2. Session Objectives
At the end of this session you will be able to ;
• Define Malaria
• List the common Etiology of malaria
• Describe the life cycle of malaria parasite and
transmission
• Clinical presentation of malaria
• Treatment of malaria
3. Introduction
• Malaria is a protozoan disease transmitted by the
bite of infected femal Anopheles mosquitoes.
• It is the most important of the parasitic diseases
of humans, with transmission in 107 countries
containing 3 billion people and causing 1–3
million deaths each year.
4. Etiology and Pathogenesis
• Four species of the genus Plasmodium cause
nearly all malarial infections in humans
– P. falciparum
– P. vivax
– P. ovale
– P. malariae
5. Some terminologies related to
malaria
• Cerebral malaria. Severe P. falciparum malaria with
cerebral manifestations, usually including coma .
– Malaria with coma persisting for > 30 min after a seizure is
considered to be cerebral malaria.
• Cure. Elimination of the symptoms and asexual blood
stages of the malaria parasite that caused the patient
or caregiver to seek treatment.
• Radical cure. In P. vivax and P. ovale infections only,
this comprises a cure plus prevention of relapses by
killing hypnozoites.
6. Terminologies cont…
• Recurrence. The recurrence of asexual parasitaemia
following treatment.
– This can be caused by a recrudescence, a relapse (in P.
vivax and P. ovale infections only) or a new infection.
• Relapse. The recurrence of asexual parasitaemia in P.
vivax and P. ovale malaria deriving from persisting liver
stages (hyponozoites)…After variable intervals of weeks
to months.
7. Terminologies
• Recrudescence. The recurrence of asexual
parasitaemia after treatment of the infection with
the same infection that caused the original illness.
– This results from incomplete clearance of
parasitaemia due to inadequate or ineffective
treatment.
– It is, therefore, different to a relapse in P. vivax
and P. ovale infections, and it differs from a new
infection or re-infection (as identified by
molecular genotyping in endemic areas).
8. Terminologies cont…
• Schizonts. Mature malaria parasites in host liver cells
(hepatic schizonts) or red blood cells (erythrocytic
schizonts) that are undergoing nuclear division. This
process is called schizogony.
• Severe falciparum malaria. Acute falciparum malaria
with signs of severity and/or evidence of vital organ
dysfunction.
9. Terminologies cont…
• Sporozoites. Motile malaria parasites that are
infective to humans, inoculated by a feeding female
anopheline mosquito. The sporozoites invade
hepatocytes.
• Trophozoites. Stage of development of the malaria
parasites within host red blood cells from the ring
stage and before nuclear division. Mature
trophozoites contain visible malaria pigment.
• Uncomplicated malaria. Symptomatic infection with
malaria parasitaemia without signs of severity and/or
evidence of vital organ dysfunction.
10. THE LIFE CYCLE OF THE MALARIA
PARASITE
• The life cycle consists of a sexual cycle, which takes
place in the female anopheline mosquito, and an
asexual cycle, which occurs in humans .
• bite of an infected female mosquito sporozoites- are
injected and reach the bloodstream.
• Within 30 minutes enter the parenchymal cells of the
liver (pre-erythrocytic stage) in 10-14 days
merozoites are produced
– intrahepatic or pre-erythrocytic schizogony or merogony
11. • The swollen infected liver cell eventually bursts,
discharging motile merozoites into the bloodstream
• Merozoites bind to and enter the red cells of the blood
(erythrocytic stage) become trophozoites.
• Following mitotic replication of its nucleus, the
parasite in the red cell is called a schizont, and its
rapid growth and division is called schizogony
12. • schizogony results in the production of further
merozoites
• Merozoites released when RBCs repture
• merozoites then bind to and enter fresh red cells
and the erythrocytic cycle starts all over again
• Some merozoites, on entering red cells,
differentiate into male and female forms of the
parasite, called gametocytes.
13. • In P. vivax and P. ovale infections, a proportion of
the intrahepatic forms do not divide immediately
but remain dormant for a period ranging from 3
weeks to a year or longer before reproduction
begins hypnozoites
16. Summary
• Asexual cycle. The life-cycle of the malaria
parasite in host from merozoite invasion of
red blood cells to schizont rupture.
