Malaria

1. Severe and Complicated
Malaria
Presenters: Carolyn Nansubuga
Asasira Christopher Agaba

2. Introduction
• Malaria is a febrile illness caused by plasmodia
species.
• Infection is transmitted by the bite of the female
anopheles mosquitoes – gambiae and fenestus.
• Four species of plasmodium exist: falciparum,
malariae, vivax and ovale.
• P.falciparum is the predominant species in
Uganda.

4. Introduction
• Malaria is an important cause of death and
illness in children and adults in tropical
countries.
• Two forms of disease exist:
– Uncomplicated malaria
– Complicated/Life-threatening/severe malaria

5. Uncomplicated Malaria
• Fever or history of fever, no danger signs and a positive
blood slide.
• Relatively mild disease
• Usually no organ involvement.
• However if not diagnosed early and treated promptly,
may deteriorate into severe malaria.

6. Severe Malaria
• Common life threatening condition in uganda and if
not managed appropriately frequently causes death
• In uganda,approx.5% of cases of malaria result in
severe malaria
• Approx.9-14% of all death are attributed to malaria
• (Ref: National malaria control program,MOH 2012)
• Definition
• Malaria illness that is serious enough to be an
immediate threat to the life of a patient.
• In a patient with P.falciparum asexual parasitemia and
no other obvious cause of their symptoms, the
presence of one or more of the following clinical or
laboratory features classifies the patient as suffering
from severe malaria:

7. Severe malaria contd
• Clinical manifestations
– Cerebral malaria:Unarousable coma not
attributable to any other cause in a patient
with falciparum malaria. CSF is normal. Blood
smear is positive for P.falciparum or RDT is
positive for malaria
– Severe anaemia:Hb<5g/dl with parasitaemia
– Respiratory distress:Tachypnea,nasal flaring
and intercostal recessions in a patient with
parasitaemia
– Hypoglycemia:Blood glucose<40mg/dl(2.2
mm/l) with parasitaemia

8. Severe malaria contd
• Circulatory collapse: Clinical shock(Systolic pressure
<50mmg for children and <80mmHg for adults, with cold
peripheries, clammy skin) with parasitaemia
• Renal failure: Urine out put <12ml/kg/24 hrs and plasma
creatinine >3.0mg/dl with parasitaemia
• Acidosis: Deep acidotic breathing, plasma bicarbonate
<15mmol/ml, with parasitaemia
• Haemoglobinuria:Parasitaemia,haemoglobinuria in
urine(dark colored urine but no RBC’s)
• Pulmonary oedema:Deep breathing first breathing,
labored breathing(nasal flaring,intercostal recession and
chest indrawing),Cheyne stokes breathing

9. Supporting manifestations
• Impaired consciousness:Parasitaemia with
depressed level of consciousness but can localize a
painful stimulus
• Jaundice: Parasitaemia with unexplained jaundice
• Prostration: Unable to sit a child normally able to do
so or unable to drink in one too young to sit
• Hyperpyrexia: Temperature >39.5oC,with
parasitaemia
• Parasite count >250,000/ul

10. Groups at risk of severe malaria
• These are people whose immunity to malaria is low
• Children aged 6 months to 5 years in areas of high
malaria endemicity
• People of all ages in areas of low malaria endemicity
• Pregnant women especially during the 1st
and 2nd
pregnancies
• Travelers from non-endemic ares
• People returning to endemic areas after a long(more
than 6 months) stay in non malaria areas
• People with HIV/AIDs
• Persons with Sickle cell anemia

11. Diagnosis of severe malaria
• Take detailed history of the illness
• Perform thorough clinical examination
• Carry out the relevant and essential lab investigations to
confirm diagnosis and complications
• Note: Most important aspect of diagnosis are the
presence of one or more of the manifestations listed
above of severe malaria and a blood smear
demonstrating the presence of asexual forms of
P.falciparum
• A complete hx aims at identifying other possibe
diagnosis and assessing for complications

12. Essential lab investigations
• Thick blood film or RDT and thin blood film for MPs.Thick
smear or RDT for screening the MPs and thin film for
typing the plasmodium
• Blood glucose: In any patient with altered
consciousness, confusion and convulsions
• Hb and PCV estimation in all patients suspected of
having severe anemia
• LP to exclude meningitis. Clear CSF does not r/o
meningitis since fluid may look clear with up to 300
cells/mm3

