CREATED BY : RAGIL BAGUS T
ENGLISH DIPLOMA PROGRAM
JENDERAL SOEDIRMAN UNIVERSITY
MALARIA
Malaria is a
mosquito-borne infectious disease of humans
and other animals caused by
protists (a type of microorganism) of the genus
Plasmodium.
It begins with a bite from an infected female
Anopheles
mosquito, which introduces the protists through saliva into the
circulatory system. In the blood, the protists
travel to the liver to mature and reproduce. Malaria causes symptoms that
typically include
fever
and
headache,
which in severe cases can progress to
coma or
death. The disease is
widespread in
tropical
and
subtropical
regions in a broad band around the equator, including much of
Sub-Saharan Africa,
Asia, and the
Americas.
Five species of
Plasmodium can infect and be transmitted by humans.
The vast majority of deaths are caused by
P. falciparum and
P. vivax,
while
P. ovale, and
P. malariae cause a generally milder
form of malaria that is rarely fatal. The
zoonotic
species
P. knowlesi, prevalent in Southeast
Asia, causes malaria in
macaques but can also cause severe infections in humans.
Malaria is prevalent in tropical and subtropical regions because rainfall, warm
temperatures, and stagnant waters provide habitats ideal for
mosquito
larvae. Disease transmission can be reduced by preventing mosquito bites by
distribution of
mosquito nets and
insect
repellents, or with mosquito-control measures such as spraying
insecticides
and draining standing water.
Malaria is typically diagnosed by the microscopic examination of blood using
blood
films, or with
antigen-based
rapid diagnostic tests. Modern
techniques that use the
polymerase chain reaction to detect the
parasite's
DNA have
also been developed, but these are not widely used in malaria-
endemic areas due to their cost and
complexity. The
World Health Organization has estimated
that in 2010, there were 219 million documented cases of malaria. That year,
between 660,000 and 1.2 million people died from the disease,
[1]
many of whom were children in Africa. The actual number of deaths is not known
with certainty, as accurate data is unavailable in many rural areas, and many
cases are undocumented. Malaria is commonly associated with poverty and may
also be a major hindrance to
economic development.
Despite a need, no effective
vaccine currently exists, although efforts to develop one are
ongoing. Several medications are available to prevent malaria in travellers to
malaria-endemic countries (
prophylaxis). A variety of
antimalarial medications are available.
Severe malaria is treated with
intravenous or
intramuscular quinine or, since
the mid-2000s, the
artemisinin derivative
artesunate,
which is superior to quinine in both children and adults and is given in
combination with a second anti-malarial such as
mefloquine.
Resistance
has developed to several antimalarial drugs; for example,
chloroquine-resistant
P. falciparum has spread to most malarial areas, and emerging
resistance to artemisinin has become a problem in some parts of Southeast Asia.
The signs
and symptoms of malaria typically begin 8–25 days following infection;[2] however, symptoms may occur later in
those who have taken antimalarial medications as prevention.[3] Initial manifestations of the
disease—common to all malaria species—are similar to flu-like
symptoms,[4] and can resemble other conditions such
as septicemia, gastroenteritis, and viral diseases.[3] The presentation may include headache, fever,
shivering, joint pain, vomiting, hemolytic anemia, jaundice, hemoglobin in the urine, retinal damage,[5] and convulsions.
The classic
symptom of malaria is paroxysm—a
cyclical occurrence of sudden coldness followed by rigor and then
fever and sweating, occurring every two days (tertian fever) in P. vivax
and P. ovale infections, and every three days (quartan fever) for P. malariae.
