Download 7.Prof.K.M.Bhatt-Current-Update-in-Treatment-of

Current update in treatment of
Malaria
Prof. K.M. Bhatt,EBS
UON
PRINCIPLES OF MANAGEMENT OF
UNCOMPLICATED MALARIA
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Prompt and accurate diagnosis
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Assess for signs of complicated/severe malaria
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Can occur with low parasitemias
Can develop after parasites clear peripherally
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Prompt use of appropriate antimalarial drugs
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Monitor clinical and parasitological improvement
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Cure – parasitic and/or clinical
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Ancillary treatment
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Instructions for future prevention of malaria
OBJECTIVES OF AN EFFICIENT
ANTIMALARIAL TREATMENT
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Allow for a lasting clinical recovery
Reduce malaria-related morbidity and mortality
Stop the evolution of a benign infecton into a serious and
potentially life-threatening disease
Reduce the impact of malaria-related placenta infection
and malaria-related maternal anemia using
chemoprophylaxis or intermittent preventive treatment
Minimize the risks and levels of resistance.
Characteristics of ideal antimalarial
combination
The elimination half life of the partner drug is
longer than that of the fast-acting drug.
 The tolerability must be good and the toxicity
acceptable
 The treatment must be active against all stages of
the parasite, including gametocytes
(Drugs, 2002, Vol. 62, No. 9, p. 1315-1329)
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Characteristics of ideal antimalarial
combination
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The total duration of the regimen must not
exceed 3 days to ensure adequate adherence
One of the drugs must be present in the
circulation after the 2 cycles exposed to the fast
acting drug
(Drugs, 2002,62(9):1315-1329)
Recommended ACTs For Uncomplicated
Falciparum Malaria
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Artemether-lumefantrine
Artesunate + amodiaquine -Significant resistance
to Amodiaquine in Kenya*
Artesunate + mefloquine
Artesunate + SP – obsolete in Kenya*
Dihydroartemisinin + piperaquine
Drug Resistance
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Drug resistance to nearly all the drugs in
current use
…
Severe Malaria
Clinical and Laboratory Investigations
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Detailed clinical
examination
Asses level of
consciousness and record
Glasgow or Blantyre
coma scale
Blood glucose
HB, platelet count
Blood slide for MPs
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Liver, renal function tests
Clotting studies
Blood cultures
Blood pH and gases
Chest x-ray
Blood cross matching
LP (after fundoscopy)
Weight
BACTERIAL INFECTION
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Patients with severe malaria are vulnerable to
bacterial infection.
Much more common in children.
Severe malaria predisposes to bacteremia, often
enteric bacteria from the gut (site of preferential
parasitized erythrocyte sequestration).
Predisposes to systemic non-typhoid salmonella
infections
Prevalence of Anaemia In Children
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More than half of children under 5 years had
moderate to severe anaemia.
Anaemia more common in younger children.
Anaemia prevalence ranging from 16% in low
endemicity areas to 34% in lake region.
Treatment of Severe and Complicated
Malaria
parenteral Artesunate at 2.4mg per Kg stat iv
and repeated after 12 hr, 24hr and then for 6
days daily
 Parenteral quinine (to be phased out soon)
Loading dose 20mg/kg thereafter 10mg/kg 8
hrly (as infusion in 5% dextrose to run over 4
hrs
 Change to oral ACT as soon as the patient can
tolerate oral medication preferably 24hrs.

Treatment of Severe and Complicated
Malaria
parenteral Artesunate at 2.4mg per Kg stat iv
and repeated after 12 hr, 24hr and then for 6
days daily
 Parenteral quinine
Loading dose 20mg/kg thereafter 10mg/kg 8
hrly (as infusion in 5% dextrose to run over 4
hrs)
 Change to oral ACT as soon as the patient can
tolerate oral medication preferably 24hrs.
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Supportive Care
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Coma – maintain airway, intubate
Hyperpyrexia – tepid sponging, antipyretic drugs
Convulsions – maintain airway, IV or rectal diazepam or IM
paraldehyde
Hypoglycaemia – maintain glucose containing infusion
Severe anaemia – transfuse fresh whole blood
Acute pulmonary oedema – prop up patient at 45 degrees,
give oxygen, give diuretics, stop IV fluids, +ve pressure
respirator
Cont…
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Acute renal failure – dialysis
Bleeding and coagulopathy – transfuse frozen plasma,
vitamin K injection
Exchange transfusion for hyperparasitaemia
In children severe respiratory distress results from severe
metabolic acidosis and anaemia. Should be treated by
blood transfusion
Manitol for raised intracranial pressure
EXCHANGE TRANSFUSION
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CDC recommends that exchange transfusion be
strongly considered for persons with a parasite
density of more than 10% or if complications such as
cerebral malaria, non-volume overload pulmonary
edema, or renal complications exist.
