Infection with malaria parasites may result in a wide variety of symptoms, ranging from absent or very mild symptoms to severe disease and even death. Malaria disease can be categorized as uncomplicated or severe (complicated) . In general, malaria is a curable
disease if diagnosed and treated promptly and
correctly.
Overview
Malaria must be recognized promptly in order to treat the patient in time and to prevent further spread of infection in the community.
Malaria should be considered a potential medical emergency and should be treated accordingly. Delay in diagnosis and treatment is a leading cause of death in malaria patients in the United States.
Malaria can be suspected based on the patient's symptoms and the physical findings at examination. However, for a definitive diagnosis to be made, laboratory tests must demonstrate the malaria parasites or their components.
Diagnosis of malaria can be difficult:
* Where malaria is not endemic any more (such as the United States), health care providers are not familiar with the disease. Clinicians seeing a malaria patient may forget to consider malaria among the potential diagnoses and not order the needed diagnostic tests. Laboratorians may lack experience with malaria and fail to detect parasites when examining blood smears under the microscope.
* In some areas, malaria transmission is so intense that a large proportion of the population is infected but not made ill by the parasites. Such carriers have developed just enough immunity to protect them from malarial illness but not from malarial infection. In that situation, finding malaria parasites in an ill person does not necessarily mean that the illness is caused by the parasites.
* In many malaria-endemic countries, lack of resources is a major barrier to reliable and timely diagnosis. Health personnel are undertrained, underequipped and underpaid. They often face excessive patient loads, and must divide their attention between malaria and other equally severe infectious diseases such as pneumonia, diarrhea, tuberculosis and HIV/AIDS.
Clinical Diagnosis
Clinical diagnosis is based on the patient's symptoms and on physical findings at examination.
The first symptoms of malaria (most often fever, chills, sweats, headaches, muscle pains, nausea and vomiting) are often not specific and are also found in other diseases (such as the "flu" and common viral infections). Likewise, the physical findings are often not specific (elevated temperature, perspiration, tiredness).
In severe malaria (caused by Plasmodium falciparum), clinical findings (confusion, coma, neurologic focal signs, severe anemia, respiratory difficulties) are more striking and may increase the suspicion index for malaria.
Thus, in most cases the early clinical findings in malaria are not typical and need to be confirmed by a laboratory test.
"Presumptive Treatment"
In highly endemic areas (particularly in Africa), the great prevalence of asymptomatic infections and lack of resources (such as microscopes and trained microscopists) have led peripheral health facilities to use "presumptive treatment". Patients who suffer from a fever that does not have any obvious cause are presumed to have malaria and are treated for that disease, based only on clinical suspicion, and without the benefit of laboratory confirmation.
This practice is dictated by practical considerations and allows the treatment of a potentially fatal disease.
But it also leads frequently to incorrect diagnoses and unnecessary use of antimalarial drugs. This results in additional expenses and increases the risk of selecting for drug-resistant parasites.
Microscopic Diagnosis
Blood smear examined under microscope showing 2 parasites of Plasmodium falciparum and a white blood cell
Blood smear stained with Giemsa, showing a white blood cell (on left side) and several red blood cells, two of which are infected with Plasmodium falciparum (on right side).
Malaria parasites can be identified by examining under the microscope a drop of the patient's blood, spread out as a "blood smear" on a microscope slide. Prior to examination, the specimen is stained (most often with the Giemsa stain) to give to the parasites a distinctive appearance. This technique remains the gold standard for laboratory confirmation of malaria. However, it depends on the quality of the reagents, of the microscope, and on the experience of the laboratorian.
item more: Diagnosis (Microscopy)
Alternate methods for laboratory diagnosis include:
Antigen Detection
Various test kits are available to detect antigens derived from malaria parasites. Such immunologic ("immunochromatographic") tests most often use a dipstick or cassette format, and provide results in 2-15 minutes. These "Rapid Diagnostic Tests" (RDTs) offer a useful alternative to microscopy in situations where reliable microscopic diagnosis is not available. Malaria RDTs are currently used in some clinical settings and programs. However, before malaria RDTs can be widely adopted, several issues remain to be addressed, including improving their accuracy; lowering their cost; and ensuring their adequate performance under adverse field conditions. The World Health Organization's Regional Office for the Western Pacific (WHO/WPRO) provides technical information, including a list of commercially available malaria RDTs, at http://www.wpro.who.int/rdt/.
