A 38 slide summary of the management of neonatal jaundice

1. MALARIA

2. Outline
• Definition
• Epidemiology
• Life Cycle
• Classification
• Diagnosis
• Treatment
• Prevention

3. Introduction
• Malaria is the most important parasitic disease of human
beings.
• Malaria is a protozoan disease transmitted by Anopheles
mosquitoes.
• Five species of the genus Plasmodium cause all malarial
infections in human beings.
• Most cases are caused by either Plasmodium falciparum (SSA) or
Plasmodium vivax (Other regions), but human infections can also
be caused by Plasmodium ovale, Plasmodium malariae, and, in
parts of southeast Asia, the monkey malaria Plasmodium
knowlesi

4. Estimated Malaria Cases (Millions) By WHO
Region

5. What is Malaria?
• Malaria is caused by the parasite
of the genus Plasmodium
• Five species of plasmodium cause
infection in humans
• P. falciparum Most
common/deadly
• P. vivax
• P. ovale
• P. malariae
• P. knowlesi

6. Plasmodium species
Falciparum
Commonest in Africa (98%) of malaria
Main cause of severe malaria
Rapidly fatal
Vivax
Responsible for half of malaria cases outside Africa
Contributes to malaria in horn of Africa
Can cause severe malaria
Relapse occurs
Ovale
Mostly occurs in sub-Sahara Africa
Incidence relatively low
Not associated with fatal disease
Relapse occurs

7. Plasmodium species
Malariae
Distribution is everywhere
Tends to occur as mixed infection; Replication is slow
Hence parasiteamia is very low
Knowlesi
Occurs as a zoonotic infection –
Difficult to differentiate from trophozoites of P
malariae
Causes severe malaria and rapidly fatal
As rule consider P knowlesi if there is microscopic
suggestion of P malariae with high parasitaemia.

8. How Do
People get
Malaria?
• Bites from infected female anopheles
mosquito
• The main method of
transmission
• Bites occur between dusk and
dawn
• Accidental
• Blood transfusion, needle stick
injury
• Mother to Child
• 1 in 20 mothers could infect
their babies if they have
malaria close to delivery
• Animal to Man
• From close interaction with the
Macaques

9. EPIDEMIOLOGY OF MALARIA

10. The Global Malaria Picture
• According to the latest
WHO estimates, released
in December 2017, there
were 216 million cases of
malaria in 2016 and 445
000 deaths
• The malaria mortality
rate, which takes into
account population
growth, is estimated to
have decreased by 60%
globally between 2000
and 2015
•91 countries and territories
•Half world at risk (3.4billion)

11. Classification on transmission rates
• Based on transmission rates:
• High transmission (>1case per 1000 pop)
• Transmission is all year round, but there may be seasonal
variation.
• Partial immunity in older children and adults.
• May be less likely to get severe disease.

12. Classification on Transmission rates
• Low transmission: (<1 case per 1000 population)
• Intermittent transmission that may be annual, bi-annual or
variable.
• Prone to occurrence of malaria epidemics.
• Malaria Free: (Zero cases)
• Usually the population has no immunity whatsoever
against malaria and
• therefore prone to severe malaria if they travel to high
transmission areas.

13. Classification based on Spleen
and Parasite rates
• The spleen rate % enlarged spleens in a sample of the
population, usually children aged 2–10 years.
• The parasite rate is the proportion of a given
population with malaria parasites in the blood.
•
• According to the classification using these two
indices, regions may be described as:

14. Endemicity of Malaria
• Hypoendemic
• Spleen and parasite rates 1–10%
• Mesoendemic
• Spleen and parasite rates 11–50%.
• Hyperendemic
• Spleen and parasite rates constantly > 50%
• Holoendemic
• Spleen and parasite rates constantly > 75% (for parasite rate
this applies to infants only)

15. Determinants of endemicity
• Presence of competent Anopheles mosquitoes
• human factors, esp. socio-economic, and control
measures
• Temperature.
• Sporogony phase requires temp between 16° and 33°C
and mean relative humidity of 60%

16. Malaria Life Cycle (3-sites, 3-steps, 1
or 2-exit)
•Zygote
•Multinucleated Oocyst
•Manysporozoites
Mosquito
•Singlesporozoites
•MultinucleatedSchizont
•ManyMerozoites
Liver
•SingleTrophozoites
•MultinucleatedSchizonts
•ManyMerozoites
Red
Blood
Cells
• Exit I:Hypnozoites
Liver
• Exit II: Gametocytes
Blood Stream

17. P. falciparum – asexual stages

18. Classification of Malaria
• Uncomplicated malaria
• Severe Malaria

19. Uncomplicated Malaria
Symptomatic infection with malaria
parasitaemia without evidence of vital organ
dysfunction

20. Clinical Features – Uncomplicated Malaria
• Symptoms
• The main manifestation is FEVER
• Cold Chills / Rigor
• Headaches and other body aches
• Malaise
• Nausea /Vomiting
• Joint weakness/pains
• Signs
• Fever
• Hepatosplenomegally
• Pallor (Children / pregnant women)

21. Clinical Features - Severe malaria
• Acute falciparum malaria
with evidence of vital organ
dysfunction.
Or.
• Patient with P. falciparum
asexual parasitaemia and
presence of one or more of
the clinical or laboratory
features listed.

