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Malaria

• Malaria is caused by
infection of red blood cells
with protozoan parasites of
the genus Plasmodium
inoculated into the human
host by a feeding female
anopheline mosquito.
The five human Plasmodium species transmitted from
person to person are
• P. falciparum,
• P. vivax,
• P. ovale
• P. malariae
• P. knowlesi
• (4) P. vivax and
P. ovale a
dormant stage
[hypnozoites]
can persist in the
liver and cause
relapses by
invading the
bloodstream
weeks, or even
years later
diagnosis of malaria

All cases of suspected malaria should have a


parasitological test (microscopy or Rapid diagnostic test
(RDT)) to confirm the diagnosis.
SUSPECTED MALARIA

The signs and symptoms of


malaria are non-specific.
• In malaria-endemic areas,
malaria should be
suspected in any patient
presenting with a history of
fever or temperature ≥
37.5 °C and no other
obvious cause
• If the initial blood film examination is negative
- a series of blood films should be examined at 6–12h
intervals, or an RDT (preferably one detecting PfHRP2)
should be performed.

• In patients with suspected severe malaria and in other


high-risk groups, such as patients living with HIV/AIDS,
absence or delay of parasitological diagnosis should not
delay an immediate start of antimalarial treatment.
textbook feature

classical paroxysm
• initial ‘cold stage’, with dramatic rigors during which the
patient shakes visibly.
• ‘hot stage’ in which the patient has a temperature of more
than 40°C, may be restless and excitable and may vomit
or convulse
• a‘sweating stage’, when the fever abates and the patient
may fall asleep
Treatment of uncomplicated P. falciparum malaria

ACTs(Artemisinin-based Combination Therapy):


• artemether + lumefantrine (riamet)
• artesunate + amodiaquine
• artesunate + mefloquine
• dihydroartemisinin + piperaquine
• artesunate + sulfadoxine–pyrimethamine (SP).
Duration of ACT treatment
• ACT regimens should
provide 3 days’ treatment
with an artemisinin
derivative.
Patients co-infected with HIV
• In people who have HIV/AIDS and uncomplicated P. falciparum malaria, avoid artesunate + SP if they are also
receiving co-trimoxazole
• avoid artesunate + amodiaquine if they are also receiving efavirenz (Hepatotoxicity) or zidovudine.(neutropenia)
First trimester of pregnancy
• Treat pregnant women with uncomplicated P. falciparum malaria during the first trimester with 7 days of quinine +
clindamycin.
Treatment Failure
• may result from drug resistance or inadequate exposure to the drug
• sub-optimal dosing
• poor adherence
• vomiting
• unusual pharmacokinetics in an individual or substandard medicines.

• FAILURE WITHIN 28 DAYS : as table below


• FAILURE AFTER 28 DAYS:
• Treat as new infection except previous AS/MQ usage, may consider alternative
• Recurrence of fever and parasitaemia > 4 weeks after treatment may
be due to either recrudescence or a new infection.
• The distinction can be made only by PCR genotyping of parasites from
the initial and the recurrent infections.
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.
• G6PD testing is not required.
Treatment of uncomplicated malaria cause by
-P.VIVAX
-P. OVALE
-P. MALARIAE
-P. KNOWLESI
Blood stage infection
• If the malaria species is not known with certainty, treat as for uncomplicated
P. falciparum malaria.

• In areas with chloroquine-susceptible infections, -> with either an ACT


(except pregnant women in their first trimester) or chloroquine.

• In areas with chloroquine-resistant infections,-> (except pregnant women in


their first trimester) with an ACT.

• Treat pregnant women in their first trimester who have chloroquine-resistant


P. vivax malaria with quinine.
Preventing relapse in P. vivax or P. ovale malaria

• only P. vivax and P. ovale form hypnozoites( dormant


parasite stages in the liver that cause relapses of infection
weeks to years after the primary infection)

• The G6PD status of patients should be used to guide


administration of primaquine

• 14-day course (0.25-0.5 mg/kg bw daily) of primaquine


• G6PD deficiency,
– primaquine base at 0.75 mg/kg bw once a week for 8 weeks, with close medical
supervision for potential primaquine-induced adverse haematological effects.

