Severe malaria is an important cause of U-5 morbidity and mortality in malaria endemic areas like the subsaharan Africa particularly Nigeria which accounts for more than half of the burden on the continent. It is a life threatening condition, a medical emergency requiring in-patient care. Early treatment curtails the dismal outcomes of this condition. The most important preventive measures is use of insecticide treated mosquito nets in addition to environmental control, seasonal chemoprophylaxis and use of Malaria Vaccine. The recent recommendations by the WHO is use of IV Artesunate or if unavailable, artemether and quinine followed by full course of ACTs. Other complications should be treated as required and those with life threatening complications should preferably be managed in the ICU.

1. MANAGEMENT OF
SEVERE MALARIA
BY
EMMANUEL ALI ADAMU
DEPARTMENT OF PAEDIATRICS, MODIBBO ADAMA
UNIVERSITY TEACHING HOSPITAL YOLA, NIGERIA
MAY 11TH, 2023

2. OUTLINE
• Introduction
• Agents of Severe Malaria
• Overview of Life Cycle
• Transmission
• Pathophysiology
• Forms of Severe Malaria
• Management
• Prognosis
• Differential Diagnoses
• Prevention and Control
• Conclusion
• References

3. INTRODUCTION
• Malaria is a major health problem in Africa, Asia,
Central America, Oceania, and South America.
• About 40% of the world's population lives in areas
where malaria is common.
• Approximately 300-500 million cases of malaria occur
every year, and 1-2 million deaths occur, most of
them in young children.
• In endemic areas, children younger than age 5 years
have repeated and often serious attacks of malaria.
WHO. World malaria report. Geneva: World Health Organization; 2021.27 May 2022

4. INTRODUCTION CONTD
• The survivors develop partial immunity.
• Most deaths resulting from malaria occur in
children younger than age 5 years.
• Nigeria had the highest number of global malaria
cases (27 % of global malaria cases) and the highest
number of deaths (32 % of global malaria deaths) in
2020.
• The country accounted for an estimated 55.2% of
malaria cases in West Africa in 2020.
WHO. World malaria report. Geneva: World Health Organization; 2021.27 May 2022

5. INTRODUCTION CONTD
• Microscopy data from the 2018 NDHS show that the
prevalence of malaria parasitaemia in children under five
years of age is 23% (a < from 27% in 2015 and 42% in 2010).
• The 2021 Nigeria Malaria Indicator Survey Report has shown
that the malaria prevalence in the country has decreased
from 23 per cent in 2018 to 22 per cent in 2021
• Prevalence ranges from 16% in the South and South East
Zones to 34% in the North West Zone.
• In rural populations, prevalence is 2.4 times that in urban
populations (31% vs. 13%)
https://www.severemalaria.org/countries/nigeria

6. INTRODUCTION
• In a study carried out at FMC Yola in 2016, the
prevalence of malaria infection was 29.2%.
• The malaria species found was P. falciparum.
• Male subjects (32.2%) were more infected than the
females (25.6%) and age-group 5-9 years had the
highest infection rate.
Samaila, A. B., Kunihya, I. Z. and Daniel, L. Prevalence of malaria infection among children attending federal medical centre yola, adamawa
state, Nigeria Int. J of Recent Advanc in Multidisc Res Vol. 03, Issue 11, pp.1991-1994, November, 2016

7. AGENTS OF SEVERE MALARIA
• Plasmodium falciparum
• Plasmodium vivax
• Plasmodium knowlesi

8. TRANSMISSION
• Vector borne: Female anopheline mosquito
• Transplacental: congenital malaria
• Blood transfusion
• Organ transplant
• Zoonotic: P. Knowlesi

9. OVERVIEW OF LIFE CYCLE

10. PATHOPHYSIOLOGY
Theories proposed in the Pathogenesis of Malaria
include:
• Sequestration
• Cytoadherence(PfEMP-1)
• Increased expression of vascular endothelial ligands
• Rossetting
• Decreased Deformability of RBCs

11. PATHOPHYSIOLOGY CONTD

12. MECHANISM OF FEVER

13. FORMS OF SEVERE
MALARIA
Severe Malaria is 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
National guidelines for the Diagnosis and Treatment of Malaria 4TH Edition, May 2020 pp 18-30

14. SEVERE FALCIPARUM MALARIA
• Cerebral Malaria (CM) is the most severe
neurological presentation of acute falciparum
malaria, the clinical hallmark of which is the presence
of coma.
• It is a diffuse encephalopathy associated with
seizures in at least 80%, and status epilepticus, in up
to a third of cases.
• Although most survivors make a full recovery,
neurological sequelae such as hemiplegia, speech
problems, cortical blindness and epilepsy occur in 3-
31%.

