Malaria, an ancient mosquito-borne infectious disease caused by the Plasmodium species, poses significant global health challenges, particularly in Sub-Saharan Africa. With approximately 584,000 annual deaths, mostly among children, the disease's transmission and clinical impact vary by region and parasite type, with Plasmodium falciparum being prevalent in Africa and Plasmodium vivax outside it. Diagnostic and treatment strategies continue to evolve, aiming for rapid disease elimination and combating drug resistance.

3. Malaria has been noted for more than 4,000
years.
 The term malaria originates from Medieval
Italian: mala aria—“bad air“
 the disease was formerly called
ague or marsh fever due to its association
with swamps and marshland

4. Malaria is a mosquito-borne infectious
disease caused by parasitic protozoan of
the genus Plasmodium.
the disease is transmitted by a bite from an
infected female Anopheles mosquito
In humans, the parasites multiply in liver
and infect the RBCs.

5. may be transmitted 9-17 days after female
Anopheles mosquito ingests blood from an
infected person
People develop symptoms 8-25 days later
Malaria kills an estimated 584,000 people
each year – the vast majority are children.

6. MALARIAL HOSTS
HUMAN: INTERMEDIATE HOST
FEMALE ANOPHELES MOSQUITO:
DEFINITIVE HOST

7. • Malaria is an infectious
disease caused by
plasmodium species.
• Transmission of this
parasite to human is by
blood sucking bite of
female anopheles
mosquito of various
species.
CAUSATIVE AGENTS OF MALARIA

8. • Out of the four species PLASMODIUM VIVAX and
PLASMODIUM FALCIPARUM are the most common.
Plasmodium species which infect humans
SPECIES TYPE OF MALARIA
Plasmodium
falciparum
Malignant tertian malaria
Plasmodium vivax Benign tertian malaria
Plasmodium malariae Benign quartan malaria
Plasmodium ovale Benign tertian malaria

9. Agent
P. vivax – 60-70 %
P. falciparum – 25-30 %
P. malariae – 1 %
P. ovale – rare
Mixed – 4-8 %

10. DISCOVERY OF MALARIAL
PARASITE:
Charles Louis Alphonse
Laveran, was the first to notice
parasites in the blood of a
patient suffering from malaria.
This occurred on the 6th of
November 1880. For his
discovery, Laveran was
awarded the Nobel Prize in
1907.

11. On August 20th, 1897,
Ronald Ross,, was the
first to demonstrate that
malaria parasites could
be transmitted from
infected patients to
mosquitoes.

12. Grassi in 1890, (with Raimondo Felleti)
discovered Haemamoeba vivax, later
renamed Plasmodium vivax
In 1898,Also found that the bite of only
female Anopheles mosquitoes could
transmit malaria

14. Malaria has been recorded in places as
far north as Archangel, Russia and as
far south as Cordoba, Argentina.
However, malaria is essentially a focal
disease and its distribution is patchy
in most parts.

17. In 2016, an estimated 216 million cases of
malaria occurred worldwide compared with
237 million cases in 2010 .
Most malaria cases in 2016 were in the WHO
African Region (90%),
South-East Asia Region (7%) and the
WHO Eastern Mediterranean Region (2%).

20. The incidence rate of malaria is estimated to
have decreased by 18% globally, from 76 to
63 cases per 1000 population at risk,
between 2010 and 2016.
The WHO South-East Asia Region recorded
the largest decline (48%) followed by the
WHO Region of the Americas (22%) and the
WHO African Region (20%).

21. Plasmodium falciparum is the most
prevalent malaria parasite in sub-Saharan
Africa, accounting for 99% of estimated
malaria cases in 2016.
Outside of Africa, P. vivax is the
predominant parasite in the WHO Region of
the Americas, representing 64% of malaria
cases, and is above 30% in the WHO South-
East Asia and 40% in the Eastern
Mediterranean regions.

23. Malaria deaths
In 2016, an estimated 445 000 deaths,
compared to 446 000 estimated deaths in
2015.
The WHO African Region accounted for 91%
of all malaria deaths in 2016,South- East
Asia Region (6%).
Fifteen countries accounted for 80% of
global malaria deaths in 2016; all of these
countries are in sub-Saharan Africa, except
for India.

26. Malaria elimination
Globally, more countries are moving towards
elimination: in 2016, 44 countries reported fewer
than 10 000 malaria cases, up from 37 countries
in 2010.
Kyrgyzstan and Sri Lanka were certified by WHO
as malaria free in 2016.

