1. Malaria II
V Term 2008 Batch
ACMS

2. Objectives
• Natural History of vivax and falciparum Malaria
• Factors influencing severity
• Clinical presentations of vivax and falciparum
Malaria
• Acute and Chronic complications
• Diagnosis
• Treatment NVBDCP Guidelines 2009 (India)
• WHO Guidelines (2010)
• Chemoprophylaxis

3. Recent Publications

4. Indian Reference
• Malaria Drug Policy (2007). Directorate of
National Vector Borne Disease Control
Programe. New Delhi. 2007. Available at
http://www.nvbdcp.gov.in/Doc/Revised%20dr
ug%20policy.pdf Accessed June 1, 2009
• Status of drug resistance in India. NVBDCP.
Available at http://nvbdcp.gov.in/DRUG.html

5. Indian Guidelines 2009

6. Definitions: Drug resistance
The World Health Organization (WHO) defines
resistance to antimalarials as
• the ability of a parasite strain to survive and/or to
multiply despite the administration and absorption of a
medicine given in doses equal to or higher than those
usually recommended but within the tolerance of the
subject, provided drug exposure at the site of action is
adequate.
• Resistance to antimalarials arises because of the
selection of parasites with genetic mutations or gene
amplifications that confer reduced susceptibility.

7. Definitions
• Relapse. The recurrence of asexual parasitaemia
in P. vivax and P. ovale malaria deriving from
persisting liver stages.
• Relapse occurs when the blood stage infection
has been eliminated but hypnozoites persist in
the liver and mature to form hepatic schizonts.
• After variable intervals of weeks to months, the
hepatic schizonts burst and liberate merozoites
into the bloodstream.

8. Definitions
• Recurrence. The recurrence of asexual
parasitaemia following treatment. This can be
caused by a recrudescence, a relapse (in P.
vivax and P. ovale infections only) or a new
infection.

9. Definitions
• Recrudescence. The recurrence of asexual
parasitaemia after treatment of the infection with
the same infection that caused the original
illness. This results from incomplete clearance of
parasitaemia due to inadequate or ineffective
treatment.
• It is, therefore different to a relapse in P. vivax
and P. ovale infections, and it differs from a new
infection or re-infection (as identified by
molecular genotyping in endemic areas).

10. Definitions
• Severe falciparum malaria: Acute falciparum
malaria with signs of severity and/or evidence
of vital organ dysfunction.
• Uncomplicated malaria: Symptomatic
infection with malaria parasitaemia without
signs of severity and/or evidence of vital organ
dysfunction

11. Natural History
• BT Malaria (vivax)-
• Incubation period (5 days – 3 months)
Davidson 8 to 25 days
• Acute Febrile illness-Malarial paroxysms every 48
– 72 hrs for weeks to months
• Asymptomatic carrier
• Chronicity- antibody response, splenomegaly,
anemia
• Reservoir

12. Natural History
MT Malaria (falciparum)-
• Incubation period (3 days to 3 weeks)
Davidson 8 to 25 days
• Acute febrile syndrome or irregular indolent
febrile illness with several accompaniments
• Often rapid progression to complications
• Fatal if untreated
• NO CHRONICITY

13. Factors influencing severity of
infection
• Pregnancy
• Infancy -newborns have some protection from
maternal Abs and fetal Hb)
• Semi- Immune/ Non- immune status
• Blood groups and Hemoglobinopathies
– Sickle Cell Anemia and Thallasemia
– Hb S, E, F and C
– G6PD Deficiency
– Duffy antigen negativity (vivax)
– Ovalocytosis
• HIV and Lympho-reticular malignancies
• Malnutrition

14. Clinical Presentation
BT Malaria (P vivax)
• Acute Febrile Syndrome- Paroxysms 48 to 72 Hrs
• Chills, Rigors, Headache, Prostration, Sweating
• Vomiting
• Flu Like Illness
• Anemia
• Mild jaundice
• Hepatosplenomegaly
• FUO
• Urticaria (rare)

15. Clinical Presentation
MT Malaria (P falciparum)
• Irregular fever

16. Clinical Presentation
MT Malaria (P falciparum)
• Irregular fever
• Jaundice, hepatosplenomegaly

17. Clinical Presentation
MT Malaria (P falciparum)
• Irregular fever
• Jaundice, hepatosplenomegaly
• Choleric form: diarrhea vomiting pain
abdomen, dehydration