On June 13, 2007, the U.S. Food and Drug Administration (FDA) approved the first RDT for use in the United States. This RDT is approved for use by hospital and commercial laboratories, not by individual clinicians or by patients themselves. It is recommended that all RDTs are followed-up with microscopy to confirm the results and if positive, to quantify the proportion of red blood cells that are infected. The use of this RDT may decrease the amount of time that it takes to determine that a patient is infected with malaria.
item more: Diagnosis (Rapid Diagnostic Test)
Molecular Diagnosis
Parasite nucleic acids are detected using polymerase chain reaction (PCR). This technique is more accurate than microscopy. However, it is expensive, and requires a specialized laboratory (even though technical advances will likely result in field-operated PCR machines).
Related Source: Molecular Diagnosis of Malaria and Babesiosis
Other techniques related to malaria diagnosis are:
Serology
Serology detects antibodies against malaria parasites, using either indirect immunofluorescence (IFA) or enzyme-linked immunosorbent assay (ELISA). Serology does not detect current infection but rather measures past experience.
item more: Serology
Drug Resistance Tests
Drug resistance tests are performed in specialized laboratories to assess the susceptibility to antimalarial compounds of parasites collected from a specific patient. Two main laboratory methods are available:
* In vitro tests: The parasites are grown in culture in the presence of increasing concentrations of drugs; the drug concentration that inhibits parasite growth is used as endpoint;
* Molecular characterization: molecular markers assessed by PCR or gene sequencing allow also the prediction, to some degree, of resistance to some drugs; however, the predictive values of these molecular tests are still being evaluated.
http://www.cdc.gov/malaria/disease.htm
Man sitting on a bench appearing ill
Patient with symptoms of malaria seen at the Moronacocha Health Center in the outskirts of Iquitos, on the Peruvian Amazon. A blood smear confirmed that he had malaria. (Image contributed by Dr. Jaime Chang, USAID/Peru)
Incubation Period
Following the infective bite by the Anopheles mosquito, a period of time (the "incubation period") goes by before the first symptoms appear. The incubation period in most cases varies from 7 to 30 days. The shorter periods are observed most frequently with P. falciparum and the longer ones with P. malariae.
Antimalarial drugs taken for prophylaxis by travelers can delay the appearance of malaria symptoms by weeks or months, long after the traveler has left the malaria-endemic area. (This can happen particularly with P. vivax and P. ovale, both of which can produce dormant liver stage parasites; the liver stages may reactivate and cause disease months after the infective mosquito bite.)
Such long delays between exposure and development of symptoms can result in misdiagnosis or delayed diagnosis because of reduced clinical suspicion by the health-care provider. Returned travelers should always remind their health-care providers of any travel in malaria-risk areas during the past 12 months.
Uncomplicated Malaria
The classical (but rarely observed) malaria attack lasts 6-10 hours. It consists of:
* a cold stage (sensation of cold, shivering)
* a hot stage (fever, headaches, vomiting; seizures in young children)
* and finally a sweating stage (sweats, return to normal temperature, tiredness)
Classically (but infrequently observed) the attacks occur every second day with the "tertian" parasites (P. falciparum, P. vivax, and P. ovale) and every third day with the "quartan" parasite (P. malariae).
More commonly, the patient presents with a combination of the following symptoms:
* Fever
* Chills
* Sweats
* Headaches
* Nausea and vomiting
* Body aches
* General malaise.
In countries where cases of malaria are infrequent, these symptoms may be attributed to influenza, a cold, or other common infections, especially if malaria is not suspected. Conversely, in countries where malaria is frequent, residents often recognize the symptoms as malaria and treat themselves without seeking diagnostic confirmation ("presumptive treatment").
Physical findings may include:
* Elevated temperature
* Perspiration
* Weakness
* Enlarged spleen.
In P. falciparum malaria, additional findings may include:
* Mild jaundice
* Enlargement of the liver
* Increased respiratory rate.
Diagnosis of malaria depends on the demonstration of parasites on a blood smear examined under a microscope. In P. falciparum malaria, additional laboratory findings may include mild anemia, mild decrease in blood platelets (thrombocytopenia), elevation of bilirubin, elevation of aminotransferases, albuminuria, and the presence of abnormal bodies in the urine (urinary "casts").