27. MALARIA IN
NEPAL

28. Malaria is a priority public health problem of
Nepal where approximately 50 % of the
population is at risk of malaria. Malaria cases
are being reported from 65 out of the 75
districts of Nepal.

29. THE HIGH AND MODERATE MALARIA RISK
AREAS CONSIST OF FOOTHILLS, FORESTS
FRINGE, FORESTS IN TERAI AND INNER
TERAI VALLEYS, WHEREAS THE LOW RISK
AREA CONSIST OF SOUTHERN PLANES AND
NORTHERN HILLS/ HILL RIVER VALLEYS.

31. AMONG THE CONFIRMED MALARIA CASES
DURING THE LAST THREE DECADES, CASES
REACHED THE PEAK IN 1985 WHEN THE
NUMBER EXCEEDED 42,321, REPRESENTING
THE HIGHEST MALARIA CASELOAD EVER
RECORDED IN NEPAL .THE LAST OUTBREAK
OCCURRED IN 2006 IN THE VILLAGES OF BANKE
ACCOUNTING FOR 36 DEATHS

32. TOTAL CONFIRMED MALARIA CASES
DECLINED BY APPROXIMATELY 90 % OVER
A DECADE (12,750 CASES IN 2002 VERSUS
1352CASES IN 2014/15)
PLASMODIUM FALCIPARUM (PF)
INFECTION 20% WHILE 80% OF THE TOTAL
CASES ARE PLASMODIUM VIVAX (PV)
INFECTIONS.

36. Life Cycle

37. Geographical location – Tropical and
subtropical.
The malarial parasite has 2 hosts
The Intermediate host – Human (
Asexual development )
The Definitive host – Female anopheles
mosquito ( Sexual development )

38. The malarial parasite has 2 cycles
 Human cycle
 Mosquito cycle
The human life cycle has 4 stages.
 The PRE-ERYTHROCYTIC schizogony
 The ERYTHROCYTIC schizogony
 The GAMETOGONY
 The EXO-ERYTHROCYTICschizogony

39. The PRE-ERYTHROCYTIC schizogony
 Liver
 Sporozoites schizont (20,000 -50,000 merozoites).
 The ERYTHROCYTIC schizogony
 RBCs
 Trophozoite, Schizont, Merozoites.
 The GAMETOGONY
 RBCs and Blood stream
 Gametocytes (Micro and Macro gametocytes)

40. The EXO-ERYTHROCYTIC schizogony
 Liver
 Not in P.falciparum
 Occurs in P.vivax and P.ovale .
 Sporozoites hypnozoites
 Remains dormant for upto 2 years.

41. The mosquito cycle.
 Only the sexual form survives.
 Midgut of the mosquito.
 Microgametocytes 4-8 microgametes
Fertilize Zygote Ookinete
 Macrogametocytes 1 macrogamete
 Ookinete Oocysts Sporozoites develop and released.
 They travel to the salivary glands of the mosquito and
infect another person during a blood meal.

43. Pathogenesis of
Malaria

44. Characteristic Features
1. Pigmentation of the involved organs
2. Release of malarial toxins on rupture of
RBCs and induced effects (periodic febrile
paroxysm)
3. Hyperplasia of reticulo-endothelial system
4. Parasitized erythrocytes filling the lumen
of capillaries of involved organs
5.Organ specific pathology

45. Effect on RBCs
Parasite obtains oxygen from the
oxyheamoglobin of RBC.
RBC globin is broken down giving Iron prophyrin.
This leads to pigmentation of organs rich in RE
cells.

46. Rupture of infected RBCs
This leads to the release of:
Merozoites
Malarial toxins
Pigment granules
Unused cytoplasm of RBCs

47. Malarial toxins and induced effects
No specific toxin for malaria.
However, a ‘soluble factor’ constituted
by Inorganic phosphate and Lactic
acid was discovered.
It causes:
Depression of cellular respiration
Halting of cellular metabolism by
interfering with mitochondrial activity.

48. Malarial antigens resemble the Toxic
Shock Syndrome Toxin 1 of S. aureus.
 It enhances host susceptibility to lethal
endotoxin shock and induces TNF release
from macrophages, and thus contributes
to the pathogenesis.