P. falciparum infection can cause recurrent fever every 36–48 hours
or a less pronounced and almost continuous fever.[6]
Complications
Infection
with P. falciparum may result in cerebral malaria, a form of severe malaria that
involves encephalopathy. It is
associated with retinal whitening, which may be a useful clinical sign in
distinguishing malaria from other causes of fever.[9] Splenomegaly, severe headache, hepatomegaly (enlarged liver), hypoglycemia, and hemoglobinuria with renal failure may occur.[4]
Cause
Malaria parasites belong to the genus Plasmodium (phylum Apicomplexa). In humans, malaria is caused by P. falciparum,
P. malariae,
P. ovale,
P. vivax
and P. knowlesi.[12][13] Among those infected, P. falciparum
is the most common species identified (~75%) followed by P. vivax
(~20%).[3] Although P. falciparum
traditionally accounts for the majority of deaths,[14] recent evidence suggests that P. vivax
malaria is associated with potentially life-threatening conditions about as
often as with a diagnosis of P. falciparum infection.[15] P. vivax proportionally is
more common outside of Africa.[16] There have been documented human
infections with several species of Plasmodium from higher apes; however, with the exception of P. knowlesi—a
zoonotic species that causes malaria in macaques[13]—these are mostly of limited public
health importance.[17]
The life cycle
of malaria parasites: A mosquito causes infection by taking a blood meal.
First, sporozoites enter the bloodstream, and migrate to the liver. They infect
liver cells, where they multiply into merozoites,
rupture the liver cells, and return to the bloodstream. Then, the merozoites
infect red blood cells, where they develop into ring forms, trophozoites and
schizonts that in turn produce further merozoites. Sexual forms are also produced, which, if taken
up by a mosquito, will infect the insect and continue the life cycle.
In the life
cycle of Plasmodium, a female Anopheles mosquito (the definitive host) transmits a motile infective
form (called the sporozoite) to a
vertebrate host such as a human (the secondary host), thus acting as a
transmission vector. A
sporozoite travels through the blood vessels to liver cells (hepatocytes), where it reproduces asexually
(tissue schizogony), producing thousands of merozoites.
These infect new red blood cells and initiate a series of asexual
multiplication cycles (blood schizogony) that produce 8 to 24 new infective
merozoites, at which point the cells burst and the infective cycle begins anew.[18] Other merozoites develop into immature
gametes, or gametocytes. When a fertilised
mosquito bites an infected person, gametocytes are taken up with the blood and
mature in the mosquito gut. The male and female gametocytes fuse and form zygotes (ookinetes), which develop
into new sporozoites. The sporozoites migrate to the insect's salivary glands, ready to infect a new vertebrate
host. The sporozoites are injected into the skin, alongside saliva, when the
mosquito takes a subsequent blood meal.[19]
Only female
mosquitoes feed on blood; male mosquitoes feed on plant nectar, and thus do not
transmit the disease. The females of the Anopheles genus of mosquito
prefer to feed at night. They usually start searching for a meal at dusk, and
will continue throughout the night until taking a meal.[20] Malaria parasites can also be
transmitted by blood transfusions,
although this is rare.[21]
Recurrent malaria
Symptoms of
malaria can reappear (recur) after varying symptom-free periods. Depending upon
the cause, recurrence can be classified as either recrudescence, relapse, or reinfection. Recrudescence is when
symptoms return after a symptom-free period. It is caused by parasites
surviving in the blood as a result of inadequate or ineffective treatment.[22] Relapse is when symptoms reappear
after the parasites have been eliminated from blood but persist as dormant
hypnozoites in liver cells. Relapse commonly occurs between 8–24 weeks and is
commonly seen with P. vivax and P. ovale infections.[3] P. vivax malaria cases in temperate areas often involve overwintering by hypnozoites, with relapses beginning
the year after the mosquito bite.[23] Reinfection means the parasite that
caused the past infection was eliminated from the body but a new parasite was
introduced. Reinfection cannot readily be distinguished from recrudescence,
although recurrence of infection within two weeks of treatment for the initial
infection is typically attributed to treatment failure.[24]
Pathophysiology
Malaria
infection develops via two phases: one that involves the liver
(exoerythrocytic phase), and one that involves red blood cells, or erythrocytes (erythrocytic phase). When an
infected mosquito pierces a person's skin to take a blood meal, sporozoites in
the mosquito's saliva enter the bloodstream and migrate to the liver where they
infect hepatocytes, multiplying asexually and asymptomatically for a period of
8–30 days.[25]
After a
potential dormant period in the liver, these organisms differentiate
