Malaria is caused by Plasmodium parasites transmitted via mosquito bites. P. falciparum is the most deadly species, causing severe malaria through cytoadherence of infected red blood cells in the microvasculature, leading to organ dysfunction. Nigeria has the highest malaria burden worldwide, with over 100 million cases and 300,000 deaths annually, mostly among young children. Diagnosis involves microscopy and rapid tests to detect the parasite and species.

1. LECTURE ON MALARIA
Dr Maria-Lauretta Orji

2. INTRODUCTION
• Malaria is a parasitic disease caused by parasites of the genus
Plasmodium transmitted to humans through the bite of an infected
female Anopheles mosquito
• Malaria infection occurs worldwide but the greatest burden is borne
by tropical and sub-tropical regions of the world
• It was reported by the WHO that an estimated 228 million malaria
cases and 405,000 malaria deaths occurred worldwide in 2018
• In 2018, African region alone was home to 93% and 94% of the global
malaria cases and deaths respectively.

3. • Nigeria accounts for the highest burden of malaria in the whole
world.
• It is estimated that about 97% of Nigeria population is at risk of
malaria with about 100million cases and 300,000 deaths occurring
each year
• The prevalence of malaria in Nigeria is 22% (2018)
• Nigeria accounts for one-third (32%) of global malaria death

4. • The most vulnerable group to malaria are the under-5 children
because they are yet to acquire considerable immunity against the
disease
• In Nigeria, malaria is responsible for about 25% of infant mortality
and 30% of under-5 mortality
• The under-5s are so predisposed because of their inability to acquire
considerable immunity against malaria.

5. • Malaria affects all age groups but the level of transmission in an area
and the level of acquired immunity determine the severity.
• In areas of high transmission severe forms of the disease tend to
occur mainly in under-5s whereas in low transmission areas the
severe forms occur in older children and adults.
• This is premised on the fact that repeated exposure to malaria
infection induces natural immunity with faster rates of its acquisition
in areas of high transmission compared to low transmission areas

6. • Malaria is a blood borne infection caused by a protozoan parasite belonging to
the genus Plasmodium.
• The parasite is inoculated into human host during blood meals by female
Anopheles mosquitoes.
• There are five plasmodium species implicated in the aetiology of human malaria
disease. These are
• Plasmodium falciparum
• Plasmodium malariae
• Plasmodium vivax
• Plasmodium ovale and Plasmodium knowlesi.
• Plasmodium falciparum is the most common and important of all the species
because it causes severe forms of the disease. Plasmodium falciparum accounts
for >95% of infections in Nigeria

7. RISK FACTORS TO MALARIA TRANSMISSION
• The factors implicated include inability to adopt malaria preventive
measures such as sleeping under long lasting insecticide treated nets,
dwelling in rural/urban slums with poor sanitary conditions that
encourage the breeding of mosquitoes
• Living in poor housing infrastructures, poor feeding with attendant
suboptimal immunity, resorting to home treatment of malaria,
unwillingness to access healthcare

8. IMMUNOSUPPRESSION BY HEMOZOIN
• Malaria parasite derived pigment called hemozoin has been shown to
dominate the mechanisms of malaria-induced immunosuppression.
• There is impairment of opsonization and phagocytic killing by macrophages
after ingestion of hemozoin.
• Hemozoin is also associated with suppression of maturation and functions
of human monocyte-derived dendritic cells, deficient cell mediated
cytotoxicity, reduced circulating T-lymphocytes and impaired proliferative
T-cell response.
• Individuals with these compromised immune functions are predisposed to
severe forms of malaria. Strengthening human immune system may
therefore play significant role in ameliorating the severity of malaria.

