Comprehensive Report on Plasmodium falciparum and Malaria Transmission

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Added on 2022/02/25

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This report provides a comprehensive overview of Plasmodium falciparum, the parasite responsible for malaria, a significant global health concern. It details the parasite's life cycle, beginning with transmission by the Anopheles mosquito, the sporozoite stage, and the subsequent invasion of the liver and red blood cells. The report explains the stages of asexual and sexual reproduction within the human host, including the formation of merozoites and gametocytes. It also examines the transmission process, emphasizing the roles of the vector, human host, and environmental factors. Furthermore, the report discusses the global prevalence of malaria, highlighting the areas most affected, such as sub-Saharan Africa, and the groups at highest risk, including children under five and pregnant women. The report delves into the genetic and acquired factors that influence an individual's susceptibility to malaria, including the sickle cell trait and acquired immunity. The report also touches on the impact of malaria on public health, the symptoms of the disease, and the importance of early detection and treatment.

PLASMODIUM FALCIPARUM (MALARIA)
INTRODUCTION
The genus of protozoa (unicellular eukaryotes) Plasmodium includes chromalveolate - protists of
the phylum - Apicomplexa, order - Haemosporida, family - Plasmodidae. Their members of the
genus are obligate parasites of vertebrate hosts; Plasmodium spp. includes Plasmodium
falciparum, Plasmodium knowlesi, Plasmodium malariae, Plasmodium vivax, and the two
closely related species Plasmodium ovale curtisi and Plasmodium ovale wallikeri, which are
genetically different. In typical human hosts, each of these six parasites causes an acute febrile
illness of varying severity and duration known as malaria.
Malaria is a global infectious disease that continues to be one of the leading causes of morbidity
and mortality in developing countries. The most severe and fatal malaria is caused mainly by
Plasmodium falciparum. Female mosquitoes of the genus Anopheles exclusively transmit
Plasmodium falciparum, feed on blood for egg production and these blood meals link humans
and host mosquitoes in the parasite's life cycle. "The successful development of the malaria
parasite in the mosquito (from the "gametocyte" stage to the "sporozoite" stage) depends on
several factors" (CDC, 2019). Of the approximately 430 species of Anopheles, only 3040
transmit malaria in nature.
Anopheles mosquitoes' life cycle is of four stages: egg, larva, pupa, and adult. The first three
stages are aquatic, depending on the species and the ambient temperature. The female Anopheles
mosquito that bites can transmit malaria. Male mosquitoes cannot transmit malaria or other
diseases; they do not bite and. Adult female mosquitoes are generally short-lived, with only a
tiny fraction living long enough (more than ten days in tropical regions) to transmit malaria.
Unlike the human host, the mosquito host does not suffer markedly from the presence of the
parasites.
Malaria is caused by Plasmodium falciparum (also known as malignant or falciparum malaria).
However, drugs are available for treatment, it is responsible for more than 90% of global malaria
mortality, and therefore it remains a significant threat to global public health. Malaria is endemic
in more than 90 countries and affects around 40% of the world's population. P. falciparum is

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prevalent in the WHO African region, accounting for 99.7% of malaria cases; it is also
widespread in Southeast Asia, the eastern Mediterranean, and the western Pacific.
The groups most affected by malaria in high transmission areas are children under five years of
age, whose deaths account for 67% of deaths from malaria globally. In low transmission areas,
all age groups are at risk due to low immunity. Its management and prognosis depend on the
knowledge of a possible diagnosis, early detection, and timely effective treatment.
LIFE CYCLE OF PLASMODIUM FALCIPARUM
The malaria pathogen is transmitted to the human host when an infected female Anopheles
mosquito ingests blood, and at the same time, passes a small number of sporozoites contained in
its salivary glands into human skin.
In humans, the agile sporozoite enters the bloodstream, allowing it to reach the liver and thus
escape host immunity or drainage through the lymphatic system. Once the sporozoites have
reached the hepatic sinusoids, they cross the sinusoidal barrier and invade the hepatocytes, in
which they build a parasitophorous vacuole and differentiate in the first round of asexual
replication; The parasites grow and multiply for two to several days, first in the liver cells and
then in red blood cells. Once in the bloodstream, the merozoites rapidly invade circulating red
blood cells (RBCs), initiating the repeated cycle of asexual replication. The parasite goes through
the ring and trophozoite stages for 48 hours before finally replicating in the schizont stage
(schizogony) in 8 to 32 daughter merozoites. At this point, the parasitized erythrocytes (pRBCs)
breakthrough and release merozoites into the circulation, initiating another round of asexual
replication. During each cycle, a small subset of parasites deviate from asexual reproduction and
instead produce sexual offspring that separate the following process into male and female sexual
forms known as gametocytes. Male and female gametocytes re-enter the peripheral circulation
(although evidence suggests that the bone marrow is the primary site of gametocyte maturation),
becoming competent for mosquito infection. Mature gametocytes can circulate in human blood
for several days, maximizing their chances of transmitting to mosquitoes. A female Anopheles
mosquito ingests gametocytes as she feeds on an infected human.

