Treating Malaria has become a lost art primarily because of changing guidelines & growing resistance.

1. MALARIA
An attempt to clean up the Mal--air
Dr.Mahesh Hiranandani
M.D (PGI)

2.  Aniket 13 yr Boy R/O Sec 38 west,CHD
Reported with h/o
Fever..High grade with chills 2 days
Bodyaches
Dry cough
 H/O travel to Muradabad 3 weeks back.
 O/E Wt 41 kg Ht 158cms
Febrile 102 f Pulse 96/min BP 130/58mm
Fine erythematous rash on trunk

3.  Congested tonsils, no pus points
 Chest NAD CVS  Tachycardia
 Abdomen NAD CNS  WNL
 Initial clinical impression
Acute febrile illness with no systemic localisation
 M/M
Oral Paracetamol every 6 hrly.
Plenty of liquids & daily bath.
Follow up
Boy continued to run fever with chills & also contd to
have dry cough….vomited out twice…

4.  Ix Hb 11.3gm TLC 10800 P/54 L/43 M/3
Plat 1.46 lacs
Blood film: Microcytic hypochrominc anemia
No MP seen.
Urine R/E NAD
Further M/M
Oral chloroquine for 3 days….Child became
afebrile on D3 .

5.  Are we witnessing a decline in incidence of
malaria ??
 Has the clinical picture changed …..
 Reliability of current diagnostic tests….
 Is this vast variability of treatment a cause of
concern………

12.  Is Classical Tertian…Quartan fever just historical.
 Atypical presentation more common than typical
 Pointers to presence of Falciparum malaria.
 Symptoms fade on repeat infections.

13. Clinical features:
The natural H/O malaria is
characterized by incubation
period, pre patent period,
primary attack (composed of
paroxysms), latent period
(parasitic latency) and
recurrences (long term
relapses)
The typical attack has 3
distinct stages:
1. cold stage ( 1 hour or so),
2. hot stage (<1 to 6 hours),
3. sweating stage ( 1 hour
or so)

14. • paroxysms associated with
synchrony of merozoite
release
• between paroxysms temper-
ature is normal and patient
feels well
• falciparum may not exhibit
classic paroxysms
(continuous fever)
Malaria
Paroxysm
tertian malaria
quartan malaria

15. Hijra

17.  Early infection.
 Patients at extremes of ages.
 Individuals on chemoprophylaxis for Malaria.
 Patients who have had multiple attacks of malaria.
 Immunocompromised patients.
 Patients with end organ failure.
 Falciparum malaria.

18.  Presence of complications of P Falciparum like
altered sensorium, convulsions, jaundice etc.
 Atypical presentation.
 Not responding to chloroquine in 48 hrs.
 Recurrence after 2 weeks.

19.  Attributed to depletion of certain immune cells
gamma T cells.
 Detrimental on account of prolonged
harbouring of MPs allowing further spread.
 Beneficial as symptoms are mild or absent.
 Malaria infection by reshaping immune
response might influence susceptibility to and
protection from ,other infectious diseases.

21. Gold standard for Diagnosis
Thin film: For species Thick film : For a good yield
Timing the sample with peak of fever ??
Examine 100 fields under 100X
Advantages:
Diagnosis along with species identity.
Degree of parasitemia
Parasitic stage ie tropho,schizont,gamate
Disadvantages
Cant detect sequestrated P faciparum
Low density parasitemia <50/ul may be missed
Time consuming & labour intensive.

22.  Based on staining of parasite
DNA with acridine orange
in a compressed &
centrifuged RBC layer &
examination under UV light.
 Plasmodia in various stages
get placed in a predictable
manner between leukocyte
& thick RBC layers .
 These appear as tiny bright
specks under UV light
adapter.
 As sensitive as a thick film
 -ve test ..1 min ,+ve test few
mins

24. Peripheral smear OBC
Method Cumbersome Quick
Time Longer 30-60 mins Shorter 15-30mins
Sensitivity Thin film 5/UL
Thick film 200/UL
As good as a thick film
Specificity Considered as a gold
standard
False positive known
Species identification Possible gold standard Difficult to impossible
Cost & acceptability Inexpensive /100% Expensive/Not so
Availability Everywhere Limited

25.  Detects antigen by Immunochromatography
using monoclonal ab against malarial antigens
Types of antigen detected
1. Histidine rich protein P. Fal specific
2. Pl lactate dehydrogenase
* P Falciparum sp
* P Vivax sp
* Pan species sp
3. Plasmodium aldolase
* Dipstick * Cassette * Card
Easy to perform Results in 10-15 mins No training
Recommended by WHO & NVBDCP

