BAHAN 1 Malaria, which predominantly occurs in tropical areas, is a potentially life-threatening disease caused by infection with Plasmodium protozoa

transmitted by an infective female Anopheles mos uito vector! "ndividuals withmalaria may present with fever and a wide range of symptoms #see the image below$! #%ee &tiology, &pidemiology, 'resentation, and (or)up!$

Malarial merozoites in the peripheral blood! Note that several of the merozoites have penetrated the erythrocyte membrane and entered the cell! *he + Plasmodium species )nown to cause malaria in humans are P falciparum, P vivax, P ovale, P malariae, and P knowlesi!,1, -, ./ *imely identification of the infecting species is e0tremely important, as P falciparuminfection can be fatal and is often resistant to standard chloro uine treatment!P falciparum and P vivax are responsible for most new infections! #%ee &tiology, 'rognosis, *reatment, and Medication!$ *he Plasmodium species can usually be distinguished by morphology on a blood smear! P falciparum is distinguished from the rest of the plasmodia by its high level of parasitemia and the banana shape of its gametocytes! #%ee (or)up!$ Among patients with malaria, +-12 are infected with more than a singlePlasmodium species! 3o-infection with different Plasmodium species has also been described in the parasites4 mos uito vectors!,-/ &ach Plasmodium species has a defined area of endemicity, although geographic overlap is common! At ris) for contraction of malaria are persons living in or traveling to areas of 3entral America, %outh America, Hispaniola, sub-%aharan Africa, the "ndian subcontinent, %outheast Asia, the Middle &ast, and 5ceania! Among these regions, sub-%aharan Africa has the highest occurrence of P falciparum transmission to travelers from the 6nited %tates! #%ee &pidemiology!$

Infection and reproduction After a mos uito ta)es a blood meal, the malarial sporozoites enter hepatocytes #liver phase$ within minutes and then emerge in the bloodstream after a few wee)s! *hese merozoites rapidly enter erythrocytes, where they develop into trophozoites and then into schizonts over a period of days #during the erythrocytic phase of the life cycle$! 7upture of infected erythrocytes containing the schizont results in fever and merozoite release! *he merozoites enter new red cells, and the process is repeated, resulting in a logarithmic increase in parasite burden! Complications P falciparum can cause cerebral malaria, pulmonary edema, rapidly developing anemia, and renal problems! An important reason that the conse uences of P falciparum infection are so severe is that, due to its ability to adhere to endothelial cell walls, the species causes vascular obstruction! (hen a red blood cell #7B3$ becomes infected with P falciparum, the organism produces proteinaceous )nobs that bind to endothelial cells! *he adherence of these infected 7B3s causes them to clump together in the blood vessels in many areas of the body, causing microvascular damage and leading to much of the damage incurred by the parasite! Patient education "ndividuals traveling to malarial regions must be provided with ade uate information regarding prevention strategies, as well as tailored and effective antiprotozoal medications! 8or patient education information, see Malaria,8oreign *ravel, and "nsect Bites History "n patients with suspected malaria, obtaining a history of recent or remote travel to an endemic area is critical! As)ing e0plicitly if they traveled to a tropical area at anytime in their life may enhance recall! Maintain a high inde0 of suspicion for malaria in any patient e0hibiting any malarial symptoms and having a history of travel to endemic areas! Also determine the patient9s immune status, age, and pregnancy status: allergies or other medical conditions that he or she may have: and medications that he or she may be using! 'atients with malaria typically become symptomatic a few wee)s after infection, although the host9s previous e0posure or immunity to malaria affects the symptomatology and incubation

period! "n addition, eachPlasmodium species has a typical incubation period! "mportantly, virtually all patients with malaria present with headache! 3linical symptoms also include the following;

3ough 8atigue Malaise %ha)ing chills Arthralgia Myalgia 'aro0ysm of fever, sha)ing chills, and sweats #every <= or 1- h, depending on species$ *he classic paro0ysm begins with a period of shivering and chills, which lasts for appro0imately 1-- hours and is followed by a high fever! 8inally, the patient e0periences e0cessive diaphoresis, and the body temperature of the patient drops to normal or below normal! Many patients, particularly early in infection, do not present the classic paro0ysm but may have several small fever spi)es a day! "ndeed, the periodicity of fever associated with each species #ie, <= h for P falciparum, P vivax, and P ovale ,or tertian fever/ ; 1- h for P malariae ,or uartan fever/$ is not apparent during initial infection because of multiple broods emerging in the bloodstream! "n addition, the periodicity is often not observed in P falciparum infections! 'atients with long-standing, synchronous infections are more li)ely to present with classic fever patterns! "n general, however, the occurrence of periodicity of fever is not a reliable clue to the diagnosis of malaria! >ess common malarial symptoms include the following;

