Malaria

pathophysiology and definition of malaria

1. Malaria

3. lternative names:
        Quartan malaria
        Falciparum malaria
        Biduoterian fever
        Blackwater fever
        Tertian malaria

4. A vector-borne infectious
disease caused by protozoan
parasites.
It is widespread in tropical and
subtropical regions

5. A bite from an infective female
Anopheles mosquito.
Anopheles must be infected
through a previous blood meal
taken on an infected person to
transmit malaria

6. Transmission differs in intensity and
regularity depending on local factors
such as:
•rainfall patterns
•proximity of mosquito breeding sites
•mosquito species.

7. At risk for malaria:
40% of the world’s population
more than 500 million are ill of malaria
yearly
If treated in the early stages, malaria can be
cured.
Commonly associated with poverty

8. The cycle takes 9-21 days at 25°C or
77°F
Warmer ambient temperatures shorten
the duration of the extrinsic cycle, thus
increasing the chances of transmission.

Climate determines human behaviors

9. Plasmodium falciparum - most
common and deadly type of malaria
infection
- can lead to cerebral malaria
P.vivax - most common
- causes relapse if treatment was not
completed.
P.malaria
P.ovale.

10. Female Anopheles are:
Anthropophilic :from humans
Zoophilic :from animals
Endophagic:prefer to bite indoors
Exophagic :prefer outdoor biting

11. In the Philippines:
Falciparum cases: 70%
Vivax cases: 30%
9
th
highest morbidity rate in the country.
WHO: Philippines included in top 10 malaria
endemic countries in the Western Pacific region
Average of 3 filipinos die daily of malaria

12. DOH Magnitude of Malaria Prevalence
CATEGORY A - > 1,000 cases per year; 25 provinces
CATEGORY B - 100 to 1,000 cases per year; 22
provinces
CATEGORY C - < 100 cases per year; 18 provinces
CATEGORY D - malaria-free provinces; 13 provinces

13. Liver Stage. Human infection is initiated when sporozoites are
injected with the saliva during mosquito feeding. The sporozoites
enter the circulatory system and within 30-60 minutes will invade a
liver cell. Host cell entry, as in all apicomplexa, is facilitated by the
apical organelles. After invading the hepatocyte, the parasite
undergoes an asexual replication. This replicative stage is often
called exoerythrocytic (or pre-erythrocytic) schizogony .
PATHOPHYSIOLOGY:
In P. vivax and P. ovale some of the sporozoites
do not immediately undergo asexual replication,
but enter a dormant phase known as the
hypnozoite. This hypnozoite can reactivate and
undergo schizogony at a later time resulting in a
relapse.

14. Blood Stage. Merozoites released from the
infected liver cells invade erythrocytes. The
merozoites recognize specific proteins on the
surface of the erythrocyte and actively
invade the cell in a manner similar to other
apicomplexan parasites.
After entering the erythrocyte the parasite undergoes a
trophic period followed by an asexual replication. The
young trophozoite is often called a ring form due to its
morphology in Geimsa-stained blood smears. As the
parasite increases in size this 'ring' morphology
disappears and it is called a trophozoite. During the
trophic period the parasite ingests the host cell
cytoplasm and breaks down the hemoglobin into amino
acids. A by-product of the hemoglobin digestion is the
malaria pigment, or hemozoin. These golden-brown to
black granules have been long recognized as a
distinctive feature of blood-stage parasites.

15. The invasion has begun. Microscopic magnification shows
Plasmodium falciparum —the most virulent of the four
malaria parasites that infect humans—destroying red blood
cells in the liver. It digests a cell's hemoglobin, multiplies
inside to the point of rupturing the cell, and rapidly spreads
a new generation of infection.

16. Nuclear division marks the end of the
trophozoite stage and the beginning of the
schizont stage. Erythrocytic schizogongy
consists of 3-5 rounds (depending on species)
of nuclear replication followed by a budding
process. Late stage schizonts in which the
individual merozoites become discernable are
called segmenters . The host erythrocyte
ruptures and releases the merozoites. These
merozoites invade new erythrocytes and
initiate another round of schizogony. The
blood-stage parasites within a host usually
undergo a synchronous schizogony. The
simultaneous rupture of the infected
erythrocytes and the concomitant release of
antigens and waste products accounts for
the intermittent fever paroxysms associated
with malaria.