In the mosquito's stomach, fertilization of a macrogamete by a microgamete results in the
formation of a zygote, which undergoes meiosis and becomes an invasive mobile ookinete that
traverses the epithelial layer of the midgut wall to form an oocyst. When the oocyst wall bursts,
it penetrates the hemolymph to enter the salivary gland. From there, the sporozoites reach the
mosquito's salivary glands and invade the gland, where they remain until they are transmitted to
a new human host.
When the Anopheles mosquito ingests blood in human, anticoagulant saliva is injected along
with the sporozoites that travel to the liver in the blood, thus continuing the life cycle of malaria.
Parasites in the blood stage are responsible for the clinical manifestations of the disease. Thus,
the infected mosquito transmits the disease from one person to another (as a "vector"), while
infected people transmit the parasite to the mosquito. Unlike the human host, the vector mosquito
does not suffer from the presence of parasites.
TRANSMISSION OF MALARIA (Plasmodium falciparum)
Malaria transmission depends on the vector, the human host, and the environment. When an
infected female Anopheles mosquito bites a human, a small amount of blood is drawn, so the
sporozoites (microscopic malaria parasites) enter the peripheral bloodstream and are taken up by
the hepatocytes, where they form a pre-erythrocyte asexual (liver stage) in the liver go through
schizonts up to 2 weeks before the start of the sanguine stage.
Within red blood cells, the merozoite develops through the process of erythrocytic schizogony
into an erythrocytic schizont (blood-stage) or a spherical or banana-shaped mononuclear
gametocyte. The time required for erythrocyte schizogony, which determines the time between
the release of successive generations of merozoites, is responsible for the classic periodicity of
fever in malaria. However, the clinical symptoms are mainly due to the asexual stages of the
parasite's multiplication in human blood. The time between infection with the pathogenic
parasite and the appearance of malaria symptoms is called malaria incubation. The infected
person may feel normal for 7 to 14 days when infected with P. falciparum because it has a
shorter incubation period.

Because malaria is found in the red blood cells of an infected person, malaria can rarely be
transmitted through organ transplants, blood transfusions, or sharing blood-contaminated needles
or syringes, and malaria can also be transmitted from mother to fetus before or during delivery.
The ability of the human body to prevent the invasion of malaria pathogens is an essential factor
in the transmission of malaria and depends on climatic conditions; Mosquito survival is based on
precipitation patterns, temperature, and humidity. Transmission is most intense where the
mosquito has a longer life (so that the parasite has time to complete its development in the
mosquito).
Where does malaria transmission occur?
For Plasmodium falciparum (malaria) transmission to occur, conditions must be such that all
three components of the malaria life cycle are present:
 Anopheles mosquitoes, which can feed on humans, and in which the parasites spend half
their cycle life of "guest without the host."
 People can complete it. Anopheles mosquitoes can bite that and in which the parasites, as
"vortex hosts," can complete half their life cycle
 Malaria parasites.
Malaria occurs worldwide but is rare in the United States. It is common in developing countries
and areas with warm temperatures and high humidity, including Africa, Central, and South
America, the Dominican Republic, Haiti and other regions of the Caribbean, Eastern -Europe,
South Asia, and some regions in Oceania.
In many malaria-endemic countries, P. falciparum (malaria) transmission does not occur in all
parts of the country. Transmission does not occur even within tropical and subtropical areas; at
very great heights; during the colder seasons in some regions; in deserts (no oases), and in some
countries where transmission has been interrupted by successful control/elimination programs.
The disease is still widespread in the tropics and subtropics and the warmer regions closer to the
equator. In these areas, malaria transmission can be endemic and predictable every year, or an
epidemic, which occurs sporadically if conditions are right. Endemic malaria transmission can

