MalariaIntroduction
In certain areas malaria is a big problem such as in Central America, the northern
part of South America, Africa and in Asia. Even in the US in the past malaria
was endemic and the Anopheles
mosquito, which is the carrier for the Plasmodium species that causes
malaria, is still breeding in swamps of Florida, California or New York. Authorities
are watching any case of imported malaria to prevent reoccurrence of malaria in
the US. More temperate zones of the northern and southern hemispheres are
devoid of malaria as the Anopheles mosquito needs a certain temperature to complete
its life cycle. There are four common strains of malaria (see table).
| The four
common malaria strains | | Name
of pathogen: | Comments: |
| Plasmodium falciparum | causes
severe , fatal disease with vital organ clotting, shock and coma |
| Plasmodium vivax | mild
form of malaria; may be missed for 1 year in a traveler who returns to temperate
climate, but is infectious nevertheless |
| Plasmodium ovale | similar
to P.vivax; can cause splenic rupture; in people without spleen causes overwhelming
sepsis | | Plasmodium
malariae | often patients have no symptoms
for some time; can cause serious kidney disease | Pathophysiology:
All
four strains of malaria have a life
cycle of the parasite,
which is very similar, but also quite complex. There are five different forms
of the parasite, two of which occur in the female Anopheles mosquito, three of
which occur in he human host. Briefly, the mosquito feeds on infected blood of
a person with malaria. This releases the gametocytes from the infected
blood into the mosquito. Within the next 7 to 14 days these multiply involving
a sexual process into sporozoites. As they have a high adaptation to
human liver cells, they multiply there after the next mosquito bite. The
patient does not feel sick during this hepatic phase of multiplication of the
parasite. In a process of asexual multiplication merozoites are produced
and released into the blood steam after about 7 to 14 days of incubation in the
liver. Merozoites are highly adapted to red blood cells and invade them en masse.
They transform into trophozoites, which mature into schizonts.
Eventually these destroy the red blood cells that are infected and further merozoites
are released into the blood stream that will infect non-infected red blood cells
further. This cycle of multiplication in the red blood cells is what makes the
patient sick. A smaller number of merozites develops in red blood cells into a
different developmental direction and they turn into gametocytes, ready to infect
new Anopheles mosquitos again. Now the life cycle repeats itself. Signs
and symptoms: After having been bitten by an infected mosquito
there is an incubation time of 2 -3 weeks for P. vivax and P.ovale, of 1 1/2 to
2 weeks for P. falciparum. The incubation time for the other strains is much longer.
P. malariae takes about 1 month before the patient becomes symptomatic. However,
if the patient travels from a tropical area to a temperate area during the time
of incubation, the clinical picture becomes modified, particularly, if the person
has taken chemoprophylaxis for a period of time (see below). Instead of getting
the episodic chills and fever, the patient might get non specific symptoms like
backaches, headaches and fevers. Typically though all forms of malaria
start with an abrupt high fever of 40°to 41°C (103 to 106°F), muscle rigidity,
frequent urination, an excruciating and worsening headache and an intense feeling
of being ill. The fever then suddenly falls, followed by a 2 to 3 hour period
of intense sweating. These bouts
of fever occur every 48 hours for P. falciparum, P. vivax and P.
ovale, for P.malariae they occur every 72 hours. Often though there are mixed
strains of Plasmodium species and the fevers are then irregular. The undulating
fevers are paralleled by the release of merozoites into the blood stream (fever)
and the mass disappearance into uninfected blood cells (breaking of the fever).
There are a number of common symptoms for all forms of malaria such as an enlargement
of spleen and liver, low red blood cell count (anemia) and jaundice. With
P.falciparum it is of utmost importance to diagnose
the disease rapidly as this form of malaria deteriorates quickly. The pathogen
has an affinity for the lining of blood vessels and this leads to plugging of
small blood vessels with subsequent lack of oxygen and nutrients in vital organs.
After only a short period of time patients experience distress with lung function
(respiratory distress), bleeding into the retina (possible blindness), kidney
failure and often the development of malaria in the brain (cerebral malaria).
This is particularly dangerous as the patient often gets into shock and coma,
which is often fatal. If a woman is pregnant and gets malaria with P. falciparum,
this often leads to placental infection with spontaneous abortion or a stillbirth.
In contrast, P.vivax and P. ovale do not cause
vital organ breakdown. The disease is much milder, there is more time to diagnose
and treat and it is rare that the patient dies from it. This would be most likely
due to sudden splenic rupture from a chronically enlarged and softened up spleen.