49. Cytoadhesion
RBCs containing trophozoites adhere to
microvascular endothelium in post capillary
venules in brain, kidney, liver, lungs and gut.
Vessels become congested and the organs
anoxic.
They don’t enter circulation again until they
rupture from schizogony.
Cytoadhesion begins in the first half of the life
cycle, and thus mature forms are not seen in
falciparum malaria.
This is in contrast to other types of malaria.

50. Rosettes
Uninfected RBCs stick to infected
RBCs
Contributes to microcirculatory
obstruction and resultant anoxia of
tissues.

51. Cerebral malaria
 Due to clogging of cerebral
microcirculation by parasitized RBCs.
 These cells develop knobs on their surface
and hence become more cytoadherent.
 Sequestration of parasites and rosetting in
deeper vessels.
 Decreased deformability of infected RBCs
increases clogging.
 Obstruction in cerebral microcirculation
 Hypoxia and increased lactate production.

52. Clinical Features

53. CLINICAL FEATURES

54. On the basis of severity:
Uncomplicated
Complicated

55. UNCOMPLICATED MALARIA
Symptoms:
• The lack of sense of well being,
• Headache
• Fatigue
• Abdominal discomfort
• Nausea
• Vomiting
• Orthostatic Hypotension
• Myalgia and Joint aches
Followed by fever.

56. Signs:
• Anemia
• Splenomegaly
• Hepatomegaly
The classical malarial paroxysms i.e.
fever spikes, chills and Infection with
rigor at regular interval P. Vivax or P. Ovalae
Fever Irregular – Falciparum Malaria

57. SEVERE FALCIPARUM
MALARIA
• Unarousable Coma / cerebral malaria,
convulsions
• Metabolic acidosis/acidemia
• Renal Impairment
• Noncardiogenic pulmonary edema
• Liver Dysfunction
• Hypoglycemia

58. • Hematological abnormality like hemoglobinuria,
normocytic anemia, bleeding, DIC
• Other complications like jaundice, extreme
weakness, hyperparasitemia, hypotension.

59. Unarousable Coma/
Cerebral Malaria
• Coma
• Diffuse symmetric encephalopathy
• Tendon reflexes : Variable, Plantars : Equivocal.
• Abdominal & cremasteric reflexes are absent
• Fundoscopy: Retinal hemorrhages, papilledema,
cotton wool spots

60. • Convulsions :In children, usually
generalised, often repeated
• Covert seizure : manifest as Tonic clonic eye
movement, hyper salivation
• Residual neurological deficit
seen in children who survive
cerbral malaria.

61. Increases the risk of mortality in children
with cerebral malaria.
May present with convulsions or a deterioration in
level of consciousness.
CAUSES
• Faliure of hepatic gluconeogenesis.
• Increased uptake by both host and malaria
parasites.
• Quinine – Powerful stimulant of pancreatic
insulin secretion.
Hypoglycemia

62. Acidosis
• This may result form renal failure, but more
commonly there is a primary lactic acidosis.

63. • Lactic acidosis results from :
1. Anaerobic glycolysis due to
microvascular obstruction.
2. Failure of hepatic and renal lactate
clearance.
3. Production of lactate by the parasite

64. This is a grave and usually fatal manifestation of
severe falciparum malaria and occurs mainly in
adults.
Predisposing factors:
Hyperparasitaemia, renal failure and pregnancy
Non Cardiogenic
Pulmonary Edema

65. Tubular abnormalities consistent with acute tubular
necrosis (ATN) are seen.
Sequestration in glomerular capillaries, mesangial
endothelial cell proliferation, and immunoglobulin
deposits may be seen.
Renal Impairment

66. • Maternal anaemia
• Abortion
• Stillbirths
• Premature delivery and
• Intra- Uterine Growth Retardation (IUGR)
Malaria In Pregnancy

67. • Septicemia
• Liver dysfunction
Other Complications

68. Chronic Complication
• Tropical Splenomegaly
• Quartan malarial nephropathy
• Burkitt's lymphoma & Epstein-Barr virus
infection

69. DIAGNOSIS OF
MALARIA

70. MICROSCOPY
a)Thick and thin blood smear study.
- Gold standard method for malaria diagnosis.
The procedure follows these steps:
 Collection of peripheral blood
 Staining of smear with Giemsa stain &
 Examination of RBC for malaria parasites under the microscope.
Infected RBCs under
microscope

71. Thick smear: Not fixed in methanol, allows the RBC to be
hemolyzed, & leukocytes and any malaria parasite present
will be the only detectable elements.
Thick and thin blood smear
Thin smear: Fixed in methanol, allow to identify malaria
species, quantify parasitemia, and recognize parasite forms like
schizonts and gametocytes.

