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What is jaundice?

Jaundice is not a disease but rather a sign that can occur in many different diseases. Jaundice is the yellowish staining of the skin and sclerae (the whites of the eyes) that is caused by high levels in blood of the chemical bilirubin. The color of the skin and sclerae vary depending on the level of bilirubin. When the bilirubin level is mildly elevated, they are yellowish. When the bilirubin level is high, they tend to be brown.

What causes jaundice?

Bilirubin comes from red blood cells. When red blood cells get old, they are destroyed. Hemoglobin, the iron-containing chemical in red blood cells that carries oxygen, is released from the destroyed red blood cells after the iron it contains is removed. The chemical that remains in the blood after the iron is removed becomes bilirubin.

The liver has many functions. One of the liver's functions is to produce and secrete bile into the intestines to help digest dietary fat. Another is to remove toxic chemicals or waste products from the blood, and bilirubin is a waste product. The liver removes bilirubin from the blood. After the bilirubin has entered the liver cells, the cells conjugate (attaching other chemicals, primarily glucuronic acid) to the bilirubin, and then secrete the bilirubin/glucuronic acid complex into bile. The complex that is secreted in bile is called conjugated bilirubin. The conjugated bilirubin is eliminated in the feces. (Bilirubin is what gives feces its brown color.) Conjugated bilirubin is distinguished from the bilirubin that is released from the red blood cells and not yet removed from the blood which is termed unconjugated bilirubin.

Jaundice occurs when there is 1) too much bilirubin being produced for the liver to remove from the blood. (For example, patients with hemolytic anemia have an abnormally rapid rate of destruction of their red blood cells that releases large amounts of bilirubin into the blood), 2) a defect in the liver that prevents bilirubin from being removed from the blood, converted to bilirubin/glucuronic acid (conjugated) or secreted in bile, or 3) blockage of the bile ducts that decreases the flow of bile and bilirubin from the liver into the intestines. (For example, the bile ducts can be blocked by cancers, gallstones, or inflammation of the bile ducts). The decreased conjugation, secretion, or flow of bile that can result in jaundice is referred to as cholestasis: however, cholestasis does not always result in jaundice.
What problems does jaundice cause?

Jaundice or cholestasis, by themselves, causes few problems (except in the newborn, and jaundice in the newborn is different than most other types of jaundice, as discussed later.) Jaundice can turn the skin and sclerae yellow. In addition, stool can become light in color, even clay-colored because of the absence of bilirubin that normally gives stool its brown color. The urine may turn dark or brownish in color. This occurs when the bilirubin that is building up in the blood begins to be excreted from the body in the urine. Just as in feces, the bilirubin turns the urine brown.

Besides the cosmetic issues of looking yellow and having dark urine and light stools, the symptom that is associated most frequently associated with jaundice or cholestasis is itching, medically known as pruritus. The itching associated with jaundice and cholestasis can sometimes be so severe that it causes patients to scratch their skin "raw," have trouble sleeping, and, rarely, even to commit suicide.

It is the disease causing the jaundice that causes most problems associated with jaundice. Specifically, if the jaundice is due to liver disease, the patient may have symptoms or signs of liver disease or cirrhosis. (Cirrhosis represents advanced liver disease.) The symptoms and signs of liver disease and cirrhosis include fatigue, swelling of the ankles, muscle wasting, ascites (fluid accumulation in the abdominal cavity), mental confusion or coma, and bleeding into the intestines.

If the jaundice is caused by blockage of the bile ducts, no bile enters the intestine. Bile is necessary for digesting fat in the intestine and releasing vitamins from within it so that the vitamins can be absorbed into the body. Therefore, blockage of the flow of bile can lead to deficiencies of certain vitamins. For example, there may be a deficiency of vitamin K that prevents proteins that are needed for normal clotting of blood to be made by the liver, and, as a result, uncontrolled bleeding may occur.
What diseases cause jaundice?

Increased production of bilirubin

There are several uncommon conditions that give rise to over-production of bilirubin. The bilirubin in the blood in these conditions usually is only mildly elevated, and the resultant jaundice usually is mild and difficult to detect. These conditions include: 1) rapid destruction of red blood cells (referred to as hemolysis), 2) a defect in the formation of red blood cells that leads to the over-production of hemoglobin in the bone marrow (called ineffective erythropoiesis), or 3) absorption of large amounts of hemoglobin when there has been much bleeding into tissues (e.g., from hematomas, collections of blood in the tissues).

