MALARIA By TARIK ZAHER Assistant Professor of Tropical Medicine ID: 336892
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Slide1
MALARIA
By
TARIK ZAHER
Assistant Professor of Tropical Medicine
Zagazig
Universty
, Egypt Slide2
What is Malaria?
Malaria, the 'King of Diseases‘
Affects more than 500 million and kills more than 3 million people every year.Slide3
Geographical distributionMalarial belt.A, B and C.Slide4Slide5
AetiologyPlasmodia=malaria parasitesSlide6
The Malaria ParasitesMalaria is caused by protozoan parasites called Plasmodia, belonging to the parasitic phylum
Apicomplexa
. More than 200 species of the genus
Plasmodium
(=plasma +
eidos
, form) have been identified that are parasitic to reptiles, birds, and mammals. Four
Plasmodium
species have been well known to cause human malaria, namely,
P.
falciparum
, P.
vivax
, P.
ovale
, and P.
malariae
.
A fifth one,
P.
knowlesi
,
has been recently documented to cause human infections in many countries of Southeast Asia.Slide7
P.
knowlesi
P.
malariae
P.
ovale
P.
vivax
P.
falciparum
Reported from SE Asia; 70% of cases in some of those areas
2-3% in Africa, sporadic in Asia and S America
8% of cases in parts of Africa, stray cases in Asia
70-90% of cases in most of Asia and S America, 50-60% of cases in SE Asia and western pacific, 1-10% in Africa
80-90% of cases in Africa, 40-50% of cases in western pacific and SE Asia, 4-30% in S Asia, S America and rest of tropics
Distribution
8-9 days
13 days
9 days
8 days
5-6 days
Tissue
schizogony
24 hours
72 hours
49-50 hours
48 hours
48 hours
Erythrocytic
phase
?
Mature RBC's
Reticulocyte
Reticulocyte
All
Red cells affected
?
2000
15000
Over 10000
40000
Merozoites
per tissue
schizont
10-16
6-12
4-16
12-24
8-32
Merozoites
per red cell
schizont
No
No, but blood forms can persist up to 30 years
Yes
(
hypnozoit
)
Yes
(
hypnozoit
)
No
Relapse from persistent liver forms
Quotidian
Quartan
Tertian
Tertian
Tertian, sub tertian
Fever pattern
6-10%
Very rare
Very rare
Up to 22%
Up to 24%
Severe malaria
No
No
No
Yes
Yes
Drug resistanceSlide8
Ring Forms of
P.
falciparumSlide9
Ring Forms of
P.
vivaxSlide10
Ring Forms of
P.
ovaleSlide11
Ring Forms of
P.
malariaeSlide12
Ring Forms of
P.
knowlesiSlide13
Life cycleVector: pregnant female Anopheles
mosquitoSlide14Slide15
PathogenesisCytokines, cytoadherence
and
rosettingSlide16Slide17Slide18
Clinical Features of MalariaAtypical features is more than typical.
Malaria can mimic any thing and every thing.Slide19
Typical featuresCold stage, Hot stage and Sweating stage. The febrile episode starts with shaking chills, usually at mid-day between 11 a.m. to 12 noon, and this lasts from 15 minutes to 1 hour (the cold stage), followed by high grade fever, even reaching above 106
0
F, which lasts 2 to 6 hours (the hot stage). This is followed by profuse sweating and the fever gradually subsides over 2-4 hours. These typical features are seen after the infection gets established for about a week. The febrile paroxysms are usually accompanied by head aches, vomiting, delirium, anxiety and restlessness.Slide20
Atypical featuresIn an endemic area, it is rather unusual to find cases with typical fever pattern. Some patients may not have fever at all and may present with other symptoms listed below. Many present with fever of various patterns - low grade to high grade, with or without chills, intermittent to continuous, or even as cases of prolonged fever. In the initial stages of the illness, fever may be quotidian, with more than one spike per day and this is due to the development of multiple broods of the parasite. As the disease progresses, these broods get
synchronised
and the fever tends to be more uniform. However in cases of
P.
falciparum
malaria and mixed infections, this pattern of multiple spikes may continue.Slide21
Atypical features
Headache.
