Tropical Infection Diseases

MALARIA
Gatot Sugiharto, Internist
Internal Medicine Department
Faculty of Medicine, Wijaya Kusuma University
Surabaya
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 Introduction
• The protozoan genus Plasmodium is
responsible for malaria
• Four important species: P. falciparum, P.
Vivax, P. malariae and P. ovale
• P. knowlesi : A monkey malaria parasite that
may occur in forested regions of South-East
Asia.
• Rapidly fatal and is responsible for most
malaria related deaths : P. Falciparum
• Malaria is an entirely preventable and
treatable disease
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Epidemiology
• Mosquito-transmitted malaria is the greatest public
health problem in large parts of the world (> 500
million clinical cases and > 3 million deaths/year)
• Occurs in most of the tropics of the world
• Prevalence of falciparum and vivax malarias being
about the same in Asia, Oceania and South America
• Malaria can be a traveler’s disease and imported
into any country.
• A rural disease due to the presence of the female
Anopheles mosquito vector.

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 Transmission

Transmision : by an infected female Anopheles biting

Others : blood transfusion or congenitally feto-maternal

Malaria-carrying Anopheles bite only near dusk and dawn.

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 Clinical manifestation on life
cycle.
• Plasmodia replicate inside the RBC  hemoliysis
 release of toxic metabolic by products into the
bloodstream.
• These symptoms include chills, headache,
myalgias and malaise, occurring in cycles.
• Also may cause splenomegaly, jaundice and
anemia
• P falciparum may induce kidney failure, coma and
death.
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 Chronic & relapse
• All infected liver cells parasitized with P. falciparum and P.
malariae rupture and release merozoites at about the
same time.
• In contrast, P. vivax and P. ovale have two
exoerythrocytic forms. The primary type develops, causes
liver cell rupture, and releases merozoites. The other
form, which develops concurrently, is known as the
hypnozoite.
• Sporozoites that enter liver cells differentiate into
nonsexual hypnozoites that remain dormant for weeks, or
even years.
• The hypnozoites activate and undergo exoerythrocytic
schizogony, forming a wave of merozoites that cause a 8
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relapse.
 Clinical symptoms (1)

Cough, fatigue, malaise, arthralgia, myalgia, and paroxysm of shaking chills and
sweats

The classic paroxysm : begins with shivering and chills, (1-2 hours) followed by high
fever

Paroxyms of varying 48 hours belong to vivax, ovale and falciparum malaria, whereas
72 hours belongs to malariae infections.

The 48 hour fever is called tertian (occurs every 3rd day)  day 1 : fever, day 2 : no
fever, day 3 : fever & so on. The 72 hour fever is called quartan (returns on every 4th
day)
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 Clinical symptoms (2)

30% of non-immune adults infected with P falciparum suffer acute renal failure, some with
seizures.

Blackwater fever : hemoglobinuria with the passage of dark-colored urine

Non-cardiogenic pulmonary edema :common in pregnant women and results in death in 80%
of patients

Profound hypoglycemia : young children and pregnant women.

The most prominent symptoms all relate to loss of RBCs: a) tachycardia, b) anemia, c) fever,
d) hypotension and e) splenomegaly.

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 Severe malaria
• 1. Cerebral malaria
2. Acute renal failure
3. ARDS
4. Severe anaemia (Hb < 5g%)
5. DIC
6. Haemoglobinuria
7. Hypotension, Shock
8. Hyperparasitemia
9. Repeated seizures
10. Hyperpyrexia
11. Haemolysis (Sr bil. >3 mg%)A

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Cerebral malaria
The principal signs : seizures and unconsciousness, preceded by a severe headache.

Neurologic examination : contracted or unequal pupils, a Babinski sign, and absent or exaggerated deep tendon reflexes

Cerebrospinal fluid examination : increased pressure, increased protein, and minimal or no pleocytosis.

High fever, 41° to 42°C, with hot, dry skin may occur.

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 ARDS
• Often fatal, develop rapidly, associated
with excessive intravenous fluid therapy.
• Fast, labored respiration, SOB, a non-
productive cough, rales and rhonchi
• Chest X-rays : increased bronchovascular
markings.

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 Confirmed Diagnosis of Malaria

Only in case where Parasitological

All clinically suspected laboratory confirmation is done by
thin-thick blood smear
malaria cases require confirmation is not
microscopy examination or
laboratory examination possible start by dipstick (Rapid
and confirmation. treatment Diagnostic Test [RDT]) or
immediately. by serologic test (ICT)

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Figure 1. Morphology of Plasmodium knowlesi in a Giemsa-stained thin blood smear. Infected
erythrocytes were not enlarged, lacked Schuffner stippling, and contained much pigment.
Shown are examples of trophozoites (A–F), a schizont (G), and a gametocyte (H). Scale bars = 5
μm.