Acute inflammation of the liver

Any condition in which the liver becomes inflamed can reduce the ability of the liver to conjugate (attach glucuronic acid to) and secrete bilirubin. Common examples include acute viral hepatitis, alcoholic hepatitis, and Tylenol-induced liver toxicity.

Chronic liver diseases

Chronic inflammation of the liver can lead to scarring and cirrhosis, and can ultimately result in jaundice. Common examples include chronic hepatitis B and C, alcoholic liver disease with cirrhosis, and autoimmune hepatitis.

Infiltrative diseases of the liver

Infiltrative diseases of the liver refer to diseases in which the liver is filled with cells or substances that don't belong there. The most common example would be metastatic cancer to the liver, usually from cancers within the abdomen. Uncommon causes include a few diseases in which substances accumulate within the liver cells, for example, iron (hemochromatosis), alpha-one antitrypsin (alpha-one antitrypsin deficiency), and copper (Wilson's disease).

Inflammation of the bile ducts

Diseases causing inflammation of the bile ducts, for example, primary biliary cirrhosis or sclerosing cholangitis and some drugs, can stop the flow of bile and elimination of bilirubin and lead to jaundice.

Blockage of the bile ducts

The most common causes of blockage of the bile ducts are gallstones and pancreatic cancer. Less common causes include cancers of the liver and bile ducts.

Drugs

Many drugs can cause jaundice and/or cholestasis. Some drugs can cause liver inflammation (hepatitis) similar to viral hepatitis. Other drugs can cause inflammation of the bile ducts, resulting in cholestasis and/or jaundice. Drugs also may interfere directly with the chemical processes within the cells of the liver and bile ducts that are responsible for the formation and secretion of bile to the intestine. As a result, the constituents of bile, including bilirubin, are retained in the body. The best example of a drug that causes this latter type of cholestasis and jaundice is estrogen. The primary treatment for jaundice caused by drugs is discontinuation of the drug. Almost always the bilirubin levels will return to normal within a few weeks, though in a few cases it may take several months.

Genetic disorders

There are several rare genetic disorders present from birth that give rise to jaundice. Crigler-Najjar syndrome is caused by a defect in the conjugation of bilirubin in the liver due to a reduction or absence of the enzyme responsible for conjugating the glucuronic acid to bilirubin. Dubin-Johnson and Rotor's syndromes are caused by abnormal secretion of bilirubin into bile.

The only common genetic disorder that may cause jaundice is Gilbert's syndrome which affects approximately 7% of the population. Gilbert's syndrome is caused by a mild reduction in the activity of the enzyme responsible for conjugating the glucuronic acid to bilirubin. The increase in bilirubin in the blood usually is mild and infrequently reaches levels that cause jaundice. Gilbert's syndrome is a benign condition that does not cause health problems.

Developmental abnormalities of bile ducts

There are rare instances in which the bile ducts do not develop normally and the flow of bile is interrupted. Jaundice frequently occurs. These diseases usually are present from birth though some of them may first be recognized in childhood or even adulthood. Cysts of the bile duct (choledochal cysts) are an example of such a developmental abnormality. Another example is Caroli's disease.

Jaundice of pregnancy

Most of the diseases discussed previously can affect women during pregnancy, but there are some additional causes of jaundice that are unique to pregnancy.

Cholestasis of pregnancy. Cholestasis of pregnancy is an uncommon condition that occurs in pregnant women during the third trimester. The cholestasis is often accompanied by itching but infrequently causes jaundice. The itching can be severe, but there is treatment (ursodeoxycholic acid or ursodiol). Pregnant women with cholestasis usually do well although they may be at greater risk for developing gallstones. More importantly, there appears to be an increased risk to the fetus for developmental abnormalities. Cholestasis of pregnancy is more common in certain groups, particularly in Scandinavia and Chile, and tends to occur with each additional pregnancy. There also is an association between cholestasis of pregnancy and cholestasis caused by oral estrogens, and it has been hypothesized that it is the increased estrogens during pregnancy that are responsible for the cholestasis of pregnancy.

Pre-eclampsia. Pre-eclampsia, previously called toxemia of pregnancy, is a disease that occurs during the second half of pregnancy and involves several systems within the body, including the liver. It may result in high blood pressure, fluid retention, and damage to the kidneys as well as anemia and reduced numbers of platelets due to destruction of red blood cells and platelets. It often causes problems for the fetus. Although the bilirubin level in the blood is elevated in pre-eclampsia, it usually is mildly elevated, and jaundice is uncommon. Treatment of pre-eclampsia usually involves delivery of the fetus as soon as possible if the fetus is mature.

