MALARIA

Dr SULAIMAN CONTEH
Medical Students
 INTRODUCTION
• Malaria is a mosquito-borne infectious disease
of humans and other animals caused by
parasitic protozoans of the genus Plasmodium.
• Commonly, the disease is transmitted via a bite
from an infected female Anopheles mosquito,
which introduces the organisms from its saliva
into the person's circulatory system.
• The disease is widespread in tropical and
subtropical regions in a broad band around the
equator, including much of Sub-Saharan Africa,
Asia, and the Americas.
 Epidemiology
• In 2018, there were an estimated 228 million cases of malaria
worldwide.
• Malaria deaths stood at 405 000 in 2018.
• Children aged under 5 years are the most vulnerable group
affected by malaria; in 2018, they accounted for 67% (272
000) of all malaria deaths worldwide.
• The WHO African Region carries a disproportionately high
share of the global malaria burden. In 2018, the region was
home to 93% of malaria cases and 94% of malaria deaths.
• Total funding for malaria control and elimination reached an
estimated US$ 2.7 billion in 2018. Contributions from
governments of endemic countries amounted to US$ 900
million, representing 30% of total funding.
 Epi in S/L
• One of the highest burdens of malaria in
the world.
• One of Sierra Leone’s leading causes of
death and illness
• The number one cause of pediatric deaths
(38%) is malaria
•  
 CAUSES
• Five species of Plasmodium can infect and be
transmitted by humans.
• P. falciparum and P. vivax-Majority of cases
• P. ovale, and P. malariae cause a generally
milder form of malaria that is rarely fatal.
• The zoonotic species P. knowlesi, prevalent in
Southeast Asia, causes malaria in macaques but
can also cause severe infections in humans.
 Life Cycle
• In the life cycle of Plasmodium, a female Anopheles mosquito (the definitive
host) transmits a motile infective form (called the sporozoite) to a vertebrate
host such as a human (the secondary host), thus acting as a transmission
vector.
• A sporozoite travels through the blood vessels to liver cells (hepatocytes),
where it reproduces asexually (tissue schizogony), producing thousands of
hepatic merozoites.
• These infect new red blood cells and initiate a series of asexual
multiplication cycles (blood schizogony) that produce 8 to 24 new infective
erythrocytic merozoites, at which point the cells burst and the infective cycle
begins anew.
• Other merozoites develop into immature gametes, or gametocytes. When a
fertilised mosquito bites an infected person, gametocytes are taken up with
the blood and mature in the mosquito gut. The male and female
gametocytes fuse and form zygotes (ookinetes), which develop into new
sporozoites.
• The sporozoites migrate to the insect's salivary glands, ready to infect a
new vertebrate host. The sporozoites are injected into the skin, alongside
saliva, when the mosquito takes a subsequent blood meal.
 Pathogenesis
• Sporozoites reach the liver and multiple
asexually and asymptomatically for a period
of 8–30 days
• The parasite escapes from the liver
undetected by wrapping itself in the cell
membrane of the infected host liver cell
• Classical descriptions of waves of fever arise
from simultaneous waves of merozoites
escaping and infecting red blood cells.
 Path Cont
• Some P. vivax sporozoites do not
immediately develop into exoerythrocytic-
phase merozoites, but instead, produce
hypnozoites that remain dormant for periods
ranging from several months (7–10 months is
typical) to several years.
• After a period of dormancy, they reactivate
and produce merozoites. Hypnozoites are
responsible for long incubation and late
relapses in P. vivax infections, although their
existence in P. ovale is uncertain.
 Path Cont
• The parasite is relatively protected from
attack by the body's immune
system because for most of its human life
cycle it resides within the liver and blood
cells and is relatively invisible to immune
surveillance
 Path Cont
• circulating infected blood cells are destroyed
in the spleen.
• To avoid this fate, the P. falciparum parasite
displays adhesive proteins on the surface of
the infected blood cells, causing the blood
cells to stick to the walls of small blood
vessels, thereby sequestering the parasite
from passage through the general circulation
and the spleen.[45] The blockage of the
microvasculature causes symptoms such as
those in placental malaria
 Path Cont
• Sequestered red blood cells can breach
the blood–brain barrier and cause cerebral
malaria
 Path Cont
• Each cycle of this process, which is called
erythrocytic schizogony, takes about
 48 hours in P. falciparum-Quatern
 P. vivax and P. ovale disease and about 72
hours in P. malariae disease-Tertian
• P. vivax and P. ovale mainly attack
reticulocytes and young erythrocytes, while
P. malariae tends to attack older cells; P.
falciparum will parasitize any stage of
erythrocyte.
 Pathology
• The pathology of malaria is related to
anaemia, cytokine release and, in the case
of P. falciparum, widespread organ
damage due to impaired microcirculation.
The anaemia seen in malaria is
multifactorial
 Pathology Cont:
Cause s of anaemia in malaria infe c tion
•Haemolysis of infected red cells
•Haemolysis of non-infected red cells
(blackwater fever)
•Dyserythropoiesis
•Splenomegaly and sequestration
•Folate depletion
 Immunity to malaria
• After repeated infections, partial immunity
develops, allowing the host to tolerate
parasitaemia with minimal ill effects.
• This immunity is largely lost if there is no
further infection for a couple of years.
 Traits that protect
• lack the Duffy antigen on the red cell
membrane (a common finding in West
Africa) are not susceptible to infection with
P. vivax
• Haemoglobinopathies-sickle cell trait,
thalassaemia traits, glucose-6-phosphate
dehydrogenase deficiency
• Iron deficiency may also have some
protective effect
 Signs and symptoms
• The normal incubation period is 10–21 days but can be longer.
• Headache, fever, shivering, joint pain, vomiting, hemolytic anemia,
jaundice, hemoglobin in the urine, retinal damage, and convulsions.