Body ache, back ache and joint pains.
Dizziness, vertigo.
Altered
behaviour
, acute psychosis.
Altered
sensorium
.
Convulsions, coma.
Cough.
Breathlessness.
Chest pain.
Acute abdomen.
Weakness.
Vomiting and
diarrhoea
.
Jaundice.
Pallor.
Puffiness of lids.
Secondary infections.
Hepatosplenomegaly
.Slide22
Severe MalariaDue to P.falciparum
.
Death from acute
P.
vivax
,
P.
ovale
or
P.
malariae
infections is rare.Slide23
1990 WHO Definition of severe malaria
1
.
Cerebral malaria
–
unrousable
coma not attributable to any other cause in a patient with
falciparum
malaria. The coma should persist for at least 30 min (1 h in the 2000 definition) after a generalized convulsion to make the distinction from transient
postictal
coma. Coma should be assessed using the Blantyre coma scale in children or the Glasgow coma scale in adults .
2.
Severe
anaemia
–
normocytic
anaemia
with
haematocrit
<15% or
haemoglobin
<5 g/
dL
in the presence of
parasitaemia
more than 10 000/
μL
. Note that finger prick samples may underestimate the
haemoglobin
concentration by up to 1 g if the finger is squeezed. If
anaemia
is
hypochromic
and/or
microcytic
, iron deficiency and
thalassaemia
/
haemoglobinopathy
must be excluded. (These criteria are rather generous; and would include many children in high transmission areas. A
parasitaemia
of >100 000/
μL
might be a more appropriate threshold.)
3.
Renal failure
– defined as a urine output of <400
mL
in 24 h in adults, or 12
mL
/kg in 24 h in children, failing to improve after rehydration, and a serum
creatinine
of more than 265
μmol
/L (>3.0 mg/
dL
). (In practice for initial assessment, the serum
creatinine
alone is used.)Slide24
4. Pulmonary oedema
or adult respiratory distress syndrome.
5.
Hypoglycaemia
– defined as a whole blood glucose concentration of less than 2.2
mmol
/L (40 mg/
dL
).
6.
Circulatory collapse(Algid malaria)
or shock – hypotension (systolic blood pressure <50 mmHg in children aged 1–5 years or <70 mmHg in adults), with cold clammy skin or core-skin temperature difference >10°C. (The more recent review declined to give precise definitions, but noted the lack of sensitivity or specificity of core-peripheral measurements.) Capillary refill time is not mentioned but recent studies indicate this simple test provides a good assessment of severity
7.
Spontaneous bleeding
from gums, nose, gastrointestinal tract, etc. and/or substantial laboratory evidence of DIC. (This is relatively unusual.)
8.
Repeated generalized convulsions
– more than two observed within 24 h despite cooling. (In young children, these may be febrile convulsions, and the other clinical and parasitological features need to be taken into account.) Clinical evidence of seizure activity may be subtle (e.g. tonic
clonic
eye movements, profuse salivation, delayed coma recovery).Slide25
9. Acidaemia – defined as an arterial or capillary pH <7.35 (note temperature corrections are needed as most patients are hotter than 37°C; add 0.0147 pH unit per degree Celsius (°C) over 37°C), or acidosis defined as a plasma bicarbonate concentration <15
mmol
/L or a base excess >10. (Operationally, the clinical presentation of ‘respiratory distress' or ‘
acidotic
breathing’ is focused upon in the 2000 recommendations. Abnormal breathing patterns are a sign of severity indicating severe acidosis, pulmonary
oedema
or pneumonia.)
10.