Acute fatty liver of pregnancy. Acute fatty liver of pregnancy (AFLP) is a very serious complication of pregnancy of unclear cause that often is associated with pre-eclampsia. It occurs late in pregnancy and results in failure of the liver. It can almost always be reversed by immediate delivery of the fetus. There is an increased risk of infant death. Jaundice is common, but not always present in AFLP. Treatment usually involves delivery of the fetus as soon as possible.
What is neonatal jaundice (jaundice in newborn infants)?

Neonatal jaundice is jaundice that begins within the first few days after birth. (Jaundice that is present at the time of birth suggests a more serious cause of the jaundice.) In fact, bilirubin levels in the blood become elevated in almost all infants during the first few days following birth, and jaundice occurs in more than half. For all but a few infants, the elevation and jaundice represents a normal physiological phenomenon and does not cause problems.

The cause of normal, physiological jaundice is well understood. During life in the uterus, the red blood cells of the fetus contain a type of hemoglobin that is different than the hemoglobin that is present after birth. When an infant is born, the infant's body begins to rapidly destroy the red blood cells containing the fetal-type hemoglobin and replaces them with red blood cells containing the adult-type hemoglobin. This floods the liver with bilirubin derived from the fetal hemoglobin from the destroyed red blood cells. The liver in a newborn infant is not mature, and its ability to process and eliminate bilirubin is limited. As a result of both the influx of large amounts of bilirubin and the immaturity of the liver, bilirubin accumulates in the blood. Within two or three weeks, the destruction of red blood cells ends, the liver matures, and the bilirubin levels return to normal.

There is another uncommon syndrome associated with neonatal jaundice, referred to as breast-milk or breast feeding jaundice. In this syndrome, jaundice appears to be caused by or at least accentuated by breast feeding. Although the cause of this type of jaundice is unknown, it has been hypothesized that there is something in breast milk that reduces the ability of the liver to process and eliminate bilirubin. With breast-milk jaundice, the bilirubin levels rise and reach peak levels in approximately two weeks, remain elevated for a week or so, and then decline to normal over several weeks or months. This timing of the elevation in bilirubin and jaundice is different than normal physiological jaundice described previously and allows the two causes of jaundice to be differentiated. The real importance of the more prolonged jaundice associate with breast-milk jaundice is that it raises the possibility that there is a more serious cause for the jaundice that needs to be sought, for example, biliary atresia (destruction of the bile ducts). Breast-milk jaundice alone usually does not cause problems for the infant.

Physiologic jaundice and breast-milk jaundice usually do not cause problems for the infant; however, there is a concern that high or prolonged elevations in levels of unconjugated bilirubin (the type of bilirubin that is not attached to glucuronic acid and the main type of bilirubin that is present in physiologic and breast-milk jaundice) will cause neurologic damage to the infant. Therefore, when unconjugated bilirubin levels are high or prolonged, treatment usually is started to lower the levels of bilirubin. Treatment may be started earlier in infants who are born prematurely since their livers take longer to mature, and the risk of higher and more prolonged elevations of bilirubin is greater. Treatment involves phototherapy with artificial or natural sunlight and, if phototherapy is not successful, exchange transfusion in which the infant's blood is exchanged for normal blood from blood donors.

The benign nature of physiologic and breast-milk allergy need to be distinguished from hemolytic disease of the newborn, a much more serious, even life-threatening cause of jaundice in newborns that is due to blood group incompatibilities between mother and fetus, for example Rh incompatibility. The incompatibility results in an attack by the mother's antibodies on the babies red blood cells leading to hemolysis. Fortunately, because of modern management of pregnancy, this cause of jaundice is rare.
How is the cause of jaundice diagnosed?

Many tests are available for determining the cause of jaundice, but the history and physical examination are important as well.

History

The history can suggest possible reasons for the jaundice. For example, heavy use of alcohol suggests alcoholic liver disease, whereas use of illegal, injectable drugs suggests viral hepatitis. Recent initiation of a new drug suggests drug-induced jaundice. Episodes of abdominal pain associated with jaundice suggests blockage of the bile ducts usually by gallstones.