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occur year-round or seasonally. In some regions of Africa, 90 to 100 percent of children under
five years old have a constant stream of malaria parasites in their blood. Since naturally acquired
immunity develops with increased exposure, malaria is more common in children in endemic
areas. On the other hand, naturally obtained immunity falls between epidemics, and malaria
affects all age groups in outbreaks.
The highest transmission is found in Africa, sub-Sahara, and parts of Oceania such as Papua
New Guinea. This parasite is widespread in many countries in sub-Saharan Africa. The WHO
African Region continues to bear a disproportionate share of the global malaria challenges. The
region, in 2019 was home to 94% of all malaria cases and deaths; about half of all malaria deaths
worldwide occurred in 6 countries: Nigeria (23%), the Democratic Republic of the Congo (11%),
the United Republic of Tanzania (5%), Burkina Faso (4%), Mozambique (4%) and Niger (4ch).
Economic development and public health efforts have eradicated malaria in many temperate
areas, such as Western Europe and the United States. However, most of these areas are home to
Anopheles mosquitoes that can transmit P. falciparum (malaria), and reintroducing the disease is
a constant threat.
Who is most likely to be infected by P. falciparum (malaria) and the
circumstances under which they may be infected?
According to the World's latest Malaria Report, released on November 30, 2020, there were 229
million malaria cases in 2019, compared with 228 million patients in 2018. The estimated
number of deaths from malaria in 2019 was 409,000, compared to 411,000 deaths in the year.
2018 4,444 people prone to mosquito bites infected with P. falciparum are at increased risk of
dying from malaria. People at high risk of infection with P. falciparum include:
 A human who has little or no immunity to P. falciparum (malaria).
 Young children are more likely to become very sick and die.
 Travelers from malaria-free regions with little or no immunity are very vulnerable to areas
with high P. falciparum (malaria) infection rates.

 Pregnant women with low immunity and HIV-infected pregnant women are at high risk of
severe anemia and impaired fetal development.
 In rural and riverine areas with limited access to health care services, people are at high risk
for malaria infection.
An estimated 90% of deaths due to malaria occur in Africa south of the Sahara, with most
children of five years and below in 2019; they accounted for 67% (274 000) of all malaria deaths
worldwide. Malaria infection results in high rates of miscarriage and causes over 10% of
maternal deaths, soaring to a 50% rate in cases of the severe disease annually. An estimated
200,000 infants die annually due to infection during pregnancy. Biological traits (innate and
acquired) and behavioral traits can affect an individual's risk of malaria and the ecology of
malaria as a whole on a larger scale.
HUMAN FACTORS AND PLASMODIUM FALCIPARUM (MALARIA)
TRANSMISSION
Genetic Factors
Biological properties that exist from birth can be protected from certain types of malaria. Two
genetic factors are epidemiologically important, both of which are associated with human
erythrocytes. Individuals with the sickle cell trait (a heterozygote of the abnormal hemoglobin
gene HbS) enjoy physical benefits because they are relatively protected from Plasmodium
falciparum. Because P. falciparum malaria has long been one of the leading causes of death in
Africa, and the sickle cell trait is now more common in Africans and people of African descent
than in other populations. In general, hemoglobin-related disorders and other hemoglobin
disorders such as hemoglobin C, thalassemia, and G6PD deficiency are more common in
endemic malaria areas. They are thought to protect against malaria disease.
Acquired Immunity
Acquired immunity has a significant impact on the impact of malaria on individuals and
communities. After repeated malaria attacks, a person can partially develop defensive immunity.

These "semi-immunized" people are still often infected with malaria parasites, but they do not
develop severe illness and may not even show the typical malaria symptoms.
In areas with a high prevalence of Plasmodium falciparum (most of sub-Saharan Africa),
newborns may be protected by maternal antibodies transmitted through the placenta during the
first few months of life. As these antibodies decrease with time, these young children become
vulnerable to disease and death by malaria. If they survive repeated infections to an older age (25
years), they will have reached a protective semi-immune status. Thus, young children are a
significant risk group in high transmission areas and are targeted preferentially by malaria
control interventions.
In areas with lower transmission (such as Asia and Latin America), infections are less frequent,
and a more significant proportion of older children and adults have no protective immunity. In
such areas, malaria disease can be found in all age groups, and epidemics can occur.
Pregnancy and malaria
Pregnancy reduces immunity to many infectious diseases. Women who have developed
protective immunity against Plasmodium falciparum tend to lose this protection during
pregnancy, especially during the first and second pregnancies. Malaria during pregnancy is
harmful not only to the mother but also to the foetation. The latter are at high risk of preterm
birth and low birth weight and are less likely to survive in the first few months of life. For this
reason, pregnant women (in addition to minor children) are specially protected by malaria
control programs in endemic countries.
Behavioral Factors
Human behavior is often determined by social and economic reasons and can affect the risk of
malaria in individuals and communities. Example:
 Rural poor in malaria-endemic areas often cannot afford shelters or mosquito nets to protect
against mosquitoes. These people often lack the knowledge to recognize malaria and treat it
correctly and at the right time. Cultural beliefs often lead to the use of traditional and
ineffective treatments.