17. Sexual Stage. As an alternative to schizogony some of
the parasites will undergo a sexual cycle and terminally
differentiate into either micro- or macrogametocytes .
Gametocytes do not cause pathology in the human host
and will disappear from the circulation if not taken up by
a mosquito.
Gametogenesis, or the formation of micro- and
macrogametes , is induced when the gametocytes are
ingested by a mosquito. After ingestion by the mosquito,
the microgametocyte undergoes three rounds of nuclear
replication. The macrogametocytes mature into
macrogametes.
The highly mobile microgametes will seek out and fuse with
a macrogamete. Within 12-24 hours the resulting zygote
develops into an ookinete. The ookinete is a motile
invasive stage which will transverse both the peritrophic
matrix and the midgut epithelium of the mosquito.

18. Sporogony. After reaching the extracellular space between
the epithelial cells and the basal lamina, the ookinete
develops into an oocyst. The oocysts undergo an asexual
replication, called sporogony, which culminates in the
production of several thousand sporozoites. This generally
takes 10-28 days depending on species and temperature.
Upon maturation the oocyst ruptures and releases the
sporozoites which cross the basal lamina into the hemocoel
(body cavity) of the mosquito.

20. Signs & symptoms:
The pathology and clinical manifestations
associated with malaria are almost
exclusively due to the asexual erythrocytic
stage parasites. Tissue schizonts and
gametocytes cause little, if any, pathology.
Plasmodium infection causes an acute
febrile illness which is most notable for its
periodic fever paroxysms occuring at either
48 or 72 hour intervals. The severity of the
attack depends on the Plasmodium species
as well as other circumstances .

21. Exoerythrocytic schizogony and
prepatent and incubation periods
200015,00010,000 40,000
Merozoite
s
produced
12-1696-85-7
Merozoite
maturatio
n (days)
18-4016-1812-177-14
Incubatio
n period
(days)
15-1810-148-126-9
Prepatent
period
(days)
P.
malariae
P. ovaleP. vivax
P.
falciparu
m

22. Sometimes the incubation periods can be prolonged
for several months in P. vivax, P. ovale, and P.
malariae. All four species can exhibit non-specific
prodromal symptoms a few days before the first
febril attack. These prodromal symptoms are
generally described as 'flu-like' and include:
headache, slight fever, muscle pain, anorexia,
nausea and lassitude. The symptoms tend to
correlate with increasing numbers of parasites.

23. These prodromal symptoms will be
followed by febrile attacks also known
as the malarial paroxysms.
The Malarial Paroxysm
·profuse
sweating
·declining
temperature
·exhausted
and weak →
sleep
·lasts 2-4
hours
·intense heat
·dry burning
skin
·throbbing
headache
·lasts 2-6
hours
·feeling of
intense cold
·vigorous
shivering
·lasts 15-60
minutes
sweating stagehot stage
cold stage
The malarial paroxysm will usually last 4-8 hours

24. The fever
paroxysm
corresponds to
the period of
infected
erythrocyte
rupture and
merozoite
invasion.

25. Disease Severity and Duration
Modified from Markell and Voge's Medical Parasitology
cerebralrenalComplications
+++++++++Anemia
6-17 months
20-50+
years
12-20
months
5-8 years
Maximum
Infection
Duration
(untreated)
2-3 weeks3-24 weeks2-3 weeks3-8+ weeks
Symptom
Duration
(untreated)
2,500,00020,00030,00050,000
Maximum
Parasitemia
(mm
3
)
50,000-500,0006,0009,00020,000
Average
Parasitemia
(mm
3
)
severe
moderate to
severe
mild
moderate to
severe
Initial Paraoxysm
Severity
falciparum
malariaeovalevivax

26. In contrast to the other three species, P. falciparum can
produce serious disease with mortal consequences. This
increased morbidity and mortality is due in part to the high
parasitemias associated with P. falciparum infections.
These potentially high parasitemias are due in part to the
large number of merozoites produced and the ability of P.
falciparum to invade all erythrocytes.

27. Other Physical symptoms:
Fever: Fever can be very high from the first day.
Temperatures of 40°C and higher are often observed.
Fever is usually continuous or irregular. Classic
periodicity may be established after some days.
Hepatomegaly: The liver may be slightly tender.
Splenomegaly: Splenomegaly takes many days, especially
in the first attack in nonimmune children. In children from
an endemic area, huge splenomegaly sometimes occurs.
Anemia: Prolonged malaria can cause anemia, and
malarial anemia causes significant mortality.
Jaundice: With heavy parasitemia and large-scale
destruction of erythrocytes, mild jaundice may occur. This
jaundice subsides with the treatment of malaria.
Dehydration: High fever, poor oral intake, and vomiting all
contribute to dehydration.