In cases where a person was born without spleen or where the spleen had been removed
for other reasons in the past, overwhelming malaria infection can lead to septicemia,
which frequently ends up to be fatal. In infection with P.
malariae there are frequently no specific symptoms with the only
positive sign being that there might be a big spleen present. However, this smoldering
infection leads to immune complexes that keep the malaria at bay. The other side
of the coin though is that these immune complexes lead to immune complex-mediated
nephritis (a chronic kidney disease) and "big spleen disease". As this
form of malaria is often without symptoms, persons who are carriers of it may
donate blood unaware of their disease and this can cause transfusion malaria.
Diagnostic tests: It is important to inquire, if
the patient has been in a region endemic for malaria in the past 3 to 5 years.
The physician has to assume when confronted with such a patient who has unexplained
chills and fevers and an enlarged spleen that the patient could have malaria.
Without that index of suspicion the physician might not order a blood smear to
look for Plasmodium. If it is positively identified, this confirms the diagnosis.
The physician still needs to know which type of malaria it is as therapy is different
for different strains. Newer
tests (polymerase chain reaction and DNA probes) are being further
refined. Also IBM antibody tests can be used in special labs. Treatment:
Obviously treatment of a patient in the US should be done by an
infection specialist knowledgeable in this field. Remarks here will be very general
just to point out the principle of the treatment of malaria. There are many chloroquine-resistant
strains in the world, so it is important to know where the patient got infected.
Usually P.ovale and P. malariae are chloroquine sensitive. Also the chloroquine
sensitive strains of P. falciparum and P. vivax can be treated with chloroquine.
Chloroquine-resistant cases of P.falciparum are treated with oral quinine sulfate
or in more severe cases with intravenous quinine dihydrochloride or quinidine
gluconade. Often the infection specialist will supplement the antimalaria regime
with other medications to suppress any recurrent malaria. Such medications include
familiar antibiotics such as doxycycline and clindamycin. But they also include
more obscure names such as sulfadoxine, mefloquine and halofantrine. Apart
from chloroquine therapy with P. ovale and P. vivax primaquine must also be given
in order to kill the developmental stages of malaria in the liver cells, as otherwise
there would be recurrences of malaria down the road. With the other forms of malaria
(P.falciparum and P. malariae) this is not a problem as these parasites do not
persist in the liver cells. Side-effects: There are a number of side-effects
of these antimalarial drugs. Ask your physician about them.
Prophylaxis:
Prophylaxis starts with planning a trip. Do you really need to
go to a malaria infested region? If the answer is "no", then don't go!
If this cannot be prevented, then it is important to be prepared to prevent mosquito
bites by spraying with pyrethrum-containing insecticide sprays.
Mosquito screens on windows and doors and netting sprayed with pyrethrum around
the sleep area should be used to keep insects out. Outside wear protective clothing.
Avoid being outside during dusk and dawn when more mosquitos are on their way. Chemoprophylaxis
used to start 2 weeks before the trip by taking chloroquine once
per week, if you travelled to an area where there is no chloroquine-resistant
P. falciparum. Mefloquine was used instead of chloroquine for those areas where
these resistant strains are present. This regime had to be followed until 4 weeks
after your return home. This prophylaxis was not 100% and close observation after
your return home was warranted, particularly if the travel destination was to
a country that is heavily infested with malaria (Ref. 1, p. 1241). A new
anti-malaria drug has been added to the list, Malarone. This is a combination
of two anti-malarials, Atovaquone and Proguanil, which work in concert. Since
1996 more than 35 countries have approved this drug for malaria treatment in people
weighing more than 22 lbs. (=11 kg). It has also been approved for malaria prophylaxis
in people weighing more than 88 lbs. (=40 kg). The traveller takes one
tablet per day 1 day before entering a malaria area, continues with one tablet
per day while there and carries on for 1 week after coming home. In other words,
it takes 5 weeks less time to do a better prophylaxis of malaria than on the old
regimen. Overall it is 98.7% effective in treating malaria and close to 100% effective
in preventing malaria. The reason for this is that malaria parasites are eradicated
in the blood as well as in liver tissue. Side effects are headaches in 1 to 2%,
some gastrointestinal upsets in 1% and 3% of neuropsychiatric events. It is effective
against P.falciparum and P. vivax (Ref. 14). Ask your family doctor
or a travel clinic for the latest malaria prophylaxis before you travel into a
malaria infested region.
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