• The classic symptom of malaria is paroxysm—a cyclical occurrence of

sudden coldness followed by rigor and then fever and sweating,
occurring every two days (tertian fever) in P. vivax and P. ovale
infections, and every three days (quartan fever) for P. malariae. P.
falciparum infection can cause recurrent fever every 36–48 hours or a
less pronounced and almost continuous fever.

• Severe malaria is usually caused by P. falciparum (often referred to as

falciparum malaria). Symptoms of falciparium malaria arise 9–30 days
after infection. Individuals with cerebral malaria frequently exhibit
neurological symptoms, including abnormal posturing, nystagmus,
conjugate gaze palsy (failure of the eyes to turn together in the same
direction), opisthotonus, seizures, or coma.
 Signs and symptoms
• In children, P. malariae infection is
associated with glomerulonephritis and
nephrotic syndrome.
• P falciparium cause nephritic syndrome
 Complications
1. Respiratory distress, which occurs in up to 25% of adults and 40%
of children with severe P. falciparum malaria. Possible causes
include:
a) respiratory compensation of metabolic acidosis,
b) noncardiogenic pulmonary oedema,
c) concomitant pneumonia, and
d) severe anaemia.
2. Acute respiratory distress syndrome (ARDS) may develop in 5–25%
in adults and up to 29% of pregnant women but it is rare in young
children.
3. Coinfection of HIV with malaria increases mortality.
4. Renal failure is a feature of blackwater fever, where hemoglobin
from lysed red blood cells leaks into the urine.
 Complications Cont:
5. Infection with P. falciparum may result in cerebral malaria,
a form of severe malaria that involves encephalopathy. It
is associated with retinal whitening, which may be a useful
clinical sign in distinguishing malaria from other causes of
fever.
6. Splenomegaly,
7. severe headache,
8. hepatomegaly (enlarged liver),
9. hypoglycemia, and
10.hemoglobinuria with renal failure may occur.
11.Malaria in pregnant women is an important cause of
stillbirths, infant mortality and low birth weight, particularly
in P. falciparum infection, but also with P. vivax.
 Diagnosis
• Malaria is usually confirmed by the microscopic
examination of blood films or by antigen-based rapid
diagnostic tests (RDT). Microscopy is the most
commonly used method to detect the malarial
parasite.Thick and thin film smear. Three films of
smear should be used to confirm negative malaria
infection.
• RDTs are often more accurate than blood films at
predicting the presence of malaria parasites, but
they are widely variable in diagnostic sensitivity and
specificity depending on manufacturer, and are
unable to tell how many parasites are present.
 Diagnosis
• PCR test for malaria is now been piloted
 Treatment
TREATMENT OF UNCOMPLICATED P. FALCIPARUM MALARIA
• Artemisinin-based combination therapies (ACTs) are the
recommended treatments for uncomplicated P. falciparum malaria.
The following ACTs are recommended:
• artemether plus lumefantrine, artesunate plus amodiaquine,
artesunate plus mefloquine, and artesunate plus sulfadoxine-
pyrimethamine.
The choice of ACT in a country or region will be based on the level of
resistance of the partner medicine in the combination. 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.
 TREATMENT OF UNCOMPLICATED P. FALCIPARUM
MALARIA IN SPECIAL RISK GROUPS