Physical examination

The most important part of the physical examination in a patient who is jaundiced is examination of the abdomen. Masses (tumors) in the abdomen suggest cancer infiltrating the liver (metastatic cancer) as the cause of the jaundice. An enlarged, firm liver suggests cirrhosis. A rock-hard, nodular liver suggests cancer within the liver.

Blood tests

Measurement of bilirubin can be helpful in determining the causes of jaundice. Markedly greater elevations of unconjugated bilirubin relative to elevations of conjugated bilirubin in the blood suggest hemolysis (destruction of red blood cells). Marked elevations of liver tests (aspartate amino transferase or AST and alanine amino transferase or ALT) suggest inflammation of the liver (such as viral hepatitis). Elevations of other liver tests, e.g., alkaline phosphatase, suggest diseases or obstruction of the bile ducts.

Ultrasonography

Ultrasonography is a simple, safe, and readily-available test that uses sound waves to examine the organs within the abdomen. Ultrasound examination of the abdomen may disclose gallstones, tumors in the liver or the pancreas, and dilated bile ducts due to obstruction (by gallstones or tumor).

Computerized tomography (CT or CAT scans)

Computerized tomography or CT scans are scans that use x-rays to examine the soft tissues of the abdomen. They are particularly good for identifying tumors in the liver and the pancreas and dilated bile ducts, though they are not as good as ultrasonography for identifying gallstones.

Magnetic resonance imaging (MRI)

Magnetic Resonance Imaging scans are scans that utilize magnetization of the body to examine the soft tissues of the abdomen. Like CT scans, they are good for identifying tumors and studying bile ducts. MRI scans can be modified to visualize the bile ducts better than CT scans (a procedure referred to as MR cholangiography), and, therefore, are better than CT for identifying the cause and location of bile duct obstruction.

Endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound

Endoscopic retrograde cholangiopancreatography (ERCP) provides the best means for examining the bile duct. For ERCP an endoscope is swallowed by the patient after he or she has been sedated. The endoscope is a flexible, fiberoptic tube approximately four feet in length with a light and camera on its tip. The tip of the endoscope is passed down the esophagus, through the stomach, and into the duodenum where the main bile duct enters the intestine. A thin tube then is passed through the endoscope and into the bile duct, and the duct is filled with x-ray contrast solution. An x-ray is taken that clearly demonstrates the contrast-filled bile ducts. ERCP is particularly good at demonstrating the cause and location of obstruction within the bile ducts. A major advantage of ERCP is that diagnostic and therapeutic procedures can be done at the same time as the x-rays. For example, if gallstones are found in the bile ducts, they can be removed. Stents can be placed in the bile ducts to relieve the obstruction caused by scarring or tumors. Biopsies of tumors can be obtained.

Ultrasonography can be combined with ERCP by using a specialized endoscope capable of doing ultrasound scanning. Endoscopic ultrasound is excellent for diagnosing small gallstones in the gallbladder and bile ducts that can be missed by other diagnostic methods such as ultrasound, CT, and MRI. It also is the best means of examining the pancreas for tumors and can facilitate biopsy through the endoscope of tumors within the pancreas.

Liver biopsy

Biopsy of the liver provides a small piece of tissue from the liver for examination under the microscope. The biopsy most commonly is done with a long needle after local injection of the skin of the abdomen overlying the liver with anesthetic. The needle passes through the skin and into the liver, cutting off a small piece of liver tissue. When the needle is withdrawn, the piece of liver comes with it. Liver biopsy is particularly good for diagnosing inflammation of the liver and bile ducts, cirrhosis, cancer, and fatty liver.

How is jaundice treated?

With the exception of the treatments for specific causes of jaundice mentioned previously, the treatment of jaundice usually requires a diagnosis of the specific cause of the jaundice and treatment directed at the specific cause, e.g., removal of a gallstone blocking the bile duct.

What is malaria?

Malaria 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 common species that cause malaria, the most serious type is Plasmodium falciparum malaria. It can be life-threatening. However, another relatively new species, Plasmodium knowlesi, is also a dangerous species that is typically found only in long-tailed and pigtail macaque monkeys. Like P. falciparum, P. knowlesi may be deadly to anyone infected. The other three common species of malaria (P. vivax, P. malariae, and P. ovale) are generally less serious and are usually not life-threatening. It is possible to be infected with more than one species of Plasmodium at the same time.

Currently, about 2 million deaths per year worldwide are due to Plasmodium infections. The majority occur in children under 5 years of age in sub-Saharan African countries. There are about 400 million new cases per year worldwide. Most people diagnosed in the U.S. obtained their infection outside of the country, usually while living or traveling through an area where malaria is endemic.

