What is Malaria?
Malaria is a serious and sometimes fatal disease caused by a parasite that commonly infects a certain type of mosquito which feeds on humans. People who get malaria are typically very sick with high fevers, shaking chills, and flu-like illness. Four kinds of malaria parasites can infect humans: Plasmodium falciparum, P. vivax, P. ovale, and P. malariae. Infection with P. falciparum, if not promptly treated, may lead to death. Although malaria can be a deadly disease, illness and death from malaria can usually be prevented.
Malaria is one of the most severe public health problems worldwide. It is a leading cause of death and disease in many developing countries, where young children and pregnant women are the groups most affected. The World Health Organization estimates that each year 300-500 million cases of malaria occur and more than 1 million people die of malaria, especially in developing countries. Most deaths occur in young children. About 60% of the cases of malaria worldwide and more than 80% of the malaria deaths worldwide occur in Africa south of the Sahara. In Africa, a child dies from malaria every 30 seconds. Because malaria causes so much illness and death, the disease is a great drain on many national economies. Since many countries with malaria are already among the poorer nations, the disease maintains a vicious cycle of disease and poverty.
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How is malaria transmitted?
Usually, people get malaria by being bitten by an infective female Anopheles mosquito. Only Anopheles mosquitoes can transmit malaria and they must have been infected through a previous blood meal taken on an infected person. When a mosquito bites an infected person, a small amount of blood is taken in which contains microscopic malaria parasites. About 1 week later, when the mosquito takes its next blood meal, these parasites mix with the mosquito's saliva and are injected into the person being bitten.
Because the malaria parasite is found in red blood cells of an infected person, malaria can also be transmitted through blood transfusion, organ transplant, or the shared use of needles or syringes contaminated with blood. Malaria may also be transmitted from a mother to her unborn infant before or during delivery ("congenital" malaria). Malaria is not spread from person to person like a cold or the flu, and it cannot be sexually transmitted. You cannot get malaria from casual contact with malaria-infected people, such as sitting next to someone who has malaria.
For most people, symptoms begin 10 days to 4 weeks after infection, although a person may feel ill as early as 7 days or as late as 1 year later. Two kinds of malaria, P. vivax and P. ovale, can occur again (relapsing malaria). In P. vivax and P. ovale infections, some parasites can remain dormant in the liver for several months up to about 4 years after a person is bitten by an infected mosquito. When these parasites come out of hibernation and begin invading red blood cells ("relapse"), the person will become sick.
Plasmodium falciparum causes severe and life-threatening malaria; this parasite is very common in many countries in Africa south of the Sahara desert. People who are heavily exposed to the bites of mosquitoes infected with P. falciparum are most at risk of dying from malaria. People who have little or no immunity to malaria, such as young children and pregnant women; or travelers coming from areas with no malaria, are more likely to become very sick and die. Poor people living in rural areas who lack knowledge, money, or access to health care are at greater risk for this disease. As a result of all these factors, an estimated 90% of deaths due to malaria occur in Africa south of the Sahara; most of these deaths occur in children under 5 years of age.
Persons most vulnerable are those with no or little protective immunity against the disease. In areas with high transmission (such as Africa south of the Sahara), the most vulnerable groups are: young children, who have not yet developed immunity to malaria; pregnant women, whose immunity is decreased by pregnancy, especially during the first and second pregnancies; and travelers or migrants coming from areas with little or no malaria transmission, who lack immunity.
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Where does malaria occur?
Malaria typically is found in warmer regions of the world -- in tropical and subtropical countries. Higher temperatures allow the Anopheles mosquito to thrive. Malaria parasites, which grow and develop inside the mosquito, need warmth to complete their growth before they are mature enough to be transmitted to humans.
Malaria occurs in over 100 countries and territories. More than 40% of the world's population is at risk. Large areas of Central and South America, Hispaniola (the Caribbean island that is divided between Haiti and the Dominican Republic), Africa, South Asia, Southeast Asia, the Middle East, and Oceania are considered malaria-risk areas. Travelers to sub-Saharan Africa have the greatest risk of both getting malaria and dying from their infection. However, all travelers to countries with malaria risk may get this potentially deadly disease.
In Africa south of the Sahara, the principal malaria mosquito, Anopheles gambiae, transmits malaria very efficiently. The type of malaria parasite most often found, Plasmodium falciparum, causes severe, potentially fatal disease. Lack of resources and political instability can prevent the building of solid malaria control programs. In addition, malaria parasites are increasingly resistant to antimalarial drugs, presenting one more barrier to malaria control in that continent.
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Symptoms and Presentation
Following the infective bite by the Anopheles mosquito (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.
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Uncomplicated Malaria
The classical (but rarely observed) malaria attack lasts 6-10 hours. It consists of:
1) a cold stage (sensation of cold, shivering) .....2) a hot stage (fever, headaches, vomiting; seizures in young children).....3) 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").
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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).
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.
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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 that may reactivate. Treatment to reduce the chance of such relapses is available and should follow treatment of the first attack.
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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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How Malaria Affects People's Health
Malaria can affect a person's health in various ways. People who have developed protective immunity (through past infections, as is the case with most adults in high transmission areas) may be infected but not made ill by the parasites they carry. In most cases, malaria causes fever, chills, headache, muscle ache, vomiting, malaise and other flu-like symptoms, which can be very incapacitating.
Some persons infected with Plasmodium falciparum can develop complications such as brain disease (cerebral malaria), severe anemia, and kidney failure. These severe forms occur more frequently in people with little protective immunity, and can result in death or life-long neurologic impairment.