Its beneficial effect by removing infected red cells,
improving the rheological properties of blood, and
reducing toxic factors such as parasite derived
toxins, harmful metabolites, and cytokines.
ERYTHROCYTAPHARESIS
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Red blood cell fraction is removed by apheresis and wherein
the plasma, leukocyte and platelet fractions are returned to
the patient [2]
Erythrocytapheresis has advantages over ET because of
speed, efficiency, haemodynamic stability and retention of
plasma components such as clotting factors, but would only
be available in specialized centres and lacks the advantage
of ET of removing and replacing plasma
2. Zhang Y, Telleria L, Vinetz JM et al. Erythrocytapheresis for Plasmodium falciparum infection complicated
by cerebral malaria and hyperparasitemia. J Clin Apheresis 2001;16:15–18.
WHO 2012 RECOMMENDS:
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A single dose 0.25mg base/Kg Primaquine dose
should be given to all patients with parasitologically
confirmed P.falciparum malaria on the 1st day of
treatment in addition to an ACT, except for
pregnant women and <1yr of age
Add quinine IV to AS IV in case of non-responding
parasitaemia in severe malaria
Treatment In Specific Populations And
Situations
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Malaria in pregnancy
Malaria in lactating women
HIV and Malaria
ARVs and antimalarials
Treatment In Specific Populations And Situations
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Pregnant Women:
Recommendations –obtain parasitological diagnisis
•
First trimester: quinine + clindamycin to be given for 7 days.
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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.
WHO guidelines 2010
Malaria in Pregnancy
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Supportive care –prevent hypoglycemia
-foetal monitoring
-treat anaemia
-antipyretics
-antenatal care
Intermittent preventive treatment for malaria in
pregnancy (IPTp)
Lactating Women:
-Lactating women should receive standard anti-malarial
treatment (including ACTs) except for tetracyclines
which should be withheld during lactation.
-Primaquine should not be used
HIV and Malaria
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HIV and Malaria co-infection frequently occur with
PF
Transient ↑in viral load - wait for approx. 2 mths if
used for monitoring HAART
HIV associated with ↑susceptibility, higher
parasitemia, and ↑risk for recurent Malaria
particularly in patients with CD4counts <200/µl
Dual infection in pregnancy → adverse maternal
and perinatal outcomes- monthly IPT
HIV and Malaria
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Suggest HIV testing in adults who present with
clinical Malaria in endemic areas
Treatment of Malaria in HIV infected is similar to
HIV uninfected
New infections may be higher in HIV +ve than in
HIV negative and recrudescence of drug resistant
parasites may occur. Close follow up.
HIV and Malaria
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WHO recommends use of TrimethoprimSulfamethoxazole daily and bed nets in HIV
infected patients with CD4 <200/µl
ART ↓the incidence of Malaria therefore particular
attention should be paid to administration of ART
to those living in malaria endemic areas
Treatment Of Uncomplicated Falciparum Malaria
In Patients With HIV Infection
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Patients with HIV infection who develop malaria
should receive standard anti-malarial treatment
regimens as recommended.
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Treatment or intermittent preventive treatment with
sulfadoxinepyrimethamine should not be given to HIVinfected patients receiving cotrimoxazole
(trimethoprim-sulfamethoxazole) prophylaxis.
ARVs and antimalarials
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Significantly impaired metabolism of Amodiaquin in
presence of efavirenz, saquinavir, and ritonavir
NNRT may compromise the therapeutic efficacy of
quinine through induction of cytochrom p450
PI inhibit Cy p450 – co- administration of
Halofantrine →cardiotoxic effect
Some PIs have antimalarial activity- saq/rit
Prevention of Malaria
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ITN
Indoor residual spraying
Repellant cream
Chemoprophylaxis
Environmental management
VACCINE?
MALARIA VACCINE
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The RTS,S vaccine. i.e. RTS,S/AS01E &
RTS/ASO2D.-GlaxoSmithKline biologicals
It is based on the circumsporozoite protein that
targets the pre-erythrocytic cycle of Plasmodium
falciparum in humans
Induces pre-erythocytic immunity ,resulting in
reduced number of merozoites released into the
blood stream.
RTS S VACCINE
October 2011 Ist results on children aged 5-17months
showed that 3 doses of the vaccine candidate reduced
the number of malaria episodes over one year of follow
up by 55%.
 November 2012 data for infants vaccinated aged 6-14
weeks showed estimated overall efficacy over
12months of follow up was 33% for all malaria
episodes.
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 2013 3 set of results after 18months of follow up
showed 27% efficacy against clinical malaria in 614weeks and 46%in 5-17months
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Rts s vaccine
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Data on efficacy of a booster dose will be out in
2014.WHO recommendation on use of the vaccine
anticipated in 2015