Presentation (from Uganda )

1. Malaria
Lecture 3
Presenter
Dr Owere Paul Odur
MBChB

2. Definition
• Malaria is an acute febrile illness caused by infection with asexual
forms of Plasmodium parasites and is transmitted from person to
person by an infected female anopheles mosquito.

3. Epidemiology
• 40% of the world’s population live in areas where malaria is
transmitted with 300–500 million new infections worldwide per year.
• Endemic areas of transmission are Africa, Asia, and South America
• In UG, malaria accounts for 30-50% of OPD visits,15-20% of all hosp.
admissions,27.2% of in pt. most deaths being children under 5yrs of
age.(MOH-National malaria control program 2014-2020).

4. High Risk groups
• Children between 3 months and 5 years
• Pregnant women
• Adults in hypo-endemic areas
• Non-immune immigrants into hyper-endemic areas
• Red cell abnormalities e.g. SCD, G6PD deficiency
• Gravid mothers esp. Prime gravidas.

5. Etiology
• There are five Plasmodium species of malaria parasites which infect
humans namely;
• P. falciparum, P. vivax, P. ovale, P. malariae and P. knowlesi.
• P. falciparum is the most virulent and also the most common malaria
parasite in Uganda.

6. pathophysiology
• Four important pathologic processes have been identified in pts with
malaria; fever, anemia immunopathologic events and tissue anoxia.
Fever; occurs w/n RBCs rupture and release merozoites into
circulation.
• Anemia; caused by hemolysis, sequestration of RBCs in the spleen
and other organs, and bone marrow suppression.
• Immunopathologic events; excessive production of pro-inflammatory
cytokines e.g. TNF, that may be responsible for most of the pathology
in the disease, including tissue anoxia;

7. pathophysiology
• Polyclonal activation resulting in both hypergammaglobulinemia and
formation of immune complexes; and immunosuppression.
• Cyto adherence of infected RBCs to vascular endothelium occurs in
p. falciparum malaria and may lead to blood flow obstruction and
capillary damage, with resultant vascular leakage of blood, protein,
and fluid and tissue anoxia.
• In addition, anaerobic metabolism of glucose leads to hypoglycemia
and lactic acidemia. The cumulative effects of these pathologic events
may lead to cerebral, cardiac, pulmonary, renal, intestinal and hepatic
failure.

8. Clinical features
• Children with malaria often lack typical paroxysms and have
nonspecific symptoms i.e., fever alternating with periods of chills and
rigors, fatigue, headache, drowsiness, anorexia, N/V, and diarrhea.
• In the presence of severe malaria, in addition to the above
manifestations, pts present with complications as shown in the table
below.

9. Severe malaria
• Malaria is regarded as severe if there are asexual forms of P.
falciparum in blood plus one or more of the following complications.

10. Complicated forms of malaria
1. Cerebral malaria-with clinical manifestation
 Deep coma (unable to localize a painful stimulus),
 Normal CSF
 parasitaemia Severe anemia Hb <5g/dl
2. Respiratory distress
Tachypnea,
Nasal flaring
 Intercostal recession in a patient with parasitaemia

11. Complicated malaria.
3. Hypoglycemia.
Blood glucose <40 mg/dl (2.2 mmol/L) with parasitaemia
4.Circulatory collapse.
Clinical shock (systolic pressure <50 mmHg for children and <80mmHg
for adults, with cold peripheries, clammy skin) with parasitaemia

12. Complicated malaria
5. Renal failure
 Urine output < 12 ml/kg in 24 hours
 plasma creatinine> 3.0 mg/dl, with parasitaemia
6.Spontaneous bleeding.
Parasitaemia with unexplained spontaneous bleeding (hematemesis,
melena, or prolonged bleeding from nose, gum or venipuncture site)

13. Complicated malaria
7.Repeated convulsions 2 or more convulsions in 24 hours, with
parasitaemia
8.Acidosis
Deep (acidotic) breathing
 plasma bicarbonate <15 mmol/L, with parasitaemia
9. Haemoglobinuria
Parasitaemia with hemoglobin in urine (dark coloured urine but no
RBC’s)

14. Complicated malaria
10.Pulmonary Edema
Deep breathing
 Fast breathing
Labored breathing (nasal flaring, intercostal recession and chest
indrawing)

15. Complicated malaria
11.Impaired consciousness.
Parasitaemia with depressed level of consciousness but can localize a
painful stimulus, or change of behavior, confusion, drowsiness
12.Jaundice Parasitaemia with unexplained jaundice

16. Complicated malaria
13.Prostration
 Unable to sit, in a child normally able to do so
Unable to drink in one too young to sit
Severe vomiting, Vomiting everything
Not able to drink or breastfeed

17. Complicated malaria
14.Severe dehydration.
Sunken eyes
Coated tongue
 Lethargy.
 inability to drink

18. Cerebral Malaria:
Definition
• Unconsciousness/ un arousable coma (unable to localize pain or a
Blantyre Coma Score of < 2) in the presence of asexual P. falciparum
parasitaemia of any density and no other obvious cause of the clinical
syndrome (e.g. meningitis, hypoglycemia).
• In practice, all children with a depressed level of consciousness and P.
falciparum on the BS are treated as CM.

