Rehab Cell

Physical Medicine and Rehabilitation

Malaria – causes, symptoms, diagnosis, treatment, pathology


Malaria is an infection that can be caused
by a few different types of Plasmodium species, which are single-celled parasites that get
spread around by mosquitoes. Once the plasmodium gets into the bloodstream,
it starts to infect and destroy mainly liver cells and red blood cells, which causes a
variety of symptoms and sometimes even death. Malaria is a serious global health problem
that affects millions of people, particularly young children under the age of 5, pregnant
women, patients with other health conditions like HIV and AIDS, and travelers who have
had no prior exposure to malaria. Tropical and subtropical regions are hit the
hardest, together the most affected regions form the malaria belt, which is a broad band
around the equator that includes much of latin america, sub-saharan africa, south asia, and
southeast asia. There are hundreds of types of Plasmodium
species, but only five cause malarial disease in humans, and those are Plasmodium falciparum,
Plasmodium vivax, Plasmodium malariae, Plasmodium ovale, and Plasmodium knowlesi. Plasmodium vivax uses a specific erythrocyte
surface receptor called the Duffy antigen. And some individuals, particularly those with
sickle-cell anemia lack this receptor, meaning that Plasmodium vivax cannot get into their
cells. In other words, having sickle cell anemia
is genetically related to having relative protection from Plasmodium vivax. Other diseases, like thalassemia and G6PD
deficiency make the parasite-infected erythrocyte more susceptible to dying from oxidative stress. So despite the obvious downside to having
any of these diseases, they do offer an upside when it comes to warding off a malaria infection. In fact, because malaria has historically
circulated in Africa, the genes underlying these diseases are thought to have conferred
a natural selection advantage and therefore become more common in the genetic pool. Now, malaria begins when a plasmodium-infected
female Anopheles mosquito hunts for a blood meal in the evening and through the night. Like a tiny flying vampire, the mosquito is
drawn to carbon dioxide that get breathed out as well as bodily smells, like foot odor. At this point, the Plasmodium is in a stage
of development called a sporozoite, waiting patiently in the mosquito’s salivary gland. When the mosquito pierces a person’s skin
with its long and needle-shaped tusk, called a proboscis, the tiny, worm-like sporozoites
spill out of the mosquito’s saliva and make it into the bloodstream. Within minutes, the sporozoites reach the
liver and mount an attack on hepatic parenchymal cells where they begin asexual reproduction
also known as schizogony. At this point, the plasmodium species vary
a bit. Over the next 1-2 weeks, Plasmodium falciparum,
Plasmodium malariae, and Plasmodium knowlesi sporozoites multiply asexually and mature
into merozoites, while host hepatic parenchymal cells die. In contrast, over the next few months to years,
Plasmodium vivax and Plasmodium ovale sporozoites enter into a dormant hepatic phase, where
they are called hypnozoites. Hypnozoites don’t divide – instead they
snooze for a period of time before entering the process of schizogony, causing a long
delay between the initial infection and symptoms from the disease. This is called the exoerythrocytic phase because
it happens outside of the erythrocyte or red blood cell, and it’s generally asymptomatic. The merozoites are then released into the
blood, and each one binds to a surface receptor and invades a red blood cell. Plasmodium ovale and Plasmodium falciparum
invade red blood cells of all ages, whereas Plasmodium vivax prefers to invade
reticulocytes which are young, immature red blood cells, and Plasmodium malariae and Plasmodium knowlesi
prefer to invade older red blood cells. Once inside the red blood cell, the merozoite
undergoes asexual reproduction and a series of transformational changes. This phase is known as the erythrocytic phase
of malaria, because it happens inside of the red blood cell and generally lasts 2 to 3
days. In the first stage of the erythrocytic phase
the merozoite looks like a tiny ring within the red blood cell and is called an early
trophozoite or a ring form. In the second stage, the ring form trophozoite
grows and is referred to as a late trophozoite. In the third and final stage, the parasite
grows some more by digesting hemoglobin and leaves behind hemozoin, which under a microscope
looks a little like a brown feces smudge on the red blood cell, and at this point the
parasite is called a schizont. This is the actual replicative phase in which
the parasite undergoes mitosis and differentiates into lots of merozoites which can get released
into the blood. Now, instead of going into the erythrocytic
phase again, some of the merozoites undergo gametogony which is where they divide and
give rise to gametocytes which are little sausage-shaped sexual forms that can be either
male or female. These gametocytes remain inside of a red blood
cell, and can get sucked up by another female Anopheles mosquito that might take a blood
meal from the infected person. The gametocytes can then reach the mosquito’s
gut where they mature a bit more and then fuse together to form a zygote. This part of the plasmodium life cycle is
called sporogony, and it’s sexual reproduction, as opposed to the schizogony or asexual reproduction
that happened in the liver and red blood cells. The zygote then goes on to develop further,
it becomes an ookinete and then an oocyst that ruptures in the mosquito’s gut, releasing
thousands of sporozoites which navigate their way into the mosquito’s salivary gland, in
order to repeat the cycle all over again. Now, the incubation time, which is the period
of time between infection and symptom onset, varies depending on the plasmodium species. Plasmodium falciparum incubates for a few
days, whereas Plasmodium malariae incubates for a few weeks. The release of tumor necrosis factor alpha
