Malaria epidemiology pathogenesis life cycle diagnosis and treatment

1. Clinical manifestations and management of Malaria
Dr Pagavath Bharathi
SR Dept of General Medicine

2. CLINICAL FEATURES
🞭 Patients are asymptomatic during the initial
phase– the incubation period
 P falciparum ---- 9-14 days
 P vivax---- 12-17 days
 P ovale---- 16-18 days
 P malariae--- 18-40 days
 Prolonged in p vivax, partial immunity and
incomplete chemoprophylaxis.

3. PRODROMAL SYMPTOMS
🞭 Headache
🞭 Fatigue
🞭 Anorexia
🞭 Myalgia
🞭 Pain in joints
🞭 Chest and abdominal pain

4. CLINICAL FEATURES (CONT…)
🞭 Fever is the cardinal symptom of malaria
🞭 Febrile paroxysms associated with rigors ,
headache, myalgia , back pain, abdominal
pain, nausea and vomiting.
🞭 Paroxysms coincide with rupture of schizonts
🞭 P vivax: every 48 hours( benign tertian
malaria)
🞭 P falciparum and mixed infections: no
periodicity or less appparent.

5. PRESENTATION
🞭 Fever 96%
🞭 Chills 96%
🞭 Headache 79%
🞭 Muscle Pain 60%
🞭 Palpable liver 33%
🞭 Palpable Spleen 28%
🞭 Nausea or vomiting 23%
🞭 Abdominal pain/diarrhea 6%

6. On the basis of severity malaria can be
classified as
uncomplicated complicated

7. UNCOMPLICATED MALARIA
🞭 Uncomplicated malaria is defined as
symptomatic malaria without signs of severity or
evidence (clinical or laboratory) of vital organ
dysfunction.
🞭 The signs and symptoms of uncomplicated
malaria are nonspecific.
🞭 Malaria is usually suspected clinically on the
basis of fever or a history of fever.
Guidelines for the treatment of malaria – 2nd edition World Health
Organization, 2010

8. COMPLICATED OR SEVERE MALARIA
In a patient with P. falciparum parasitaemia
presence of certain clinical features or
laboratory parameters classify the patient as
severe or complicated malaria

9. COMPLICATED MALARIA (CONT..)
Clinical features
🞭 Impaired consciousness or unrousable coma
🞭 prostration
🞭
🞭 Multiple convulsions (more than 2 episodes in 24 h)
🞭 Deep breathing, respiratory distress

10. COMPLICATED MALARIA (CONT..)
Clinical features (cont..)
🞭 Circulatory collapse or shock, systolic blood
pressure < 70 mm Hg in adults and < 50 mm Hg
in children
🞭 Clinical jaundice ( serum bil > 3 mg/dl) plus
evidence of other vital organ dysfunction
🞭 Haemoglobinuria
🞭 Abnormal spontaneous bleeding
🞭 Pulmonary oedema (radiological)

11. COMPLICATED MALARIA (CONT…)
Laboratory parameters
🞭 Hypoglycemia (blood glucose < 2.2 mmol/l or < 40 mg/dl)
🞭 Metabolic acidosis (plasma bicarbonate < 15 mmol/l)
🞭 Severe normocytic anaemia (Hb < 5 g/dl)
🞭 Haemoglobinuria
🞭 Hyperparasitaemia (> 2%in low intensity transmission areas or > 5%
in ar eas of high stable malaria transmission intensity)
🞭 Hyperlactataemia (lactate > 5 mmol/l)
🞭 Renal impairment (serum creatinine 3 mg/dl)

12. CLINICAL PROFILE OF SEVERE MALARIA IN
INDIA

13. CEREBRAL MALARIA
• 🞭 Cerebral malaria is the most severe
neurological complication of Plasmodium
falciparum
• 🞭 It is a major cause of acute non-traumatic
encephalopathy in tropical countries

14. CEREBRAL MALARIA (CONT..)
Clinical syndrome characterised by
🞭 Coma (inability to localise a painful stimulus)
at least 1 h after termination of a seizure or
correction of hypoglycaemia
🞭 Detection of asexual forms of P falciparum
malaria parasites on peripheral blood
smears, and exclusion of other causes

15. CEREBRAL MALARIA (CONT...)
🞭 Seizures
Seizures are commonly reported and occur in
over 60% of children
causes of seizures
 In children not associated with fever at the time
of the seizure or electrolyte disturbances.
 Sequestration of infected erythrocytes
 Parasite-derived toxins
 Immune mechanisms