19. Clinical features of CM
• Coma/ altered consciousness
• Convulsions (60–80%)
• Hypertonic posturing (decorticate or decerebrate rigidity,
opisthotonos)
• Abnormal respiratory pattern (Kussmaul’s, Cheyne-Stokes, periodic
apnoea)
• Gaze abnormalities (eyes wide open, conjugate gaze deviation,
nystagmus)

20. Mgt of cerebral malaria
Convulsions
• IV diazepam slow 0.2 mg/kg (max 10mg)
• IM Diazepam 0.5mg/kg rectally
• If convulsions still persist: Child: 10-15 mg/kg loading dose
then2.5mg/kg once or twice daily prn
• Or phenytoin15 mg/kg loading dose.

21. Blantyre Coma Scale
Used for quick assessment in children
Best Response Score Best Motor Response:
 Localizes painful stimuli 2
Withdraws from a painful stimulus 1
Extends/No response 0
Best Verbal Response:
Normal cry 2
Abnormal cry/ moan 1
 No response 0

22. BCS
Eye movements:
Follows mother’s face/ moving object 2
 Unfocused gaze/ Does not follow mother’s face 1
No response 0

23. BCS
 Total score = sum of individual scores from the three categories;
 (Max = 5, Min = 0)
Un arousable Coma = BCS score of 2 or less
NB Standard pressure on a nail bed, gentle sternal rub, gentle pressure
on supraorbital ridge.

24. Glasco Coma Scale
Used in assessment of consciousness level in adolescents
Best Motor
Normal movements- 6
 Localizes pain -5
Withdraws -4
Abnormal flexion -3
Abnormal extension - 2
None -1

25. GCS
Eye Opening
Spontaneous -4
To speech -3
To pain - 2
 None -1

26. GCS
Verbal Response
• Coos, babbles -5
• Irritable -4
• Cries to pain -3
• Moans to pain -2
• None - 1

27. GCS
• Total Score 15
• 14-15 mild injury
• 8-13 moderate
• 3-7 Severe Injury

28. Severe anaemia
Definition
• Packed Cell Volume<15%, Hemoglobin<5 g/dl
• Results from Hemolysis/ destruction of parasitized RBCs or by
erythrophagocytosis in the spleen
• Unparasitized RBCs also have a shorter lifespan during malaria
infection
• Preexisting Iron deficiency or hemoglobinopathies
• Dyserythropoiesis-impaired erythropoesis.

29. Clinical features
• Severe pallor of mucous membranes, palms and soles
• Respiratory distress (deep, labored breathing)
• Hyper dynamic circulation (gallop rhythm, tachycardia,
hepatomegaly, pulmonary edema)
• Confusion, restlessness, coma, retinal hemorrhages

30. Mgt
• Do PCV or Hb estimation, Thick and thin film
• If Hb =/< 4g/dl, transfuse.
• If Hb >4 but <6g/dl, with features of cardiac failure,
hyperparasitaemia, respiratory distress, impaired consciousness;
transfuse.

31. Mgt
• Transfuse with packed cells 10 – 15ml/Kg or whole blood 20ml/Kg
over 2 -3 hours
• A diuretic is not often required but IV furosemide (1-2mg/Kg) may be
given if there fluid overload
• Folic acid and/or iron at discharge

32. Outcome if untreated
• Mortality rate is 4.7 – 16% but is higher if severe anemia occurs with
other complications like cerebral malaria and respiratory distress

33. Hypoglycemia
• Very common in children who have been undernourished, those
below 3 years, those with convulsions and in 10 – 20% of those with
cerebral malaria.
Clinical presentation
• Blood glucose =/< 2.5 mmol/l
• Convulsions/ altered consciousness
• Sweating,
• Extreme weakness

34. Pathophysiology
Malaria infection causes;
• Impaired gluconeogenesis from the liver
• Accelerated metabolism- increased BMR
• Reduced food intake- nausea and vomiting.
• Parasite glucose consumption

35. Mgt of complicated malaria
During treatment:
• Quinine stimulates insulin secretion from pancreas.
• Rapid infusions of quinine (>10mg/kg in 1 hour) can precipitate
hypoglycaemia

36. Mgt of hypoglycemia
• Check random blood sugar before and even after correcting
hypoglycaemia
• Intravenous dextrose 10% infusion or bolus push of 5ml/kg
• Feed the patient on nutritious meals
• Prepare a solution of sugar which may be given by NGT
Treatment outcome:
• Mortality of pretreatment hypoglycemia in children with cerebral
malaria is 22 – 37%
• Recurrent hypoglycaemia has a 71% mortality

37. Respiratory Distress
Clinical presentation.
• Alae nasi flaring
• Chest/ subcostal recessions
• Use of accessory muscles of respiration
• Deep acidotic breathing
• Grunting