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 Travelers from non-epidemic areas can choose not to use insect repellents or drugs to prevent
malaria. The reason could be cost, inconvenience, or lack of knowledge.
 Human activity can create breeding grounds for larvae (irrigation canals, stagnant water in
construction pits). Agricultural work such as harvesting (which is also affected by climate)
can increase the chances of being bitten by mosquitoes at night. Keeping pets near the home
can provide an alternative blood meal for Anopheles mosquitoes, thus reducing human
exposure.
 Wars, migration (voluntary or compulsory), and tourism can expose non-immunized
individuals to an environment high in malaria infection.
Human behavior in endemic countries also determines how successful malaria control is in
reducing infections. Governments in malaria-endemic countries often lack financial means. As a
result, public health workers are often overwhelmed with low wages. They lack equipment,
medicine, training, and supervision. Locals are familiar with these situations and are no longer
dependent on public sector medical facilities.
On the contrary, the private sector is suffering from problems. In many cases, regulatory
measures have not been implemented. This facilitates unlicensed and costly face-to-face
consultations with healthcare providers and the messy prescription and sale of narcotics (some of
which are counterfeit products). Correcting this situation is a significant challenge that must be
addressed to control malaria and eradicate it successfully.
But apart from global warming, P. falciparum (malaria) epidemiology has several other
determinants, including political, economic development, urbanization, population growth, and
migration changes.
DIAGNOSIS OF MALARIA (Plasmodium falciparum)
Diagnosis of malaria usually relies on the detection of parasites in the blood by microscopy.
Additional laboratory findings may include:
 Mild anemia.
 A slight decrease in platelets (thrombocytopenia).
 An increase in bilirubin and aminotransferases.

Diagnosis of malaria requires a high level of suspicion. People who have a fever, visit malaria-
endemic areas, receive blood transfusions, or receive intravenous medication should consider
malaria. 95% of people infected with malaria develop the underlying disease within six weeks of
exposure. However, some people have a direct attack within one year of exposure, while others
recurrence malaria within 23 years of exposure. There is a possibility. Therefore, people who
have recently contracted a febrile illness should be screened for malaria. A definitive malaria
diagnosis generally requires direct observation of malaria parasites on thick and thin blood
smears stained with Giemsa. Thick blood films are more difficult to interpret than thin blood
films, but they are much more sensitive because more blood is tested. A thin blood smear
showing parasites in red blood cells determines the parasite-infected. The existence of diagnosis
forms varies greatly depending on the life cycle stage, especially the onset of the disease. In P.
falciparum malaria, most organisms are isolated in the microvascular tissue of the internal organs
and are therefore absent in peripheral blood. If malaria is suspected, blood smears should be
tested every 6 - 12 hours for at least two days. New diagnostic methods include rapid antigen
capture dipstick testing and techniques to detect parasites with fluorescent dyes. Both tests are
quick and easy to run. You are vulnerable and concrete. Other diagnostic methods include
malaria antibodies and antigens and polymerase chain reaction / DNA and RNA probe
techniques. These techniques are primarily used in epidemiological studies and immunization
trials and rarely diagnose individual patients. People who show signs of malaria should be tested
and treated immediately.
WHO strongly recommends testing for parasites by microscopic or rapid diagnostic testing
(RDT), depending on the available facilities. Parasite testing is essential for detecting and
treating malaria, as the combination of symptoms does not reliably distinguish malaria from
other causes. In some malaria-endemic areas, such as sub-Saharan Africa, the severity of the
disease can provide mild immunity to most local populations. As a result, some people carry
parasites in their blood, but they do not get sick.
SIGNS AND SYMPTOMS OF MALARIA (Plasmodium falciparum)
Malaria is an acute febrile illness. In non-immune people, symptoms usually appear 10 to 15
days after being bitten by an infectious mosquito. The first symptoms (fever, headache, chills)