18. Clinical Presentation
MT Malaria (P falciparum)
• Irregular fever
• Jaundice, hepatosplenomegaly
• Choleric form: diarrhea vomiting pain
abdomen, dehydration
• Dark urine (acute hemolysis)

19. Clinical Presentation
MT Malaria (P falciparum)
• Irregular fever
• Jaundice, hepatosplenomegaly
• Choleric form: diarrhea vomiting pain
abdomen, dehydration
• Dark urine (acute hemolysis)
• Renal failure

20. Clinical Presentation
MT Malaria (P falciparum)
• Irregular fever
• Jaundice, hepatosplenomegaly
• Choleric form: diarrhea vomiting pain abdomen,
dehydration
• Dark urine (acute hemolysis)
• Oliguria (Renal failure)
• Cerebral Malaria- Headache, confusion, abnormal
behaviour, coma, seizures, focal deficits

21. Clinical Presentation
MT Malaria (P falciparum)
• Irregular fever
• Jaundice, hepatosplenomegaly
• Choleric form: diarrhea vomiting pain abdomen,
dehydration
• Dark urine (acute hemolysis)
• Renal failure
• Cerebral Malaria- Headache, confusion,
abnormal behaviour, coma, seizures, focal deficits
• Respiratory symptoms- Variable degree

22. WHO: Definition of 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, therefore,
suspected clinically mostly on the basis of fever
or a history of fever.

23. Severe Malaria
• Evidence (clinical or laboratory) of vital organ
dysfunction.
• Usually due to falciparum/ mixed infections

24. Acute Complications- falciparum
• Metabolic acidosis
• Hypoglycemia
• Peripheral circulatory failure
• Blackwater Fever- acute intravascular hemolysis (G6PD,
Quinine, high parasitemia, immune hemolysis
• Cerebral Malaria
• Renal failure
• Respiratory Failure-ARDS
• Hepatitis
• DIC

25. Chronic Complications- vivax
• Tropical Splenomegaly Syndrome (HMS)-
Chronic/ repeated P vivax infections
Hypergammaglobulinemia, NN anemia/
pancytopenia, splenomegaly & Hepatomegaly.
HMS- Hyper-reactive Malarial Splenomegaly

26. Chronic Complications- vivax
• Tropical Splenomegaly Syndrome (HMS)-
Chronic/ repeated P vivax infections
Hypergammaglobulinemia, NN anemia/
pancytopenia, splenomegaly & Hepatomegaly.
• Lump and pain abdomen.
•

27. Chronic Complications- vivax
• Tropical Splenomegaly Syndrome (HMS)-
Chronic/ repeated P vivax infections
Hypergammaglobulinemia, NN anemia/
pancytopenia, splenomegaly & Hepatomegaly.
• Lump and pain abdomen.
• Skin and respiratory infections.

28. Chronic Complications
• Tropical Splenomegaly Syndrome (HMS)-
Chronic/ repeated P vivax infections
Hypergammaglobulinemia, NN anemia/
pancytopenia, splenomegaly & Hepatomegaly.
• Lump and pain abdomen.
• Skin and respiratory infections.
• Death due to sepsis/ lympho-proliferative
malignant transformation

29. Chronic Complications
• Tropical Splenomegaly Syndrome (HMS)-
Chronic/ repeated P vivax infections
Hypergammaglobulinemia, NN anemia/
pancytopenia, splenomegaly & Hepatomegaly.
• Lump and pain abdomen. Skin and respiratory
infections.
• Death due to sepsis/ lympho-proliferative
malignant transformation
• Treatment: Antimalarials and supportive
therapy

30. Chronic Complications -Others
• TSS
• Immune Hemolytic Anemia- Coomb’s Positive
• Quartan Malarial Nephropathy- rare
• Burkitt’s Lymphoma and EBV infection

31. Diagnosis
• Clinical setting- residence, travel, other cases

32. Diagnosis
• Clinical setting
• Presentation

33. Diagnosis
• Clinical setting
• Presentation
• Exclude other causes-

34. Diagnosis
• Clinical setting
• Presentation
• Exclude other causes of
– Hyperpyrexia- heat stroke, sepsis, drugs, pontine lesion

35. Diagnosis
• Clinical setting
• Presentation
• Exclude other causes of
– Hyperpyrexia- heat stroke, sepsis, drugs, pontine lesion
– Acute Febrile Syndrome- Influenza, Viral fevers, Enteric,
Sepsis & Bacteremia, Dengue, Leptospirosis,
Rickettsiosis