26. Sensitivity : Upto 90% at density >100/ul
> 95% at 500/ul, rare occurrence
False positive
Persistent antigen( up to 2 weeks)
Cross reaction with Rheumatoid factor
False negative
Severe malaria with parasite load>40000/ul
Early parasitemia
Poor storage/temp instability of kit

28.  Over 50 doctors from across country………..
 Low index of suspicion for malaria in fevers.
 Confirmation of diagnosis not a priority.
 Lacked awareness about recent malaria
treatment protocols.
 Chloroquine was the commonest drug used.
 SP & Artemisinin monotherapy was common.
 Hesitation in using Primaquine for radical cure.
Are they to be blamed ????

29. The aims of the Malaria case management
 Prompt and complete treatment to all suspected/
confirmed cases of malaria
 To prevent progression of mild cases of malaria to
severe or complicated forms of malaria
 Prevent deaths from severe and complicated
malaria.
 To prevent transmission of malaria
 To minimize risk of spread of drug resistant
parasites by use of effective drugs in appropriate
dosage by everyone.

30. Abbe macchhar
bahar nikal
Masal ke rakh
doonga

31. Motivated doctors
DDT
CQ
Peaking of cases
Inadequate CQ & PQ
PF stable
Species sp Rx
% PF cases
CQ RESIS
SLIDE +
MALARIA DEATHS

32.  Presumptive single dose CQ abandoned.
 All suspected malaria case  PBF & RDT.
 Clinical diagnosis not possible Full dose CQ.
 Even at 10% Rx failure…area declared CQ resistant.
 Areas with > 30% PF cases…2nd line drugs used.
 Radical cure for PV extended to 14 days.
 Single dose PQ & SP stopped.
 .CQ resistant Pf crossed 90%.
 2009 Artemisinin monotherapy banned.
 2010 ACT + SP universal for Pf + Single dose PQ
 2013 Lumifantrine replaces SP in NE states.

33.  The rationale for combining anti-malarials with
different modes of action is twofold:
(1) The combination is often more effective; and
(2) If the mutant parasite is spared by one drug the
other one in ACT will eliminate it.
To realize the two advantages, the partner drugs in
a combination must be independently effective.
The possible disadvantages of combination
treatments are the potential for increased risk of
adverse effects and the increased cost.

36. TABLET SYRUP DOSE ADVERSE
EFFECTS
CHLOROQUINE 250mg/500mg 50mg/5ml 25/kg in 3 days
10..10..5mg/kg
GI upset
Leukopenia
PRIMAQUINE 2.5mg 7.5 mg
15mg
DT 2.5 mg 250ug/kg
For 14 days
GI Aplastic an
Hemolysis
MEFLOQUINE 250mg NONE 250mg/wk
20mg/kg/wk
GI Vertigo
AV blocks
SULFADOXINE
PYRIMETHAMI
500mg/25mg 250mg/12.5mg
In 5 ml
2-3 tab
0.5ml/kg
GI Urticaria
SJ synd
ARTEMETHER
LUMIFANTRINE
80mg
480mg
20/120mg
In 5ml
5-15kg 20/120
15-25 40/240
25-34 60/360
Leukopenia
AV blocks
GI upsets
ARTESUNATE 50mg
Inj 60mg/2ml
NONE 2.4mg/kg Drug fever
Rash
QUININE 100/300/600
Inj 300mg/ml
150mg/5ml 10mg/kg/day Cinchonism
Blood dysc

39. Strength:
* Artemisinin monotherapy banned in 2009.
* Antimalarial Rx only after Dx confirmation on PBF
which reduces drug pressure for resistance ,prevent
side effects, decrease drug costs & improve
management of fevers.
* CQ recommended as a blanket Rx for PV in spite of
reports of CQ resistance from various areas. Proven
therapeutic efficacy with 100% cure rates.
* ACT-SP for Pf yields 98% success.
* ACT-Lumifantrine for NE states .

40. Weakness :
* Blister pack of ACT-SP results in poor
compliance, potential for mono therapy & poor
bioavailability.
* Difficult access to delivery system for malaria
Dx & Rx .
* Lack of awareness of National drug policy
amongst private sector doctors .
* Completion of PQ for radical cure poor 
Burden of relapses .