22. Severe Malaria (WHO 2015)
Features Description
Impaired
consciousness
A Glasgow coma score < 11 in adults or a
Blantyre coma score < 3 in children
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).

23. Severe Malaria (WHO 2015)
Features Description
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
adults) 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

24. Severe Malaria (WHO 2015)
Features Description
Pulmonary oedema
Radiologically confirmed or oxygen saturation <
92% on room air with a respiratory rate >
30/min, often with chest in-drawing and
crepitation on auscultation
Significant bleeding
Including recurrent or prolonged bleeding from
the nose, gums or venepuncture sites;
haematemesis or melena
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 in children or < 80
mmHg in adults, with evidence of impaired
perfusion (cool peripheries or prolonged
capillary refill).
Hyperparasitaemia P. falciparum parasitaemia > 10%

25. Who is at Risk for Malaria?
• Children
• Pregnant
Women
• Adults
• Every One

26. Groups at Special Risk
• People who are heavily exposed to the
bites of mosquitoes infected with P.
falciparum.
• People who have little or no immunity to
malaria, such as young children and
pregnant women
• Travelers coming from areas with no
malaria, are more likely to become very sick
and die.

27. Groups at Special Risk
• Poor people living in rural areas who lack
access to health care are at greater risk for this
disease.
• People suffering from Sickle Cell Anaemia (Not
SCD)
• Refugees or Internally Displaced Persons
• Those who have had their spleens removed

28. CLINICAL ASSESSMENT

29. HISTORY
• General information such as
• age, place of residence and travel.
• Specific features of uncomplicated disease
• fever, chills / rigor,
• head aches and other aches in the older
patient
• Ask about
• Features of severe disease
• Previous treatment with antimalarial drug

30. CLINICAL EXAMINATION
•Physical Examination:
• Check body temperature.
• Pallor (children/pregnant women)
• Check state of hydration
• Pulse and BP
• Enlarged spleen or liver, especially in children

31. CLINICAL EXAMINATION
• Exclude signs of severe
disease.
• Central nervous system:
• Assess the level of
consciousness using an
objective coma scale
• Evidence of Seizure
• Posturing
• Fundoscopy
• Respiratory system:
check for respiratory
distress
• Cardiovascular: rate,
volume of pulse, BP
• Abdomen: Feel for the
spleen and liver
• Identifying other possible
causes of disease.

34. Diagnosis
• Clinical
• Fever+ other symptoms
• Exclusion of focal point of disease
• Endemicity
• Parasitological
• Required to confirm diagnosis in all patients
• To monitor response to treatment/treatment failure
• Other Tests
• HCT, Blood glucose,
• Lumbar Puncture

35. Laboratory Diagnosis- Microscopy
• Involves staining and direct visualization of the parasite
under the microscope.
• Peripheral smear study on light microscopy using
various stains
• Thick blood film
• Thin blood films
• Quantitative Buffy Coat test (QBC)

36. Light Microscopy –Thick Blood
Film
• Parasite
identification
• Parasite
density

37. Light Microscopy –Thin Blood Film
• Speciation
• Parasite
Density

38. Quantitative Buffy Coat test (QBC)
• Blood is mixed
with acridine
orange
• Centrifuge in a
capillary tube
• Read directly with
a fluorescent
microscope.
Red blood cell
Granulocyte
Lymphocytes
Platelet

39. QBC

40. Non-Microscopic Tests
• Involves identification of the parasitic antigen or the anti-
plasmodial antibodies or the parasitic metabolic products.
• RDTs
• PfHRPII antigens
• pLDH enzyme
• OTHER TESTS
• Polymerase Chain Reaction
• Detection of antibodies by Radio immuno assay,
immunofluorescence or enzyme immuno assay.

41. Rapid Diagnostic Tests
• Detects specific antigens
(proteins) produced by
malaria parasites
• These antigens are present
in the blood of infected or
recently infected people.
• The RDT signifies their
presence by a colour
change on nitrocellulose
strip

42. RDT: PfHRP-2 Based Test
• This is a dip stick antigen
capture assay, using a
monoclonal antibody
against P. falciparum
histidine rich protein-2
(PfHRP-2)

43. RDTs: pLDH Based Test
• Dip stick coated with
monoclonal antibodies
against the intracellular
metabolic enzyme
parasite lactate
dehydrogenase (pLDH)
• Allows for speciation
between the pLDH
isoforms.
• pLDH is produced only
by live parasites,
• Hence the ability to
differentiate live from
dead organisms