Anore0ia and lethargy Nausea and vomiting ?iarrhea @aundice Notably, infection with P vivax, particularly in temperate areas of "ndia, may cause symptoms up to A-1- months after the host leaves the endemic area! "n addition, patients infected with P vivax or P ovale may relapse after longer periods, because of the hypnozoite stage in the liver!

P malariae does not have a hypnozoite stage, but patients infected with P malariae may have a prolonged, asymptomatic erythrocytic infection that becomes symptomatic years after leaving the endemic area! *ertian and uartan fevers are due to the cyclic lysis of red blood cells that occurs as trophozoites complete their cycle in erythrocytes every - or . days, respectively! P malariae causes uartan fever: P vivax and P ovalecause the benign form of tertian fever, and P falciparum causes the malignant form! *he cyclic pattern of fever is very rare! *ravelers to forested areas of %outheast Asia and %outh America have become infected by Plasmodium knowlesi, a dangerous species normally found only in long-tailed and pigtail maca ue mon)eys #Macaca fascicularisand M nemestrina, respectively$! *his species can cause severe illness and death in humans, but, under the microscope, the parasite loo)s similar to the more benign P malariae and has sometimes been misdiagnosed! Because P malariae infection is typically relatively mild, Plasmodium knowlesi infection should be suspected in persons residing or traveling in the above geographical areas who are severely ill and have microscopic evidence of P malariae infection! ?iagnosis may be confirmed via polymerase chain reaction #'37$ assay test methods! Physical Examination Most patients with malaria have no specific physical findings, but splenomegaly may be present! %ymptoms of malarial infection are nonspecific and may manifest as a fluli)e illness with fever, headache, malaise, fatigue, and muscle aches! %ome patients with malaria present with diarrhea and other gastrointestinal #B"$ symptoms! "mmune individuals may be completely asymptomatic or may present with mild anemia! Nonimmune patients may uic)ly become very ill! %evere malaria primarily involves P falciparum infection, although death due to splenic rupture has been reported in patients with nonC P falciparummalaria! %evere malaria manifests as cerebral malaria, severe anemia, respiratory symptoms, and renal failure! "n children, malaria has a shorter course, often rapidly progressing to severe malaria! 3hildren are more li)ely to present with hypoglycemia, seizures, severe anemia, and sudden death, but they are much less li)ely to develop renal failure, pulmonary edema, or Daundice!

Cerebral malaria *his feature is almost always caused by P falciparum infection! 3oma may occur: coma can usually be distinguished from a postictal state secondary to generalized seizure if the patient does not regain consciousness after .E minutes! (hen evaluating comatose patients with malaria, hypoglycemia and 3N% infections should be e0cluded! Severe anemia *he anemia associated with malaria is multifactorial and is usually associated with P falciparum infection! "n nonimmune patients, anemia may be secondary to erythrocyte infection and a loss of infected 7B3s! "n addition, uninfected 7B3s are inappropriately cleared, and bone marrow suppression may be involved! Renal failure *his is a rare complication of malarial infection! "nfected erythrocytes adhere to the microvasculature in the renal corte0, often resulting in oliguric renal failure! 7enal failure is typically reversible, although supportive dialysis is often needed until )idney function recovers! "n rare cases, chronic P malariaeinfection results in nephrotic syndrome! Respiratory symptoms 'atients with malaria may develop metabolic acidosis and associated respiratory distress! "n addition, pulmonary edema can occur! %igns of malarial hyperpneic syndrome include alar flaring, chest retraction #intercostals or subcostal$, use of accessory muscles for respiration, or abnormally deep breathing! edication Summary *he < maDor drug classes currently used to treat malaria include uinoline-related compounds, antifolates, artemisinin derivatives, and antimicrobials! No single drug that can eradicate all forms of the parasite9s life cycle has been discovered or manufactured yet! *herefore, 1 or more classes of drugs often are given at the same time to combat malarial infection synergistically! *reatment regimens are dependent on the geographic location of infection, the li)ely Plasmodium species, and the severity of disease presentation!