What are malaria symptoms and signs?

The symptoms characteristic of malaria include flulike 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.

How is malaria transmitted?

The life cycle of the malaria parasite (Plasmodium) is complicated and involves two hosts, humans and Anopheles mosquitoes. The disease is transmitted to humans when an infected Anopheles mosquito bites a person and injects the malaria parasites (sporozoites) into the blood. This is shown in Figure 1, where the illustration shows a mosquito taking a blood meal (circle label 1 in Figure 1).
Figure 1: CDC illustration of the life cycles of malaria parasites, Plasmodium spp.
Figure 1: CDC illustration of the life cycles of malaria parasites, Plasmodium spp. SOURCE: CDC

Sporozoites travel through the bloodstream to the liver, mature, and eventually infect the human red blood cells. While in red blood cells, the parasites again develop until a mosquito takes a blood meal from an infected human and ingests human red blood cells containing the parasites. Then the parasites reach the Anopheles mosquito's stomach and eventually invade the mosquito salivary glands. When an Anopheles mosquito bites a human, these sporozoites complete and repeat the complex Plasmodium life cycle. P. ovale and P. vivax can further complicate the cycle by producing dormant stages (hypnozoites) that may not develop for weeks to years.
Malaria Treatment

Learn about the pill (drugs) used in the treatment of malaria.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.

Learn more about malaria treatment »

Top Searched Malaria Terms:
yellow fever, cholera, tuberculosis, P. falciparum, travel, Plasmodium
Where is malaria a particular problem?

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. To get information on countries that have current malaria infection problems, the CDC (Centers for Disease Control) has a constantly updated web site (http://www.cdc.gov/malaria/travelers/
country_table/a.html) that lists the problem areas in detail.

HIV (AIDS) and malaria co-infection is a significant problem across Asia and sub-Saharan Africa. Research suggests that malaria and HIV co-infection can lead to worse clinical outcomes in patients. It seems that co-infections enhance the disease process of both pathogens.

What is the incubation period for malaria?

The period between the mosquito bite and the onset of the malarial illness is usually one to three weeks (seven to 21 days). This initial time period is highly variable as reports suggest that the range of incubation periods may range from four days to one year. The usual incubation period may be increased when a person has taken an inadequate course of malaria prevention medications. Certain types of malaria (P. vivax and P. ovale) parasites can also take much longer, as long as eight to 10 months, to cause symptoms. These parasites remain dormant (inactive or hibernating) in the liver cells during this time. Unfortunately, some of these dormant parasites can remain even after a patient recovers from malaria, so the patient can get sick again. This situation is termed relapsing malaria.

How is malaria diagnosed?

Clinical symptoms associated with travel to countries that have identified malarial risk (listed above) suggest malaria as a diagnosis. Malaria tests are not routinely ordered by most physicians so recognition of travel history is essential. Unfortunately, many diseases can mimic symptoms of malaria (for example, yellow fever, dengue fever, typhoid fever, cholera, filariasis, and even measles and tuberculosis). Consequently, physicians need to order the correct special tests to diagnose malaria, especially in industrialized countries where malaria is seldom seen. Without the travel history, it is likely that other tests will be ordered initially. In addition, the long incubation periods may tend to allow people to forget the initial exposure to infected mosquitoes.

The classic and most used diagnostic test for malaria is the blood smear on a microscope slide that is stained (Giemsa stain) to show the parasites inside red blood cells (see Figure 2).
Figure 2: CDC slide of a Giemsa stained smear of red blood cells showing Plasmodium malariae and Plasmodium falciparum parasites.
Figure 2: CDC slide of a Giemsa stained smear of red blood cells showing Plasmodium malariae and Plasmodium falciparum parasites. SOURCE: CDC/Steven Glenn, Laboratory & Consultation Division

Although this test is easily done, correct results are dependent on the technical skill of the lab technician who prepares and examines the slides with a microscope. Other tests based on immunologic principles exist; including RDTs (rapid diagnostic tests) approved for use in the U.S. in 2007 and polymerase chain reaction (PCR) tests. These are not yet widely available and are more expensive than the traditional Giemsa blood smear. Some investigators suggest such immunologic based tests be confirmed with a Giemsa blood smear.
What is the treatment for malaria?

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 in the hospital.

