Malaria

Fitria Nurul H., M.D

Internal Medicine Department
FK UMY

ITMSS 2016
 MALARIA
• 40% of the world’s population lives in
endemic areas
• 3-500 million clinical cases per year
• 1.5-2.7 million deaths (90% Africa)
• increasing problem (re-emerging disease)
• resurgence in some areas
• drug resistance ( mortality) • P. falciparum
• causative agent = • P. vivax
Plasmodium species • P. malariae
• protozoan parasite • P. ovale
• member of Apicomplexa • P. Knowlesi
• 4 species infecting humans • (in Southeast Asia—
• transmitted by anopholine the monkey malaria
parasite )
mosquitoes
 Life Cycle
• sporozoites injected during
mosquito feeding
• invade liver cells
• exoerythrocytic schizogony
(merozoites)
• merozoites invade RBCs
• repeated erythrocytic
schizogony cycles
• gametocytes infective for
mosquito
• fusion of gametes in gut
• sporogony on gut wall in
hemocoel
• sporozoites invade salivary
glands
 Transmission
• sporozoites injected
with saliva
• enter circulation
• trapped by liver
(receptor-ligand)

Anopheles
Exoerythrocytic Schizogony
• hepatocyte invasion
• asexual replication
• 6-15 days
• 1000-10,000 merozoites
• no overt pathology
 Hyponozoite Forms
• some EE forms exhibit delayed
replication (ie, dormant)
• merozoites produced months after
initial infection
• only P. vivax and P. ovale
relapse = hypnozoite
recrudescence = subpatentt
 Erythrocytic
Stage
• intracellular parasite
undergoes trophic phase
• young trophozoite called
‘ring form’
• ingests host hemoglobin
• cytostome
• food vacuole
• hemozoin (malarial
pigment)
Erythrocytic Schizogony
• nuclear division =
begin schizont stage
• 6-40 nuclei
• budding merozoites =
segmenter
• erythrocyte rupture
releases merozoites
• blood stage results in
disease symptoms
 Clinical Features
• characterized by acute febrile attacks
(malaria paroxysms)
• periodic episodes of fever alternating with
symptom-free periods
• manifestations and severity depend on
species and host status
• immunity, general health, nutritional state,
genetics
• recrudescences and relapses can occur
over months or years
• can develop severe complications
(especially P. falciparum)
 Malaria
Paroxysm
• paroxysms associated with
synchrony of merozoite
release
• between paroxysms temper-
ature is normal and patient
feels well
• falciparum may not exhibit
classic paroxysms
(continuous fever)

tertian malaria
quartan malaria
erythrocytic schizogony
• 48 hr in Pf, Pv, Po
• 72 hr in Pm

gametocytes
Severe malaria
reduced deformability of the
uninfected erythrocytes
compromises their passage
through the partially obstructed
capillaries and venules and
shortens RBC survival.
In the other three ("benign") human malarias,
sequestration does not occur, and all stages of
the parasite's development are evident on
peripheral-blood smears
Whereas Vivax, Ovale, and Malariae show a
marked predilection for either young RBCs
(Vivax, Ovale) or old cells (Malariae) and
produce a level of parasitemia that is seldom
>2%, Falciparum can invade erythrocytes of all
ages and may be associated with very high levels
of parasitemia.
 Host Response
Initially, nonspecific defense mechanisms
Splenic immunologic and filtrative
clearance
Removal of both parasitized and
uninfected erythrocytes
Strain-specific immune response then
controls the infection
Exposure to sufficient strains confers protection from
high-level parasitemia and disease but not from
infection
Infection without illness ,asymptomatic parasitemia is
common among adults and older children living in
regions with stable and intense transmission
Passively transferred IgG from immune
adults has been shown to reduce levels of
parasitemia in children

Passive transfer of maternal antibody

contributes to the relative (but not
complete) protection of infants from severe
malaria in the first months of life
Immunity to disease declines when
a person lives outside an endemic
area for several months or longer.