49. Misdiagnosis
Overdiagnosis ie, obsession with malaria.
Underdiagnosis ie, forgetting malaria.
Misreport
False positive : dirty slides, contaminated
stain, recycled QBC tubes.
False neagtive : Inadequate smear,dirty stain
Inexp microscopist,

50. Over estimation
 Panic reaction to PF malaria over reaction
Over treatment .
 Proper assessment for criteria for severe malaria
Under estimation
 High fever ,severe pallor, icterus , bleeding
altered sensorium, resp distress suggest severe
 Extremes of age , pregnant,immunocompromised
are at increased risk for complicated malaria

53.  Artemisinin and its derivatives (artesunate, artemether, artemotil,
dihydroartemisinin) produce rapid clearance of parasitaemia and rapid
resolution of symptoms. They reduce parasite numbers by a factor of
approximately 10 000 in each asexual cycle, which is more than other current
antimalarials (which reduce parasite numbers 100- to 1000-fold per
cycle).
 Artemisinin and its derivatives are eliminated rapidly . When given in
combination with rapidly eliminated compounds (tetracyclines, clindamycin),
a 7-day course of treatment with an artemisinin compound is required; but
when given in combination with slowly eliminated antimalarials, shorter
courses of treatment (3 days) are effective. The evidence of their superiority
in comparison to monotherapies has been clearly documented.

59. Protozoan Disease
108 countries
3 billion people
1 million deaths each year
H2012
H2012

60. Prevalence rose in many parts of the
tropics

63.  Malaria is probably one of the oldest diseases known to
mankind that has had profound impact on our history.
 It is a huge social, economical and health problem,
particularly in the tropical countries.
 Malaria is a vector-borne infectious disease caused by
single-celled protozoan parasites of the genus
Plasmodium.
 Malaria is transmitted from person to person by the
bite of female mosquitoes.

64.  Malaria is caused by a parasite called
Plasmodium, which is transmitted via the bites
of infected mosquitoes. In the human body, the
parasites multiply in the liver, and then infect
red blood cells.
 Transmission of Malaria does not occur <160c
and >330c
 Does not occur > 2000 meters altitude.

66.  Malaria is caused by an infection by one of four
single celled Plasmodia species, they are:
Falciparum
Vivax,
Malariae
Ovale.
 The most dangerous of the four is.P.falciparum

67.  Malaria remains the world's most
devastating human parasitic
infection. Malaria affects over 40%
of the world's population. WHO,
estimates that there are 350 - 500
million cases of malaria worldwide,
of which 270 - 400 million are
Falciparum malaria, the most
severe form of the disease.

69. Falciparum
Usually only ring forms; Banana-shaped gametocytes
Vivax
Irregularly shaped large rings and trophozoites; enlarged
erythrocytes; Schüffner's dots
Ovale
Infected erythrocytes, enlarged and oval with tufted ends;
Schüffner's dots
Malariae
Band or rectangular forms of trophozoites common

70. Sporozoites
Liver
Asexual Reproduction
Single Sporozoite eventually 10,000 to >30,000 Daughter
Merozoites
Liver cell eventually bursts
100 million parasites in the blood of an adult, the
symptomatic stage of the infection begins

72. Intrahepatic forms
Dormant(Hypnozoites) for a
period ranging from 3 weeks to a
year or longer before reproduction
begins
Relapses

74. Falciparum 48 h
Vivax 48 h
Ovale 50 h
Malariae 72 h

75. Vivax , Ovale :Yes
Falciparum , Malariae : No

76.  P.vivax
 P.malariae Infectes only young or
 P.ovale Old Erythocytes
 P.falciparum Infects all age groups
Also adhere to the endothelial lining of Blood vessesl
Causes the obstruction, Thrombosis and Local Ischemias

77. Parasitemias of >2% are
suggestive of Falciparum
infection

78. Falciparum predominates in Africa, New
Guinea, and Hispaniola (i.e., the Dominican
Republic and Haiti)
Vivax is more common in Central America
Malariae is found in most endemic areas
Ovale is relatively unusual outside of Africa

79. Parasitemia rates or palpable-Spleen
rates in children 2–9 years
Hypoendemic (<10%)
Mesoendemic (11–50%)
Hyperendemic (51–75%)
Holoendemic (>75%)