36. Diagnosis
• Clinical setting
• Presentation
• Exclude other causes of
– Hyperpyrexia- heat stroke, sepsis, drugs, pontine lesion
– Acute Febrile Syndrome- Influenza, Viral fevers, Enteric,
Sepsis & Bacteremia, Dengue, Leptospirosis,
Rickettsiosis
– Fever with splenomegaly

37. Diagnosis
• Clinical setting
• Presentation
• Exclude other causes of
– Hyperpyrexia- heat stroke, sepsis, drugs, pontine lesion
– Acute Febrile Syndrome- Influenza, Viral fevers, Enteric,
Sepsis & Bacteremia, Dengue, Leptospirosis,
Rickettsiosis
– Fever with splenomegaly
– Fever with Anemia / Jaundice

38. Diagnosis
• Clinical setting
• Presentation
• Exclude other causes of
– Hyperpyrexia- heat stroke, sepsis, drugs, pontine lesion
– Acute Febrile Syndrome- Influenza, Viral fevers, Enteric,
Sepsis & Bacteremia, Dengue, Leptospirosis,
Rickettsiosis
– Fever with splenomegaly
– Fever with Anemia / Jaundice
– Fever with Cerebral Symptoms – meningitis,
encephalitis

39. Diagnosis
• Clinical setting
• Presentation
• Exclude other causes of
– Hyperpyrexia- heat stroke, sepsis, drugs, pontine lesion
– Acute Febrile Syndrome- Influenza, Viral fevers, Enteric,
Sepsis & Bacteremia, Dengue, Leptospirosis,
Rickettsiosis
– Fever with splenomegaly
– Fever with Anemia / Jaundice
– Fever with Cerebral Symptoms – meningitis,
encephalitis
– Fever with ARDS

40. Aims of Early Diagnosis
• Complete cure
• Prevention of progression to severe malaria
• Prevention of deaths
• Interruption of transmission
• Minimizing selection and spread of drug
resistance

41. Diagnostics
• Routine

42. Diagnostics
• Routine
• Specific

43. Diagnostics
• Routine
• Specific
• Thick and Thin blood smears- Giemsa /
Wright’s/ Lieshman’s stain stain. view 100 to
200 fields/ 200 wbcs in tail of smear.
Detection & species identification
Relevance ?

44. Diagnostics
• Routine
• Specific
• Thick and Thin blood smears- Giemsa /
Wright’s/ Lieshman’s stain stain. view 100 to
200 fields/200 wbcs in tail of smear.
Detection & species identification
Relevance ?
Parasitemia: No of parasitized RBCs per 1000
RBCs/ per 200 WBCs. Relevance ?

45. Diagnostics
• Routine
• Specific
• Thick and Thin blood smears- Giemsa stain /
Wright’s/ Lieshman’s stain. view 100 to 200
fields/ wbcs in tail of smear.
Detection & species identification
Relevance ?
Parasitemia: No of parasitized RBCs per 1000
RBCs/ per 200 WBCs. Calculated as xxx/ micro L
Relevance ?
• Antigen Detection- HRP or LDH (RDTs)

46. Diagnostics
• Routine
• Specific
• Thick and Thin blood smears- Giemsa/ Wright’s/
Lieshman’s stain. view 100 to 200 fields/ wbcs in
tail of smear.
Detection & species identification
Relevance ?
Parasitemia: No of parasitized RBCs per 1000
RBCs/ per 200 WBCs. Converted to No/ microL
Relevance ?
• Antigen Detection- HRP or LDH (RDTs)
• PCR- Resistance testing

47. The QBC Test, developed by Becton
and Dickenson Inc.
• It is a new method for identifying the malarial
parasite in the peripheral blood. It involves
staining of the centrifuged and compressed
red cell layer with acridine orange and its
examination under UV light source. It is fast,
easy and claimed to be more sensitive than
the traditional thick smear examination.
• Not recommended anymore

48. Peripheral smear QBC
Method Cumbersome Easy
Time Longer, 60 - 120 minutes Faster
Sensitivity 5 parasites/µl in thick
film and 200 / µl in thin
film
Claimed to be more
sensitive, at least as good
Specificity Gold standard ? False positives, artifacts
may be reported as
positive by not-so-well-
trained technicians
Species
identification
Accurate, gold standard Difficult to impossible
Cost Inexpensive Costly equipment and
consumabl
Acceptability 100% Not so