16. CEREBRAL MALARIA (CONT..)
🞭 Coma
 Cerebral malaria is a diffuse encephalopathy characterised
by coma and bilateral slowing on Electroencephalography
 coma is potentially reversible.
🞭 Brainstem signs
 Changes in pupillary size and reaction
 Disorders of conjugate gaze and eye movements.
 Abnormal respiratory patterns (such as
hyperventilatory, ataxic, and periodic breathing)
 posture (decerebrate, decorticate, or opisthotonic
posturing), and motor abnormalities of tone and reflexes

17. CEREBRAL MALARIA (CONT..)
• 🞭 Cerebral malaria should be considered in the
differential diagnosis of any patient who has
a febrile illness with impaired consciousness
who lives in or has recently travelled to
malaria endemic areas
• 🞭 The mortality rate in children is about
20%, and most deaths happen within 24 h
of admission.

18. CEREBRAL
MALARIA
Lancet Neurol 2005; 4: 827–40

19. NEUROLOGICAL SEQUELAE
🞭 Hemiplegia
🞭 Cortical blindness
🞭 Aphasia
🞭 Ataxia
🞭 Cognitive impairment
Richard Idro ,Lancet Neurol 2005; 4: 827–40

20. MALARIAL RETINOPATHY
🞭 Common in children with
cerebral malaria(60%)
and may be related to
pathological changes
🞭 Malarial retinopathy
consists of four main
components: retinal
whitening, vessel
changes(whitening of
retinal vessels), retinal
hemorrhages, and
papilledema
🞭 Bad prognostic indicator
Lancet Neurol 2005; 4: 827–40

21. ANEMIA OFMALARIA
• Hemoglobin less than 8 g/dl, which is equivalent
to a hematocrit of less than 24% in a
parasitemic individuals.
• World Health Organization has defined severe
malarial anemia (SMA) as a hemoglobin less
than 5 g/dL or a hematocrit less than 15% seen
in the context of malaria but without specifying
parasitemia .
WHO (2000). Severe falciparum malaria. Trans. R. Soc. Trop. Med. Hyg. 94: Suppl.
1.

22. PANCYTOPENIA
• 🞭 Pancytopenia can occur in both falciparum
and vivax infections.
• 🞭 Can be due to microangiopathic
hemolytic anemia, hypersplenism
• 🞭 Few cases due to bone marrow suppression
have and hemophagocytosis have been
reported
J Fam Community Med. 2009;16:71-73

23. HEPATIC DYSFUNCTION
🞭 In patients with severe malarial infestation,
the incidence of jaundice is reported to be
around 2.5%
🞭 Transient abnormalities of liver enzymes are
most commonly seen
🞭 If serum bil > 3 mg/dl---- severe malaria
🞭 Hepatic encephalopathy is almost never
seen.
Bhalla A J Postgrad Med 2006 Oct-
Dec;52(4):315-20.

24. RENAL FAILURE
• In P. falciparum malaria, acute renal failure may
develop in 0.1-0.6% of the patients
🞭 Defined as Urine output <400 ml/24 hours in
adults (<12 ml/kg/24 hours in children) and a
serum creatinine >265 µmol/l (> 3.0 mg/dl)
despite adequate volume repletion
🞭 Renal failure is rare in children
• High mortality (upto 45%)
Indian Academy of Clinical Medicine Vol. 3, No. 2 April-June
2002

25. RENAL FAILURE CONTD..
The vulnerable group of patients are:
🞭 with high parasitaemia
🞭 with deep jaundice
🞭 with prolonged dehydration
🞭 patients receiving NSAIDs
🞭 Manifests as ATN ,renal cortical necrosis
never develops

26. MET
ABOLICACIDOSIS
Venous lactate concentration at 4 hours after
admission to hospital is the BEST PROGNOSTIC
INDICATOR in severe malaria. (>5mmol/l has
bad prognosis)
 This may result form renal failure, but more
commonly there is a primary lactic acidosis

27. HYPOGLYCEMIA
🞭 Hypoglycemia occurs in 30% of
children
🞭 Hypoglycemia is a sign of poor
prognosis with a mortality rate as high
as 40%.