72. Advantages:
Inexpensive method.
Gives the examiner the opportunity to quantify
parasites and differentiate malaria species.
Disadvantages:
Diagnostic accuracy depends on quality of blood smear and
equipment, abilities of the microscopist, parasite density.
Not suitable for large- scale epidemiological studies.
False positive.
False negative.

73. b) Quantitative Buffy Coat
(QBC) test
Method involve centrifuged & compressed RBC stained with
acridine orange and then examinee under an UV light source.
Whole procedure tales place in a glass hematocrit tube.
The tube is filled with 55-65µl of blood & then centrifuged.
Fluorescing parasites are then observed, with a UV
microscope.
QBC test is easier and faster than classical peripheral blood
smear microscopy.
But the equipment required is expensive and species
identification and accurate enumeration are impossible.

74. QBC, bands formed after
centrifugation
Fluorescent parasites under UV
microscope

75. IMMUNOLOGICAL TECHNIQUES
Antibody-based techniques
a) Indirect fluorescent antibody test(IFAT)
A drop of diluted washed infected RBC is allowed to dry &
then incubated with the serial dilutions of the test serum,
followed by a solution of anti-human immunoglobulin
labelled with fluorescence isothiocyanine which contains
Evans blue as a counter stain. When the slides are dried,
they are examined by fluorescence microscopy.

76. The disadvantages of this method are the
requirement of a fluorescence microscope and the
need for high technical skills.
Fluorescence microscopy
Antibody in the test
serum reacts with
antigen of parasites is
demonstrated by the
fluorescence of the
parasites as shown in
Figure.

77. b) Enzyme-linked immunosorbent assay (ELISA)
This method uses a soluble malarial antigen coated on the
walls of a microtitre plate.
If the test is positive, the antibody binds the antigen resulting
in a visible color change.
If test is negative, no change in color of substrate.
ELISA plate

78. Antigen-based techniques
Rapid Diagnostic Test (RDT)
A device that can detect malaria antigen in a small amount of
blood (5µl) by immunochromatographic assay with monoclonal
antibodies directed against the parasite antigen.
Depending on the target antigen, rapid tests that now exist may
involve combinations of the following.
HRP-2(Histidine Rich Protein-2) is a protein produced by
asexual stages and gametocytes of P. falciparum
LDH is a glycolytic enzyme produced by asexual and sexual
stages of parasites and released by RBC.

79. Two and three line RDTs positive for P. falciparum or mixed infection

80. Advantages
Doesn’t require electricity .
Simple to perform .
HRP-2 tests have sensitivity of >90% for P.falciparum and LDH
tests >95%
.

81. Disadvantages
Low sensitivity in detecting asymptomatic patients
particularly in low parasitemias.
Cross reactions to autoantibody.
False positivity.
False negativity.
In Conclusion, a RDT test should always be
followed-up by microscopy confirmation of the
result

82.  MOLECULAR TECHNIQUES
Polymerase Chain Reaction (PCR)
Possible to detect all 4 species of malaria parasites.
New technologies such as Saponin lysed erythrocytes
NAT(nucleic acid amplification) & LAMP (loop-mediated
isothermal amplification) can provide a lower cost diagnosis
with greater sensitivity and specificity.

83. Advantages
High sensitivity & specificity.
Detection of mixed species infections & drug –resistant strains.
Disadvantages
Too sensitive for clinical use.
Unsuitable for field conditions.
Expensive
Technically demanding.

84. Treatment of malaria

85. Objectives:
 Ensure rapid and complete elimination of Plasmodium
parasite
 Prevent progression of disease to severe cases or
death
 Prevent emergence and spread of resistance
 Reduce spread of disease:
• Reducing human to mosquito transmission

86. Drugs used:
 Chloroquine (CQ)
 Quinine
 Artemisinin derivatives
 Primaquine

87. Chloroquine
 Erythrocytic Schizontocide
 Acts on trophozoites
MECHANISM OF ACTION
 Inhibits digestion of hemoglobin -> hematin via CQ-heme complex
 Accumulation of toxic heme – damages plasmodial membrane
ADVERSE REACTIONS
 Nausea, vomiting, epigastric pain, anorexia, uncontrollable itching
 CNS toxicity, hypotension, cardiac depression, arrhythmia
 High doses + prolonged use – loss of vision