Drug treatment of malaria is not always easy. Chloroquine phosphate (Aralen) 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 it's acquired in sub-Sahara African countries, it's usually resistant to chloroquine. The WHO's treatment policy, recently established in 2006, is to treat all cases of uncomplicated P. falciparum malaria with artemisinin-derived combination therapy (ACTs). ACTs are drug combinations (for example, artesunate-amodiaquine, artesunate-mefloquine, artesunate-pyronaridine, dihydroartemisinin-piperaquine, and chlorproguanil-dapsoneartesunate) used to treat drug-resistant P. falciparum. Unfortunately, as of 2009, a number of P. falciparum-infected individuals have parasites resistant to ACT drugs.

New drug treatments of malaria are currently under study because Plasmodium species continue to produce resistant strains that frequently spread to other areas. One promising drug class under investigation is the spiroindolones, which have been effective in stopping P. falciparum experimental infections.
Is malaria a particular problem during pregnancy?

Yes. Malaria may pose a serious threat to a pregnant woman and her fetus. Malaria infection in pregnant women may be more severe than in women who are not pregnant. Malaria may also increase the risk of problems with the pregnancy, including prematurity, abortion, and stillbirth. Statistics indicate that in sub-Saharan Africa, between 75,000-200,000 infants die from malaria per year; worldwide estimates indicate about 2 million children die from malaria each year. Therefore, all pregnant women who are living in or traveling to a malaria risk area should consult a doctor and take prescription drugs (for example, sulfadoxine-pyrimethamine) to avoid contracting malaria. Treatment of malaria in the pregnant female is similar to the usual treatment described above; however, drugs such as primaquine (Primaquine), tetracycline (Achromycin, Sumycin), doxycycline, and halofantrine (Halfan) are not recommended as they may harm the fetus. In addition to monitoring the patient for anemia, an OB/GYN specialist often is consulted for further management.

Is malaria a particular problem for children?

Yes. All children, including young infants, living in or traveling to malaria risk areas should take antimalarial drugs (for example, chloroquine and mefloquine [Lariam]). Although the recommendations for most antimalarial drugs are the same as for adults, it is crucial to use the correct dosage for the child. The dosage of drug depends on the age and weight of the child. A specialist in pediatric infectious diseases is recommended for consultation in prophylaxis (prevention) and treatment of children. Since an overdose of an antimalarial drug can be fatal, all antimalarial (and all other) drugs should be stored in childproof containers well out of the child's reach.

How do people avoid getting malaria?

If people must travel to an area known to have malaria, they need to find out which medications to take, and take them as prescribed. Current CDC recommendations suggest individuals begin taking antimalarial drugs about one to two weeks before traveling to a malaria infested area and for four weeks after leaving the area (prophylactic or preventative therapy). Doctors, travel clinics, or the health department can advise individuals as to what medicines to take to keep from getting malaria. Currently, there is no vaccine available for malaria, but researchers are trying to develop one.

Avoid travel to or through countries where malaria occurs if possible. If people must go to areas where malaria occurs, they should take all of the prescribed preventive medicine. In addition, the 2010 CDC international travel recommendations suggest the following precautions be taken in malaria and other disease-infested areas of the world; the following CDC recommendations are not unique for malaria but are posted by the CDC in their malarial prevention publication.

Avoid outbreaks: To the extent possible, travelers should avoid traveling in areas of known malaria outbreaks. The CDC Travelers' Health web page provides alerts and information on regional disease transmission patterns and outbreak alerts (http://www.cdc.gov/travel).


Be aware of peak exposure times and places: Exposure to arthropod bites may be reduced if travelers modify their patterns of activity or behavior. Although mosquitoes may bite at any time of day, peak biting activity for vectors of some diseases (for example, dengue, chikungunya) is during daylight hours. Vectors of other diseases (for example, malaria) are most active in twilight periods (for example, dawn and dusk) or in the evening after dark. Avoiding the outdoors or focusing preventive actions during peak hours may reduce risk.


Wear appropriate clothing: Travelers can minimize areas of exposed skin by wearing long-sleeved shirts, long pants, boots, and hats. Tucking in shirts and wearing socks and closed shoes instead of sandals may reduce risk. Repellents or insecticides such as permethrin can be applied to clothing and gear for added protection; this measure is discussed in detail below.


Check for ticks: Travelers should be advised to inspect themselves and their clothing for ticks during outdoor activity and at the end of the day. Prompt removal of attached ticks can prevent some infections.