to yield thousands of merozoites, which,
following rupture of their host cells, escape into the blood and infect red
blood cells to begin the erythrocytic stage of the life cycle.[25] The parasite escapes from the liver
undetected by wrapping itself in the cell membrane of the infected host liver cell.[26]
Within the
red blood cells, the parasites multiply further, again asexually, periodically
breaking out of their host cells to invade fresh red blood cells. Several such
amplification cycles occur. Thus, classical descriptions of waves of fever
arise from simultaneous waves of merozoites escaping and infecting red blood
cells.[25]
Some P. vivax
sporozoites do not immediately develop into exoerythrocytic-phase merozoites,
but instead produce hypnozoites that remain dormant for periods ranging from
several months (7–10 months is typical) to several years. After a period of
dormancy, they reactivate and produce merozoites. Hypnozoites are responsible
for long incubation and late relapses in P. vivax infections,[23] although their existence in P. ovale
is uncertain.[27]
The parasite
is relatively protected from attack by the body's immune system because for most of its human life
cycle it resides within the liver and blood cells and is relatively invisible
to immune surveillance. However, circulating infected blood cells are destroyed
in the spleen. To avoid this fate, the P. falciparum
parasite displays adhesive proteins on the surface of
the infected blood cells, causing the blood cells to stick to the walls of small
blood vessels, thereby sequestering the parasite from passage through the
general circulation and the spleen.[28] The blockage of the microvasculature
causes symptoms such as in placental malaria.[29] Sequestered red blood cells can breach
the blood–brain barrier
and cause cerebral malaria.[30]
Although the
red blood cell surface adhesive proteins (called PfEMP1,
for P. falciparum erythrocyte membrane protein 1) are exposed
to the immune system, they do not serve as good immune targets because of their
extreme diversity; there are at least 60 variations of the protein within a
single parasite and even more variants within whole parasite populations. The
parasite switches through a broad repertoire of PfEMP1 surface proteins,
thereby avoiding detection by protective antibodies.[31]
Genetic resistance
The impact
of sickle cell trait on malaria immunity is of particular interest. Sickle cell
trait causes a defect in the hemoglobin molecule in the blood. Instead of
retaining the biconcave shape of a normal red blood cell, the modified hemoglobin S molecule causes the cell to
sickle or distort into a curved shape. Due to the sickle shape, the molecule is
not as effective in taking or releasing oxygen. Infection causes red cells to
sickle more, and so they are removed from circulation sooner. This reduces the
frequency with which malaria parasites complete their life cycle in the cell.
Individuals who are homozygous (with two
copies of the abnormal hemoglobin beta allele) have sickle-cell anaemia,
while those who are heterozygous (with one abnormal allele and one normal
allele) experience resistance to malaria. Although the shorter life expectancy
for those with the homozygous condition seems to be unfavourable to the trait's
survival, the trait is preserved because of the benefits
provided by the heterozygous form.[33][34]
Liver dysfunction
Liver
dysfunction as a result of malaria is rare and is usually a result of a
coexisting liver condition such as viral hepatitis or chronic liver disease.
The syndrome is sometimes called malarial hepatitis, although
inflammation of the liver (hepatitis) does not
actually occur. While traditionally considered a rare occurrence, malarial
hepatopathy has seen an increase, particularly in Southeast Asia and India.
Liver compromise in people with malaria correlates with a greater likelihood of
complications and death.[35]
Diagnosis
Approximately
30% of people will no longer have a fever upon arriving to a health care
facility. Owing to the non-specific nature of the presentation, diagnosis of
malaria in non-endemic areas requires a high degree of suspicion, which might
be elicited by any of the following: recent travel history, enlarged spleen, fever without localizing signs, low platelets, and hyperbilirubinemia
combined with a normal peripheral blood leukocyte count.[3]
Malaria is
usually confirmed by the microscopic examination of blood films or by antigen-based rapid
diagnostic tests (RDT).[36][37] Microscopy is the most commonly used
method to detect the malarial parasite—about 165 million blood films were
examined for malaria in 2010.[38] Despite its widespread usage, diagnosis
by microscopy suffers from two main drawbacks: many settings (especially rural)
are not equipped to perform the test, and the accuracy of the results depends
on both the skill of the person examining the blood film and the levels of the
parasite in the blood. The sensitivity
of blood films ranges from 75–90% in optimum conditions, to as low as 50%.