88. Quinine
 Erythrocytic Schizontocide
 Less effective & more toxic than Chloroquine
 Used in chloroquine resistant strains of infection
 MECHANISM OF ACTION
 Works in analogous manner to Chloroquine
 ADVERSE REACTIONS
 In high doses – Cinchoinism: ringing in ears, difficulty hearing,
vertigo, visual defects, nausea, vomiting, mental confusion

89. Artemsinin Derivatives
 Erythrocytic Schizontocide – potent & rapid
 Action: Fast onset, short acting
 Lethal to early gametes - exerts action on ring forms
MECHANISM OF ACTION
 Endoperoxide – forms free radicals with heme – damages and
cause lysis of parasite
ADVERSE REACTIONS
 Nausea, vomiting, epigastric pain, dark urine, Q-T prolongation,
first degree AV block

90. Primaquine
 Active against pre-erythrocytic stage
 Poor blood schizontocidal effect
 Highly effective against gametocytes and Hypnozytes
MECHANISM OF ACTION
 Unknown
ADVERSE REACTIONS
 Abdominal pain, GI upset, weakness, uneasiness in
chest
 High doses – Leucopenia
 Hemolysis – G6PD deficient patients

91. Uncomplicated Malaria –
P. Vivax, P. ovale & P. malariae
Sulfadoxine
1500mg (25mg/kg)
75mg (1.25mg/kg)
single dose
Pyrimethamine
Chloroquine
600mg (10mg/kg) &
300 mg (5mg/kg) –
after 8 hours till next 2 days
Quinine
600mg (10mg/kg)
8 hourly
Primaquine
15mg daily
(.25mg/kg)
Artesunate
100mg BD
(mg/kg/day)
Doxycycline
10mg daily
(.25mg/kg)
+ +
+
+
x 14 days x 7 days
x 3 days

92. Uncomplicated Malaria – P. Falciparum
 Artemisinin-Based Combination Therapy (ACT)
Arthemeter Artesunate Artesunate
80mg BD 100 mg BD (4mg/kg/day) 200mg(4mg/kg)
x 3 days
+ + +
Lumefantrine Mefloquine Amodiaquine
480 mg BD (750mg) 15mg/kg ×3days 600mg
x 3 days x 3 days

93. Severe & Complicated
 Parenteral drugs (i.m/i.v) must be used till condition
improves
Artesunate
(2.4mg/kg) I.V/I.M
followed by same dose
after 12 & 24 hours
Switch to Oral ACT
when patient can tolerate
oral drugs
& then once daily x 7 days
Quinine dil. HCl
(20mg/kg) diluted in
5% Dextrose (10mg/kg)
Infused I.V over 4 hours
LOADING DOSE
& (10mg/kg) I.V over 4 hours
MAINTENANCE DOSE
Switch to Oral Quinine
(10mg/kg) 8 hourly – 7 day course
when patient can tolerate oral drugs

94. During pregnancy
 Poses serious threat to mother and fetus
 Prompt aggressive treatment required
 Used especially during first trimester
 ACT is used for 3 days as alternative during
2nd and 3rd trimester
Quinine Clindamycin
600 mg + 300mg (20mg/kg) x 7 days
TDS TDS

95. Prevention and Control

96. Approaches to Malaria Control
Surveillance and case management
 Case detection
 Early diagnosis and complete treatment
 Sentinel surveillance
• Intergrated vector management
 Epidemic preparedness and early response.

97. Approaches to Malaria Control (contd.)
• Supportive interventions
 Complete cure
 Behavioral change communication
 Intersectoral collaboration
 Monitoring and evaluation
 Operational and applied field research

98. Vector Control Strategies
Anti adult measures
Residual spraying
DDT, Parathion, Malathion
• Space application
Application of pesticide in the form of fog or mist.
• Individual protection
Repellents
Protective clothing
Bed nets
Mosquito coils

99. Vector Control Strategies (Contd.)
Antilarval measures
Larvicides
 Temephos
Source Reduction
 Drainage or filling
 Deepening or flushing
 Management of water level
 Changing the salt content of water
 Intermittent Irrigation

100. • Intergrated Control
Biological control
Personal protection

101. Thank You