Plasmodium falciparum Malaria

What is Plasmodium falciparum Malaria?

Malaria is a disease that is spread through mosquito bites and is caused by five tiny organisms known as protozoa: Plasmodium falciparum, P. vivax, P. malariae, P. ovale, and the most recent one identified, P.knowlesi. Infections caused by P. falciparum are responsible for more than 90% of the deaths from malaria globally, making it a significant public health issue.

The World Health Organization’s 2019 World Malaria report estimates that there were 228 million cases of malaria across the world leading to 405,000 deaths in 2018, many of whom were children under the age of 5. Malaria is commonly found, or endemic, in more than 90 countries and affects about 40% of the global population.

There are also a significant number of malaria cases reported in countries where malaria is not usually found, like North America and Europe. These cases usually happen when people who have travelled to countries where Malaria is common return home and the disease spreads locally.

Malaria is often seen in people who travel to areas where the disease is common. Due to the increase in cases of imported malaria, it is essential to understand the often vague symptoms, the challenges in diagnosing malaria, and treatment options available.

What Causes Plasmodium falciparum Malaria?

There are five species of a parasite named Plasmodium that can cause malaria in humans. The vehicle that helps these parasites spread is a kind of mosquito known as a female Anopheles mosquito. When these mosquitos bite humans, they release these parasites, which are in the mosquito’s saliva, into the person’s blood. This is the start of the malaria infection.

These spread parasites, called sporozoites, can get into a person’s liver cells, where they change and multiply without sexual reproduction. This is termed as the liver stage and can last up to two weeks before the parasites enter the next stage, i.e., the blood stage. After multiplying in the liver cells, they transform into different parasites called merozoites, which can move around and are set free into the person’s blood, where they start to attack the red blood cells.

These merozoites continue to multiply by cloning themselves, going through different stages to create new merozoites. These new merozoites can then, in turn, infect new red blood cells. This process leads to an increase in the number of parasites in the body.

A specific type of these parasites, P. falciparum, can bring about high levels of parasites in the blood and can modify the surface of the red blood cells it infects. This modification makes the blood cells stick together and to the walls of small and medium-sized blood vessels. Sticking in this way allows these parasites to avoid being cleared out of the bloodstream by the spleen and damages the cells lining the blood vessels while blocking the micro blood vessels.

Some of these parasites in the red blood cells change into a different form. They produce distinct male and female forms that eventually end up in the skin layers and are swallowed by a mosquito when it bites. This makes the mosquito capable of spreading the malaria parasite to other humans.

After a female Anopheles mosquito ingests these forms of parasites, male micro-parasites go through a process called ex-flagellation in the mosquito’s gut, which involves them fusing with female macro-parasites to shape a structure known as a zygote. This zygote advances into a stage known as an ookinete, then forming another structure called an oocyst. This oocyst matures, ruptures, and releases numerous sporozoites that can spread throughout the mosquito’s body, eventually making their way to the mosquito’s salivary glands. This process completes the malaria parasite’s lifecycle, and the mosquito is now ready to transmit malaria to another human.

It’s important to note that the symptoms of malaria primarily result from the parasite replication in the human blood.

Risk Factors and Frequency for Plasmodium falciparum Malaria

According to the WHO World Malaria Report 2019, around 228 million cases of malaria were recorded globally in 2018, with this number gradually declining since 2010. The majority of these cases, about 85%, occurred in nineteen countries in sub-Saharan Africa and India. The P. falciparum strain of the malaria parasite is the most prevalent and dangerous, responsible for severe illness and death, and is especially widespread in the WHO African region. However, it’s also common in South-East Asia, the Eastern Mediterranean, and the Western Pacific regions.

The people most susceptible to malaria in high-risk areas are children under the age of 5, accounting for 67% of malaria deaths globally, and women experiencing their first pregnancy. In areas with low transmission, all age groups are at risk due to reduced immunity levels.

In the United States, most malaria cases are imported from countries where the disease is widespread. The risk of contracting malaria depends on the length of exposure and the intensity of malaria transmission in the area visited. In 2015, the CDC recorded 1517 confirmed cases of malaria in the United States, the majority of which were found in people who had travelled to malaria-endemic countries.

• Malaria is expected to become more widespread with climate change, as warmer climates are more suitable for the transmission of the disease.
• Other factors affecting malaria spread include politics, economic development, urban growth, population growth, and changes in migration patterns.
• There is a growing concern about the rise of malaria strains resistant to multiple drugs, especially the P. falciparum strain, in the Greater Mekong Subregion.