Commercially available RDTs are often more accurate than blood films at
predicting the presence of malaria parasites, but they are widely variable in
diagnostic sensitivity and specificity depending on manufacturer, and are
unable to tell how many parasites are present.[38]
In regions
where laboratory tests are readily available, malaria should be suspected, and
tested for, in any unwell patient who has been in an area where malaria is
endemic. In areas that cannot afford laboratory diagnostic tests, it has become
routine to use only a history of subjective fever as the indication to treat
for malaria—a presumptive
approach exemplified by the common teaching "fever equals malaria unless
proven otherwise". A drawback of this practice is overdiagnosis of malaria and mismanagement of
non-malarial fever, which wastes limited resources, erodes confidence in the
health care system, and contributes to drug resistance.[39] Although polymerase chain
reaction-based tests have been developed, these are not widely
implemented in malaria-endemic regions as of 2012, due to their complexity.[3]
Classification
Malaria is
classified into either "severe" or "uncomplicated" by the World Health Organization
(WHO).[3] It is deemed severe when any of
the following criteria are present, otherwise it is considered uncomplicated.[40]
Cerebral
malaria is defined as a severe P. falciparum-malaria presenting
with neurological symptoms, including coma (with a Glasgow coma scale
less than 11, or a Blantyre coma scale
greater than 3), or with a coma that lasts longer than 30 minutes after a
seizure.[41]
Prevention
Methods used
to prevent malaria include medications, mosquito elimination and the prevention
of bites. The presence of malaria in an area requires a combination of high
human population density, high mosquito population density and high rates of
transmission from humans to mosquitoes and from mosquitoes to humans. If any of
these is lowered sufficiently, the parasite will eventually disappear from that
area, as happened in North America, Europe and much of the Middle East.
However, unless the parasite is eliminated from the whole world, it could
become re-established if conditions revert to a combination that favours the
parasite's reproduction.[42]
Many
researchers argue that prevention of malaria may be more cost-effective than
treatment of the disease in the long run, but the capital costs required are out of reach of many
of the world's poorest people. There is a wide disparity in the costs of
control (i.e. maintenance of low endemicity) and elimination programs between
countries. For example, in China—whose government in 2010 announced a strategy
to pursue malaria elimination in the Chinese provinces—the required investment is a
small proportion of public expenditure on health. In contrast, a similar
program in Tanzania would cost an estimated one-fifth of the public health
budget.[43]
Vector control refers to preventative methods
used to decrease malaria and morbidity and mortality by reducing the levels of
transmission. For individual protection, the most effective chemical insect repellents to reduce human-mosquito
contact are those based on DEET and picaridin.[44] Insecticide-treated mosquito nets (ITNs) and indoor residual
spraying (IRS) have been shown to be highly effective vector control
interventions in preventing malaria morbidity and mortality among children in
malaria-endemic settings.[45][46] IRS is the practice of spraying
insecticides on the interior walls of homes in malaria-affected areas. After
feeding, many mosquito species rest on a nearby surface while digesting the
bloodmeal, so if the walls of dwellings have been coated with insecticides, the
resting mosquitoes can be killed before they can bite another victim and
transfer the malaria parasite.[47] As of 2006, the World Health
Organization advises the use of 12 insecticides in IRS operations, including DDT and the pyrethroids cyfluthrin and deltamethrin.[48] This public health use of small
amounts of DDT is permitted under the Stockholm Convention
on Persistent
Organic Pollutants (POPs), which prohibits the agricultural use of
DDT.[49]
One problem
with all forms of IRS is insecticide resistance via evolution. Mosquitoes
affected by IRS tend to rest and live indoors, and due to the irritation caused
by spraying, their descendants tend to rest and live outdoors, meaning that
they are less affected by the IRS, which greatly reduces its effectiveness as a
defense mechanism.[50]
Mosquito nets
help keep mosquitoes away from people and significantly reduce infection rates
and transmission of malaria. Nets are not a perfect barrier and are often
treated with an insecticide designed to kill the mosquito before it has time to