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 Malaria Therapy (Old Protocol)
Plasmo Condition 1st reg Formula 2nd reg Formula 3rd reg/ Formula
dium relaps
Un Non Chloroquin 4-4-2 Kina 3x2 (7)
known pregnant Primaquin 3 Primaquin 2-3
Pregnant Chloroquin 4-4-2 Kina 3x2 (7)
Falci Sensitive Chloroquin 4-4-2 SP 3 Kina 3x2 (7days)
parum Chloroquin Primaquin 3 Primaquin 2-3 Primaquin 2-3
Resisten Chloroquin 4-4-2
Chloroquin SP 3
< 25% Primaquin 3
Resisten Kina 3x2 (7) SP 3
Chloroquin Primaquin 3 Tetra/doxy 4x2/2x1 (7)
>25% Primaquin 3
Resisten Chloroquin 4-4-2 Chloroquin 4-4-2
SP >25% Tetra/doxy 4x2/2x1(7) Kina 3x2 (7)
Primaquin 3 Primaquin 3
Resinten Kina 3x2 (7)
both SP+C Tetra/doxy 4x2/2x1(7)
Primaquin 3 CI for pregnancy, infant : Primaquin, SP
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Plasm Condi 1st reg Formula 2nd reg Formula 3rd reg/ Formula
odium tion relaps
Vivax/ Chloroquin 4-4-2 Kina 3x2 (7) Chloroquin 4 (8-12week)
ovale Primaquin 1 (14) Primaquin 1 Primaquin 3 (8-12week)
Resisten Chloroquin 4-4-2
Chloroqui Tetra/doxy 4x2/2x1(7)
n < 25% Primaquin 1 (14)
Resisten Kina 3x2 (7)
Chloroqui Tetra/doxy 4x2/2x1(7)
n >25% Primaquin 1 (14)

Aim Regimen Dose Condition Duration

Prophylaxis Chloroquin 2 tabs/week Temporary visitation 1 week before –
4 week after visitation

Permanent visitation Max for 3 months

Doxycycline 1.5 mg/kg/day Only for Chloroquin Max for 3 months

resistan Falciparum

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 Artemisinin-based combination therapy
(ACT)
• Skizontoside for P. falciparum & P. vivax. Obat
• ini berkembang dari obat tradisional Cina
untuk
• penderita demam yang dibuat dari ekstrak
• tumbuhan Artemesia annua L (qinghao) yang
• sudah dipakai sejak ribuan tahun lalu dan
• ditemukan peneliti Cina tahun 1971.

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 Artemicin based combined therapy (ACTs) for
uncomplicated falciparum malaria
• Treat children and adults with uncomplicated P. falciparum malaria
(except pregnant women in their first trimester) with one of the
following recommended ACTs:
– artemether + lumefantrine (R/Co-artem)
– artesunate + amodiaquine(R/Artesdiaquine, Arsuamoon)
– artesunate + mefloquine
– dihydroartemisinin + piperaquine
– artesunate + sulfadoxine–pyrimethamine (SP)
• The artemisinin derivatives (oral formulations) and partner
medicines of ACTs should not be used as monotherapy in the
treatment of uncomplicated malaria
*Update in 2015 WHO Revised Guidelines
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Reducing the transmissibility of treated P. falciparum infections
In low-transmission areas, give a single dose of 0.25 mg/kg bw
primaquine with ACT to patients with P. falciparum malaria (except
pregnant women, infants aged < 6 months and women
breastfeeding infants aged < 6 months) to reduce transmission.

First trimester of pregnancy :

Treat pregnant women with uncomplicated P.
falciparum malaria during the first
trimester with 7 days of quinine + clindamycin.

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 Uncomplicated malaria treatment
P. falciparum malaria
• The treatment of uncomplicated P. falciparum malaria is
undertaken after diagnosis of malaria by light microscopy or
Dipstick.
• Patients with positive think-thick blood smears or dipstick for
P. falciparum malaria is treated by blisters of Coartem®
(artemether 20mg/lumefantrine 120mg). See Table 1 for
details of prescription.

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 Coartem® Dosage Schedule

Source: WHO, 2007

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Pengobatan Lini III (Artesunate + Amodiakuin)

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Kombinasi Kina + Doksisiklin/ Tetra- siklin/ Clindamycin (bila gagal
pengobatan ACT) :

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 Treatment of severe malaria

Where injectable treatment cannot be

Severe malaria should be treated with
given, patients with severe malaria
injectable artesunate (intramuscular or
should immediately receive pre-referral
intravenous) and followed by a
treatment with intra-rectal artesunate
complete course of an ACT as soon as
and be referred to an appropriate
the patient can take oral medicines.
facility for full parenteral treatment

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 Monitoring Malaria Treatment

Early Tx failure Late Tx failure

• H1-3 show sign of severe • Late clinical failure
malaria – In 4th-28th shows sign of
• H2 parasite count > H0 severe malaria
– Sexual parasite still (+) or
• H3 parasite count > 25% H0 temp >37.5
• H3 sexual parasite still (+) or • Late parasitologic failure
temp >37.5 – Sexual parasite still (+) in
7th, 14th, 21st, 28th day or
temp > 37.5

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