Macroscopic
haemoglobinuria
(Black water fever)
– if definitely associated with acute malaria infection and not merely the result of oxidant
antimalarial
drugs in patients with erythrocyte enzyme defects such as G6PD deficiency. (This is difficult to ascertain in practice: if the G6PD status is checked following massive
haemolysis
, the value in the remaining red cells may be normal even in mild G6PD deficiency. This part of the definition is not very useful.)Slide26
11. Postmortem confirmation of diagnosis. In fatal cases a diagnosis of severe
falciparum
malaria can be confirmed by histological examination of a postmortem needle
necroscopy
of the brain. The characteristic features, found especially in cerebral grey matter, are
venules
/capillaries packed with erythrocytes containing mature
trophozoites
and
schizonts
of
P.
falciparum
. (These features may not be present in patients who die several days after the start of treatment, although there is usually some residual pigment in the cerebral vessels.)
The 2000 recommendations also include the following:
12
.
Impairment of consciousness less marked than
unrousable
coma
. (Any impairment of consciousness must be treated seriously.
Assessment using the Glasgow Coma Scale is straightforward, but the Blantyre Scale needs careful local standardization particularly in younger children.)
13.
Prostration
: Inability to sit unassisted in a child who is normally able to do so. In a child not old enough to sit, this is defined as an inability to feed. This definition is based on examination not history.Slide27
14.
Hyperparasitaemia
– the relation of
parasitaemia
to severity of illness is different in different populations and age groups, but in general very high parasite densities are associated with increased risk of severe disease, e.g. >4%
parasitaemia
is dangerous in non-immunes, but may be well tolerated in semi-immune children. In non-immune children studied in Thailand a
parasitaemia
≥4% carried a 3% mortality (30 times higher than in all uncomplicated malaria) but in areas of high transmission values much higher may be tolerated well. Many use a threshold definition of 10%
parasitaemia
in higher transmission settings.
The followings were not considered criteria of severe malaria:
Jaundice – detected clinically or defined by a serum
bilirubin
concentration >50
μmol
/L (3.0 mg/
dL
). This is only a marker of severe malaria when combined with evidence of other vital organ dysfunction such as coma or renal failure.
Hyperpyrexia – a rectal temperature above 40°C in adults and children is no longer considered a sign of severity.Slide28
DiagnosisRepeat blood film(MPS) many times to catch diagnosisSlide29
1-Blood filmPeripheral smear examination for malarial parasite is the gold-standard in confirming the diagnosis of malaria. Thick and thin smears prepared from the peripheral blood are used for the purpose.Slide30Slide31
2-Rapid Diagnosis of Malaria
The
immunochromatographic
tests for the detection of malaria antigens, developed in the past decade, have opened a new and exciting avenue in malaria diagnosis. However, their role in the management and control of malaria appears to be limited at present.Slide32Slide33
TreatmentChloroquine resistant is now worldwide.Slide34
Treatment of P. vivax, P.
ovale
, P.
malariae
and
P.
knowlesi
Infections
Dose of
Primaquine
For 14 days
(P.
vivax
and
P.
ovale
only)
Dose of
Chloroquine
(as base)
(Each 250 mg tablet contains 150 mg base and
each 5 ml of suspension contains 50 mg base)
Age in years
4
th
dose (Tab
)
48 h
3
rd
dose (Tab
)
24 h
2
nd
dose
(Tab)
8 h
1
st
dose (Tab
)
0 h
Nil
37.5 mg (¼)
37.5 mg (¼)
37.5 mg (¼)
75 mg (½)
0-1
2.5 mg
75 mg (½)
75 mg (½)
75 mg (½)
150 mg (1)
1-5
5 mg
150 mg (1)
150 mg (1)
150 mg (1)
300 mg (2)
5-9
10 mg
225 mg (1½)
225 mg (1½)
225 mg (1½)
450 mg (3)
9-14
15 mg
300 mg (2)
300 mg (2)
300 mg (2)
600 mg (4)
>14Slide35
Treatment of Uncomplicated P. falciparum Malaria
Dosing of
Artesunate
+
Mefloqine
(WHO, 2010)
Dose of
Mefloquine
(250mg) Tablet
Dose of
Artesunate
(50mg) Tablet
Age
HALF tablet on second day
HALF tablet once daily for 3 days
5-11 months
ONE tablet on second day
ONE tablet once daily for 3 days
≥1-6 years
TWO tablets on second day, ONE tablet on third day
TWO tablets once daily for 3 days
≥7-13 years
FOUR tablets on second day, TWO tablets on third day
FOUR tablets once daily for 3 days
>13 yearsSlide36
Dosing of
Artemether
+
Lumefantrine
Tablets (WHO, 2010)
Dose (No. of 20/120mg tablet) Twice daily for 3 days
Age (years)
Weight (
kgs
)
20/120 (1 tablet)
<3
5-14
40/240 (2 tablets)
3-8
15-24
60/360 (3 tablets)
9-14
25-34
80/480 (4 tablets)
>14
>35
Dosing of
Artemether
+
Lumefantrine
Suspension
Dose of suspension (5 ml containing 15 mg
artemether
and 90 mg
lumefantrine
) once daily for 3 days
Weight (kg)
7 ml
5
10 ml
5-7.5
14 ml
7.5-10
20 ml
10-15Slide37
Recommendations for Treatment of Uncomplicated P. falciparum Malaria in Pregnancy (WHO, 2010, NVBDCP, 2010)
First trimester
:Quinine +
Clindamycin
for 7 days. ACT should be used if it is the only effective treatment available.