38. pathophysiology
• Metabolic acidosis (PH < 7.3) from anaerobic glycolysis
• Pulmonary edema
• Anaemia, Hypogylcamia

39. Mgt
• Correct reversible causes of acidosis;-Anaemia, dehydration,
hypoglycaemia, treat convulsions
• Prop the child up in bed
• +/- oxygen

40. Shock
• A diastolic BP of 50mmhg or less signifies shock & a systolic of
80mmhg or less.
• Children may have cold clammy cyanotic skin; constricted
peripheral veins and a rapid thin pulse.
• Circulatory collapse may result from a complicating gram negative
septicaemia, hypovolaemia from dehydration, pulmonary edema
or metabolic acidosis.
• Possible foci of infection should be sought e.g. lungs, urinary tract,
meninges, intravenous lines and sites.

41. Mgt of shock
• Correct hypovolaemia with normal saline or appropriate plasma
expander(sodium chloride 0.9% by fast IV infusion bolus 20 ml/kgin
15 min)
• if peripheral pulse absent and capillary refill is slow(>2 seconds)
• Raise the foot of the bed to aid venous return to the heart
• Review fluid balance and urinary outputs.
• Look for evidence of hemorrhage or septicemia and treat
accordingly.
• Take blood for culture and sensitivity, and start broad spectrum
antibiotics which can be modified when results are available.

42. Hyperpyrexia
• Axillary temperature of 39o C and above
Pathophysiology:
• Release of metabolites and cytokines from red blood cell
breakdown leading to elevation of the
hypothalamic(thermoregulatory centre) set point
• Rapid rise in temp may lead to febrile convulsions.
Management:
• Antipyretics – Paracetamol 10mg/kg rectally or orally
• Tepid sponging, fanning

43. Disseminated intravascular
coagulopathy/Bleeding Tendency
• Bleeding from gums, epistaxis, petechiae, subconjunctival
haemorrhages, and sometimes GI bleeding may occur.
• Thrombocytopenia is common in falciparum malaria, often without
other coagulation abnormalities and resolves soon after treatment
Management:
• Transfusion with blood, platelets, clotting factors
• Vitamin K- 10mg IM
• Tranexamic acid

44. Acute Renal Failure;
• Urine output: <0.3 ml/kg/hour for a child
• Ensure that the cause of oliguria is not dehydration or shock.
• If due to acute renal failure: Give a challenge dose of furosemide at 1
mg/kg
• If this fails: Refer for peritoneal dialysis or hemodialysis

45. Mgt of severe forms of malaria
First line IV artesunate.
• Child less than 20kg:3mg/kg
• Child >20kg:2.4 mg/kg at 0, 12 and 24 hrs.
• Then once a day until patient is able to tolerate oral medication, then
give a full course of oral ACT.

46. Mgt Complicated malaria
Alternative first line
• IV Quinine is the drug of choice for the treatment of complicated
malaria
• Presentation: IV/IM Quinine dihydrochloride 300mg/ml, 2ml
ampoule
• Dosage: 10mg/kg 8 hourly
• Administration:
IV: slow infusion of 10mg/kg in 10ml/kg of 5% dextrose solution ran
over 4 hours 8hourly till the patient can take orally, then give oral
quinine 10mg/kg to complete 7 days.

47. Mgt of complicated malaria
• Side effects of Qnn
• Cinchonism: Tinnitus, headache, nausea, visual disturbances
• Others: Vertigo, reduced hearing, blurred vision, diplopia
• Cardiac: Prolongation of QT interval, AV block, sinus arrest, ventricular
tachycardia
• Hypoglycemia.

48. Mgt of complicated malaria
IM Artemether;
• First dose: on admission, Loading dose at 0 hours 3.2 mg/kg
• Second dose at 24 hours 1.6 mg/kg
• Third dose at 48 hours 1.6 mg/kg
• Then once a day until patient is able to tolerate oral medication,
Then give a full course of oral ACT

49. Differential diagnosis of malaria
• Respiratory tract infection
• Urinary tract infection
• Meningitis
• otitis media
• tonsillitis
• Abscess or skin sepsis
• Measles or other infections with rashes (before rash comes)

50. Investigations
• All suspected malaria patients MUST be tested by BS or RDT before
they are treated.
• RDT or thick blood slide for diagnosis of malaria.
• Random blood sugar and Hb level if clinically indicated.
• Lumbar puncture: in case of convulsion/coma and negative malaria
tests.
• Thin film for parasite identification.

51. Investigations
• RDTs (Rapid Diagnostic tests) detect malaria antigen and remain
positive for 2 weeks after effective treatment.
• RDT do not become negative if the patient has already taken
antimalarials.
• RDTs are reliable, quick and easily accessible tools for malaria
diagnosis.

52. Investigations
• A blood slide for microscopy is specifically recommended over RDT in
the following situations;
• Patients who have taken antimalarial treatment for 2 days and
symptoms persist
• Patients who completed treatment but come back within 2weeks
• RDT negative patients without any other evident cause of
fever(current RDTs detect only P . Falciparum).

53. THE END
• THANK YOU