Severe cases of malaria usually appear in patients with low or no immunity to the disease. In places where P. falciparum transmission is high and steady, severe malaria mainly affects children under the age of 5, since immunity tends to increase with age due to repeated infections. However, severe malaria can occur at any age in areas with low or inconsistent transmission rates.

Pregnant women, especially those in their second trimester, have an increased risk of malaria infection. This risk is influenced by age and the number of pregnancies, with young women experiencing their first pregnancy at higher risk in high transmission areas. Women living in areas with inconsistent and low malaria transmission rates have low immunity, leading to a rapid progression to severe malaria and even death.

Signs and Symptoms of Plasmodium falciparum Malaria

Malaria is a complicated illness that affects people differently based on their age and health condition. It affects both children and adults and the experience can range from having no symptoms to experiencing non-life-threatening symptoms, all the way to severe and deadly symptoms. The typical time it takes for symptoms to start appearing after being infected is around 12 days. It’s extremely important to keep the possibility of malaria in mind when diagnosing a person who has been in a region where malaria is common, and has come down with a fever or a history of fever.

Malaria is categorized into two types: uncomplicated and severe. Uncomplicated malaria is characterized by symptoms that don’t indicate severe illness or dysfunction of important organs. These symptoms can often be mistaken for other illnesses and include things like fever, chills, body aches, headaches, loss of appetite, and cough. Symptoms only occur at specific intervals and are fairly uncommon, but when they do occur they are typically a sign of infection with certain types of malaria. Severe symptoms tend to appear 3 to 7 days after the initial, non-specific symptoms and can result in death in some cases.

• Fever
• Chills
• Body aches
• Headache
• Loss of appetite
• Cough

Severe malaria is characterized by more serious, life-threatening symptoms such as difficulty breathing, multiple seizures, and abnormal bleeding. Other symptoms can include jaundice, shock, coma, and acute kidney injury. Laboratory tests for severe malaria might show severe anemia, low blood sugar level, increased levels of lactate, and renal impairment.

Physical examination of a patient with uncomplicated malaria typically indicates a fever which might come along with restlessness or confusion. Yellowish skin or eyes (jaundice) and low blood pressure when standing up might also be seen in patients. In some cases, an enlarged liver or spleen may be detected after several days.

Children with malaria typically exhibit non-specific symptoms and symptoms related to the digestive system such as fever, tiredness, nausea, vomiting, abdominal cramps, and excessive sleepiness. Pregnant women’s symptoms can range from having no symptoms to severe symptoms, and this depends on the state of their immune system when they became pregnant. Malaria during pregnancy can not only negatively affect the health of the mother, but it can also contribute to increased infant mortality because of low birthweight from growth restriction inside the womb or premature birth.

Testing for Plasmodium falciparum Malaria

If malaria is thought to be a possibility, tests should be done as soon as possible to confirm the diagnosis. It’s crucial to determine whether the patient has non-falciparum or falciparum malaria, two types of the disease. Malaria symptoms often include fever, and can appear in people who have recently traveled to places where the disease is common.

The signs of malaria can be quite general and not specific to the disease, so it is usually diagnosed through blood tests or a rapid diagnostic test (RDT). The results of these tests should be passed on to the patient’s doctor as quickly as possible, usually within a few hours.

Besides the specific tests for malaria, your doctor may also check your blood count, kidney function, blood sugar, and liver function. Thrombocytopenia, or low platelet count, can suggest malaria. In more serious cases, other tests like blood gases, blood culture, lactate levels, and clotting studies may be necessary. If a patient has a fever and is confused or has an altered mental state, the doctor might perform a lumbar puncture to rule out meningitis, an infection of the spinal cord and brain.

The best way to diagnose malaria is to analyze blood smears under a microscope. This makes it possible to see the parasites that cause malaria in your blood. It’s also important to know which species of these parasites is causing the infection, because that can determine how severe the disease might become, and how it should be treated. They usually take three sets of blood films, spaced 12 to 24 hours apart, to make sure they can confidently rule out or confirm the presence of malaria.

The number of infected red blood cells can vary greatly and can be hard to estimate, especially in severe cases of malaria. While a low count (as few as 30-50 per microL) can signal severe malaria, a higher count points at a greater risk for disease progression and failed treatments. A measure of more than 2% of infected red blood cells could mean a higher risk for developing severe malaria, and a measure of over 10% is seen as one of the criteria for diagnosing severe malaria and is linked to higher mortality.

Rapid diagnostic tests (RDTs) are also often used, usually in combination with microscopic blood examination. These tests detect malaria antigens or enzymes, which are signs of infection. However, they do have limitations as they cannot provide a count of how many parasites are present, can still show a positive result months after a P. falciparum infection, or only show a positive result for pLDH (an enzyme in Plasmodium, the parasite that causes malaria) while there are living parasites in the blood.