Second and third trimesters
:ACT known to be effective in the country/region or
artesunate
+
clindamycin
to be given for 7 days or quinine +
clindamycin
to be given for 7 days.Slide38
Treatment of Severe
P.
falciparum
Malaria
Follow-on Treatment (Full course of any ACT)
First Drug
Artesunate
plus
Sulfadoxine-pyrimethamine
Artesunate
plus
Amodiaquine
Artesunate
plus
clindamycin
or
doxycycline
[See below for dose]
Artesunate
a
2.4 mg/kg
bw
iv or
im
on admission; then at 12 h and 24 h, then once a day for
at least 24 hours, followed by full course of ACT
Artemether
plus
Lumefantrine
OR
Artemether
b
3.2 mg/kg
bw
i.m
. given on admission then 1.6 mg/kg
bw
per day for
at least 24 hours, followed by full course of ACT
Doxycycline
d
100mgs BID (2.2mg/kg BID for <45kgs[5]) for 7 days OR
Clindamycin
20mg base/kg/day divided in three doses for 7 days[5] in pregnancy
Quinine
b,c
20 mg salt/kg
bw
on admission (iv infusion or divided
im
injection), then 10 mg/kg
bw
every 8 h; infusion rate should not exceed 5 mg salt/kg
bw
per hour; course for 3 days for malaria acquired in Africa and South America, 7 days for malaria acquired in SE Asia
Doxycycline
OR
Clindamycin
as above
Quinidine
gluconate
c
10 mg salt/kg (equivalent to 6.2 mg base/kg) iv infused over 1–2 hours, followed immediately by 0.02 mg/kg/min salt (equivalent to 0.0125 mg/kg/min base) continuous iv infusion;
course for 3 days for malaria acquired in Africa and South America, 7 days in SE AsiaSlide39
a.Recommended by WHO in low transmission areas or outside malaria endemic areas.b.Recommended by WHO for children in high transmission areas; regimen 1 can also be used.
c.For
areas where
artesunate
or
artemether
are not available, mainly the US. National Vector Borne Disease Control
Programe
in India recommends quinine as the treatment for severe malaria in pregnancy. Loading dose should not be administered to patients who received quinine,
quinidine
,
halofantrine
, or
mefloquine
within the preceding 12 hours.
d.Not
for children below 8 years of age and pregnant women
e.Mefloquine
has important neuropsychiatric and cardiac adverse effects; not an ideal drug for pregnancy; cannot be used concomitantly with quinine or
quinidine
.
f.For
pregnant women.
Clindamycin
5 mg/kg (usually 300 mg)
po
or iv every 8 hours can be administered if the patient is unable to take
doxycycline
.Slide40
PreventionInsecticide treated bed nets.Repellents.
Chemoprophylaxis.