• 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 treatment
with 7-day
• quinine plus clindamycin fails or uncertainty of
compliance with a 7-day treatment.
 Second and third trimesters:

• ACTs known to be effective in the country/region or artesunate plus

clindamycin to be given for 7 days, or quinine plus clindamycin to be
given for 7 days.
• Lactating women:
• 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.
 TREATMENT OF SEVERE
MALARIA
For adults, artesunate IV or IM:
• quinine is an acceptable alternative if parenteral
artesunate is not available.
For children (especially in the malaria endemic areas of
Africa) the following antimalarial medicines are
recommended as there is insufficient evidence to
recommend any of these antimalarial medicines over
another:
• artesunate IV or IM;
• quinine (IV infusion or divided IM injection);
• artemether IM (should only be used if none of the
alternatives are available as its absorption may be
erratic).
 TREATMENT OF SEVERE MALARIA
CONT:
• Give parenteral antimalarials in the treatment of severe malaria for a
minimum of 24 h, once
• started (irrespective of the patient’s ability to tolerate oral medication
earlier) and, thereafter, complete treatment by giving a complete
course of:
• an ACT;
• artesunate plus clindamycin or doxycycline;
• quinine plus clindamycin or doxycycline.
• If complete treatment of severe malaria is not possible, patients
should be given pre-referral treatment and referred immediately to
an appropriate facility for further treatment. The following are
options for pre-referral treatment : rectal artesunate, quinine IM,
artesunate IM, artemether IM.
 TREATMENT OF UNCOMPLICATED P.
VIVAX MALARIA
• Chloroquine combined with primaquine is the treatment
of choice for chloroquine-sensitive infections.
• In mild-to-moderate G6PD deficiency, primaquine 0.75
mg base/kg body weight given once a week for 8 weeks.
• In severe G6PD deficiency, primaquine is
contraindicated and should not be used.
• Where ACT (exception AS+SP) has been adopted as the
first-line treatment for P. falciparum malaria, it may also
be used for P. vivax malaria in combination with
primaquine for radical cure.
• Artesunate plus sulfadoxine-pyrimethamine is not
effective against P. vivax in many places.
 TREATMENT OF UNCOMPLICATED
P. FALCIPARUM MALARIA
• Artemisinin-based combination therapies should be used
in preference to sulfadoxinepyrimethamine (SP) plus
amodiaquine (AQ) for the treatment of uncomplicated P.
falciparum malaria.
• 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.
• Addition of a single dose primaquine (0.75 mg/kg) to
ACT treatment for uncomplicated falciparum malaria as
an antigametocyte medicine, particularly as a component
of pre-elimination or an elimination programme.
 TREATMENT OF SEVERE P.
FALCIPARUM MALARIA
• Intravenous (IV) artesunate should be
used in preference to quinine for the
treatment of severe P. falciparum malaria
in adults.
 TREATMENT OF UNCOMPLICATED
P. VIVAX MALARIA
• In areas with chloroquine resistant P.
vivax, artemisinin-based combination
therapies (particularly those whose partner
medicines have long half-lives) are
recommended for the treatment of P. vivax
malaria.
• At least a 14-day course of primaquine is
required for the radical treatment of P.
vivax.
 Prevention-Strategies to control
Malaria
• . Aggressive control in highly endemic
countries, to reduce mortality and
decrease transmission
• Progressive eradication at the endemic
margins, to shrink the ‘malaria map’
• Research into new vaccines, new drugs,
new diagnostics and better ways of
delivering malaria care
 Individual prevention
• case treatment,
• vector eradication and personal protection from vector
bites, such as that provided by insecticide
(permethrin)-treated nets.
• Mosquito eradication is usually achieved by a
combination of insecticide use (e.g. house spraying
with DDT) and manipulation of the habitat (e.g. marsh
drainage)
• Mass drug administration
• Intermittent preventive treatment in pregnancy (IPTp)
• Intermittent preventive treatment in Infants (IPTi)
• vaccine for malaria (known as RTS,S) which is
licensed for use
 Non-immune
Malaria prophylaxis-
•Mefloquine 250mg weekly,
•Malarone 1 tablet daily
•Proguanil 200 mg daily
Thanks