Polymerase chain reaction (PCR) is another possible diagnostic test. However, it is usually too slow to be used for the first diagnosis and immediate treatment of malaria. It’s used most often for research and epidemiology to identify the type of parasite causing the infection. It’s also recommended to test the parasites for drug resistance.

Treatment Options for Plasmodium falciparum Malaria

The Centers for Disease Control and Prevention (CDC) recommends that treatment for malaria shouldn’t start before laboratory tests confirm the diagnosis. Once confirmed, treatment should begin immediately. However, in extreme cases where malaria is strongly suspected due to symptoms and exposure history, severe disease, or lack of availability of laboratory testing, empirical treatment, or “best guess” treatment, could be used.

Three main factors should guide malaria treatment: the specific malaria parasite causing the infection (Plasmodium species), the patient’s health conditions, and the resistance of the parasite to drugs. This resistance is often determined by the geographical area where the infection occurred. However, in the absence of confirmed diagnosis or if the infecting species can’t be determined, the doctor should opt for a treatment option effective against a type of malaria parasite that is resistant to chloroquine, also known as P. falciparum, due to its global spread.

After starting the treatment, additional blood tests might be conducted to ensure the medications are effectively reducing the amount of the parasite infecting the blood.

For managing malaria, the World Health Organization (WHO) provides comprehensive guidelines including optimum medication dosages. The CDC’s website also offers treatment guidelines for malaria cases in the USA.

When dealing with uncomplicated falciparum malaria, artemisinin-based combination therapies (ACT) are considered the main treatment. ACT is highly effective as it targets a wide stage of parasite life cycle stages, clearing them faster. ACT is also recommended for pregnant women in their second and third trimesters of pregnancy, and only in the first trimester if other treatments aren’t available. During the first trimester, a combination of quinine and clindamycin is usually prescribed. Also, with lower transmission areas, additional medication such as primaquine is sometimes added to ACT treatment to reduce the potential to infect others.

There are other treatment options, but they are not as effective as ACT. These include mixtures of atovaquone-proguanil, quinine sulfate plus doxycycline, tetracycline, or clindamycin, and mefloquine. The choice of medication can be adjusted for each patient based on various factors such as their weight and age.

In severe cases of falciparum malaria, intravenous or intramuscular artesunate is the recommended first-line treatment for everyone including children, pregnant and breastfeeding women. If artesunate isn’t available, artemether or quinine is an alternative. Once the patient starts tolerating oral medications, they should be switched from intravenous artesunate to a regimen of follow-up oral medications.

Artesunate, while being effective against severe malaria, isn’t currently commercially available in the U.S., but it can be requested from the CDC under specific circumstances. Meanwhile, the CDC suggests oral treatment that can be used while waiting for IV artesunate to arrive. It’s important that patients with severe malaria be admitted to the hospital for close monitoring of their condition.

Patients with uncomplicated malaria can be treated as outpatients after ensuring that they can handle oral therapy and after their blood parasite levels have decreased. They should ideally be placed under close observation in an intensive care unit or special care ward.

Supportive therapy such as blood sugar management, fever control, fluid management, blood transfusion, seizure control, and antibiotics in severe malaria cases or concurrent shock are among the important care considerations in severe malaria cases.

What else can Plasmodium falciparum Malaria be?

If someone has travelled recently and is now feeling sick, they might have caught one of many possible diseases. These could include severe illnesses like Ebola or Lassa fever, liver diseases like hepatitis, mosquito-borne diseases like dengue fever, gut infections like enteric fever, lung infections like avian influenza or tuberculosis, HIV, brain infections like meningitis and encephalitis, and more. However, it’s important to also consider common illnesses that aren’t specifically related to travel, such as bacterial pneumonia, blood infections (septicemia), and the flu.

In some cases, malaria affecting the brain can look a lot like other serious conditions. For example, it can mirror the symptoms of bacterial meningitis, measles, and certain types of viral brain inflammation that are common in the local area. It can also mimic the effects of harmful substances or events happening inside the brain.

What to expect with Plasmodium falciparum Malaria

Patients who are diagnosed with uncomplicated malaria and get treated promptly often recover fully from the disease. Uncomplicated malaria generally has a low mortality rate of around 0.1%. However, if the disease progresses to severe falciparum malaria, which includes certain symptoms and signs of worsening condition, the mortality rate can increase significantly.

