 1. Krause, m., Richard (1998) Emerging Infections 2.Goljan, F. Edward (1998) Pathology 3. Andreoli, (1996) Cecil Essentials of Medicine 4. Noah, Norman, 1998 Communicable Disease Epideniology and control 5. Jawetz E. (1996) Medical Microbiology and Immunology 6.Hentges, David Medical Microbiology

B. Web sites: 1. CDC home page 2. www.foodsafety.org/ny/ny035.htm 3.www.state.sd.us/doh/pubs/malaria.htm 4. www.georgetown.edu/icidr/icidr.html

5. www.drugbase.co.za/data/med-info/malaria.htm 6. WHO home page

7. www.nevdgp.org.au/travel/tinf/p_malar.htm

8. http://11.cyberhost.net/travelbu/malaria.html