28. PULMONARYEDEMA/ADUL
TRESPIRAT
ORY DISTRESS
SYNDROME (ARDS)
🞭 May develop even after several days of
antimalarial therapy
🞭 Mortality >80%

29. COMPLICATIONS OF P VIVAX CONTD..
🞭 Severe anemia
🞭 Acute respiratory distress syndrome (ARDS)
 Incidence is less in children compared adults
🞭 Coma
🞭 Malnutrition
🞭 Splenic rupture
🞭 Thrombocytopenia
🞭 Acute renal failure and shock
🞭 mortality rate - 1.6% among hospitalized patients
Trends in Parasitology Vol.25 No.5

30. Diagnosis
• Microscopy
• Rapid diagnostic test
• Other tests
22-12-2014 3
0

31. DIAGNOSIS
🞭 Symptom-based (clinical) diagnosis
Not possible to accurately diagnose malaria using any one
set of clinical criteria
🞭 Microscopy
Microscopy of stained thick and thin blood smears remains
the gold standard for confirmation of diagnosis of malaria.

32. DIAGNOSIS(CONT..)
🞭 In profound anemia ---parasite --often absent
🞭 malaria pigment in polymorphonuclear
leukocytes and monocytes-- malaria
🞭 If more than 5% of PNM contains visible
pigment it denotes poor prognosis.
Recommendations and IAP plan of action indian pediatrics volume 42
november 2005

33. EXAMINATION OF BLOOD FILM
🞭 A minimum of 100 fields should be examined
before concluding the slide to be negative.
🞭 Samples may be examined for at least three
consecutive days where clinical suspicion of
malaria persists.

34. ADVANTAGE OF MICROSCOPY
🞭 Advantages of microscopy are:
🞭 The sensitivity is high. It is possible to detect
malaria parasites at low densities.
🞭 It also helps to quantify the parasite load.
🞭 It is possible to distinguish the various
species of malaria parasite and their different
stages
WHO Expert Committee on Malaria. Twentieth report. Geneva, World Health
Organization, 2000

35. DIAGNOSIS (CONT..)
🞭 Rapid diagnostic tests are
immunochromatographic tests that detect
parasite-specific antigens in a finger-prick
blood sample
🞭 WHO recommends that such tests should
have a sensitivity of > 95% in detecting
plasmodia at densities of more than 100
parasites per μl of blood

36. DIAGNOSIS RDT..
🞭 Current tests are based on the detection of
histidine-rich protein 2 (HRP2), (specific for
P
. Falciparum)
🞭 pan-specific or species-specific Plasmodium
lactate dehydrogenase (pLDH)
🞭 pan-specific aldolase
🞭 Commercially available kit can detect
falciparum, vivax and other malaria but
cannot differentiate ovale and malarie
malaria.

37. DIAGNOSIS RDT..
🞭 HRP-II tests can remain positive for 7-14
days following malaria treatment even when
blood doesn't show parasitemia by
microscopy
🞭 p LDH is produced by only viable parasite
so the tests detecting this antigen becomes
negative within 3-5 days of treatment

38. ADVANTAGES OF RDTS IN COMPARISON TO
MICROSCOPY
🞭 simple, straight forward ,less time
consuming, requiring no special equipment
or skill/training
🞭 They can detect P.falciparum infection even
when the parasite is sequestered
🞭 This test can exclude mixed falciparum and
vivax malaria where the former may not be
evident microscopically

39. DISADVANTAGE OF RDTS IN COMPARISON
TO MICROSCOPY
🞭 RDTs that target HRP-II of P.Falciparum is
unsuitable for assessment of treatment
failure and monitoring of drug resistance.
🞭 They do not quantify the parasite load so
they do not have prognostic value

40. DISADVANTAGES RDT CONT...
🞭 Under optimal conditions an expert
microscopist can detect even 5-10 parasite
per μl of blood, detection threshold of RDTs
are 40- 60 parasite per μl of blood
Currently, available RDT kits are required to be
stored up to or under 30ºC

41. Microscopy :
• Peripheral blood smears – Gold standard
• Thick and thin smears
Advantages
• Sensitivity is high
• Detects parasites even at low densities
• Quantify the load
• Distinguish between various species and different stages
• Requires skills to identify.
22-12-2014 4
1

42. 22-12-2014 4
2
Other tests
• QBC
• Serological test
• Parasight F,Optimal assay
• PCR
• Sternal or liver puncture
• Radioimmuno assays, Immuno fluorescence