are mild and can be identified as malaria. If Plasmodium falciparum is not treated within 24
hours, it can lead to severe illness and often death.
Doctors divide P. falciparum (malaria) symptoms into two categories: Uncomplicated and severe
malaria.
Uncomplicated malaria
A typical (rare) explanation for a malaria attack is a 6-12 hour cold. It chills that alternate
between fever and headache, followed by sweating and malaise (sometimes divided into cold and
hot stages).
These symptoms are very non-specific. It is essential to assess whether a patient has a risk factor
for malaria (regular travel to endemic areas).
The most common symptoms are:
 Fever and chills,
 Headaches,
 Nausea and vomiting, and
 General weakness and body aches.
Complicated or severe malaria
A simplified list of risk signs such as fatigue, shortness of breath (acidic breathing), and impaired
consciousness is used for rapid clinical evaluation. Other clinical symptoms of severe malaria
include multiple convulsions, radiological confirmed pulmonary edema (respiratory failure due
to acute lung injury leading to acute respiratory distress syndrome), and abnormal bleeding
(disseminated intravascular coagulation), acute renal failure, seizures, shock, strange behavior, or
confusion and coma. Laboratory features of severe malaria may indicate severe anemia (due to
the destruction of red blood cells), hypoglycemia, acidosis, and hyperparasitemia.
Children with severe malaria often develop severe anemia, shortness of breath with metabolic
acidosis, or one or more symptoms of brain malaria. Multiple organ failure is also common in
adults. In malaria-endemic areas, people can develop partial immunity, which can lead to
asymptomatic infections.

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Other Manifestations of Plasmodium falciparum:
Neurological deficits can persist after cerebral malaria, especially in children. These deficiencies
include movement disorders (ataxia), cardiovascular collapse, paralysis, speech disorders,
deafness, and blindness. Recurrent infections with Plasmodium falciparum can lead to severe
anemia. This is most common in tropical African infants, who frequently develop inadequately
treated diseases.
Plasmodium falciparum infection during pregnancy can cause serious illness in the mother,
leading to preterm birth and low birth weight infants. is associated with complications such as
hypoglycemia (especially after treatment with quinine), maternal anemia, miscarriage, stillbirth,
and congenital malaria, pulmonary edema late in pregnancy than non-pregnant adults.
PREVENTION AND CONTROL MALARIA (Plasmodium
falciparum)
Prevention focuses on reducing the transmission of the disease by controlling the mosquitoes that
carry P. falciparum (malaria). WHO recommends to all people at risk of malaria protection
through effective malaria vector management. Two forms of vector control, insecticide-treated
nets (ITN) and Indoor residual spraying (IRS), are effective in many situations.
Insecticide-treated mosquito nets:
Sleeping under an insecticide treatment net (ITN) can reduce mosquito-human contact by
providing a physical barrier and insecticidal effect. Population-wide protection can result from
the killing of mosquitoes on a large scale where there is high access and usage of such nets
within a community.
There are no drugs that are 100% effective, so it is of utmost importance to avoid mosquito
bites. These precautions include:
 Sleep under bed nets: These should cover the entire bed to the floor. These nets are
most effective when treated with pesticides.

 Clothing: Clothing that covers the most exposed skin and closed shoes can reduce the
risk of bites. Put all clothing and trousers in socks so that the area around your ankles is
not exposed. In addition, treating clothing with pesticides can further prevent bites.
 Apply insect repellent to all exposed skin areas.
In 2019, an estimated 46% of people at risk of malaria in Africa were protected by pesticide-
treated nets, compared to 2% in 2000. However, ITN coverage has been inactive since 2016.
Indoor spraying with residual insecticides:
Indoor residual spraying (IRS) with insecticides is another effective way to reduce malaria
transmission quickly. The interior of a house is usually sprayed with insecticides once or twice a
year. To provide critical community protection, the IRS must be implemented with a high level
of coverage.
Globally, IRS protection fell from a high of 5% in 2010 to 2% in 2019, declining in all WHO
regions except the WHO Eastern Mediterranean. The coverage of the IRS decreases as the
country switches from pyrethroid pesticides to more expensive alternatives to reduce mosquito
resistance to pyrethroids.
There are no 100% effective interventions to prevent infections, but several different approaches
are available that can be used alone or in combination. Personal protective measures can reduce
the risk of exposure to infectious mosquitoes, and chemoprophylaxis can reduce the risk of
adverse consequences in the event of infection.
A commonly applied approach is malaria "ABCD."
 A represents risk awareness,
 B represents bite avoidance,
 C represents chemoprophylaxis compliance, and
 D represents fever diagnosis.