9. MALARIA ENDEMICITY
The degree of malaria transmission in an area.
• Malaria holoendemicity: Presence of intense malaria transmission
occurring throughout the year in an area resulting in considerable degree
of immunity in the population outside childhood with parasite and spleen
rate constantly >75% in children aged 2-9 years with a low adult spleen
rate.
• Malaria hyperendemicity: Presence of intense but seasonal malaria
transmission in an area with parasite and spleen rate >50% in children aged
2-9 years
• ***spleen rate is the proportion of persons of a defined age range in a
given population who have enlarged spleen, expressed in percentage***

10. MALARIA ENDEMICITY (2)
• Malaria mesoendemicity: Presence of wide geographical variations in
malaria transmission in an area with parasite and spleen rate of 11-
50% in children aged 2-9 years.
• Malaria hypoendemicity: Presence of little malaria transmission in an
area and the disease has little effect on the population with parasite
and spleen rate of 0-10% in children aged 2-9 years.
• Most parts of Nigeria are categorized as holo-endemic for malaria

11. SEVERE MALARIA
• It is therefore defined by the presence of Plasmodium falciparum
identifiable by microscopy or rapid diagnostic test or both and at least
one of the WHO set criteria for the definition of severe malaria.
• There is evidence of end-organ damage
• Severe malaria is caused by Plasmodium falciparum predominantly
although Plasmodium vivax and Plasmodium knowlesi have also been
reported to cause severe disease.

12. PATHOGENESIS OF SEVERE MALARIA
• The development of severe malaria in a child is dependent on factors, which are
complex and multifactorial and are related to both the parasite and the host.
The key processes involved in the pathogenesis of severe malaria are
• Cyto-adherence
• Sequestration
• Rosetting
• Agglutination
• Aggregation
• The roles of reduced red cell deformability, chemokines, cytokines and more
recently, some acute phase reactants [C-Reactive Protein (CRP) and Nitic Oxide
(NO)] have also been recognized in the pathogenesis of severe malaria. Another
key pathogenetic mechanism implicated in severe malaria is oxidative stress.

13. • By cyto-adherence parasite-laden cells adhere to the endothelium of
microvasculature in several organs
• Sequestration is the process by which red blood cells containing mature
parasites are pooled away from circulation in organs including the spleen
and liver thereby evading clearance and perpetuating the parasite.
• Infected red blood cells can also bind to uninfected red cells to form
rossetes (rosetting).
• Agglutination is the process by which infected erythrocytes adhere to one
another, thus forming large auto-agglutinates
• Uninfected erythrocytes can also bind to one another forming large
aggregates of uninfected erythrocytes.

14. SUMMARY OF PATHOGENESIS OF SEVERE
MALARIA
• Red blood cells infected with mature stages of Plasmodium
falciparum adhere to the endothelium of microvasculature (cyto-
adherence) leading to the sequestration of the infected erythrocytes
within the microvasculature and ultimately narrowing the lumen of
the microvasculature and causing obstruction.
• Binding of the infected erythrocytes to uninfected ones (rosetting),
auto-agglutination of the infected erythrocytes and aggregation of
uninfected erythrocytes all contribute to the phenomenon of
microvasculature luminal obstruction.

15. • The resultant effect of the luminal obstruction is a compromised
blood flow through the microvasculature which results in hypoxia,
excessive lactate production and a decline in pH of blood and tissues,
causing a release of pro-inflammatory mediators that cause damages
to various organs causing them to malfunction.
• The resultant organ dysfunction is responsible for the various clinical
features of severe malaria

16. FEATURES OF UNCOMPLICATED MALARIA
• Presence of elevated body temperature
• Other non-specific symptoms such as loss of appetite, vomiting,
headache, body pains, passage of loose stools
• Dwelling in a malaria endemic area
• The presence of Plasmodium falciparum identifiable by microscopy or
rapid diagnostic test or both

17. CLINICAL COMPONENT OF SEVERE MALARIA
• Impaired consciousness: Blantyre score < 3 in children < 2 years or
Glasgow coma score of <11 in older children lasting for >30minutes
• Multiple convulsions: Occurrence of more than two episodes of
convulsion in a 24-hour period.
• Prostration: Extreme weakness such that the child is unable to sit or
stand unsupported in those who have attained the milestones or
inability to breastfeed in younger children yet to start sitting.