find a way past the net. Insecticide-treated nets are estimated to be twice as
effective as untreated nets and offer greater than 70% protection compared with
no net.[51] Between 2000 and 2008, the use of ITNs
saved the lives of an estimated 250,000 infants in Sub-Saharan Africa.[52] Although ITNs prevent malaria, only
about 13% of households in Sub-Saharan countries own them.[53] A recommended practice for usage is to
hang a large "bed net" above the center of a bed to drape over it
completely with the edges tucked in. Pyrethroid-treated nets and long-lasting
insecticide-treated nets offer the best personal protection, and are most
effective when used from dusk to dawn.[54]
Other methods
Community
participation and health education
strategies promoting awareness of malaria and the importance of control measures
have been successfully used to reduce the incidence of malaria in some areas of
the developing world.[55] Recognizing the disease in the early
stages can stop the disease from becoming fatal. Education can also inform
people to cover over areas of stagnant, still water, such as water tanks that
are ideal breeding grounds for the parasite and mosquito, thus cutting down the
risk of the transmission between people. This is generally used in urban areas
where there are large centers of population in a confined space and
transmission would be most likely in these areas.[56] Intermittent
preventive therapy is another intervention that has been used
successfully to control malaria in pregnant women and infants,[57] and in preschool children where
transmission is seasonal.[58]
Medications
Several
drugs, most of which are used for treatment of malaria, can be taken to prevent
contracting the disease during travel to endemic areas. Chloroquine may be used where the parasite is
still sensitive.[59] Because of the prevalence of
drug-resistant Plasmodium, one of three medications—mefloquine (Lariam), doxycycline (available generically), or the combination
of atovaquone and proguanil hydrochloride (Malarone)—is
frequently needed.[59] Doxycycline and the atovaquone and
proguanil combination are the best tolerated; mefloquine is associated with
death, suicide, and higher rates of neurological and psychiatric symptoms.[59]
The
prophylactic effect does not begin immediately upon starting the drugs, so
people temporarily visiting malaria-endemic areas usually begin taking the
drugs one to two weeks before arriving and should continue taking them for four
weeks after leaving (with the exception of atovaquone proguanil that only needs
to be started two days prior and continued for seven days afterwards).[60] Use of prophylactic drugs is seldom
practical for full-time residents of malaria-endemic areas, and their use is
usually restricted to short-term visitors and travellers to malarial regions.
This is due to the cost of purchasing the drugs, negative adverse effects
from long-term use, and because some effective anti-malarial drugs are
difficult to obtain outside of wealthy nations.[61] The use of prophylactic drugs where
malaria-bearing mosquitoes are present may encourage the development of partial
immunity.[62]
Treatment
The
treatment of malaria depends on the severity of the disease. Uncomplicated
malaria may be treated with oral medications. The most effective strategy for P. falciparum
infection is the use of artemisinins in combination
with other antimalarials (known as artemisinin-combination
therapy, or ACT), which reduces the ability of the parasite to
develop resistance to any single drug component.[63] These additional antimalarials include
amodiaquine, lumefantrine, mefloquine or sulfadoxine/pyrimethamine.[64] Another recommended combination is dihydroartemisinin
and piperaquine.[65][66] ACT is about 90% effective when used
to treat uncomplicated malaria.[52] To treat malaria during pregnancy, the
WHO recommends the use of quinine plus clindamycin early in the pregnancy (1st
trimester), and ACT in later stages (2nd and 3rd trimesters).[67] In the 2000s (decade), malaria with
partial resistance to artemisins emerged in Southeast Asia.[68][69]
Severe malaria requires the parenteral
administration of antimalarial drugs. Until the mid-2000s the most
used treatment for severe malaria was quinine, but artesunate has been shown to be superior to
quinine in both children and adults.[70] Treatment of severe malaria also
involves supportive measures that are optimally performed in a critical care unit,
including management of high fevers (hyperpyrexia) and the subsequent seizures that
may result from it, and monitoring for respiratory depression,
hypoglycemia, and hypokalemia.[14] Infection with P. vivax, P. ovale