Severe Malaria
Severe malaria occurs when P. falciparum infections are complicated by serious organ failures or abnormalities in the patient's blood or metabolism. The manifestations of severe malaria include:
* Cerebral malaria, with abnormal behavior, impairment of consciousness, seizures, coma, or other neurologic abnormalities
* Severe anemia due to hemolysis (destruction of the red blood cells)
* Hemoglobinuria (hemoglobin in the urine) due to hemolysis
* Pulmonary edema (fluid buildup in the lungs) or acute respiratory distress syndrome (ARDS), which may occur even after the parasite counts have decreased in response to treatment
* Abnormalities in blood coagulation and thrombocytopenia (decrease in blood platelets)
* Cardiovascular collapse and shock
Other manifestations that should raise concern are:
* Acute kidney failure
* Hyperparasitemia, where more than 5% of the red blood cells are infected by malaria parasites
* Metabolic acidosis (excessive acidity in the blood and tissue fluids), often in association with hypoglycemia
* Hypoglycemia (low blood glucose). Hypoglycaemia may also occur in pregnant women with uncomplicated malaria, or after treatment with quinine.
Severe malaria occurs most often in persons who have no immunity to malaria or whose immunity has decreased. These include all residents of areas with low or no malaria transmission, and young children and pregnant women in areas with high transmission.
In all areas, severe malaria is a medical emergency and should be treated urgently and aggressively.
Malaria Relapses
In P. vivax and P. ovale infections, patients having recovered from the first episode of illness may suffer several additional attacks ("relapses") after months or even years without symptoms. Relapses occur because P. vivax and P. ovale have dormant liver stage parasites ("hypnozoites") that may reactivate. Treatment to reduce the chance of such relapses is available and should follow treatment of the first attack.
Other Manifestations of Malaria
* Neurologic defects may occasionally persist following cerebral malaria, especially in children. Such defects include troubles with movements (ataxia), palsies, speech difficulties, deafness, and blindness.
* Recurrent infections with P. falciparum may result in severe anemia. This occurs especially in young children in tropical Africa with frequent infections that are inadequately treated.
* Malaria during pregnancy (especially P. falciparum) may cause severe disease in the mother, and may lead to premature delivery or delivery of a low-birth-weight baby.
* On rare occasions, P. vivax malaria can cause rupture of the spleen or acute respiratory distress syndrome (ARDS).
* Nephrotic syndrome (a chronic, severe kidney disease) can result from chronic or repeated infections with P. malariae.
* Hyperreactive malarial splenomegaly (also called "tropical splenomegaly syndrome") occurs infrequently and is attributed to an abnormal immune response to repeated malarial infections. The disease is marked by a very enlarged spleen and liver, abnormal immunologic findings, anemia, and a susceptibility to other infections (such as skin or respiratory infections).
disease if diagnosed and treated promptly and
correctly.
Overview
Malaria must be recognized promptly in order to treat the patient in time and to prevent further spread of infection in the community.
Malaria should be considered a potential medical emergency and should be treated accordingly. Delay in diagnosis and treatment is a leading cause of death in malaria patients in the United States.
Malaria can be suspected based on the patient's symptoms and the physical findings at examination. However, for a definitive diagnosis to be made, laboratory tests must demonstrate the malaria parasites or their components.
Diagnosis of malaria can be difficult:
* Where malaria is not endemic any more (such as the United States), health care providers are not familiar with the disease. Clinicians seeing a malaria patient may forget to consider malaria among the potential diagnoses and not order the needed diagnostic tests. Laboratorians may lack experience with malaria and fail to detect parasites when examining blood smears under the microscope.
* In some areas, malaria transmission is so intense that a large proportion of the population is infected but not made ill by the parasites. Such carriers have developed just enough immunity to protect them from malarial illness but not from malarial infection. In that situation, finding malaria parasites in an ill person does not necessarily mean that the illness is caused by the parasites.
* In many malaria-endemic countries, lack of resources is a major barrier to reliable and timely diagnosis. Health personnel are undertrained, underequipped and underpaid. They often face excessive patient loads, and must divide their attention between malaria and other equally severe infectious diseases such as pneumonia, diarrhea, tuberculosis and HIV/AIDS.
Clinical Diagnosis
Clinical diagnosis is based on the patient's symptoms and on physical findings at examination.
The first symptoms of malaria (most often fever, chills, sweats, headaches, muscle pains, nausea and vomiting) are often not specific and are also found in other diseases (such as the "flu" and common viral infections). Likewise, the physical findings are often not specific (elevated temperature, perspiration, tiredness).
In severe malaria (caused by Plasmodium falciparum), clinical findings (confusion, coma, neurologic focal signs, severe anemia, respiratory difficulties) are more striking and may increase the suspicion index for malaria.
Thus, in most cases the early clinical findings in malaria are not typical and need to be confirmed by a laboratory test.