People subjected to frequent malaria infections (such as young children and pregnant women in high transmission areas) can develop anemia due to frequent destruction of the red blood cells by the malaria parasites. Severely anemic patients might receive blood transfusions which, in developing countries, can expose them to HIV and other bloodborne diseases.
Babies born to women who had malaria during their pregnancy are more often born with a low birth weight or prematurely, which decreases their chances of survival during early life
In developing countries, the harmful effects of malaria may combine with those of other highly prevalent diseases and conditions, such as malnutrition, HIV/AIDS, and anemia of all causes. Such combinations can have severe results, especially if they occur repeatedly.
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Clinical Diagnosis
Malaria must be recognized promptly in order to treat the patient in time and to prevent further spread of infection in the community. 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. 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 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
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"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.
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Microscopic Diagnosis
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. Alternate methods for laboratory diagnosis include exist (such as molecular diagnosis through PCR) but these tests are expensive and requires a specialized laboratory generally not available in a field clinic.
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Social and Economic Toll
Malaria imposes substantial costs to both individuals and governments. Costs to individuals and their families include: purchase of drugs for treating malaria at home; expenses for travel to, and treatment at, dispensaries and clinics; lost days of work; absence from school; expenses for preventive measures; expenses for burial in case of deaths.
Costs to governments include: maintenance of health facilities; purchase of drugs and supplies; public health interventions against malaria, such as insecticide spraying or distribution of insecticide-treated bed nets; lost days of work with resulting loss of income; and lost opportunities for joint economic ventures and tourism.
Such costs can add substantially to the economic burden of malaria on endemic countries and impede their economic growth. It has been estimated in a retrospective analysis that economic growth per year of countries with intensive malaria was 1.3% lower than that of countries without malaria.
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Our Treatment Plan in Kiburara, Uganda 2009
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Many people when coming to our clinic in Kiburara would list "malaria" as one of their chief complaints. It took a little experience to realize that "malaria" did not always mean they had or sufffered from the disease that was explained above. Sometimes a complaint of "malaria" meant that they had a fever - either recently or sometime in the past.
The patients that presented with current complications from malaria were obvious to identify. Most of these were very small children or infants that had a history of 2-3 days of nausea, vomiting, and fever. These children looked very ill and medical immediate medical treatment was imperative.
Our medicine of choice for treatment was Coartem - the commercial name of artemether–lumefantrine, a drug combination effective in treating malaria
It was added to the WHO essential drug list showing a success rate above 95%. To help fight malaria mostly in Third-World countries, the WHO and Novartis concluded an agreement to help manufacture and sell the drug at lower costs in countries where the average income rarely exceeds two dollars a day. An audit found that Novartis lost 80 cents for every dose sold. The expected number of orders for 2006 was 100 million, but due to local difficulties, namely the lack of a proper health infrastructure in Third World countries, the number of doses actually sold will be far less than that. A dose of Coartem now costs 55 cents for a child up to age 3. Even so, Uganda has had its share of difficulty precuring and manufacturing enough of this medicine for it population (see here)
DOSAGE:
A standard three days treatment schedule with a total of 6 doses is recommended as follows for adults and children >35kg: four tablets as a single dose at the time of initial diagnosis, again four tablets after eight hours and then four tablets twice daily (morning and evening) on each of the following two days (total comprises 24 tablets).
For infants and children weighing 5 to less than 35 kg, a six-dose regimen is recommended with 1 to 3 tablets per dose, depending on bodyweight. With very small children the tablet should be crushed before giving it to the child.
The dose should be taken with high fat food or drinks such as milk. In Kiburara, we had plenty of packaged milk (unrefrigerated type) available for administration. Patients should be encouraged to resume normal eating as soon as food can be tolerated since this improves absorption of artemether and lumefantrine. In the event of vomiting within 1 hour of administration a repeat dose should be taken. Note that patients with acute malaria are frequently averse to food.
Two associated clinical manifestations of malaria required treatment often prior to administration of Coartem.
DEHYDRATION:
cases where there was a stated history of mild nausea, oral rehydration therapy was attempted. The parent, generally the mother, was encouraged to either breast feed infants or in the case of older children encourage oral rehydration generally through a syringe. For the future a solution like Pedialyte or similar would be very helpful here. The children were then monitored for fluid tolerance. If oral feedings were tolerated, then Coartem was administered as directed.If there was a stated history of severe vomiting and poor food tolerance, we would provide fluid rescisitation for dehydration. In this case our protocol was to provide boluses of 10-20 mL/kg of 0.9% NaCl solution. For infants we often provided this through slow IV push, otherwise a IV drip was established.
NAUSEA and VOMITING:
It was frequently the case that children entering the clinic were unable to tolerate food for a significant period of time. In addition to fluid resuscitation to reverse dehydration, it was imperative that we administer a fact-acting antiemetic so that the required doses of Coartem could be administered.
Children were given orally disintegrating ondansetron tablets according to the guidelines: 2 mg for children 8-15 kg, 4 mg for children 15-30 kg, and 8 mg for children over 30 kg. Occasionally 1mg was given to children <8kg.>
Fluid rescusitation and administration of Zofran was successful in allowing us to provide the required Coartem oral regimen for treatment. After a short stay in our treatment room, children were recovered well enough to return to the community. Parents were sent home with the remaining required doses of Coartem and an antipyretic for fever - in our case Panadol (paracetamol).
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