49. Treatment
• Supportive
• Antipyretics
• Fluids
• Dextrose
• Specific
Antimalarials

50. vivax Malaria
• Chloroquine 25 mg base/kg bw divided over 3
days, combined with primaquine 0.25 mg
base/kg bw, taken with food once daily for 14
days is the treatment of choice for
chloroquine-sensitive infections. In Oceania and
South-East Asia the dose of primaquine should be 0.5 mg/kg bw.[

51. vivax Malaria
• Chloroquine – total 25mg/Kg over 3 days
• +
• Primaquine – 15 mg/ day X 14 days

52. vivax Malaria
• Chloroquine – total 25mg/Kg (BASE)
• Day 1 -10 mg/kg (600 mg) 4
• Day 2 -10 mg/kg (600 mg) 4
• Day 3 -5 mg/kg (300 mg) 2
Earlier-
• Day 1- 10 mg/kg (600 mg) 4
• +12 hrs -5 mg/kg (300 mg) 2
• +24 hrs- 5 mg/kg (300 mg) 2
• +36 hrs- 5 mg/kg (300 mg) 2

53. WHO 2010: vivax Malaria
• For chloroquine-resistant vivax malaria,
Amodiaquine (30 mg base/kg divided over 3 days
as 10 mg/kg bw single daily doses) + primaquine
should be given.
• Where ACT has been adopted as the first-line
treatment for P. falciparum malaria, it may also
be used for P. vivax malaria in combination with
primaquine for radical cure.
• Artesunate + sulfadoxine-pyrimethamine is the
exception as it will not be effective against P.
vivax in many places.

54. Other Choices - vivax
• Q + Tetra/ Doxy/ Clinda
• ACT
• Mefloquine

55. Uncomplicated falciparum: NVBDCP
• Treatment of P. falciparum cases
• The treatment of P. falciparum malaria is based
on areas identified as chloroquine resistant/
sensitive as listed in annexure.
• Artemisinin Combination Therapy (ACT) should
be given in resistant areas whereas chloroquine
can be used in sensitive areas. ACT should be
given only to confirmed P. falciparum cases found
positive by microscopy or RDT.

56. Severe Malaria
• Severe manifestations can develop in P. falciparum
infection over a span of time as short as 12 – 24 hours
and may lead to death, if not treated promptly and
adequately. Severe malaria is characterized by one or
more of the following features:
• • Impaired consciousness/coma
• • Repeated generalized convulsions
• • Renal failure (Serum Creatinine >3 mg/dl)
• • Jaundice (Serum Bilirubin >3 mg/dl)
• • Severe anaemia (Hb <5 g/dl)
• • Pulmonary oedema/acute respiratory distress
syndrome

57. Severe Malaria
• • Hypoglycaemia (Plasma Glucose <40 mg/dl)
• • Metabolic acidosis
• • Circulatory collapse/shock (Systolic BP <80 mm
Hg, <70 mm
• Hg in children)
• • Abnormal bleeding and DIC Haemoglobinuria
• • Hyperthermia (Temperature >104o F)
• • Hyperparasitaemia (>5% parasitized RBCs in low
endemic and
• >10% in hyperendemic areas)

58. Severe Malaria
• Requirements for management of complications
• For management of severe malaria, health facilities should
• be equipped with the following:
• • Parenteral antimalarials, antibiotics, anticonvulsants,
• antipyretics
• • Intravenous infusion equipment and fluids
• • Special nursing for patients in coma
• • Blood transfusion
• • Well-equipped laboratory
• • Oxygen
• If these items are not available, the patient must be
referred without delay to a facility, where they are
available.

59. Severe Malaria: Treatment
• Parenteral artemisinin derivatives or quinine should
be used irrespective of chloroquine sensitivity
• • Artesunate: 2.4 mg/kg 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 i.m. given on admission
then 1.6 mg/kg per day.
• • ab Arteether: 150 mg daily i.m. for 3 days in adults
only (not recommended for children).

60. Severe Malaria: Treatment
• Quinine: 20 mg quinine salt/kg on admission (i.v.
infusion in 5% dextrose/dextrose saline over a period
of 4 hours)
• followed by maintenance dose of 10 mg/kg 8 hourly;
infusion rate should not exceed 5 mg/kg per hour.
• Loading dose of 20 mg/kg 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
8 hourly.

61. Other Drugs and Combinations
• Numerous

62. Drugs unsafe in pregnancy
• Sulfadoxine-Pyremethamine
• Doxycycline/ Tetracycline
• Primaquine

63. Treatment Follow- up
• In all cases of malaria, follow-up MP tests
should be done on the 6th and 28th days after
treatment.
• The 6th day smear is done to assess clearance
of parasitemia
• 28th day smear is done to identify resistance in
vivax and recrudescence in falciparum.