or P. malariae is usually treated on an outpatient basis (while a
person is at home). Treatment of P. vivax requires both treatment
of blood stages (with chloroquine or ACT) as well as clearance of liver forms
with primaquine.[71]
|
no
data
<10
0–100
100–500
500–1000
1000–1500
1500–2000
|
2000–2500
2500–2750
2750–3000
3000–3250
3250–3500
≥3500
|
When
properly treated, people with malaria can usually expect a complete recovery.[72] However, severe malaria can progress
extremely rapidly and cause death within hours or days.[73] In the most severe cases of the disease,
fatality rates can reach 20%, even with intensive
care and treatment.[3] Over the longer term, developmental
impairments have been documented in children who have suffered episodes of
severe malaria.[74] Chronic infection without severe
disease can occur, a form of acquired immunity where the immune system is also
less responsive to Salmonella and the Epstein–Barr virus.[75]
Malaria
causes widespread anemia during a period of rapid brain development, and also
direct brain damage. This neurologic damage results from cerebral malaria to
which children are more vulnerable.[74] Some survivors of cerebral malaria
have an increased risk of neurological and cognitive deficits, behavioural
disorders, and epilepsy.[76] Malaria prophylaxis was shown to
improve cognitive function and school performance in clinical trials when compared to placebo groups.[74]
The WHO
estimates that in 2010 there were 219 million cases of malaria resulting in
660,000 deaths,[78] equivalent to roughly 2000 deaths
every day.[3] Using a different set of predictive
models to estimate mortality, a 2012 study determined the number of documented
and undocumented deaths in 2010 to be 1.24 million.[79] The majority of cases (65%) occur in
children under 15 years old.[79] About 125 million pregnant women are
at risk of infection each year; in Sub-Saharan Africa,
maternal malaria is associated with up to 200,000 estimated infant deaths
yearly.here are about 10,000 malaria cases per year in Western Europe, and
1300–1500 in the United States. About 900 people died from the disease in
Europe between 1993 and 2003. Both
the global incidence of disease and resulting mortality have declined in recent
years. According to the WHO, deaths attributable to malaria in 2010 were
reduced by over a third from a 2000 estimate of 985,000, largely due to the
widespread use of insecticide-treated nets and artemisinin-based combination
therapies.
Malaria is
presently endemic in a broad band around the equator, in areas of the Americas,
many parts of Asia, and much of Africa; in Sub-Saharan Africa, 85–90% of
malaria fatalities occur. An estimate for 2009 reported that countries with the
highest death rate per 100,000 of population were Ivory Coast with 86.15, Angola (56.93) and Burkina Faso (50.66). An estimate for 2010 said
the deadliest countries per population were Burkina Faso, Mozambique and Mali.The
Malaria Atlas Project
aims to map global endemic
levels of malaria, providing a means with which to determine the global spatial
limits of the disease and to assess disease burden.[82][83] This effort led to the publication of
a map of P. falciparum endemicity in 2010. As of 2010, about 100 countries have
endemic malaria. Every year, 125 million international travellers visit these countries,
and more than 30,000 contract the disease.
The
geographic distribution of malaria within large regions is complex, and
malaria-afflicted and malaria-free areas are often found close to each other. Malaria is prevalent in tropical and
subtropical regions because of rainfall, consistent high temperatures and high
humidity, along with stagnant waters in which mosquito larvae readily mature,
providing them with the environment they need for continuous breeding. In drier areas, outbreaks of malaria have
been predicted with reasonable accuracy by mapping rainfall.Malaria is more
common in rural areas than in cities. For example, several cities in the Greater Mekong
Subregion of Southeast Asia are essentially malaria-free, but the
disease is prevalent in many rural regions, including along international
borders and forest fringes. In contrast, malaria in Africa is present in both
rural and urban areas, though the risk is lower in the larger cities.
Conclusion :
Malaria is a dangerous disease, it can strike anyone who has a place to stay
dirty, we have to keep our families from danger is, in many ways I have explained
above. start now, start living healthy and clean in order to avoid the disease.
with diligent exercise, and clean up the places that become mosquito breeding.
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http://en.wikipedia.org/wiki/Malaria