– Merozoite → ring stage → trophozoite → schizont
→ merozoites).
• Duration approximately 48 h in Plasmodium
falciparum, P. ovale and P. vivax; 72 h in P.
malariae.
17. Clinical Features
• The first symptoms of malaria are nonspecific; the
lack of a sense of well-being, headache, fatigue,
abdominal discomfort, and muscle aches followed
by fever
• Nausea, vomiting, and orthostatic hypotension are
common
• The classic malarial paroxysms, in which fever
spikes, chills, and rigors occur at regular intervals
suggest infection with P. vivax or P. ovale
18. • generalized seizures are specifically associated
with falciparum malaria and may herald the
development of cerebral disease
uncomplicated infections
• fever, malaise, mild anemia, and (in some cases) a
palpable spleen
• Mild jaundice
22. Malaria in Pregnancy
• low birth weight
• increased infant and childhood mortality
• Fetal distress, premature labor, and stillbirth
• anemia, hypoglycemia, and acute pulmonary
edema.
23.
24. Malaria Prophylaxis
• Actions
– Causal (true) prophylaxis – drug acts on early stages
in liver, before release of merozoites into blood
– Blood schizontocidal drugs (clinical prophylaxis or
cure)– attack parasite in RBC, preventing or ending
clinical attack
– Gametocidal – destroy sexual forms in human,
decreases transmission
– Hypnozoitocidal – kill dormant hypnozoites in liver,
anti relapse drugs….p.vivax + p. ovale
– Sporontocidal – inhibit development of oocysts in
mosquito, decreases transmission
25. Malaria Treatment
o Uncom plicated P. falciparum malaria
o Artemisinin-based combination therapies
(ACTs) are the recommended treatments for
uncomplicated P. falciparum malaria.
– Artemether plus lumefantrine,
– Artesunate plus amodiaquine,
– Artesunate plus mefloquine,
– Artesunate plus sulfadoxin pyrimethamine.
26. Uncom plicated P. falciparum
cont…
• ACTs should include at least 3 days of
treatment with an artemisinin derivative.
• Dihydroartemisinin plus piperaquine
(DHA+PPQ) is an option for the first-line
treatment of uncomplicated P. falciparum
malaria worldwide.
27. Uncom plicated P. falciparum cont…
• Artemisinin and its derivatives should not be used as
monotherapy.
Second-line antimalarial treatment:
■ artesunate plus tetracycline or doxycycline or
clindamycin; any of these combinations to be given
for 7 days;
■ quinine plus tetracycline or doxycycline or
clindamycin; any of these combinations should be
given for 7 days.
28. Uncom plicated P. falciparum in
special population
• Pregnancy
– First trimester:
■ quinine plus clindamycin to be given for 7 days
(artesunate plus clindamycin for 7 days is indicated if this
treatment fails);
■ An ACT is indicated only if this is the only treatment
immediately available, or if the above regimens failed.
• Artesunate plus clindamycin to be given for 7 days, or
quinine plus clindamycin to be given for 7 days….for
2nd & 3rd trimester
29. Special popn cont….
• Lactating women:
■ should receive standard antimalarial treatment (including
ACTs) except for dapsone, primaquine and tetracyclines.
• Infants and young children:
■ ACTs for first-line treatment in infants and young children with
attention to accurate dosing and ensuring the administered
dose is retained.
• Travellers returning to non-endemic countries:
■ atovaquone-proguanil;
■ artemether-lumefantrine;
■ quinine plus doxycycline or clindamycin.
30. Treatment of uncomplicated P.
vivax malaria
• Chloroquine combined with primaquine is the treatment
of choice for chloroquine-sensitive infections.
• At least a 14-day course of primaquine is required for
the radical treatment of P. vivax.
• In areas with chloroquine resistant P. vivax,
artemisinin-based combination therapies are
recommended.
31. Dosing
Chloroquine 600 mg (base) initially
followed by 300 mg (base) 6 hrs later, and
then 300 mg (base) daily for 2 days.
32. Treatment of severe malaria
• Is a medical emergency.