13. Other lab Investigations if possible
• Not essential to Mgt but if available may be helpful of
prognostic usefulness
• Plasma creatinine(urea is an alternative)
• Electrolytes to correct abnormalities like hyponatraemia
• Blood culture: Septicemia may complicate Severe FP
malaria and cause shock or unresolving fever
• FBC and differential WBC.May indicate possibility for an
additional diagnosis e.g. leucocytosis for pyogenic
infections, leucopenia for typhoid and viral diseases and
profound thrombocytopenia for DIC
• Blood gases,PH and anion gap to help identify acidosis
• etc

14. Treatment and management
• Management of severe malaria is a team effort and
involves clinicians,nurses,lab staff pharmacists and
administrators.
• Management involves
1. Priority triage
2. Antimalarial chemotherapy
3. Management of complications
4. Regular monitoring
5. Continual treatment

15. Triage
• Process of rapidly sorting ill patients in priority
groups depending on the severity of illness and
need for attention
• Category 1:Emergency cases; critically ill,
require emergency resuscitation
• Category 2:Priority cases: signs that require
specific treatment but not necessarily and
emergency
• Category 3:No urgent cases
• Most severe malaria patients fall in category 1

16. Antimalarial therapy

17. Treatment Objectives
• For uncomplicated malaria, primary aim of
treatment is to cure infection as rapidly as possible
• Secondary objective is to:
– reduce transmission of infection
– prevent emergence and spread of resistance
• For severe malaria primary aim of treatment is to
prevent death
• Secondary objective is to
– prevent emergence and spread of resistance
– prevention of disabilities

18. Classification of Antimalarials
Antimalarials can be classified according to mode of
action of the drug:
1. Tissue schizonticide (primaquine)
2. Blood schizonticide (chloroquine, sulphadoxine-
pyrimethamine, quinine, mefloquine and artemisinins)
3. Gametocytocidal drugs (artemisinins and
primaquine)

19. Site of action of Antimalarials

20. Site of Action
Artemisinin
Artemisinin
Quinine

21. Antimalarial chemotherapy in severe malaria
• Parenteral artesunate recommended drug of choice for the
treatment of severe malaria.I.V injection is the preferred
route of administration
• Parenteral quinine or Artemether as alternatives to be used
when artesunate is not available
• Clinical trials (AQUAMAT and SEAQUAMAT) provided
sufficient evidence to recommend artesunate in preference
to quinine or artemether.Trials showed a significant mortality
reduction (22.5% and 34.7% respectively) when compared to
quinine
• Studies also showed incidence of convulsions,coma,and
hypoglycemia developing after hospitalization were
significantly reduced
• Artesunate also does not require rate controlled infusion or
cardiac monitoring and takes a shorter time for health
workers to administer

22. Management of severe malaria
Severe malaria is a medical emergency
After rapid clinical assessment and confirmation of the
diagnosis, full doses of parenteral antimalarial treatment
should be started without delay
Management comprises of:
Clinical assessment
Specific antimalarial treatment
Adjunctive therapy
Supportive care

23. Adjunctive therapy of severe Malaria
Start immediate resuscitation measures using the
ABCD principle or procedure.
Establish I.V access and take the necessary blood
samples for investigations
Take weight to guide correct dosing with
antimalarials and other medicines.
Start definitive treatment for specific manifestation
of severe Malaria.
Ensure proper nursing care as it is essential.

24. Antimalarial chemotherapy in severe Malaria
Two classes of medicines available for the
parenteral treatment of severe malaria:
Cinchona alkaloids
Artemisinin derivatives
Give parenteral antimalarials for a minimum of
24 hrs, once started (irrespective of the patient’s
ability to tolerate oral medication earlier)
Thereafter complete treatment by giving a
complete course of an oral antimalarial drug

25. Antimalarial chemotherapy in severe malaria:
Quinine
Give Initial dose by IV infusion over 4 hours: Quinine
dihydrochloride 10 mg salt/kg of body weight diluted in
10 ml isotonic fluid/kg body weight.
Repeated every 8 hours, from the beginning of the
previous infusion, until the patient can tolerate oral
treatment.
Complete the treatment by giving
quinine tablets, 10 mg salt/kg 8-hourly to complete a 7-day
course of treatment
OR by giving a full course of artemether/lumefantrine (AL).