15. • P. Falciparum is the only species that appear to
directly affect the central nervous system causing
neurological deficits and cognitive sequelae
• Death among hospitalized children with CM is often
due to respiratory arrest and brainstem signs; most
deaths occur within 24 hours of presentation in the
hospital.
• CM causes impairment in level of consciousness
defined by mGCS<11 or a Blantyre coma score < 3
SEVERE FALCIPARUM MALARIA

16. SEVERE FALCIPARUM MALARIA
• Prostration: Generalized weakness so that the person
is unable to sit, stand or walk without assistance
• Multiple convulsions: More than two episodes within
24 h
• Acidosis: A base deficit of > 8 mEq/L or, if not
available, a plasma bicarbonate level of < 15 mmol/L
or venous plasma lactate ≥ 5 mmol/L. Severe acidosis
manifests clinically as respiratory distress (rapid,
deep, laboured breathing).

17. SEVERE FALCIPARUM MALARIA
• Hypoglycaemia: Blood or plasma glucose < 2.2
mmol/L (< 40 mg/dL)
• Severe malarial anaemia: Haemoglobin
concentration ≤ 5 g/dL or a haematocrit of ≤ 15% in
children < 12 years of age (< 7 g/dL and < 20%,
respectively, in >12years) with a parasite count
> 10 000/μL
• Renal impairment: Plasma or serum creatinine
> 265 μmol/L (3 mg/dL) or blood urea > 20 mmol/L
• Jaundice: Plasma or serum bilirubin > 50 μmol/L
(3 mg/dL) with a parasite count > 100 000/ μL

18. SEVERE FALCIPARUM MALARIA
• Hyperparasitaemia: P. falciparum parasitaemia >
10% or malaria parasite density of ≥200,000
parasite/μL of blood
• Pulmonary oedema: Radiologically confirmed or
oxygen saturation < 92% on room air with a
respiratory rate > 30/min, often with chest
indrawing and crepitations on auscultation
• Significant bleeding: Including recurrent or
prolonged bleeding from the nose, gums or
venepuncture sites, haematemesis or melaena.

19. Shock:
• Compensated shock is defined as capillary refill ≥ 3
s or temperature gradient on leg (mid to proximal
limb), but no hypotension.
• Decompensated shock is defined as systolic blood
pressure < 70 mm Hg with evidence of impaired
perfusion (cool peripheries or prolonged capillary
refill).
SEVERE FALCIPARUM
MALARIA

20. 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.

21. MANAGEMENT

22. History
• The signs and symptoms of malaria are non-specific.
• Malaria is suspected clinically primarily on the basis of
fever or a history of fever.
• There is no combination of signs or symptoms that
reliably distinguishes malaria from other causes of fever.
• Diagnosis based only on clinical features has very low
specificity and results in overtreatment

23. • Fever
• Convulsions
• Coma
• Billous vomiting
• Passage of dark urine
• Reduced urine output
• Bleeding from orifices
• Difficulty in breathing
History

24. Physical Examination
• Pyrexia
• Lethargy
• Abnormal behavior or altered consciousness
• Papilloedema on fundoscopy
• Tachycardia or acidotic breathing
• Weak or Thready pulse
• Increased capillary refill time
• Hypotension
• Cold extremities
• Tachypnoea and respiratory distress
• Hepatosplenomegally
• Decreased urine output

25. Laboratory Diagnosis
• All cases of suspected malaria should have a
parasitological test (microscopy or Rapid diagnostic
test (RDT)) to confirm the diagnosis.
• Blood smear, thick and thin films:
• A negative finding on examination does not rule out
malaria.
• Only 50% of children with malaria have positive smear
findings, even on repeated examination.
• Malaria RDTs
• Plasmodium falciparum Histidine rich protein-2(PfHRP-
2)
• Parasite Lactate Dehydrogenase(pLDH)