Beware of counterfeit antimalarial drugs being ta)en by patients that may have been purchased overseas or via the "nternet! *hey may not contain any active ingredients at all and may contain dangerous materials! Antipyretics, such as acetaminophen or nonsteroidal anti-inflammatory drugs #N%A"?s$, are indicated to reduce the level of discomfort caused by the infection and to reduce fever! N%A"?s should be used with caution if bleeding disorder or hemolysis is suspected! Antimalarials can cause significant prolongation of the F* interval, which can be associated with an increased ris) of potentially lethal ventricular dysrhythmias! 'atients receiving these drugs should be assessed for F* prolongation at baseline and carefully monitored if this is present! 'atients with normal F* intervals on electrocardiogram #&3B$ may not be at a significantly increased ris) for drug-induced dysrhythmia, but caution is advised, particularly if the patient is ta)ing multiple drug regimens or if he or she is on other drugs affecting the F* interval! Methemoglobinemia is a complication that may be associated with high-dose regimens of uinine or the derivatives chloro uine and prima uine!,-G/ A patient presenting with cyanosis and a normal 'a5- on room air should be suspected of having methemoglobinemia!

BAHAN Malaria Overview

Malaria is caused by parasites from the genus Plasmodiumwhich are spread to people by infected mos uitoes! *here are five species of Plasmodium that can infect humans! %tatistics show that there are -+E million to +EE million cases of malaria each year in the world, causing up to 1 million deaths! ?eaths are more common in children!

Although North America, (estern &urope, and 7ussia are free of malaria, transmission still occurs in many other tropical and subtropical countries of the world! ?isease rates are highest in sub-%aharan Africa!

*he hallmar) of malaria is fever! "nitially, symptoms may mimic the flu! 8ever may be accompanied by sha)ing chills and muscle aches! Anemia is common!

%evere cases may cause organ failure or death! Malaria is diagnosed from a blood smear when the parasite is seen under the microscope! 5ther tests are available, but microscopy remains the cornerstone of diagnosis! Malaria is treated with specific medications! 5ral medications are usually used, e0cept in severe cases!

Most patients recover completely after being treated! However, infection withP. vivax or P. ovale may be associated with organisms that hide in the liver for months or years, resisting treatment! %pecial medications are used to help eradicate these organisms!

'eople who travel to areas with malaria should visit their physician prior to departure! *he ris) of malaria may be reduced by ta)ing medications and using mos uito precautions! Malaria Causes Malaria is caused by protozoan of the genusPlasmodium! *here are several stages in the life cycle of Plasmodium, including sporozoites, merozoites, and gametocytes! %porozoites are the form that is inDected by the mos uito into humans! "nfection begins with a bite from an infected mos uito! After being inDected into the human host by the mos uito, the parasite travels into the bloodstream and eventually ma)es its way to the liver, where the parasite begins to reproduce and develop into merozoites! *he merozoites leave the liver and enter red blood cells to reproduce! %oon, new parasites burst out in search of new red blood cells to infect! %ometimes, the reproducing Plasmodia will create a form )nown as a gametocyte in the human bloodstream, which is infectious to mos uitoes! "f a mos uito ta)es a blood meal when gametocytes are present, the parasite begins to reproduce in the insect and create sporozite forms that are infectious to people, completing the life cycle! *here are five species of Plasmodium that infect humans;

P. vivax; *hough it9s most common in "ndia and 3entral and %outh America, it9s found worldwide! "nfections can sometimes lead to life-threatening rupture of the spleen! *his type of malaria can hide in the liver and return later to cause a relapse years after the first infection! %pecial medications are used to eradicate P. vivax from the liver!

P. ovale; "t9s rarely found outside Africa! %ymptoms are similar to those of P. vivax! >i)e P. vivax, P. ovale can hide in the liver for years before bursting out again to cause symptoms!

P. malariae; "t9s found worldwide but is less common than the other forms! *his form of malaria is hard to diagnose because there are usually very few parasites in the blood! "f untreated, the infection can last many years!

P. falciparum; *his is the most life-threatening species of malaria! Although present throughout much of the tropical and subtropical world, it is particularly common in sub%aharan Africa! P. falciparum is resistant to many of the older drugs used to treat or prevent malaria!