28. Examine blood under microscope
(geimsa stain)
chest x-ray: helpful if respiratory symptoms are
present
CT scan: to evaluate evidence of cerebral edema or
hemorrhage
Medical intervention:

29. Polymerase chain reaction (PCR)
-determine the species of plasmodium
dipstick test
- not as effective when parasite levels
are below 100 parasites/mL of blood
Blood smears- repeated over a 72-hour period
RDT's (rapid diagnostic tests)

30. Other tests:
CBC
electrolyte panel
renal function tests
pregnancy test
urinalysis
urine and blood cultures
and thick and thin blood smears
Antibody tests are not usually helpful

31. Antimalarial drugs:
chloroquine (Aralen) – DOC
-except for chloroquine-resistant Plasmodium
strains
combination of quinine and tetracycline
- for Falciparum strains suspected to be
resistant to chloroquine

32. • useful in areas where there is known to
be a high level of resistance to Chloroquine,
Mefloquine and sulfa drug combinations
with pyrimethamine
Quinine
• less effective and more toxic as a blood
schizonticidal agent than Chloroquine
• used in post-exposure treatment

33. For quinine resistance other treatments
include clindamycin (Cleocin),
mefloquin (Lariam), or
sulfadoxone/pyrimethamine (Fansidar).
primaquine
prevent relapses after recovery from P.
vivax or P. ovale
artemisinin-based combination therapies (ACTs)
- derived from an ancient Chinese herbal remedy

34. Most persons receive an antibiotic for seven days
Intensive care
intravenous (IV) malaria treatment for the first
three days.
NO vaccine is currently available
Red blood cell transfusions
Kidney dialysis
Assistance breathing

35. Alternative treatment
· qiinghaosu (artemisinin)
usually combined with another
antimalarial drug (mefloquine) to boost its
effectiveness.
Wormwood (Artemesia annua)
Western herb that is taken as a daily
dose

36. Herbs that protect the liver or used as
preventive treatment:
goldenseal (Hydrastis canadensis)
Chinese goldenthread (Coptis chinensis)
 milk thistle (Silybum marianum)

37. NURSING INTERVENTIONS:
Maintain a clear airway. In cases of
prolonged, deep coma, endotracheal intubation
may be indicated.
Turn the patient every two hours.
Avoid soiled and wet beds.
Position in semi-prone to prevent aspiration

38. Maintain strict intake/output record.
Observe for high colored or black urine.
 Observe for changes in levels of sensorium
and occurrence of convulsions
Naso-gastric aspiration to prevent aspiration
pneumonia
Monitor vital signs every 4-6 hours.

39. TSB if the temperature is above 39
0
C
Urethral catheter can be inserted for monitoring
urine output as indicated
NSAIDs should be used with caution if bleeding
disorder or hemolysis is suspected.

40. If evidence of life-threatening hemolytic anemia is
determined:
• establish large-bore intravenous (IV) lines
• initiate fluid resuscitation
•administer transfusion of type-specific packed
RBCs.

41. Health teachings:
Use topical insect repellent (30-35% diethyltoluamide
or [DEET]) esp. at dusk to dawn
•DEET - toxic in large amounts;
children = < 35%
•DEET should not be inhaled
•not be rubbed onto the eye area, on any broken or
irritated skin, or on children's hands
•should be thoroughly washed off after coming
indoors

42. Remain indoors in well-screened areas
between dusk and dawn
Sleep inside pyrethrin or permethrin
repellent-soaked mosquito nets.
Avoid wearing perfumes and colognes.
•
Wear appropriate clothing: long-sleeved
shirts and long pants.

43. •Remove or poison breeding grounds
•Swamp draining
•Use of Indoor Residual Spraying of long-
acting insecticide (IRS)
•use of pesticide DDT – certain issues

44. •Consult physician for proper prophylaxis before
traveling to endemic areas
usually anti-malarial drugs starting a day or
two, usually chloroquine or mefloquine
•Treatment - continued through at least four
weeks after leaving the endemic area
•Seek medical help : if having flu-like symptoms

45. Bibliography:
http://www.emedicine.com/emerg/topic305.htm
http://www.who.int/mediacentre/factsheets/fs094/en/index.html
http://www.medicinenet.com/malaria/page2.htm
http://www.brown.edu/Courses/Bio_160/Projects1999/malaria/cermal.html
http://en.wikipedia.org/wiki/Malaria#Treatment
http://www.irinnews.org/Report.aspx?ReportId=77917
http://www.cdc.gov/malaria/distribution_epi/epidemiology.htm
http://www.enotes.com/nursing-encyclopedia/malaria

46. END