26. Laboratory Diagnosis
• Random Blood Glucose
• PCV
• Urinalysis
• Lumbar Puncture
• E/U/Cr
• FBC+DIFF
• Blood culture
• Arterial blood gas
• LFTs

27. TREATMENT
• Severe malaria is a medical emergency requiring in-
patient care.
• Deaths from severe malaria can result either from
the direct effect of the disease or it's complications.
• Ensure patency of the airway, give respiratory
support and maintain adequate circulation

28. Treatment
• In 2012, the NMEP changed the first-line
treatment for severe malaria from quinine to
injectable artesunate, consistent with WHO
treatment guidelines.
• Treat patients with intravenous or intramuscular
artesunate for at least 24 h and until they can
tolerate oral medication.
• Once a patient has received at least 24 h of
parenteral therapy and can tolerate oral therapy,
complete treatment with 3 days of an ACT.

29. Treatment
• Children weighing < 20 kg should receive a higher dose
of artesunate(3 mg/kg bw per dose) than larger
children and adults (2.4 mg/kg bw per dose) to ensure
equivalent exposure to the drug.
• If parenteral artesunate is not available, use artemether
(at initial dose of 3.2 mg/kg BW intramuscularly (to the
anterior thigh), then maintenance dose of 1.6 mg/kg
bw intramuscularly daily.
• If artemether is not available, quinine hydrochloride at
a loading dose of 20 mg/kg BW then maintenance dose
of 10 mg/kg BW is administered at 8-h intervals,
starting 8 h after the first dose

30. Treatment
• In young children, high fevers are often associated
with vomiting, regurgitation of medication and
seizures.
• They are thus treated with antipyretics and, if
necessary, fanning and tepid sponging.
• Antipyretics should be used if the core temperature
is > 38.5ºC.
• Paracetamol at a dose of 15 mg/kg bw every 6h is
widely used.

31. Treatment
• Maintain airway, place patient on his or her side,
pass an OGT, establish IV access, exclude other
treatable causes of coma (e.g. hypoglycaemia,
bacterial meningitis); intubate if necessary.
• Treat seizures promptly with intravenous(0.1-
0.3mg/kg) or rectal(0.5mg/kg) diazepam,
lorazepam, midazolam or intramuscular
paraldehyde(0.1mg/kg) or IM phenobarbitone 10-
15mg/kg

32. Treatment
• Check blood glucose, correct hypoglycaemia with
200mg/kg of IV Dextrose and maintain with
glucose-containing infusion( 4 to 6 mg/kg/min).
• Although hypoglycaemia is defined as glucose < 2.2
mmol/L, the threshold for intervention is < 3
mmol/L for children < 5 years and < 2.2 mmol/L for
older children.
• In acute pulmonary oedema, Prop patient up at an
angle of 45o, give oxygen, give a diuretic 2-4mg/kg
IV, stop intravenous fluids, intubate and add
positive end-expiratory pressure or continuous
positive airway pressure in life-threatening

33. Treatment
• Acute kidney injury: exclude pre-renal causes,
check fluid balance and urinary sodium; if in
established renal failure, give diuretic challenge
furosemide 1-2mg/kg, if no urine output, restrict
fluids to 400ml/m2 BSA.
• Add haemofiltration or haemodialysis, or, if not
available, peritoneal dialysis.
• Spontaneous bleeding and coagulopathy:
Transfuse with screened fresh whole blood at
15mg/kg(cryoprecipitate, fresh frozen plasma and
platelets, if available), give vitamin K injection.

34. Treatment
• Metabolic acidosis: Exclude or treat
hypoglycaemia, hypovolaemia and septicaemia. If
severe, add haemofiltration or haemodialysis.
• Shock: Suspect septicaemia, take blood for
cultures; give parenteral broadspectrum
antimicrobials, correct haemodynamic
disturbances.
• Transfuse with packed cells at 10ml/kg or screened
fresh whole blood at 15ml/kg in severe anaemia

35. Prognosis
• Acidosis, seizures, impaired consciousness, renal
impairment, and pre-existing chronic diseases are
associated with poor outcomes in children with
severe malaria.
• Malaria in children younger than age 5 years carries
the worst prognosis in endemic areas.
• The case fatality rate of CM ranges between 5% and
50%.
• Mortality from untreated severe malaria
(particularly cerebral malaria) approaches 100%.
With prompt, effective antimalarial treatment and
supportive care, the rate falls to 10–20% overall.