"Presumptive Treatment"
In highly endemic areas (particularly in Africa), the great prevalence of asymptomatic infections and lack of resources (such as microscopes and trained microscopists) have led peripheral health facilities to use "presumptive treatment". Patients who suffer from a fever that does not have any obvious cause are presumed to have malaria and are treated for that disease, based only on clinical suspicion, and without the benefit of laboratory confirmation.
This practice is dictated by practical considerations and allows the treatment of a potentially fatal disease.
But it also leads frequently to incorrect diagnoses and unnecessary use of antimalarial drugs. This results in additional expenses and increases the risk of selecting for drug-resistant parasites.
Microscopic Diagnosis
Blood smear examined under microscope showing 2 parasites of Plasmodium falciparum and a white blood cell
Blood smear stained with Giemsa, showing a white blood cell (on left side) and several red blood cells, two of which are infected with Plasmodium falciparum (on right side).
Malaria parasites can be identified by examining under the microscope a drop of the patient's blood, spread out as a "blood smear" on a microscope slide. Prior to examination, the specimen is stained (most often with the Giemsa stain) to give to the parasites a distinctive appearance. This technique remains the gold standard for laboratory confirmation of malaria. However, it depends on the quality of the reagents, of the microscope, and on the experience of the laboratorian.
item more: Diagnosis (Microscopy)
Alternate methods for laboratory diagnosis include:
Antigen Detection
Various test kits are available to detect antigens derived from malaria parasites. Such immunologic ("immunochromatographic") tests most often use a dipstick or cassette format, and provide results in 2-15 minutes. These "Rapid Diagnostic Tests" (RDTs) offer a useful alternative to microscopy in situations where reliable microscopic diagnosis is not available. Malaria RDTs are currently used in some clinical settings and programs. However, before malaria RDTs can be widely adopted, several issues remain to be addressed, including improving their accuracy; lowering their cost; and ensuring their adequate performance under adverse field conditions. The World Health Organization's Regional Office for the Western Pacific (WHO/WPRO) provides technical information, including a list of commercially available malaria RDTs, at http://www.wpro.who.int/rdt/.
On June 13, 2007, the U.S. Food and Drug Administration (FDA) approved the first RDT for use in the United States. This RDT is approved for use by hospital and commercial laboratories, not by individual clinicians or by patients themselves. It is recommended that all RDTs are followed-up with microscopy to confirm the results and if positive, to quantify the proportion of red blood cells that are infected. The use of this RDT may decrease the amount of time that it takes to determine that a patient is infected with malaria.
item more: Diagnosis (Rapid Diagnostic Test)
Molecular Diagnosis
Parasite nucleic acids are detected using polymerase chain reaction (PCR). This technique is more accurate than microscopy. However, it is expensive, and requires a specialized laboratory (even though technical advances will likely result in field-operated PCR machines).
Related Source: Molecular Diagnosis of Malaria and Babesiosis
Other techniques related to malaria diagnosis are:
Serology
Serology detects antibodies against malaria parasites, using either indirect immunofluorescence (IFA) or enzyme-linked immunosorbent assay (ELISA). Serology does not detect current infection but rather measures past experience.
item more: Serology
Drug Resistance Tests
Drug resistance tests are performed in specialized laboratories to assess the susceptibility to antimalarial compounds of parasites collected from a specific patient. Two main laboratory methods are available:
* In vitro tests: The parasites are grown in culture in the presence of increasing concentrations of drugs; the drug concentration that inhibits parasite growth is used as endpoint;
* Molecular characterization: molecular markers assessed by PCR or gene sequencing allow also the prediction, to some degree, of resistance to some drugs; however, the predictive values of these molecular tests are still being evaluated.
http://www.cdc.gov/malaria/disease.htm
Man sitting on a bench appearing ill
Patient with symptoms of malaria seen at the Moronacocha Health Center in the outskirts of Iquitos, on the Peruvian Amazon. A blood smear confirmed that he had malaria. (Image contributed by Dr. Jaime Chang, USAID/Peru)
Incubation Period
Following the infective bite by the Anopheles mosquito, a period of time (the "incubation period") goes by before the first symptoms appear. The incubation period in most cases varies from 7 to 30 days. The shorter periods are observed most frequently with P. falciparum and the longer ones with P. malariae.
Antimalarial drugs taken for prophylaxis by travelers can delay the appearance of malaria symptoms by weeks or months, long after the traveler has left the malaria-endemic area. (This can happen particularly with P. vivax and P. ovale, both of which can produce dormant liver stage parasites; the liver stages may reactivate and cause disease months after the infective mosquito bite.)