43. TREATMENT OF UNCOMPLICATED
MALARIA
General recommendations
• Avoid starting treatment on an empty stomach. The first dose - under observation.
• Dose repeated if vomiting < 30 minutes.
• Report back, if there is no improvement after 48 hours or if the situation deteriorates.
Treatment of P. vivax malaria
• Confirmed Cases - Chloroquine in full therapeutic dose of 25 mg/kg divided over
three days.
• To prevent relapse (Hypnozoites )-Primaquine 0.25 mg/kg bw daily for 14 days
under supervision
22-12-2014 * 10

45. 22-12-2014 45
Treatment of P. falciparum malaria
• Artemisinin Combination Therapy (ACT) should be given to all
confirmed P. falciparum cases found positive by microscopy or RDT.
• ACT --an artemisinin derivative + with a long acting antimalarial
(amodiaquine, lumefantrine, mefloquine or sulfadoxine-pyrimethamine).
• On day 2 ,single dose primaquine (0.75 mg/kg body weight).
• TheACT recommended in the National Programme of India is artesunate (4
mg/kg body weight) daily for 3days and sulfadoxine (25 mg/kg body
weight) -pyrimethamine (1.25mg/kg body weight) on Day 0.

46. 22-12-2014 46
• Presently, fixed dose combinations of artemether + lumefantrine, artesunate +
amodiaquine and blisterpack of artesunate + mefloquine are registered for
marketing in India and are available for use.
These rapidly acting drugs, if used alone, can lead to development of drug resistance.
Treatment of Malaria in pregnancy
• ACT : second and third trimesters
• Quinine : in the first trimester
• P. vivax malaria can be treated with chloroquine
Oral artemisinin monotherapy is banned
in India

47. 22-12-2014 47
Treatment of mixed infections
• Mixed infections should be treated as falciparum malaria.
• However, antirelapse treatment with primaquine can be given for 14
days, if indicated.
• Clinical malaria (clinical criteria without laboratory confirmation) is
treated with chloroquine in full therapeutic dose of 25 mg/kg body
weight over three days.
If a slide result is obtained later, the treatment should be completed according
to species.
•Suspected cases of malaria ,negative on diagnostic tests should be treated with
full therapeutic dose of choloroquine

48. 22-12-2014 52
Drug Resistance: Malaria
Major public health problem ,hinders the control of malaria
• In India resistance of falciparum to chloroquine, the first reported in the year 1973
(Diphu of Karbi-Anglong district inAssam state. )
• NVDCP monitors the response of antimalarial drug in Pf malaria parasite in the
through 13 monitoring teams located in 11 Regional Office for Health & Family
Welfares
Objectives:
• To assess the therapeutic response of P.falciparum to currently used anti-malarials
• To establish and generate information on sensitivity of local strains for formulation
of National Drug Policy and recommend needful changes in the control

49. 22-12-2014 53
Tools for monitoring
• From 2002-03 onward, new WHO protocol on "Therapeutic efficacy of anti-malarial
drugs in uncomplicated P.falciparum malaria" is being followed to assess the
efficacy of antimalarial drugs.
• The classification of response according to new protocol is interpreted into three
categories as per the WHO criteria i.e Adequate Clinical and Parasitological
Response (ACPR), Early and Late Treatment Failure (LTF).
• Adequate response : if no fever or parasitaemia till Day 28.

50. Early treatment failure (ETF):
Development of danger signs or
22-12-2014 54
• severe malaria on Day 1, 2 or 3, in the presence of parasitaemia;
• PARASETIMIAon
•
•
Day 2 > on Day 0, irrespective of axillary temperature;
Day 3 with axillary temperature>37.5°C;
Day 3, >25% of count on Day 0.
Late clinical failure (LCF):
Development of danger signs or
•Severe malaria in the presence of parasitaemia on any day between Day 4 and
Day 28 (Day 42)
•Presence of parasitaemia on any day between Day 4 and Day 28 (Day 42) with
axillary temperature >37.5°C