36. DIFFERENTIAL DIAGNOSES
• Aseptic meningitis
• Bacterial meningitis
• Ascending cholangitis
• Enteric fever
• Encephalitis
• Septicemia
• Viral pneumonia
• Hepatitis
• Tetanus
• Tonsillitis
• Lassa fever
• Yellow fever
• Diabetic ketoacidosis
• Epilepsy
• Toxic Shock Syndrome
• Bacterial Endocarditis
• Heatstroke
Parang N Mehta, Mary L Windle,Russell W Steele,Gary J Noel,. Paediatric Malaria, https//:medscape.emedicne.com

37. PREVENTION AND CONTROL
• Environmental control
• Insecticide-treated nets, the most widespread
intervention, were by far the largest contributor to the
reduction in malaria related deaths.
• The current 2021–2025 National Malaria Strategic Plan
(NMSP) is based on the vision of achieving a malaria-
free Nigeria with a goal of reducing malaria morbidity to
less than 10% parasite prevalence and mortality
attributable to malaria to <50 deaths per 1,000 by
2025.

38. PREVENTION AND CONTROL
• The Government of Nigeria has secured credits from
three multilateral banks (the World Bank, African
Development Bank, and Islamic Development Bank)
totalling $364 million to fund health sector interventions
in 13 states of the Federation for five years (2020–2024)
for malaria.
• The NMEP strategy recommends seasonal malaria
chemoprevention (SMC) in nine states in the Sahel
region: Sokoto, Kebbi, Zamfara, Bauchi, Katsina, Kano,
Jigawa, Yobe, and Borno.

39. PREVENTION AND CONTROL
• The recommendation is for four doses of SP +
amodiaquine [SPAQ] at monthly intervals over the 4-
month malaria transmission season).
• There are approximately 11 million children under the
age of five years in these states.
• Malaria Vaccine:The Federal Government has said the
RTS,S/AS01 malaria vaccine(Mosquirix)is expected to
be in the country by April 2024.

40. CONCLUSION
• Severe malaria is a life-threatening medical emergency
and requires prompt and effective treatment to prevent
death.
• The presentation of severe malaria varies depending on
such factors as country, age, immunity, socioeconomic
factors, drug resistance and type of intervention
measures used.
• Within the broad definition of severe malaria some
syndromes are associated with lower mortality rates
(e.g. severe anaemia) and others with higher mortality
rates (e.g. acidosis).
• The risk for death increases in the presence of multiple
complications.

41. REFERENCES
• WHO. World malaria report. Geneva: World Health Organization; 2021.27 May 2022
• Chandy C. John and Peter J. Krause: Malaria (plasmodium) in Nelson's Textbook of Paediatrics 19th
ed. Chapter 280 pp 1198-1207
• National guidelines for the Diagnosis and Treatment of Malaria 4TH Edition, May 2020 pp 18-30
• Samaila, A. B., Kunihya, I. Z. and Daniel, L. Prevalence of malaria infection among children
attending federal medical centre yola, adamawa state, Nigeria Int. J of Recent Advanc in Multidisc
Res Vol. 03, Issue 11, pp.1991-1994, November, 2016
• Oluwayemi OI, Brown BJ, Oyedeji OA, Adegoke SA, Adebami OJ, et al. (2013) Clinical and
laboratory predictors of outcome in cerebral malaria in suburban Nigeria. J Infect Dev Ctries 7:
600-607.
• Olumese PE, Gbadegesin RA, Adeyemo AA, Brown B, Walker A (1999) Neurological features of
cerebral malaria in Nigerian children. Ann Trop Paediatr 19: 321-325.
• Sergiev VP, Popov AF, Chirkov VP (2005) [Cerebral malaria: pathogenesis, clinical picture and
treatment]. Med Parazitol (Mosk) : 58-62.
• Isaac OO, Malaria Chemotherapy Control and Elimination 2014, 3:1 DOI: 10.4172/ 2090-
2778.1000116
• Parang N Mehta, Mary L Windle,Russell W Steele,Gary J Noel,. Paediatric Malaria,
https//:medscape.emedicne.com
• https://www.severemalaria.org/countries/nigeria

42. THANK YOU
FOR LISTENING