Such long delays between exposure and development of symptoms can result in misdiagnosis or delayed diagnosis because of reduced clinical suspicion by the health-care provider. Returned travelers should always remind their health-care providers of any travel in malaria-risk areas during the past 12 months.
Uncomplicated Malaria
The classical (but rarely observed) malaria attack lasts 6-10 hours. It consists of:
* a cold stage (sensation of cold, shivering)
* a hot stage (fever, headaches, vomiting; seizures in young children)
* and finally a sweating stage (sweats, return to normal temperature, tiredness)
Classically (but infrequently observed) the attacks occur every second day with the "tertian" parasites (P. falciparum, P. vivax, and P. ovale) and every third day with the "quartan" parasite (P. malariae).
More commonly, the patient presents with a combination of the following symptoms:
* Fever
* Chills
* Sweats
* Headaches
* Nausea and vomiting
* Body aches
* General malaise.
In countries where cases of malaria are infrequent, these symptoms may be attributed to influenza, a cold, or other common infections, especially if malaria is not suspected. Conversely, in countries where malaria is frequent, residents often recognize the symptoms as malaria and treat themselves without seeking diagnostic confirmation ("presumptive treatment").
Physical findings may include:
* Elevated temperature
* Perspiration
* Weakness
* Enlarged spleen.
In P. falciparum malaria, additional findings may include:
* Mild jaundice
* Enlargement of the liver
* Increased respiratory rate.
Diagnosis of malaria depends on the demonstration of parasites on a blood smear examined under a microscope. In P. falciparum malaria, additional laboratory findings may include mild anemia, mild decrease in blood platelets (thrombocytopenia), elevation of bilirubin, elevation of aminotransferases, albuminuria, and the presence of abnormal bodies in the urine (urinary "casts").
Severe Malaria
Severe malaria occurs when P. falciparum infections are complicated by serious organ failures or abnormalities in the patient's blood or metabolism. The manifestations of severe malaria include:
* Cerebral malaria, with abnormal behavior, impairment of consciousness, seizures, coma, or other neurologic abnormalities
* Severe anemia due to hemolysis (destruction of the red blood cells)
* Hemoglobinuria (hemoglobin in the urine) due to hemolysis
* Pulmonary edema (fluid buildup in the lungs) or acute respiratory distress syndrome (ARDS), which may occur even after the parasite counts have decreased in response to treatment
* Abnormalities in blood coagulation and thrombocytopenia (decrease in blood platelets)
* Cardiovascular collapse and shock
Other manifestations that should raise concern are:
* Acute kidney failure
* Hyperparasitemia, where more than 5% of the red blood cells are infected by malaria parasites
* Metabolic acidosis (excessive acidity in the blood and tissue fluids), often in association with hypoglycemia
* Hypoglycemia (low blood glucose). Hypoglycaemia may also occur in pregnant women with uncomplicated malaria, or after treatment with quinine.
Severe malaria occurs most often in persons who have no immunity to malaria or whose immunity has decreased. These include all residents of areas with low or no malaria transmission, and young children and pregnant women in areas with high transmission.
In all areas, severe malaria is a medical emergency and should be treated urgently and aggressively.
Malaria Relapses
In P. vivax and P. ovale infections, patients having recovered from the first episode of illness may suffer several additional attacks ("relapses") after months or even years without symptoms. Relapses occur because P. vivax and P. ovale have dormant liver stage parasites ("hypnozoites") that may reactivate. Treatment to reduce the chance of such relapses is available and should follow treatment of the first attack.
Other Manifestations of Malaria
* Neurologic defects may occasionally persist following cerebral malaria, especially in children. Such defects include troubles with movements (ataxia), palsies, speech difficulties, deafness, and blindness.
* Recurrent infections with P. falciparum may result in severe anemia. This occurs especially in young children in tropical Africa with frequent infections that are inadequately treated.
* Malaria during pregnancy (especially P. falciparum) may cause severe disease in the mother, and may lead to premature delivery or delivery of a low-birth-weight baby.
* On rare occasions, P. vivax malaria can cause rupture of the spleen or acute respiratory distress syndrome (ARDS).
* Nephrotic syndrome (a chronic, severe kidney disease) can result from chronic or repeated infections with P. malariae.
* Hyperreactive malarial splenomegaly (also called "tropical splenomegaly syndrome") occurs infrequently and is attributed to an abnormal immune response to repeated malarial infections. The disease is marked by a very enlarged spleen and liver, abnormal immunologic findings, anemia, and a susceptibility to other infections (such as skin or respiratory infections).
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