- Malaria-Overview
- Most important
parasitic infection
- New
cases/year = 120 million; deaths
= > 1 million
- Over the
past 10 years, incidence of P
falciparum imported cases
(USA) has risen > 10X
- increase
secondary:
- to
failure of mosquito
eradication programs
- and to
increasing resistance of P.
falciparum to
antimalarial drugs
- Most U.S.
cases found in travelers
[occasionally: transfusion
recipients & intravenous drug
users]
return
to main menu
- "Causal Agents:Blood
parasites of the genus Plasmodium.
There are approximately 156 named
species of Plasmodium which
infect various species of
vertebrates.""-CDC )
- Four Plasmodium
species causative for human malaria
- Plasmodium vivax
- Plasmodium malariae
- Plasmodium ovale
- Plasmodium
falciparum
- produces most serious
complications; including
death
- Factors which determined
antimalarial agent efficacy:
- species
- life-cycle
stage-dependencies
return
to main menu
- Etiology:
- Transmission:
bite of the female anopheline
mosquito, only arthropod vector
- transmission
does not occur < 60 oF
or when temperature >
100 oF
- incubation
period: 8-10 days at
least (ambient
temperature dependent)
- Widely
distributed in Asia, Africa,
Latin America and the Caribbean
Basin.
return
to main menu
- Diagnosis
- Suggestive:
- fever/flu-like
symptoms in an individual
returning from travel (or
native to) a malarious
geographical region
- disease not ruled
out if the patient has taken prophylactic
drugs during travel
- Definitive:
- observing characteristic,
intraerythrocytic
parasites in thick/thin
blood smears (Giemsa or
similar stain)
- if thin blood smear
negative, examine thick
smear (may be positive in
20-25% of patients)
- examination of blood
smear is may be required
at intervals over several
days
- Critical factor:
determined whether
patient has falciparum
malaria because this form
may be fatal due to
high-rate of erythrocyte
parasitization
- In
falciparum malaria actual
parasite counts (e.g.
percentage of
erythrocytes containing
parasites) should be
monitored every eight
hours during the first
two-three days of
treatment
return
to main menu
- Clinical Presentations
(subjective)
- mild,
"viral"-like prodrome
(headache + myalgia), preceding
by 24-48 hours major symptoms
- Major symptoms-three
phases:-6-10 hour cycle
- cold phase-patient
complains of chills
- hot phase-associated with
high fever, headache,
vomiting, nausea,
delirium
- defervescence, perfused
sweating and sleep
- Clinical Presentations
(objective)
- Physical Exam:
- During paroxysmal period:
high fever (up to 106 oF)
- Orthostatic hypotension
(falciparum malaria)
- Splenomegaly +/-
hepatomegaly: frequency =
33% of cases
-
Faint scleral
icterus (scleral
icterus-definition:
jaundice observed in the
white supporting tunic of
the eyeball) -commonly seen
- Neurological
complications-occasionally
seen in falciparum
malaria; symptoms include
seizures, hallucinations, meningismus (meningismus-definition:
excitation, followed by
cortical depression with
vomiting, constipation,
and thermic disorders due
to pain in the
meningeocortical region
of the brain)
- Laboratory:
- mild, normochromic, normocytic
anemia-usually present
- falciparum
malaria: anemia may be
severe - schistocytes
present on blood smear
return
to main menu
- Clinical Considerations:
- Infection by P
falciparum (non-immune
individual) = medical emergency
- Death may
occur within several
hours
- If > 20%
of erythrocytes are
parasitized,: mortality
equals 50%
- Consequences of
significant parasitization:
- Rapidly progressing
hemolytic anemia, splenic
erythrocyte
sequestration, possible
immune hemolytic anemia,
significant intravascular
hemoglobin release
causing hemoglobinuria
and renal failure (blackwater fever)
- Vasodilation
causing significant,
rapid fluid shifts
resulting in orthostasis,
hyponatremia, cerebral
& pulmonary edema
-
 Parasitized
erythrocytes (P
falciparum) become
"stickier",
less deformable resulting
in microthrombus
formation (capillary sludging)
- Most
important factors resulting in
fatal outcomes:
- failure to
take prophylaxis
- delay in
obtaining medical
attention
- misdiagnosis
- advanced
age
return
to main menu
- Parasitic Life Cycle
- Mosquitoes become infected by
ingesting human blood containing
parasites (in the sexual form).
- Sporozoites (developed in
mosquito) are transmitted into humans
during the mosquito's next feeding
- Developmental stages
in the human:
- exoerythrocytic stage
{sprorozoites
multiplying (liver)
forming tissues schizonts}
- parasites leave
the liver, entering the
bloodstream, as
merozoites, beginning the erythrocytic
stage
- invasion
of red blood cells
- multiplying
in red blood cells
forming blood schizonts
- cell
rupture, releasing new
merozoites
- cycle
repetition
- Concurrently,
gametocytes {sexual
stage} form, released
into circulation where
they may be ingested by
another mosquito
Center for
Disease Control Description of Life Cycle
- "The malaria
parasite life cycle involves two
hosts.