64. World Malaria Report 2009
• RDT Rapid diagnostic test
• SPR Slide positivity rate
• API Annual parasite incidence
• IRS Indoor residual spraying
• IPT Intermittent preventive treatment
• ACT Artemisinin-based combination therapy
• ITN Insecticide-treated nets
• LLIN Long-lasting insecticidal nets

65. Abbreviations of antimalarial
medicines
• AQ Amodiaquine
• AL Artemether-
lumefantrine
• AM Artemether
• ART Artemisinin
• AS Artesunate
• CL Clindamycin
• CQ Chloroquine
• D Doxycycline
• DHA Dihydroartemisinin
• MQ Mefloquine
• NQ Naphroquine
• PG Proguanil
• PPQ Piperaquine
• PQ Primaquine
• PYR Pyronaridine
• QN Quinine
• SP Sulfadoxine-
pyrimethamine
• T Tetracycline

66. WHO: Main objectives of
Antimalarial Treatment Policy
1. To reduce morbidity and mortality by
• ensuring rapid, complete cure of the infection
and thus preventing the progression of
uncomplicated malaria to severe, potentially fatal
disease
• malaria-related anaemia and, during pregnancy
• the negative impact of malaria on the fetus
2. To curtail the transmission of malaria by reducing
the parasite reservoir of infection and infectivity.

67. WHO recommendations for diagnosis
and treatment of malaria
• Prompt parasitological confirmation by
microscopy or alternatively by rapid diagnostic
tests (RDTs) is recommended for all patients
with suspected malaria before treatment is
started.
• Treatment solely on the basis of clinical
suspicion should be considered only when a
parasitological diagnosis is not accessible.

68. Uncomplicated Cases
• Uncomplicated falciparum malaria should be treated
with Artemesinin - based combination therapy (ACT).
• Vivax malaria should be treated with Chloroquine
where it is effective or an appropriate ACT in areas
where P vivax resistance to Chloroquine has been
documented.
• Both Chloroquine and ACT should be combined with
Primaquine for 14 days in the treatment of P vivax
malaria for the prevention of relapses, subject to
considering the risk of hemolysis in patients with G6
PD Deficiency.

69. Five ACTs are currently recommended
for use
• Artemether – Lumifantrine
• Artesunate – Amodiaquine
• Artesunate - Mefloquine
• Artesunate – Sulfadoxine- Pyremethamine
• Dihydroartemisinin- Pipraquine
• The choice of ACT should be based on the
efficacy of the combination in the country or area
of intended use

70. The National Vector Borne Disease
Control Programme (NVBDCP)
• While the WHO recommends Artemether-
lumefantrine in areas of multidrug resistance
such as South-East Asia, the NVBDCP does not
recommend this ACT for use anywhere in
India.[1,2]
• Therefore, this ACT, now widely marketed in
India by the private pharma, need not be used
to treat malaria in India.

71. Avoid Monotherapy
• Artemesinin derivatives should not be used as
monotherapies for the treatment of
uncomplicated malaria as this will promote
resistance to this important class of
antimalarials.

72. Public Health Measure: Eliminate
Gametes
• A single dose of Primaquine to be added as an
anti – gametocyte medicine to ACT treatment
of P falciparum malaria, particularly as a
component of elimination / pre- elimination
programme is recommended provided the risk
of hemolysis in G6PD deficient patients is
considered

73. Severe Malaria
• Severe malaria should be treated with a
parenteral artemesinin derivative or quinine
• to be followed by a complete course of an
effective ACT as soon as the patient can take oral
medications.
• When IV/ IM treatment is not feasible , e.g.
peripheral health posts, patients should receive
pre- referral treatment with an artemesinin
suppository and be transferred to a health facility
capable of providing definitive treatment with
parenteral antimalarial medicines.

74. Resource Poor Settings
• In settings with limited health facility access,
diagnosis and treatment should be provided
at community level through a programme of
community case management (home – based
management) of malaria.

75. • Furthermore, in light of evidence of resistance
to artemisinins, WHO urges more strongly the
continued routine monitoring of therapeutic
efficacy of antimalarial medicines and halting
the use of all monotherapies for the
treatment of uncomplicated malaria.

76. Chemoprophylaxis
• Several factors to be considered