No 100% protection.Slide41
Antimalarial
chemoprophylaxis
Adult dose
Weight adjusted dose for children
CHLOROQUINE-SENSITIVE MALARIA
300 mg base
5 mg base/kg weekly
Chloroquine
and/or
200 mg base
3.5 mg/kg daily
Proguanil
CHLOROQUINE-RESISTANT MALARIA
250 mg base
5 base/kg weekly
Mefloquine
Or
100 mg
1.5 mg/kg daily
Doxycycline
Or
30 mg base
0.5 mg base/kg daily with food
Primaquine
Or
250/100 mg
4/1.6 mg/kg daily
Atovaquone-proguanil
(
Malaron
)Slide42
a
Chloroquine
should not be taken by people with a history of seizures, generalized psoriasis or
pruritus
previously on
chloroquine
.
b
Mefloquine
is not recommended for babies <3 months of age.
Mefloquine
should not be taken by people with psychiatric disorders, epilepsy, or those driving heavy vehicles, trains,
aeroplanes
etc. or deep sea diving.
c
Doxycycline
may cause photosensitivity. Use of sunscreens is
recommended.Not
for
childern
under 8 years.
d
Chloroquine
,
pyrimethamine
and
proguanil
are all considered safe in pregnancy, but are now largely
ineffective
against
P.
falciparum
.
Mefloquine
is considered safe, although there are uncertainties as treatment use has been associated with stillbirth in one large series.
Tetracyclines
and
primaquine
are contraindicated in pregnancy (although some argue that they are safe in first trimester before the formation of fetal bones and dentition, and before the risk of acute fatty liver), and
atovaquone-proguanil
has not been evaluated.
e
The use of
antimalarial
prophylaxis by children living in an endemic area has been shown to reduce mortality; in The Gambia administration of
pyrimethamine
and
dapsone
(
Maloprim
) in the 1–4 year age group reduced mortality by 25%.
Slide43
Chronic complications of malariaMalarial nephropathy(
Quartan
nephropathy).
Tropical
splenomegaly
(hyper reactive malarial
splenomegaly
) syndrome.
Chronic anemia .
Failure to thrive.Slide44
Quartan nephropathy
The
nephrotic
syndrome, with
albuminuria
,
hypoalbuminaemia
,
oedema
and variable renal impairment, is common in the
tropics.Repeated
or continuous
P.
malariae
infection is associated with childhood
nephrotic
syndrome in West Africa and Papua New Guinea. In the past,
quartan
nephropathy was also described in eastern Asia. It has disappeared from countries where
P.
malariae
has been eradicated, such as Guyana, where
Giglioli
first described the relationship between malaria and
nephrosis
.Slide45
Hyper-reactive malarial splenomegaly
This is also known as the tropical
splenomegaly
syndrome. It occurs where transmission of malaria is intense and has been reported throughout the tropics. The highest incidence of hyper-reactive malarial
splenomegaly
(HMS) yet reported was in the Upper
Watut
Valley of Papua New Guinea, where 80% of adults and older children had large spleens. Genetic factors undoubtedly also play a role because within a
malarious
area the geographical distribution of HMS does not follow closely that of malaria transmission. In Ghana first degree relatives have a four times higher incidence of HMS than age and location matched controls.Slide46
Hyper-reactive malarial splenomegaly
There is gross
splenomegaly
with normal architecture, and lymphocytic infiltration of the hepatic sinusoids with
Kupffer
cell hyperplasia. The massively enlarged spleen leads to
hypersplenism
with
anaemia
, leucopenia and thrombocytopenia. There is a polyclonal
hypergammaglobulinaemia
with high with high serum concentrations of
IgM
. High
titres
of malaria antibodies and a variety of
autoantibodies
(antinuclear factor, rheumatoid factor) are usually present. The
hypergammaglobulinaemia
is believed to result from polyclonal B-cell activation in the absence of adequate numbers of CD8+ suppressor T-cells, which have been removed by an antibody-dependent
cytotoxic
mechanism. Cell-mediated immune responses are otherwise normal. Immunoglobulin gene rearrangements have been demonstrated in a sub-group of patients with HMS. This indicates
clonal
lymphoproliferation
and the potential for progression to malignant lymphoma or
leukaemia
.