26. Quinine Dosing
A loading dose of quinine is not recommended in
Uganda because:
The outcome of treatment with quinine is the
same with or without the loading dose
Giving a loading may increase risk of cardio
toxicity in patient especially in those who have
taken medicines and herbal remedies that may
be related to quinine.

27. Antimalarial Chemotherapy in severe Malaria:
Artemisinin derivatives
Use Parenteral artemisinin derivatives: alternative therapy
Artesunate
Loading dose: IV Artesunate 2.4 mg/kg followed by 1.2 mg/kg
at 12 and 24 hours, then 1.2 mg/kg daily for 6 days. When the
patient has improved and is able to swallow, complete the
course of treatment by giving a full course of AL or any other
appropriate ACT).
Artemether:
Loading dose: Artemether 3.2 mg/kg IM followed by 1.6 mg/kg
daily. When the patient has improved and is able to swallow,
complete the course of treatment by giving a full course of AL

28. Management of complications of severe
malaria
• Complications present higher risk of death
• Manage the complications immediately
• General(For any patient with a dx of severe malaria)
• Immediate resuscitation (ABCD)
• Position in Left lateral position if unconscious
• Establish iv access (rehydration, drugs)
• Take necessary samples for investigations
• Manage immediate complications appropriately
• Start definitive treatment for severe malaria
• Note: Take pxs weight to guide correct dosing with
antimalarials and other medicines

29. Management of complications contd
• Ensure proper nursing care
• Keep patient warm
• Correct position if unconscious and turn regularly to
avoid bed sores
• Monitor and record vital signs, fluid input and output,
level of consciousness and convulsions
• Insert NG tube for feeding and administration of drugs
• Timely and safe administration of drugs
• Ensure appropriate bladder care and general body
hygiene
• Report any changes in the vital signs and general
condition of the patient.

30. Hypoglycemia
• Hypoglycemia: Blood sugar<40mg/dl (2.2mmol/dl)
Correct hypoglycemia if present. If the patient is in coma,
assume there is hypoglycemia and treat
accordingly(2mls/kg of 25% iv slowly over 3-5 minutes
(as bolus) or 5mls/kg of 10% dextrose by slow iv infusion
over 5-7 minutes
• Avoid giving 50% dextrose due to risk of
thrombophlebitis and rebound hypoglycemia
• Recheck blood glucose 2-4 hourly during course of
treatment particularly in a comatose patient
• Don’t use 5% glucose to correct hypoglycemia. Small
proportions of glucose-fluid overload

31. Severe anaemia
• If PCV below 15% or Hb below 5g/dl patient has severe
anaemia and give whole blood transfusion or packed
cells. Transfuse in 2 hours
• If parasitaemia is too high and you can predict acritical
drop in Hb level,give blood transfsion even when the Hb
is between 5-7g/dl
• Amount of blood to transfuse is usually 20ml/kg body
weight of WB or 10ml/kg of packed cells
• Indications for transfusion of adults with malaria
• Hb < 6g/dl with hyperparasitaemia
• Any Hb with heart failure secondary to anaemia
• Hb level of less than 5g/dl with any complication of
severe malaria(algid malaria,hypoglycemia,cerebral
malaria,PE,shock).

32. Convulsions
• Ensure safety
• Quickly assess ABCD(start oxygen as
appropriate)
• Give Iv injection of diazepam slowly over I
minute;0.2mg/kg of body weight or rectal
diazepam 0.5mg/kg.Repeat the dose if
convulsions have not stopped after 10
mins

33. Regular monitoring
• Breathing
• Temperature
• Pulse rate and volume
• Fluid balance(in-put,out-put,vomitus,diarrhea,urine
• LOC
• Convulsions
• BP
• Spontaneous hemorrhage (DIC)

34. When there are no facilities to manage Severe
Malaria
Refer the patient to the next level of care as quickly as
possible.
Ensure that before referral, you take the following
measures:
Inject 10 mg/kg body weight of Quinine I.M. after dilution.
Artemisinin derivatives in the form of suppositories or injections
may be given instead of quinine as a pre-referral treatment
Control temperature by undressing, tepid sponging and giving
Paracetamol
Control convulsions if present and give dextrose to any patient who
has had convulsions or is drowsy.
Give the patient oral fluids if she/he is dehydrated, and if necessary
through nasogastric tube.
Counsel the patient or caretaker on the need for referral
Write a referral note stating the treatment given and the time.