18. CLINICAL COMPONENT CONT’D
• Circulatory collapse or shock: Capillary refill time of ≥3 seconds or
systolic BP of < 70mmHg in children and ˂ 80mmHg in adults
• Pulmonary edema: Oxygen saturation of < 92% in room air with
increased respiratory rate, chest retractions and crepitations on
auscultation
• Abnormal bleeding: Recurrent or prolonged bleeding from nose,
gums, venipuncture sites, vomiting of blood or passing of blood in
stool
• Hemoglobinuria: Presence of haemoglobin in urine

19. • Severe anaemia: Presence of asexual forms of Plasmodium
falciparum parasitaemia with haemoglobin concentration of <5g/dl or
hematocrit of <15%
• Hypoglycemia: Blood glucose level of <40mg/dl (2.2mmol/l).
• Metabolic Acidosis: Base deficit of >8meq/l, arterial PH <7.25 or
plasma bicarbonate level of <15mmol/l or hyperlactaemia (serum
lactate >5.0mmol/l
• Renal impairment (AKI): Urine output of < 0.5ml/kg/hour (or <
12ml/kg/day) in children or plasma/serum creatinine of >265μmol/l
(3mg/dl) or blood urea of >20mmol/l
LABORATORY COMPONENT

20. LABORATORY CONT’D
• Hyperparasitemia: Plasmodium falciparum count of >5% infected
erythrocytes (100,000 parasites/µl) in low transmission areas or >10%
infected erythrocytes (250,000 parasites/µl) in high stable
transmission areas.
• Hyperbilirubinemia: serum bilirubin level of >51mmol/l or >3mg/dl
• Pulmonary edema: CXR evidence of pulmonary oedema (Bat’s wing
shadowing and Kerly B lines)

21. DIAGNOSIS
• The methods used for parasitological diagnosis in routine clinical
setting are the light microscopy and rapid diagnostic tests (RDT)
• Microscopy: Microscopy is the gold standard for the diagnosis of
malaria in endemic areas as it identifies both the parasites and the
species present.
• Malaria Rapid Diagnostic Test (mRDT): This is an
immunochromatographic-based test that detects specific antigens
(proteins) produced by malaria parasites. It detects malaria antigens
in blood by immunochromatographic assay with monoclonal
antibodies directed against target antigens impregnated on a test
strip

22. DIFFERENTIAL DIAGNOSES
• Typhoid fever
• Meningitis
• Pneumonia
• Pharyngotonsillitis
• Sepsis
• Acute gastroenteritis
• Febrile seizure

23. TREATMENT OF UNCOMPLICATED MALARIA
Use of oral artemisinin combination therapy (ACT)
• Artesunate + lumefantrine (AL)
• Artesunate + Amodiaquinine (AA)
• Dihydroartesunate piperaquinine (DHAP)
• Pyronaridine Artesunate (PA)

24. TREATMENT FOR COMPLICATED/SEVERE
MALARIA
• Parenteral Artemisinin is used (intravenous artesunate) ***for rapid
suppression of parasite***
Given:
• At 2.4mg/ kg at 0, 12 and 24 hours for children 20kg and above
• At 3.0mg/kg at 0, 12 and 24hours for children <20kg
• Subsequently, the dose of 2.4mg/kg (or 3mg/kg) is given daily until
the patient can tolerate oral medication or for the maximum of 7days.
• When patient can tolerate orally, give a full 3-day course of
Artemisinin-based combination therapy (ACT)---- to clear the
parasites from the blood

25. SUPPORTIVE CARE
• Blood transfusion
• Monitoring blood sugar
• Use of anticonvulsants
• Fluid therapy and monitoring to avoid overload
• Monitor electrolyte and correct in-balance
• Good nursing care for the unconscious patient

26. MALARIA CONTROL
• Prevention-----Use of LLITNs, clearing of bushes and drainages,
• Indoor residual spraying (IRS)
• Use malaria vaccine-----still in the pipeline
• Use of chemoprophylaxis for SCA and non malaria immune
population