It’s been observed that adults often have a higher mortality rate than children when suffering from severe falciparum malaria. The respective numbers are around 18.5% for adults and 9.7% for children. Two crucial aspects that influence the outcomes for both adults and children are the state of consciousness and the level of metabolic acidosis. The state of consciousness can be assessed by coma scales. Metabolic acidosis measures how acidic your blood is, and it can be assessed by analyzing your breathing pattern or by testing your blood for bicarbonate, base deficit, and plasma lactate levels. These measurements help to understand how severe the disease is and how it’s evolving.

The general mortality rate for patients with severe malaria, who get treatment, is between 10% to 20%. But in the case of pregnant women with severe malaria, this rate can go up to roughly 50%. So, you can see the severity and outcome of malaria can vary widely based on various factors.

Possible Complications When Diagnosed with Plasmodium falciparum Malaria

One specific complication related to P. falciparum malaria is cerebral malaria. This condition causes a general and balanced disorder of the brain. It leads to a lack of consciousness that cannot be linked to other causes such as seizures, low blood sugar, sedative drugs, or non-malaria related issues. It happens with a clear diagnosis of a malaria infection. There can be many other reasons for altered consciousness, which is why signs of eye disease have been used to try to improve the accuracy of a cerebral malaria diagnosis and classify severe malaria better.

There can be several other complications, mainly caused by P. falciparum:

• Acute kidney injury can complicate up to 40% of P. falciparum malaria cases.
• Non-heart related lung edema, acute breathing distress syndrome, and lack of oxygen.
• Variances in electrolyte and fluid levels.
• Disturbances in acid-base balance – primarily acidity and high lactic acid.
• Low blood sugar is often worsened by a type of malaria therapy.
• Anemia with a drop in blood oxygen levels being proportionate to the severity and length of illness before treatment.

Other potential complications related to blood (delayed hemolytic anemia after a certain kind of therapy, hyper-reactive malarial spleen enlargement, and splenic rupture). Serious kidney disease and blood in urine due to damage in blood vessels in patients with severe manifestations of falciparum malaria. Low platelet count is often linked with P. falciparum infection; however, bleeding and spread-out clotting inside blood vessels are rare. Liver malfunction, shock, and linked infections (such as Salmonella bacteremia, aspiration pneumonia, hospital-acquired infections, etc.).

Possible complications also include nervous system after-effects (epilepsy, lasting localized deficits, etc.). The three most common complications in children are cerebral malaria, severe anemia, and acidosis, which can happen separately or together.

Preventing Plasmodium falciparum Malaria

While no method can provide 100% protection against infections, there are different tactics that can be used either on their own or together. Personal protective actions help to lessen the chance of coming in contact with mosquitoes carrying diseases, and medication (chemoprophylaxis) can help improve the outcomes if someone does get infected. A common strategy is the “ABCD” of malaria – A for being aware of the risk, B for avoiding mosquito bites, C for taking medication as directed, and D for getting a diagnosis if a fever develops. It’s also critical to consider a person’s health (especially if they are pregnant, elder, or have a weak immune system) when determining their risk for severe malaria and choosing the right antimalarial drug.

Personal protective actions deserving emphasis include wearing barrier clothing, using bed nets treated with insecticides, using effective mosquito repellents, and spraying homes with insecticide. Recommended repellents are those that contain 20%-40% DEET (N, N-Diethyl-meta-toluamide), picaridin, oil of lemon eucalyptus or PMD (p-menthane-3,8-diol), and IR3535. Minimizing exposure to mosquitoes, such as staying indoors from dusk until dawn and choosing accommodations with window screens, is also encouraged. Popular tools for controlling and getting rid of malaria are indoor residual spraying and long-lasting insecticidal nets, despite some mosquitoes developing resistance to insecticides.

Those traveling to areas where malaria is common should strictly follow the recommended medication protocol. There are several available drugs, which are prescribed after considering the specific risks of the individual (including how common transmission is locally, length of exposure, rural vs urban travel, type of travel, season), the traveler’s health status, any present contraindications, level of parasite resistance to drugs (mostly chloroquine and mefloquine), and the traveler’s preference based on timing, cost and possible side effects. It’s worth noting that counterfeit and subpar medicines are a growing issue in some Sub-Saharan countries. Travelers should, therefore, buy the required medications before they set off. The CDC’s website provides a comprehensive list of medication recommendations based on each country.

As pregnant women face an increased risk for severe malaria, organizations like the WHO and others advise against traveling to areas where malaria is common. It is also important to inform travelers, former residents of malaria-endemic areas, and people diagnosed with malaria that they are not allowed to donate blood for 1 year after travel, or 3 years after leaving or revisiting the country, or 3 years after treatment, according to the FDA guidelines. Also, travelers should be aware that malaria can be fatal if treatment is delayed. Therefore, if symptoms develop while abroad, they should seek immediate medical attention and not wait until they return home as treatment may not be readily available during transit.