Bed nets: When accommodations are not adequately screened or air conditioned, bed nets are essential to provide protection and to reduce discomfort caused by biting insects. If bed nets do not reach the floor, they should be tucked under mattresses. Bed nets are most effective when they are treated with an insecticide or repellent such as permethrin. Pretreated, long-lasting bed nets can be purchased prior to traveling, or nets can be treated after purchase. The permethrin will be effective for several months if the bed net is not washed. (Long-lasting pretreated nets may be effective for much longer.)


Insecticides: Aerosol insecticides, vaporizing mats, and mosquito coils can help to clear rooms or areas of mosquitoes; however, some products available internationally may contain pesticides that are not registered in the United States. Insecticides should always be used with caution, avoiding direct inhalation of spray or smoke.


Optimum protection can be provided by applying repellents. The CDC recommended insect repellent should contain up to 50% DEET (N,N-diethyl-m-toluamide), which is the most effective mosquito repellent for adults and children over 2 months of age.
What is the prognosis (outcome) for people with malaria?

The majority of people who become infected with P. malariae, vivax, or ovale do well and the fevers abate after about 96 hours. However, in endemic areas, reinfection is common. Malaria caused by P. falciparum or P. knowlesi, even when treated, have outcomes ranging from fair to poor, depending on how the parasites react to treatment. Untreated people often die from these infections. In general, patients who are infants, children under the age of 5 (especially in sub-Saharan countries), and those with depressed immune systems (for example, AIDS or cancer patients) have a more guarded prognosis.

Where can people get more information about malaria?

"The History of Malaria, an Ancient Disease," Centers for Disease Control and Prevention

"About Malaria," Centers for Disease Control and Prevention

Traveler's Health - Yellow Book, Centers for Disease Control and Prevention

"Malaria," eMedicine.com
Malaria At A Glance

Malaria is a disease caused by Plasmodium spp. parasites that infects about 400 million people per year with about 2 million deaths.
Symptoms include recurrent cycles (every one to three days) of fever, chills, muscle aches, headaches; nausea, vomiting, and jaundice also may occur.
Anopheles mosquitoes transmit the parasites to humans when they bite. The parasites undergo a complicated life cycle in both mosquitoes and humans; the cycle begins again when the mosquitoes take a blood meal from a human that is contaminated with mature parasites.
Africa, Asia, and Central and South America are the areas with high numbers of malarial infections.
The incubation period for malaria symptoms is about one to three weeks but may be extended to eight to 10 months after the initial infected mosquito bites occur. Some people may have dormant parasites that may get reactivated years after the initial infection.
Malaria is diagnosed by the patient's history of recurrent symptoms and the identification of the parasites in the patient's blood, usually by a Giemsa blood smear.
Malaria is usually treated by using combinations of two or more anti-parasite drugs incorporated into pills that are taken before exposure (prophylactic or preventative therapy) or during infection. More serious infections are treated by IV anti-parasitic drugs in the hospital.
Infants, children, and pregnant females, along with immunodepressed patients are at higher risk for worse outcomes when infected with malaria parasites.
To reduce the chance of getting malaria, people should avoid malaria-endemic areas of the world, use mosquito repellents, cover exposed skin, and use mosquito netting covered areas when sleeping.
The prognosis for the majority of malaria patients is good; most recover with no problems, unless infected with P. falciparum or P. knowlesi, which may have fair to poor outcomes unless treated immediately. Infants, children under 5 years of age, pregnant females, and those with depressed immune systems frequently have a fair to poor prognosis unless effectively treated early in the infection.

REFERENCES:

D'Acremont, V., C. Lengeler, and B. Genton. "Reduction in the Proportion of Fevers Associated With Plasmodium falciparum Parasitaemia in Africa: A Systematic Review." Malaria Journal 9.240 Aug. 22, 2010 doi:10.1186/1475-2875-9-240.

Rottmann, M., C. McNamara, B. Yeung, et al. "Spiroindolones, a Potent Compound Class for the Treatment of Malaria." Science 329 (2010): 1175-1180.

What is typhoid fever?

Typhoid fever is an acute illness associated with fever that is most often caused by the Salmonella typhi bacteria. It can also be caused by Salmonella paratyphi, a related bacterium that usually leads to a less severe illness. The bacteria are deposited in water or food by a human carrier and are then spread to other people in the area.