P. knowlesi; 8ound in Malaysia, this species can cause high levels of parasites in the blood, leading to organ failure or death! 3linicians who treat malaria in the 6nited %tates are sometimes as)ed, H"s it contagiousIH *he answer is that malaria is not spread directly from person to person! A few cases have occurred in other countries through blood transfusion, intravenous drug abuse with shared needles, or organ transplant! An infected mother can spread malaria through the placenta to her unborn child! Malaria Symptoms (ith malaria, the patient develops a high fever, which comes and goes! *he pattern of febrile and afebrile periods may vary according to the species of malaria that is present! However, there does not have to be a pattern to the fever! "nitially, malaria feels li)e the flu with high fever and body aches! %ymptoms in children may be nonspecific, leading to delays in diagnosis! 'eople also will complain of headache, nausea, sha)ing chills #rigors$, sweating, and wea)ness! Anemia is common in patients with malaria, in part due to the effects of thePlasmodium parasite on the red cells! P. falciparum causes a particularly severe form of malaria! "n addition to fever, patients may e0perience severe hemolytic anemia caused by destruction of the red cells, )idney failure,pulmonary edema #fluid in the lungs$, cerebral malaria, coma, or death!

'eople who have lived for years in areas with malaria may develop a partial immunity to new infections, although this will wane if they leave the area! Malaria ia!nosis Many diseases cause fever in the tropical and subtropical world, including malaria,tuberculosis, yellow fever, dengue fever, typhoid, and cholera! &ach of these is managed differently! *hus it is very important to ma)e a specific diagnosis! Malaria is diagnosed by seeing the parasite under the microscope! Blood ta)en from the patient is smeared on a slide for e0amination! %pecial stains are used to help highlight the parasite! %ometimes, it is possible to identify the species of Plasmodium by the shape of the parasite, especially if gametocytes are seen! (henever possible, smears should be reviewed by someone with e0pertise in the diagnosis of malaria! "f the smears are negative, they can be repeated every 1- hours! %mears that are repeatedly negative suggest another diagnosis! *wo types of other tests are available for diagnosis of malaria! 7apid tests can detect proteins called antigens that are present inPlasmodium! *hese tests ta)e less than .E minutes to perform! However, the 8ood and ?rug Administration and the 3enters for ?isease 3ontrol and 'revention recommend that these new tests be used in conDunction with microscopy! A second type of test that is newly available is the polymerase chain reaction #'37$, which detects malaria ?NA! Because this test is not widely available, it is important not to delay treatment while waiting for results! Malaria "reatment Self#Care at Home "n much of the world, malaria is treated at home with oral medications and fluids! %evere infections re uire "J drug therapy! "n the 6!%!, the disease probably should be treated first in a hospital or through a clinic that specializes in tropical diseases! 'eople who have malaria should drin) lots of fluids! Hydration will not treat or cure malaria, but it will reduce side effects associated withdehydration!

Malaria Prevention

Malaria is a potentially fatal illness! 'eople planning to travel to an area with malaria should see their physician before travel, preferably si0 wee)s before departure! *ravelers should use mos uito precautions and ta)e medications to reduce the ris) of disease!

Mos uito precautions include wearing light, protective clothing and using window screens and bed nets when available! *he mos uito that spreads malaria is active between dus) and dawn! "nsect repellants should be used and should contain ?&&*! 7oom sprays may be used to reduce the mos uito population in sleeping areas!

%everal medications are available to prevent malaria! *he choice of medication used for prophyla0is depends on the area of the world that is being visited and the drug-resistance pattern in that area! "n general, the medications are started before travel, ta)en while in the malarious area, and continued for a period of time after leaving the area! Although there are no immunizations or vaccinations commercially available to prevent malaria, phase . trials reported in 5ctober -E11 are encouraging that a moderately effective vaccine will be available soon!

*he 3enters for ?isease 3ontrol maintains a web page #7egional Malaria "nformation$ that gives specific recommendations for every country! Malaria Pro!nosis "f promptly diagnosed and treated, malaria is usually not fatal! ?elays in diagnosis come because the disease is rarely seen by clinicians in the 6nited %tates! ?elays increase the ris) of serious complications or death! Because of the large burden of disease, scientists have been trying to ma)e a malaria vaccine! After decades of disappointment, progress is finally being made although results are still preliminary!