• Full doses of parenteral antimalarial treatment should be
started without delay.
• For pediatrics & adults, artesunate IV or IM:
■ artemether or quinine is an acceptable alternative if
parenteral artesunate is not available.
• Give parenteral antimalarials in the treatment of severe
malaria for a minimum of 24 h,
33. Rx of severe malaria cont…
• Complete treatment by giving a complete
course of: an ACT; artesunate plus
clindamycin or doxycycline; quinine plus
clindamycin or doxycycline.
• Intravenous (IV) artesunate should be used in
preference to quinine for the treatment of
severe P. falciparum malaria in adults.
34. Quinine Dosage for Severe Falciparum Malaria
• Wherever IV administration of quinine is not
possible.
1. Quinine dihydrochloride 20 mg salt per kg loading
dose intramuscularly (divided in to two sites,
anterior thigh)
2. Then quinine dihydrochloride 10 mg salt per kg
IM every 8 hours until patient can swallow.
3. Then administer artemether-lumefantrine or oral
quinine if the first drug is not available
35. Where IV administration of quinine is possible
Loading dose:
• Quinine 20 mg salt/kg of body weight by infusion
over 4 hours, in 5 % dextrose saline (5-10 ml/kg of
body weight depending on the patient's overall
fluid balance).
Maintenance does:
• Twelve hours after the start of the loading dose,
give quinine 10 mg salt/kg of body weight in
dextrose saline over 4 hours.
37. Artemether Injection
• 3.2 mg/kg loading dose on the first day followed
by 1.6 mg/kg daily for two days.
• Side effects:
• Adverse effect may include headache, nausea,
vomiting, abdominal pain, itching, drug fever,
abnormal bleeding and dark urine.
• Contraindications:
• IM Artemether is not recommended during the
first trimester of pregnancy.
38. Case 1
• M.T., a 31-year-old male college student, presents to the
emergency department (ED) with complaints of malaise,
myalgia, headache, and fever of 5 days’ duration.
• A native of Ghana, West Africa, he recently visited his parents
who live in a remote area of Ghana, and he returned home to
the United States 4 weeks ago.
• Two days prior to admission to the ED, he had an abrupt onset
of coldness and chills, followed 1 hour later by a high fever,
sweating, headache, nausea, and vomiting.
• The episode of chills and fever lasted about 24 hours, after
which he became asymptomatic.
• On the afternoon on admission, he had another bout of chills
that preceded a fever of 40°C.
39. • When interviewed for his medical and travel history, he
mentioned that he did not take malaria prophylaxis because he
thought that he was protected since he was born and raised in
Ghana and then as a teenager moved to the United State to live
with relatives and to attend school.
• He also did not use mosquito-avoidance measures during his
recent trip to Ghana.
• Physical examination reveals who is acutely ill and
complaining of severe abdominal pain.
40. • Abdominal examination reveals a soft, tender spleen that is
slightly enlarged.
• Blood pressure (BP) is 110/70 mm Hg; pulse, 120
beats/minute; respiration rate, 32 breaths/minute; and
temperature, 40°C.
Laboratory findings include the following:
• Hemoglobin (Hgb), 11 g/dL
• Hematocrit (Hct), 34%
• White blood cell (WBC) count, 5,300 cells/μL with 76%
neutrophils (normal, 45%–65%), 23% lymphocytes (normal,
15%–35%), and 1% monocytes.
41. • Platelets 26,000/microliter
• Creatinine 1.5 mg/dL
• CRP 228.9 mg/dL
• Total Bilirubin, 1.0 mg/dL
• Urinalysis reveals trace amounts of albumin and the presence
of urobilinogen.
• Thick and thin films of M.T.’s blood are prepared and a
parasitemia of 20% is reported.
• A Giemsa stain of the thin film demonstrates P. falciparum
gametocytes.
42. Questions
1. Describe how M.T.’s presentation is
consistent with P. falciparum malaria and
explain his risk factors.
2. How should P. falciparum malaria in M.T. be
treated?
3. If artesunate injection is not available, what
other treatment option is recommended?
4. How would M.T.’s treatment of malaria differ
if it had been a different Plasmodium species?