Parasites may persist in the blood

for months (or, in the case of P.
malariae, for many years)
 Clinical Features
First symptoms of malaria are nonspecific
Lack of a sense of well-being
Headache
Fatigue
Abdominal discomfort
Muscle aches
Fever
followed by

similar to the symptoms of a minor viral illness

 Headache
Chest pain
Abdominal pain
Arthralgia
Myalgia
Diarrhea
Common

Nausea
Vomiting
Orthostatic hypotension
Classic malarial paroxysms

Fever spikes
Chills and rigors
occur at regular intervals
 Fever

Irregular at first (that of falciparum

malaria may never become regular); the
temperature of nonimmune
individuals and children often rises
above 40°C in conjunction with
Tachycardia and sometimes
Delirium.
Physical Findings

Fever
Malaise
Mild Anemia
Palpable Spleen
(in some cases)
 Laboratory Findings
Anemia
• Common among young children living in areas with stable
transmission

Slight enlargement of the liver

• Common, particularly among Young Children

Mild jaundice
• Common among adults; it may develop in patients with
otherwise uncomplicated malaria and usually resolves over 1–3
weeks
 Malaria is not associated
with a rash

Petechial hemorrhages in the skin or mucous

develop only rarely in severe falciparum
malaria
 Severe Falciparum Malaria
Cerebral malaria/convulsion
Acidemia/acidosis
Severe normochromic, normocytic anemia
Renal failure
Pulmonary edema/adult respiratory distress
syndrome
Hypoglycemia
Hypotension/shock
Bleeding/disseminated intravascular coagulation
Hemoglobinuria
 Hypoglycemia
Important and common complication of severe
malaria, is associated with a poor prognosis
and is particularly problematic in Children
and Pregnant women.
Hepatic Gluconeogenesis
Increase in the consumption of glucose by
both host and, to a much lesser extent, the
malaria parasites
Quinine ,Quinidine
 Jaundice
Mild hemolytic jaundice is common in malaria

Severe jaundice is associated with P. falciparum; is

more common among adults and results from:

Hemolysis
Hepatocyte injury
Cholestasis
 Other
HIV/AIDS predisposes to more severe malaria
in nonimmune individuals
Worsened by intestinal helminths, Hookworm
in particular
Septicemia may complicate severe malaria,
particularly in children(specifically
Salmonella bacteremia )
Aspiration Pneumonia
 Pregnancy
Stable transmission area:
Mothers Asymptomatic
Falciparum malaria in primi- and
secundigravid women is associated with Low
Birth Weight
Increased infant and childhood mortality
Maternal HIV infection predisposes
newborns to congenital malarial
 Pregnancy
Unstable Transmission
Mother:
High-level parasitemia
Anemia
Hypoglycemia
Acute pulmonary edema

Fetal distress, premature labor, and stillbirth or low

birth weight are common
 Pregnancy

Congenital malaria occurs in <5% of

newborns
P. Vivax malaria in pregnancy is also
associated with a reduction in birth weight
but, in contrast to the situation in
falciparum malaria, this effect is more
pronounced in Multigravid
 Transfusion
Blood Transfusion
Needle-Stick Injury
IVDU
Organ Transplantation
Incubation period in these settings is often short
because there is no preerythrocytic stage
Clinical features and management are the same as
for naturally acquired infections.
Primaquine is unnecessary for transfusion-
transmitted P. vivax and P. ovale infections.
 Tropical Splenomegaly
(Hyperreactive Malarial Splenomegaly)

Chronic or repeated
in some cases malarial parasites cannot be found in
peripheral-blood smears
Massive Splenomegaly, Hepatomegaly
Hypergammaglobulinemia; normochromic,
normocytic anemia
Antimalarial chemoprophylaxis; results usually good
Diagnosis
Asexual
Giemsa (preferred)

Field's
Wright's
Leishman's stain
Both thin and thick
 RDTs

Rapid, simple, sensitive, and specific antibody-based

diagnostic stick or card tests that detect P.
falciparum–specific, in finger-prick blood samples
are now being used widely in control programs

RDTs are replacing microscopy in many areas

because of their simplicity and speed, but they are
relatively expensive and do not quantify
parasitemia.
 PCR
Antibody and PCR tests have NO
role in the diagnosis of malaria
except that PCR is increasingly
used for genotyping and
speciation in mixed infections
 Laboratory Findings
Normochromic, Normocytic Anemia is usual
WBC count is generally normal, although it may
be raised in very severe infections
Monocytosis, Lymphopenia, and Eosinopenia, with
reactive Lymphocytosis and Eosinophilia in the
weeks after the acute infection
ESR,CRP High
Severe infections may be accompanied by
prolonged PT and partial thromboplastin times and
by more severe Thrombocytopenia
 Treatment