and other inflammatory cytokines, causes fevers that typically occur in paroxysms or short
bursts, and correspond to the rupture of the infected red blood cells, which happens in
waves of reproductive cycles unique for each plasmodium species. For Plasmodium malariae, fevers happen every
72 hours, and is called quartan fever. For Plasmodium vivax and Plasmodium ovale,
fevers happen every 48 hours, and these are called tertian fever. For Plasmodium knowlesi, the fever happens
every 24 hours, and for Plasmodium falciparum, the pattern can vary – sometimes following
the pattern of tertian fever, while other times the fevers happen daily, earning it
the name malignant tertian fever. In addition to fevers, the hemolytic anemia,
which is the destruction of red blood cells, also causes symptoms like extreme fatigue,
headaches, jaundice, and splenomegaly. Most plasmodium infections have a mild course
of symptoms and are generally regarded as uncomplicated malarial infections. Out of all of the Plasmodium species, though,
Plasmodium falciparum is known for causing the worst infections. Most plasmodium-infected red blood cells get
screened and destroyed by the spleen. Plasmodium falciparum, though, avoids this
fate by generating a sticky protein that coats the surface of the infected red blood cells
and these look like “knobs” or little bumps. The protein causes the red blood cells to
clump together and jam up tiny blood vessels – a process called cytoadherence. This literally blocks the flow of blood so
that infected cells aren’t able to flow into the spleen, and it also blocks blood
flow from reaching other vital organs which can wreak havoc on them. Between hemolytic anemia and ischemic damage
from blocked blood flow, organ-failure can set in pretty quickly. When the brain is affected, it’s termed cerebral
malaria, and it results in altered mental status, seizures, and coma. When the liver is affected, it’s termed bilious
malaria, and it results in diarrhea, vomiting, jaundice, and liver failure. Other commonly affected organs include the
lungs, the kidneys, and the spleen, which taken together create a sepsis-like clinical
picture that can eventually lead to death. Together, all of these scenarios are called
complicated malaria. Malaria is usually diagnosed with a thick
blood smear that locates parasites sitting within the red blood cells and a thin blood
smear, which directly identifies the plasmodium species. It’s also important to know the percentage
of red blood cells infected by a parasite because patients with greater than 5% parasitemia
can have worse outcomes. Some common lab findings include thrombocytopenia,
which is a low platelet count, elevated lactate dehydrogenase levels due to hemolysis, and
a normochromic, normocytic type of anemia, meaning that the red blood cells are few in
number but those that remain are of normal size and color. Treatment for malaria is generally divided
into the different stages of infection. Suppressive treatment or chemoprophylaxis
is aimed at killing sporozoites before they infect hepatocytes, so it’s usually given
to travelers that are headed to a country with endemic malaria. Therapeutic treatment is aimed at eliminating
merozoites in the erythrocytic phase, so it’s usually given during an active infection. The exact medication or group of medications
that are to treat an active infection depends largely on the severity of infection, the
age and pregnancy status of the patient, the local malarial resistance pattern which depends
on the geography, and the plasmodium species causing the infection. It’s also important to not take the same
medication to treat an active infection that was previously used as chemoprophylaxis. Gametocidal treatment is aimed at killing
gametocytes, which prevents spread of disease, and thus, the creation of future resistant
forms of the parasite. Lastly, radical treatment is aimed at killing
hypnozoites in the liver from a Plasmodium vivax and Plasmodium ovale infection. For the most part, cases of uncomplicated
malaria resolve with treatment. Even after recovery, some individuals can
get symptoms after a period of time – and this is called recurrent malaria, and it’s
broadly divided into three underlying causes: recrudescence, relapse, and reinfection. Recrudescence refers to ineffective treatment
that didn’t completely clear the infection – a problem common when there are high rates
of antimalarial resistance. Relapse refers to situations where the blood
was cleared of merozoites but hypnozoites persisted in the liver, and then emerged to
cause more problems. And reinfection is when an individual was
effectively treated, but a completely new infection caused a new bout of malaria – a
problem common in endemic areas, since a single infection doesn’t make an individual immune
to malaria. Instead, there is an acquired ability to tolerate
Plasmodium infections, which relates to the degree of exposure to a variety of different
strains. Since malaria is spread by mosquitos, anything
that prevents mosquito bites can help, like full body clothing, mosquito repellent, sleeping
in insecticide covered mosquito nets, and using indoor insecticide sprays. In addition, Anopheles mosquitoes like to
lay their eggs in small, shallow collections of freshwater, like containers sitting outdoors
during the rainy season in tropical countries. To control the mosquito population, it’s
important to empty out these containers and any other stagnant collections of water. All right, as a quick recap, malaria is a
life-threatening mosquito transmitted infection caused by plasmodium parasites in which the
parasite feeds and grows inside hepatocytes and red blood cells. Symptoms are primarily caused by the rupture
of red blood cells, that usually result in high grade fever paroxysms that improve over
time, but can occasionally cause severe complications and death. Thanks for watching, you can help support
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