• When the G6PD status is unknown /testing is not available


– based on an assessment of the risks and benefits of adding primaquine.

• pregnant /breastfeeding
– weekly chemoprophylaxis with chloroquine until delivery and breastfeeding are
completed, then, on the basis of G6PD status, treat with primaquine to prevent
future relapse.
SEVERE FALCIPARUM MALARIA

• defined as one or more of the following, occurring in the


absence of an identified alternative cause and in the
presence of P. falciparum asexual parasitaemia
• Impaired consciousness: GCS < 11 in • Severe acidosis
adults – respiratory distress (rapid, deep,
• Prostration: Generalized weakness so laboured breathing).
that the person is unable to sit, stand
or walk without assistance
• Hypoglycaemia:
• Multiple convulsions: >2 in 24 h – glucose < 2.2 mmol/L (< 40 mg/dL)
• Acidosis: • Severe malarial anaemia:
– A base deficit of > 8 mEq/L or, – Hb ≤ 5 g/dL or
– plasma bicarbonate level of < 15 – HCT ≤ 15% in children < 12 years
mmol/L of age (< 7 g/dL and < 20%,
– venous plasma lactate ≥ 5 mmol/L. respectively, in adults) with a
parasite count > 10 000/μL
• Renal impairment: • Shock:
– creatinine > 265 μmol/L (3 mg/dL) or
– Compensated shock is defined as
– blood urea > 20 mmol/L
capillary refill ≥ 3 s or temperature
• Jaundice:
gradient on leg (mid to proximal limb),
– Plasma bilirubin > 50 μmol/L (3 mg/dL) with a
parasite count > 100 000/ μL
but no hypotension. Decompensated
• Pulmonary oedema: – shock is defined as systolic blood
– Radiologically confirmed or
pressure < 70 mm Hg in children or <
– oxygen saturation < 92% on room air with a
80 mm Hg in adults, with evidence of
respiratory rate > 30/min, often with chest impaired perfusion (cool peripheries or
indrawing and crepitations on auscultation prolonged capillary refill).
• Significant bleeding: • Hyperparasitaemia:
– Including recurrent or prolonged bleeding from
the nose, gums or venepuncture sites;
– P. falciparum parasitaemia > 10%.
haematemesis or melaena
Treament of severe malaria
• IV/IM artesunate for at least 24 h and until they can
tolerate oral medication.
• Once a patient has received at least 24h of parenteral
therapy and can tolerate oral therapy,
– complete treatment with 3 days of an ACT (add single dose
primaquine in areas of low transmission).

• If parenteral artesunate is not available, use artemether in


preference to quinine for treating children and adults with
severe malaria.
Treating cases of suspected severe malaria pending
transfer to a higher-level facility (pre-referral treatment)
Pre-referral treatment options
• give a single IM/IV dose of artesunate-> refer to an
appropriate facility
• If IM/IV artesunate is not available use IM artemether or, if
that is not available, use IM quinine.
SEVERE VIVAX AND KNOWLESI MALARIA

• Severe vivax malaria is defined as for falciparum malaria


but with no parasite density thresholds.
• Severe knowlesi malaria is defined as for falciparum
malaria but with two differences:
– P. knowlesi hyperparasitaemia: parasite density > 100 000/μL
– Jaundice and parasite density > 20 000/μL.
Reminder

• These patients should be referred to hospitals with


specialists for further management:
a. all patients with severe and complicated malaria
b. immuno-compromised patients with significant co-
morbidities e.g. hepatic or renal dysfunction
c. pregnant mothers
General Management for Severe Malaria