Repeat blood smears

at least every 12–24 h for 2 days
Alternatively, a rapid antigen
detection card or stick test
 Currently available antimalarial drugs

•Chloroquine ARTEMISININ
COMBINED THERAPY
•Sulfadoxine/ (ACTs)
Pyrimethamine •Artemether-
lumefantrine (Coartem)

•Quinine •Artemisinin-piperaquine

•Dihydroartemisinin-piperaquinr
•Mefloquine •Artesunate – mefloquine

•Artesunate-pyronaridine
•Atovaquone –
•Artesunate -sulfadoxine/
Chloroguanide pyrimethamine

•Artesunate - amodiaquine
•Antibiotics

Primaquine
Espino, FE, PIDSP Annual Convention February 2012
 WHO now recommends
Artemisinin-based combinations as
first-line treatment for
uncomplicated Falciparum
 Chloroquine

Choice for the non-falciparum malarias

Vivax
Ovale
Malariae
Knowlesi
except in Indonesia and Papua New Guinea,
where high levels of resistance in P. vivax are
prevalent.
Chloroquine
(10 mg of base/kg stat followed by 5 mg/kg at 12, 24, and 36 h or by
10 mg/kg at 24 h and 5 mg/kg at 48 h)

or

Amodiaquine
(10–12 mg of base/kg qd for 3 days)
 Radical Treatment
Vivax or Ovale
Primaquine
(0.5 mg of base/kg qd) should be given for 14
days to prevent relapse.
In mild G6PD deficiency, 0.75 mg of base/kg
should be given once weekly for 6–8 weeks.
Not be given in severe G6PD deficiency
Falciparum
Artesunatec (3 days)
+
Sulfadoxine/Pyrimethamine
as a single dose

or

Artesunatec (3 days)
+
Amodiaquine (3 days)
 Second-line treatment/treatment of imported
Artesunatec (7 days) or Quinine (tid for 7 days)
plus 1 of the following 3:

1. Tetracycline (qid for 7 days)

2. Doxycycline (qd for 7 days)

3. Clindamycin (bid for 7 days)

or

Atovaquone-Proguanil
(qd for 3 days with food)
 Severe Falciparum
Artesunatec (IV followed by at 12 and 24 h and then daily if necessary)
or, if unavailable, one of the following:

Artemetherc (IM followed by qd)

or

Quinine dihydrochloride (infused over 4 h, followed infused over 2–8 h q8h)

or

Quinidine (infused over 1–2 h, followed by houriwith electrocardiographic

monitoring)
 Prevention

no safe, effective, long-lasting

vaccine is likely to be available
for general use in the near
future
 Malaria vaccines
Goal Target population

Block infection of Non-immune travelers

liver in low transmission
areas
Block emergence Children and pregnant
from liver or RBC women in high
infection transmission areas

Goal Target population

Reduce disease Children and pregnant

severity and women in high
death transmission areas

Goal Target population

In Africa
AMA 1 –based vaccine – Phase I and II Prevent Endemic communities
RTS,S - Phase III transmission
Together with Any population and
blood-stage situation
vaccines, limit
spread of vaccine
resistance
Espino, FE, PIDSP Annual Convention February 2012
 Personal Protection Against
Avoidance of exposure to mosquitoes at their
peak feeding times (usually dusk to dawn)
Insect repellents containing 10–35% DEET (or, if
DEET is unacceptable, 7% Picaridin),
Suitable Clothing
Insecticide-impregnated bed nets or other
materials.
Widespread use of bed nets treated with residual
Pyrethroids reduces the incidence of malaria in areas
where vectors bite indoors at night
 Chemoprophylaxis
Chemoprophylaxis is never entirely reliable

Chloroquine phosphate
Atovaquone-Proguanil (Malarone)
Doxycycline
Mefloquine
Very few areas now have chloroquine-sensitive P.
falciparum

Tetracycline and Doxycycline should not be given

to pregnant women or to children <8 years of age

Oral treatment should be substituted as soon as the

patient recovers sufficiently to take fluids by mouth
prevention
THANK YOU