The incidence of typhoid fever in the United States has markedly decreased since the early 1900s. Today, approximately 400 cases are reported annually in the United States, mostly in people who recently have traveled to endemic areas. This is in comparison to the 1920s, when over 35,000 cases were reported in the U.S. This improvement is the result of improved environmental sanitation. Mexico and South America are the most common areas for U.S. citizens to contract typhoid fever. India, Pakistan, and Egypt are also known high-risk areas for developing this disease. Worldwide, typhoid fever affects more than 13 million people annually, with over 500,000 patients dying of the disease.

If traveling to endemic areas, you should consult with your health-care professional and discuss if you should receive vaccination for typhoid fever.
How do patients get typhoid fever?

Typhoid fever is contracted by the ingestion of the bacteria in contaminated food or water. Patients with acute illness can contaminate the surrounding water supply through stool, which contains a high concentration of the bacteria. Contamination of the water supply can, in turn, taint the food supply. About 3%-5% of patients become carriers of the bacteria after the acute illness. Some patients suffer a very mild illness that goes unrecognized. These patients can become long-term carriers of the bacteria. The bacteria multiplies in the gallbladder, bile ducts, or liver and passes into the bowel. The bacteria can survive for weeks in water or dried sewage. These chronic carriers may have no symptoms and can be the source of new outbreaks of typhoid fever for many years.

How does the bacteria cause disease, and how is it diagnosed?

After the ingestion of contaminated food or water, the Salmonella bacteria invade the small intestine and enter the bloodstream temporarily. The bacteria are carried by white blood cells in the liver, spleen, and bone marrow. The bacteria then multiply in the cells of these organs and reenter the bloodstream. Patients develop symptoms, including fever, when the organism reenters the bloodstream. Bacteria invade the gallbladder, biliary system, and the lymphatic tissue of the bowel. Here, they multiply in high numbers. The bacteria pass into the intestinal tract and can be identified for diagnosis in cultures from the stool tested in the laboratory. Stool cultures are sensitive in the early and late stages of the disease but often must be supplemented with blood cultures to make the definite diagnosis.

What are the symptoms of typhoid fever?

The incubation period is usually one to two weeks, and the duration of the illness is about four to six weeks. The patient experiences

poor appetite,


headaches,


generalized aches and pains,


fever,


lethargy,


diarrhea.

People with typhoid fever usually have a sustained fever as high as 103 F-104 F (39 C-40 C).

Chest congestion develops in many patients, and abdominal pain and discomfort are common. The fever becomes constant. Improvement occurs in the third and fourth week in those without complications. About 10% of patients have recurrent symptoms (relapse) after feeling better for one to two weeks. Relapses are actually more common in individuals treated with antibiotics.
How is typhoid fever treated, and what is the prognosis?

Typhoid fever is treated with antibiotics that kill the Salmonella bacteria. Prior to the use of antibiotics, the fatality rate was 20%. Death occurred from overwhelming infection, pneumonia, intestinal bleeding, or intestinal perforation. With antibiotics and supportive care, mortality has been reduced to 1%-2%. With appropriate antibiotic therapy, there is usually improvement within one to two days and recovery within seven to 10 days.

Several antibiotics are effective for the treatment of typhoid fever. Chloramphenicol was the original drug of choice for many years. Because of rare serious side effects, chloramphenicol has been replaced by other effective antibiotics. The choice of antibiotics needs to be guided by identifying the geographic region where the organism was acquired and the results of cultures once available. (Certain strains from South America show a significant resistance to some antibiotics.) Ciprofloxacin (Cipro), ampicillin (Omnipen, Polycillin, Principen), and trimethoprim-sulfamethoxazole (Bactrim, Septra) are frequently prescribed antibiotics. If relapses occur, patients are retreated with antibiotics.

The carrier state, which occurs in 3%-5% of those infected, can be treated with prolonged antibiotics. Often, removal of the gallbladder, the site of chronic infection, will cure the carrier state.

For those traveling to high-risk areas, vaccines are now available.
Typhoid Fever At A Glance

Typhoid fever usually is caused by Salmonellae typhi bacteria.
Typhoid fever is contracted by the ingestion of contaminated food or water.
Diagnosis of typhoid fever is made when the Salmonella bacteria is detected with a stool culture.
Typhoid fever is treated with antibiotics.
Typhoid fever symptoms are poor appetite, headaches, generalized aches and pains, fever, and lethargy.
Approximately 3%-5% of patients become carriers of the bacteria after the acute illness.

REFERENCE:

United States. Centers for Disease Control and Prevention. "Typhoid Fever." Oct. 24, 2005. .