Labaran CPIPP ABU Zaria MALARIA THE PROBLEM Every year worldwide gt 200 million clinical cases gt 2 million deaths from malaria mainly in Africa DRUGS ARE FAILING Pilot implementation of RTSSAS01 vaccine ID: 738858
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Slide1
Treatment of malaria
K S
Labaran
, CPIPP ABU Zaria Slide2
MALARIA: THE PROBLEM
Every year: worldwide
> 200 million clinical cases
> 2 million deaths from malaria mainly in Africa
DRUGS ARE FAILING
Pilot implementation of RTS,S/AS01 vaccineSlide3
Female
Anopheles
mosquitoSlide4Slide5
Several species of the Plasmodium protozoan parasite
can
infect humans under natural circumstances
–
P
.
falciparum
(frequently fatal malignant tertian malaria: drug-resistance)
P
.
vivax
, P
. o v a l
e,
(“benign” relapsing)
P
.
malariae
(chronic childhood infection:
nephrotic
syndrome)
P
.
knowlesi
. Slide6
Malaria diagnosis:
Microscopy
Thin blood films: better for morphology
Thick blood films are 10x more sensitive than thin
Rapid diagnostic test (RDT)Slide7Slide8
Morbidity due to
infection with
P. falciparum
can
range from mild febrile illness which is difficult to
distinguish
clinically from other similar illnesses,
to
life-threatening disease with coma, respiratory
distress
, severe
anaemia
or circulatory shock.
In
young
children
and non-immune adults in particular, the
clinical
picture can change within 24 hours, from an
apparently
mild condition to a life-threatening illness. Slide9
Severe morbidity and mortality from falciparum malaria result from sequestration of infected erythrocytes and associated vital organ dysfunction.
Sequestration
causes
microvascular
obstruction-related brain pathology, metabolic acidosis compounded by severe
anaemia
due to accelerated erythrocyte destruction,
hypoglycaemia
, circulatory shock, and in older children and adults, renal failure and pulmonary
oedema
.Slide10
Symptoms
High fever
Profuse sweating
Vomiting
Headache
Cold shivers
Muscle pains
Convulsions
Diarrhoea
Cough Slide11
Blood stages: responsible for pathology
Fever is associated with synchronous bursting of the infected blood cells
Anaemia
: loss of blood cells
Cerebral malaria:
cytoadherence
in brain capillaries
Late stage infected red cells block brain capillariesSlide12
Morbidity and mortality control
Prompt diagnosis and drug treatment Slide13
Suggestion to control malaria?
Preventing mosquito bites
Prevention of man-mosquito contacts
Pyrethroid
-impregnated bed-net
Repellants
Residual insecticide house-spray
Health education Slide14
How does the infection persist?
The only reservoir is man, since mosquito populations loose their infections within weeks in the absence of infective humans
Persistence in man depends on the persistence in the blood stage
P. falciparum
up to 3 years
P.
malariae
> 50 years
Persistence in the liver
P.
vivax
and
P.
ovale
,
the dormant parasite may remain in the liver for up to 5 years Slide15
P. Vivax
and
P
.
ovale
Some
sporozoites
become dormant
hypnozoites
and delay development for 3,6 or more months up to 5 years Slide16
Drug treatment
Therapeutic: speedy effect on growing blood forms
Hypnozoitocide
/
gametocytocide
: kills dormant forms in liver or blood
Sporontocide
: kills growing mosquito stages
Radical cure: therapeutic +
hypnozoitocide
for relapsing malarias, therapeutic alone for non-relapsing malariasSlide17
Choice of regimen is based on:Availability
Cost
Drug resistance pattern of
P. falciparum
Known allergies
Age
pregnancy
Drug treatment Slide18
Blood schizontocides
Used for therapeutic cure
Some are also used in suppressive prophylaxis
Attack
haemoglobin
-digesting blood stages only
Chloroquine
Quinine
Mefloquine
Halofantrine
Lumefantrine
ArtemisininsSlide19
Prophylaxis
Suppressive prophylaxis: prevent growth of blood forms
Causal prophylaxis: prevent growth of liver forms Slide20
The chloroquine-resistance problem
Chloroquine
was introduced for malaria treatment and prevention in the late 1940s
It was safe and effective
P. falciparum
resistance to
chloroquine
, was first seen in 1950-60 in SE Asia and S. AmericaSlide21
Possibility of artemisinin resistance
Artemisia
annua
“
Qinghao
”
Source of
artemisinin
No 100% confirmed cases of
artemisinin
resistance seen yet
The first reports of higher
recrudescence rates
of
P. falciparum
malaria
after treatment with ACTs emerged
in
Cambodia since
2004
Reduced susceptibility to
artemether
in French
Guianan
isolatesSlide22
December 2008 showed the strongest indication of potential
artemisinin
resistance yet in Cambodia
Parasites persisted 7 days after
artesunate
treatment or re-emerg
ed 28 days after treatm
ent
All pharmacology results were normal – i.e. drug reached required concentration in patients
Possibility of
artemisinin
resistance
Artemisia
annua
“
Qinghao
”
Source of
artemisininSlide23
May be linked to widespread availability of artemisinin
monotherapy
and multidrug resistance
Possibility of
artemisinin
resistance
Artemisia
annua
“
Qinghao
”
Source of
artemisininSlide24
The management of malaria and avoiding drug resistance
Diagnosis
Minimising
the development of resistance
The strategic use of drugs
Previous treatment regimens
ACT combinations
WHO recommendations Slide25
Diagnosis
Prompt and accurate diagnosis of malaria is part of effective disease management and will if implemented effectively help reduce unnecessary use of antimalarial medicines Slide26
Clinical diagnosis
Least expensive and the most widely practiced
Traditional among medical doctors
It is based on signs and symptoms and on physical findings and examination
Diagnosis Slide27
A clinical
diagnosis of malaria is still challenging because of
the non-specific
nature of the signs and symptoms, which
overlap considerably
with other common, as well as potentially
life-threatening diseases
, e.g. common viral or bacterial infections,
and other
febrile illnesses.