80. (e.g., certain regions of tropical Africa or coastal
New Guinea) where there is intense Falciparum
transmission, people may sustain more than
one infectious mosquito bite per day and are
infected repeatedly throughout their lives
Morbidity and Mortality during early
Childhood
Adulthood, most infections are Asymptomatic

81. Constant
Frequent
Year-round infection

82. Transmission is low, Erratic, or
Focal, full protective immunity is
not acquired, and symptomatic
disease may occur at All Ages
Usually exists in Hypoendemic

83. Changes in Environmental, Economic, or
Social conditions, such as heavy rains or
migrations (usually of Refugees or Workers)
from a nonmalarious region to an area of high
transmission; a breakdown in malaria control
and prevention service
All Age Groups

84. the number of sporozoite-positive
mosquito bites per person per
year is the most common measure of malaria
transmission and varies from <1 in some parts
of Latin America and Southeast Asia to >300
in parts of tropical Africa.

85. Initially, nonspecific defense mechanisms
Splenic immunologic and filtrative
clearance
Removal of both parasitized and
uninfected erythrocytes
Strain-specific immune response then
controls the infection

86. Direct effects of RBC invasion
and destruction by the asexual
parasite and the host's reaction

87. First symptoms of malaria are nonspecific
Lack of a sense of well-being
Headache
Fatigue
Abdominal discomfort
Muscle aches
followed by Fever
similar to the symptoms of a minor viral illness

88.  Fever and shivering. The attack begins with
fever, with the temperature rising as high as
40ºC and falling again over a period of several
hours.
 A poor general condition, feeling unwell and
having headaches like influenza.
 Diarrhea, nausea and vomiting often occur as
well.

89.  The symptoms often associated with malaria
are due to bursting red blood cells and clogged
capillaries of major organs. Infection occurs
when an infected anopheles mosquito feeds on
an individual releasing sporozites into the
blood stream. Mosquitos can carry more than
one species and thus can infect peoples with
more than one species

90.  Fever
 Sweating
 Anemia
 Splenomagaly (enlarged spleen)
 Irratability
 Coma, Retinal Hemorrages
 Algid Malaria ( a shocklike syndrome)
 Respiratory distress syndrome

91. Childhood Febrile Convulsions
may occur with any of the
malarias, generalized seizures are
specifically associated with
falciparum malaria

92. Petechial hemorrhages in the
skin or mucous develop only
rarely in severe falciparum
malaria

95.  Antimalarial Combination Therapy
To counter the threat of resistance of P. falciparum to
monotherapies, and to improve treatment outcome, combinations
of antimalarials are now recommended by WHO for the treatment
of falciparum malaria.
 Definition
The concept is based On the potential of two or more
simultaneously administered schizontocidal drugs with
independent modes of action to improve therapeutic efficacy and
also to delay the development of resistance to the individual
components of the combination.

96.  The objective of treating uncomplicated malaria is to cure
the infection. This prevents progression to severe disease.
 Cure of the infection means eradication from the body of
the infection that caused the illness. Needs a strict follow
up.
 The public health goal of treatment is to reduce
transmission of the infection to others, i.e. to reduce the
infectious reservoir.
 A secondary but equally important objective of treatment
is to prevent the development of resistance

99. Non-artemisinin based combinations (non-ACTs) include:-
i. sulfadoxine–pyrimethamine with chloroquine (SP+CQ) or
ii. amodiaquine (SP+AQ).
However, the prevailing high levels of resistance have
compromised the efficacy of these combinations. There is no
convincing evidence that SP+CQ provides any additional
benefit over SP, so this combination is not recommended;
SP+AQ can be more effective than either drug alone, but
needs to be considered in the light of comparison with
ACTs.

100.  On the basis of the evidence from current practice and
the consensus opinion of the Guidelines Development
Group, the following second-line treatments are
recommended, in order of preference:
1. Alternative ACT known to be effective in the region,
2. Artesunate + tetracycline or doxycycline or
clindamycin,
3. Quinine + tetracycline or doxycycline or clindamycin.
 The alternative ACT has the advantages of simplicity,
and where available, co-formulation to improve
adherence. The 7-day quinine regimes are not well
tolerated and adherence is likely to be poor if treatment
is not observed.

101.  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.
 Amodiaquine (30 mg base/kg bw divided over 3 days as 10 mg/kg bw
single daily doses) combined with primaquine should be given for
chloroquine-resistant vivax malaria.
 In moderate G6PD deficiency, primaquine 0.75 mg base/kg bw should be
given once a week for 8 weeks. In severe G6PD deficiency, primaquine
should not 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.