1. Take a complete History and PE.


a. GCS , presence of neck stiffness, BP/PR/RR . Examine
the fundi as well.
2)investigation
a. Blood C+S
b. FBC
c. Prothrombin Time (PT), Partial Thromboplastin Time
(PTT).
d. Serum Urea and Electrolytes, Creatinine.
e. Blood glucose.
f. Liver Function Test.
g. Chest X-ray.
h. Arterial Blood gas.
i. Serum Lactate (if available)
• Admit the patient to the ICU or the High Dependency Unit
• Give IV Artesunate (2.4 mg/kg) stat.
– If this is not possible, give it IM.
• Administer IV Quinine if IV Artesunate is not available (and IM, if no IV
access).
• Administer the intravenous antimalarial for at least 24 hours before
switching to an oral formulation if the patient improves and can tolerate
orally
Pulmonary oedema is a grave complication of severe knowlesi and falciparum.
• It has a high mortality (over 80%in falciparum malaria); the prognosis is better in
vivax malaria. Pulmonary oedema may develop several days after chemotherapy ,
at a time when the patient’s general condition is improving and the peripheral
parasitaemia is falling.

• a) 1-2ml/kg /H until able tolerate oral fluids.


• b) Rapid fluid boluses are contraindicated in severe malaria resuscitation.

• Fluid is guided by urine output (with a urine output goal of > 1ml/kg/h), unless the
patient has anuric renal failure or pulmonary oedema, for which fluid management
should be tailored to the needs of the patient and reassessed frequently.
• If the patient‘s GCS is reduced
– look for other causes such as meningitis.
– A lumbar puncture may then be indicated and antibiotics instituted.
• There is considerable clinical overlap between septicaemia,
pneumonia and severe malaria, and these conditions may coexist
.
– broad spectrum IV antibiotic such as Ceftriaxone 2g OD ( after a septic
workout is done).
Discharge

• cleared of gametocytes
– -which play a crucial role in the spread of malaria and thus of
public health concern.
• can be discharged once they are clinically well with two
negative BFMP slides within 48 hours
Follow up

• Patients should be followed up weekly for a month.


• P. vivax infection should be followed up monthly for one
year.
• if antimalarial drug resistance is suspected, follow-up
should be extended; for example, in the case of
suspected P. falciparum resistance, beyond one month.
Such cases should be notified to the state and ministerial
level for further action.
MALARIA CHEMOPROPHYLAXIS

• combination of mosquito avoidance measures and


chemoprophylaxis.

Risk groups include:


• a. Travelers or visitors to endemic areas
• b. Army personnel
• c. Loggers/rubber tappers
• d. Workers in endemic areas e.g. dam construction,
plantation
mosquito avoidance measures
• insect repellant
• wearing long sleeves
• long pants
• sleeping in a mosquito-free
setting or using an insecticide-
treated bednet.
• diethyltoluamide (DEET) 20-
50% in lotions, spray or roll-on
formulation is safe and
effective when applied to the
skin of adults and children
Chemoprophylaxis

• Suppressive prophylaxis
– Chloroquine, proguanil, mefloquine, and doxycycline are
suppressive prophylactics.
– Only effective at killing the malaria parasite once it has entered
the erythrocytic stage (blood stage) of its life cycle, and
therefore have no effect until the liver stage is complete.
– these prophylactics must continue to be taken for four weeks
after leaving the area of risk.
Causal prophylaxis
• target not only the blood stages of malaria, but the initial
liver stage as well.
• user can stop taking the drug 7 days after leaving the
area of risk.
• Example: Atovaquone/Proguanil (Malarone) and
primaquine
Considerations when choosing a drug for malaria
prophylaxis
• Check risk of exposure to malaria

• consider the possibility of drug-drug interactions with other medicines that the person might be
taking as well.

• When deciding which drug to use, consider length of trip, previous adverse reactions and current
medical history.

• Start chemoprophylaxis earlier if there are particular concerns about tolerance to the medications.
For example, mefloquine can be started 3–4 weeks in advance to allow potential adverse events
(AE) to occur before travel.

• The use of the same or related drugs that have been taken for prophylaxis is not recommended
to treat malaria.
• Thanks

• References
• WHO Guideline for
treatment of Malaria 3rd
edition 2015
• Manegement guideline of
malaria in malaysia 2013

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