The
overlapping of malaria symptoms
with other
tropical diseases impairs diagnostic specificity, which
can promote
the indiscriminate use of
antimalarials
and
compromise the
quality of care for patients with non-malarial fevers in
endemic
areasSlide28
Laboratory
diagnosis
Detection of the causative parasite or its products
The most commonly used being microscopic diagnosis and more recently rapid diagnostic tests (RDT) based on
immunochromatographic
techniques.
Diagnosis Slide29
Development of resistance
Point mutations leading to amino acid change and resistance occur at most once in a million cell divisions. In the absence of drug pressure they are unfit and die out.
Intensive use of drugs selects these rare changes. Level of drug resistance may increase by sequential mutations. So inadequate treatment courses can predispose to resistance development.Slide30
Controlling the spread of resistance
Reduce transmission overall, using insecticide-impregnated bed nets and mosquito control activities
Use
primaquine
to kill the sexual stages in the blood to prevent mosquitos getting infected (care in G6PD deficient-
haemolysis
)
Qinghaosu
(
Artemisinin
) drugs also reduce numbers of sexual stages. These drugs are especially useful in combination with other
antimalarialsSlide31
Make sure FULL COURSE of treatment and PROPER DOSING (BY WEIGHT) is adhered toSlide32
Artemisinin COMBINATION therapies (ACTs)
First line treatment of malaria
Promote rational drug use abandon the use of oral
artemisinin
MONOTHERAPIESSlide33
Features of ACT
Rapid resolution of clinical symptoms
Rapid parasite clearance
Rapid and substantial reduction of the parasite biomass
Effective action against multi-drug resistant
P. falciparum
Reduction of gametocyte carriage, which potentially reduces transmission of resistant allelesSlide34
WHO recommendations
1.
artemether
+
lumefantrine
2.
artesunate
+
amodiaquine
3.
artesunate
+
sulfadoxine
/
pyrimethamine
(where SP efficacy is high)
4.
amodiaquine
+
sulfadoxine
/
pyrimethamine
,
in areas where efficacy of all three drugs remains
high
5.
artesunate
+
mefloquine
6.
dihydroartemisinin
+
piperaquineSlide35
P. vivax
Use
chloroquine
Clear
erthrocytic
stages of the parasite but has no effect on the liver stage
Use course of
primaquine
for radical cure
Patient may suffer a relapse which will occur weeks, months or sometimes years after the original attackSlide36
Malaria in pregnancy
Malaria in pregnancy poses a substantial risk to the mother, the fetus and the newborn infant
Pregnant women are less capable of coping with and clearing malaria infections
Attacks of severe malaria, which may result in stillbirths or spontaneous abortions, or the death of the motherSlide37
In areas of high transmission, levels of acquired immunity tend to be high and women may have asymptomatic infections, which may result in maternal
anaemia
and placental
parasitaemia
.
These conditions can lead to low birth weight, an important contributor to neonatal mortality
Malaria in pregnancy Slide38
Intravenous
artesunate
should be used in preference to quinine for the treatment of SEVERE
P. falciparum
malaria in adults
Rapid administration of quinine is unsafe. Each dose of parenteral quinine must be administered as a slow, rate-controlled infusionSlide39
Prophylaxis
Travellers
to malaria risk areas (tropical and subtropical areas)
Over 100 countries
About 30,000 international travelers fall ill annually
Fever occurring in a traveler one week or more after entering a malaria risk area, and up to 3 months after departure, is a medical emergency that should be investigated urgently.Slide40
Children travelers are at special risk
Chloroquine
+(or)
proguanil
HCl
remains the drug of choice in areas where malaria remains sensitive
Mefloquine
is the preferred agent in
chloroquine
-resistant areas
Doxycycline Slide41
Protection against bites
Permethrin
impregnated mosquito nets
Diethyltoluamide
(DEET) lotions, sprays or roll on formulations
Long sleeves and trousers Slide42
Mosquirix
™
Pilot implementation program
Young children
P. falciparum
Ghana, Kenya, Malawi