51. Late parasitological failure (LPF):
• Presence of parasitaemia on any day between Day 7 and Day 28 with axillary
temperature <37.5°C in patients who did not previously meet any of the criteria of
early treatment failure or late clinical failure.
Alternative treatment -Alternative ACT or quinine with Doxycycline.
• To combat the drug resistant in malaria, the National Drug Policy on Malaria
recommends the use of combination therapy in chloroquine resistant areas,
surrounding cluster of Blocks and 117 high endemic districts
• Criteria for change of drug policy
Drug policy is changed for the area/Block PHC reporting 10% or more total
treatment failure (ETF+LTF) to the currently used antimalarials in a sample of
minimum 30 P.falciparum test cases.
22-12-2014 55

52. SEVERE MALARIA
22-12-2014 56

53. Management of Complicated malaria
Requirements for management of complications
Health facilities should be equipped :
•Parenteral antimalarials, antipyretics,
antibiotics,anticonvulsants
• Intravenous infusion facilities
• Special nursing for patients in coma
• Blood transfusion
• Well-equipped laboratory
• Oxygen
22-12-2014
24

54. Management of other signs and complications
Hyper pyrexia (rectal temp >39 c) •Tepid sponging
•Cool environment
•Para 5mg/kg/bw
•IV fluids
•Monitor I/O
Dehydration
Acute renal failure(with
anuria/oliguria/blackwaterfever)
Hyperkalemia
•IV fluids
•Furosemide IV or IM
•Dialysis
•Watch on urea/creatinine/k levels
•Alkanize the urine
•>7mmol
•Ca charged resins 15-30gms TDS
•If >60mol NaHco3 infusion with insulin
•10 cc KCl in 24 hrs
Hypo2
k2
-
a1
l2
e-
2
m0
1
i4
a 25

55. Pulmonary edema •Prop up 45 ,oxygen
•Fluid balance and diuretics
GIT symptoms •IV fluids, chlorpromazine IV or IM
Shock
•IV plasma expanders
•Corticosteriods
•Dopamine
Anemia(PCV <20, HB <7), bleeding •Whole blood /Packed cell transfusion
•Vit K (bleeding)
Convulsions •Diazepam (0.2 mg/kg/Bw)IM or IV 8hrly
•Phenytoin sodium 5 mg/kg/bw
•Phenobarbitone 5-10 mg/kg/Bw
Hypoglycemia •IV glucose 50% followed by 5-10% glucose
•Monitor blood sugar levels
•Exchange transfusion
Hype2r2p-1a2-r2a01s4aitemia 26

56. Specific antimalarial treatment of severe malaria
• Parenteral artemisinin derivatives or quinine should be used irrespective of
chloroquine sensitivity.
DRUG DOSE
• Artesunate: 2.4 mg/kg body weight i.v. or i.m. given on admission (time=0),
then at 12 hours and 24 hours, then once a day (Care should be
taken to dilute artesunate powder in 5% Sodium bi-carbonate
provided in the pack).
Artemether: 3.2 mg/kg body weight i.m. given on admission then 1.6 mg/kg
body weight per day
• Arteether:
22-12-2014
150 mg daily i.m. for 3 days in adults only(not recommended
for children)
28

57. 22-12-2014 62
Quinine:
20 mg quinine salt/kg body weight on admission
• (i.v. infusion in 5% dextrose/dextrose saline over a period of 4 hrs)
followed by maintenance dose of 10 mg/kg bodyweight 8 hrly;
• infusion rate should not exceed 5mg/kg body weight per hr
• Loading dose of 20 mg/kg body weight should not be given, if the
patient has already received quinine.
• NEVER GIVE BOLUS INJECTION OF QUININE.
• If parenteral quinine therapy needs to be continued beyond 48 hours,
dose should be reduced to 7 mg/kg body weight 8 hourly

58. 22-12-2014 63
Once the patient can take oral therapy, further follow-up treatment should be as
below:
• Patients on parenteral quinine should be treated
• oral quinine 10 mg/kg body weight TDS to complete a course of 7 days,
• Along with doxycycline 3 mg/ kg body weight per day for 7 days. (If
contraindicated, Clindamycin 12 hourly for 7 days should be used).
• Patients receiving artemisinin derivatives should get full course of oral
ACT. However, ACT containing mefloquine should be avoided in cerebral
malaria due to neuropsychiatric complications.

59. 22-12-2014 64
• IV prefered over IM , should be given for min of 24 hours once
started.
•
Severe malaria due to P. Vivax
• Rare in India
• Treated like severe P. falciparum malaria
First trimester Parenteral quinine (DOC)
Artemisinin derivatives
In Second and Third trimester Parenteral Artemisinin

60. Thank you