44. Malaria Diagnosis -
RDTs
A

45. C

46. TREATMENT OF MALARIA

47. Principles of Antimalarial Rx
Aims Causation Therapy Drugs
To alleviate
symptoms
Symptoms are caused
by blood forms of the
parasite
Blood schizonticidal
drugs
Chloroquine, quinine,
pyrimethamine/ sulphadoxine,
artemisinin and its derivatives
To prevent
relapse
Relapses due to
hypnozoites of P. vivax/
P. ovale
Tissue schizonticidal
drugs
Primaquine
To prevent
spread
Spread is through the
gametocytes
Gametocytocidal
drugs
Primaquine for P. falciparum,
Chloroquine for all others

48. Uncomplicated Malaria
• Artemether-lumefantrine
• 1.5/9 mg/kg twice daily for three days
• Artesunate-Amodiaquine
• Artesunate 4 mg/kg + Amodiaquine 10mg base/kg once
daily for 3-days
• Artesunate+Mefloquine
• Artesunate 4 mg/kg once daily for 3 days + mefloquine
25 mg base/kg (mefloquine 8.3mg/kg daily for 3 days)

49. Uncomplicated Malaria
• Artesunate+Sulfadoxine/pyrimethamine
• Artesunate 4mg/kg once dly for 3-days + SP 25/1.25mg/kg
once
• Dihydroartemisinin+ piperaquine
• In children <25kg 2.5mg/kg DHA and 20mg/kg PPQ once
daily for 3-days
• New
• Pyronaridine-Artesunate
• Granules and Tablets

50. What is Antimalarial Combination Therapy
• Simultaneous use of two or more blood
schizonticidal drugs with
• independent modes of action and
• different biochemical targets in the parasite:
• fixed-dose formulations or co-administrated
therapy

51. Management of severe malaria
• This comprises of four main
steps
• clinical assessment of the
patient,
• specific anti-malarial treatment;
• Treatment of complications and
• Supportive care

52. Clinical assessment
• Rapid evaluation
• To make a clinical diagnosis of severe malaria
• Identify life threatening complications

53. Treatment of Severe Malaria
• For children ≤20kg, artesunate 3 mg/kg BW IV or IM
given on admission (time = 0), then at 12 h and 24 h,
then once a day is the recommended treatment.
• For adults and children >20kg, artesunate 2.4 mg/kg
Body Weight (BW) IV or IM given on admission (time
= 0), then at 12 h and 24 h, then once a day is the
recommended treatment.
• There is no upper limit to the total dose of
artesunate.

54. Treatment of Severe Malaria
• Artemether, or quinine, is an acceptable alternative
if parenteral artesunate is not available:
• artemether 3.2 mg/kg BW IM given on admission then
1.6mg/kg BW per day; or
• quinine 20 mg salt/kg BW on admission (IV infusion or
divided IM injection), then 10 mg/kg BW every 8 hrs;
• Parenteral antimalarials used in the treatment of
severe malaria should be given for a minimum of
24hours, once started (irrespective of the patient's
ability to tolerate oral medication earlier), and,
thereafter, complete treatment a full course of the
recommended ACT.

55. Treatment of Severe Malaria
• At community or health facility levels where complete
management of severe malaria is not possible, patients with
severe malaria should be given pre-referral treatment and
referred immediately to an appropriate facility for further
treatment.
• The following options for pre-referral treatment are
recommended in a ranked order:
• For children: artesunate IM; rectal artesunate; artemether IM;
quinine IM
• For adults: artesunate IM, artemether IM; quinine IM

56. Tx of complications & supportive care
• Coma (cerebral malaria):
• Standard care for the unconscious patient
• avoid harmful ancillary treatment such as
corticosteroids, heparin and adrenaline, intubate if
necessary
• Hyperpyrexia:
• Tepid sponging, fanning, cooling blanket and antipyretic
drugs
• Convulsions:
• Maintain airways; treat promptly with intravenous or
rectal benzodiazepine or intramuscular paraldehyde

57. Treatment Of Complications 2
• Hypoglycaemia:
• correct hypoglycaemia and maintain with glucose containing
infusion
• Severe anaemia:
• (Hb <5g%, or PCV <15%) Transfuse
• Acute pulmonary oedema
• Prop up at 45o, give oxygen, give diuretic, stop intravenous fluids,
intubate and add PEEP/CPAP in life threatening hypoxaemia;
haemofilter
• Acute renal failure
• Exclude pre-renal causes, check fluid balance, urinary sodium; if in
established renal failure; haemofilter or haemodialysis, or if
unavailable, peritoneal dialysis.

58. Treatment of complications 3
• Spontaneous bleeding and coagulopathy
• Transfused screened fresh whole blood (cryoprecipitate,
/fresh frozen plasma and platelets if available; vitamin K
injection
• Metabolic acidosis
• Exclude or treat hypoglycaemia, hypovolaemia and
septicaemia.
• Shock
• Suspect septicaemia, make blood cultures; give parenteral
antimicrobials, correct haemodynamic disturbances.
• Hyperparasitaemia
• >250,000 parasites per μl of blood.