- During a blood
meal, a malaria-infected female Anopheles
mosquito inoculates sporozoites
into the human host.
- After initial
replication in the liver
(exoerythrocytic schizogony), the
parasites undergo asexual
multiplication in the
erythrocytes (erythrocytic schizogony).
- Multiplication of
the blood stage parasites is
responsible for the clinical
manifestations of the
disease.
- In the blood, some
parasites differentiate into
sexual erythrocytic stages
(gametocytes).
- The gametocytes,
after ingestion by an Anopheles
mosquito during a blood meal,
undergo a sporogonic cycle
yielding sporozoites.
- Inoculation of the
sporozoites into a new human host
perpetuates the malaria life
cycle.
- Of note, in P.
vivax and P. ovale,
a dormant stage (hypnozoites) can
persist in the liver and cause
relapses by invading the
bloodstream weeks, or even years
later."
|
return to main menu
- Life Cycle Differences
between Species
- P falciparum
&
P. malariae:
- one cycle of
liver invasion and
multiplication
- infection
(hepatic) ends in <
four weeks
[spontaneously]
- infection
confined to erythrocytes
- after
four weeks, treatment of
erythrocytic infection
would be curative
- P vivax &
P ovale:
- Following liver
invasion, sprorozoites
induce a dormant stage
(hypnozoite)-causes
recurrences or relapses
- Treatment
must eliminate parasites
both from liver and
erythrocytes
- P falciparum:
- blood stage
parasites
- gametocytes
- ring-stage
parasites
- schizonts
- trophozoites
return
to main menu
return
to main menu
- Site of Drug Action: Parasite Life-Cycle-- classification
- Tissue schizonticides --
drugs eliminating tissue schizonts or
latent hypnozoites (hepatic)
- Blood schizonticides or
suppressive agents (acting on blood
schizonts) -- e.g.: chloroquine, amodiaquine, proguanil (Paludrine),
pyrimethamine (Daraprim), mefloquine
(Lariam), quinine (Quinamm)
- Gametocides: -- prevent
infection by mosquitoes by destroying
blood gametocytes
- P. falciparum
-- primaquine
- P vivax, P.
malariae, P ovale --
chloroquine
- Sporonticidal drugs --cause gametocides to become
noninfective in the mosquito {example
drugs: pyrimethamine (Daraprim),
proguanil (Paludrine)}
return
to main menu
- Drugs that prevent infection:
- Pyrimethamine (Daraprim)
& proguanil (Paludrine)-- dihydrofolate reductase
inhibitors
- Mechanism: prevent
maturation of P falciparum
hepatic schizonts
return
to main menu
- Drugs that prevent attacks and cure
- Blood
schizonticides --destruction of
circulating plasmodia
- when used long
enough (four weeks) cures P
falciparum and P.
malariae malaria
- Primaquine: eliminates persistent liver
hypnozoites of P vivax and P
ovale; when given in combination
with a blood schizonticide is curative
return
to main menu
- Malaria
Chemoprophylaxis-prevents
attacks of all malaria forms and eliminates P
falciparum & P. malariae infections
- For
regions with chloroquine-sensitive P.
falciparum malaria {Central America west of the
Panama Canal; Caribbean; North Africa;
parts of the middle East}-Chloroquine
- For
regions with chloroquine-resistant P
falciparum malaria:
- Preferred: mefloquine (Lariam)
- Alternative #1: doxycycline
(Vibramycin, Doryx)
- Alternative #2: chloroquine
+ proguanil (Paludrine)
- Eradication
of P vivax & P ovale
malaria infections:
return
to main menu
- Treatment
of malaria:
- All species
(except chloroquine-resistant P
falciparum)
- Oral treatment (P
falciparum or P.
malariae): chloroquine
phosphate
- Oral treatment of P
vivax or P ovale infection:chloroquine
+ primaquine phosphate
- Parenteral treatment
(severe attacks): quinine (Quinamm) or quinidine gluconate
(Quinaglute, Quinalan) followed by oral chloroquine when possible {followed
with primaquine if infection is caused
by P vivax or P ovale}
- Treatment of infection in
chloroquine-resistant P falciparum
- Oral: quinine sulfate:
- plus doxycycline (Vibramycin,
Doryx) or
clindamycin (Cleocin) OR
- quinine sulfate plus
pyrimethamine (Daraprim) and sulfadiazine OR
- quinine sulfate plus
tetracycline (Achromycin) OR
- quinine sulfate
plus pyrimethamine
(Daraprim) + sulfadoxine (once only)
- Oral alternative: mefloquine (Lariam)
- Oral alternative:
halofantrine (Halfan)
- Parenteral (severe
attacks)
- quinine
dihydrochloride or
quinidine gluconate + intravenous
doxycycline (Vibramycin, Doryx) or
clindamycin (Cleocin) {note begin
oral treatment with
quinine sulfate plus the
second drug as soon as
possible}
return
to main menu
|