103. P. Vivax malaria is considered to be a benign malaria, with a very low
case-fatality ratio, it may still cause a severe and debilitating febrile illness.
It can also very occasionally result in severe disease as in falciparum malaria.
Severe Vivax malaria manifestations that have been reported are:
1. Cerebral malaria
2. Severe anaemia
3. Severe thrombocytopenia
4. Pancytopenia
5. Jaundice,
6. Spleen rupture
7. Acute renal failure
8. Acute respiratory distress syndrome.
9. Severe anaemia and acute pulmonary oedema are not uncommon.
The underlying mechanisms of severe manifestations are not well understood.
Prompt and effective treatment and case management should be the same as
for severe and complicated falciparum malaria

106. Nausea
Vomiting
Orthostatic hypotension

107. Irregular at first (that of falciparum
malaria may never become regular); the
temperature of nonimmune
individuals and children often rises
above 40°C in conjunction with
Tachycardia and sometimes Delirium.

108. Artesunate 4mg/kg for 3 days SP as in chart on D1 PQ 0.75mg/kg on D2

109. Fever
Malaise
Mild Anemia
Palpable Spleen
(in some cases)

110. Fever spikes
Chills and rigors
occur at regular intervals, are
relatively unusual and suggest
infection with P. Vivax or P. Ovale

111. Common, particularly among
Young Children

112. Common among adults; it may
develop in patients with
otherwise uncomplicated malaria
and usually resolves over 1–3
weeks

113. Common among young
children living in areas with
stable transmission

114. Falciparum
Younger cells (but can invade cells of all ages)
Vivax
Reticulocytes and cells up to 2 weeks old
Ovale
Reticulocytes
Malariae
Older cells

115. Life Cycle
•sporozoites injected during
mosquito feeding
•invade liver cells
•exoerythrocytic schizogony
(merozoites)
•merozoites invade RBCs
•repeated erythrocytic
schizogony cycles
•gametocytes infective for
mosquito
•fusion of gametes in gut
•sporogony on gut wall in
hemocoel
•sporozoites invade salivary
glands

116. Hyponozoite Forms
• some EE forms exhibit delayed
replication (ie, dormant)
• merozoites produced months after
initial infection
• only P. vivax and P. ovale
relapse = hypnozoite
recrudescence = subpatentt

117. Anopheles
Transmission
•sporozoites injected
with saliva
•enter circulation
•trapped by liver
(receptor-ligand)

118. Clinical Features
• characterized by acute febrile attacks
(malaria paroxysms)
• periodic episodes of fever alternating with
symptom-free periods
• manifestations and severity depend on
species and host status
• immunity, general health, nutritional state,
genetics
• recrudescences and relapses can occur
over months or years
• can develop severe complications
(especially P. falciparum)

119. 1 Pre erythrocytic
schizogony
2 Erythrocytic
Schizogony
3 Gametogony
4 Exoerythrocytic
schizogony

120.  Man – Intermediate host.
 Mosquito – Definitive host
– Sporozoites are infective
forms
 Present in the salivary
gland of female anopheles
mosquito
 After bite of infected
mosquito sporozoites are
introduced into blood
circulation.

121. Duffy blood-group antigen Fya or Fyb
Most West Africans and people with
origins in that region carry the Duffy-
negative FyFy phenotype and are
therefore resistant to P. vivax

122. >400 can transmit malaria, and the 40
considerably in their efficiency as malaria
vectors
Life cycle within the mosquito—from
gametocyte ingestion to subsequent
inoculation (sporogony)—lasts 8–30 days
mosquito must survive for >7

123. Headache
Chest pain
Abdominal pain
Arthralgia
Myalgia
Diarrhea

126.  Laboratory diagnosis of malaria can be made
through microscopic examination of thick and
thin blood smears. Thick blood smears are
more sensitive in detecting malaria parasites
because the blood is more concentrated
allowing for a greater volume of blood to be
examined; however, thick smears are more
difficult to read

130. Comparisons between RDTs
and Microscopy
Microscopy RDTs
Technically difficult Easy
Requires functional
Equipment
No Equipment Required
Cheap / test Expensive/test
Large working space
required
Minimal space required
Long waiting time Short waiting time
Difficult to use Easy to use
Sequestration not
detected
Able to detect
sequestration
Differentiates parasite Differention in some
High training needs Minimal training needs
Parasite Detection level
 60g/ml
Parasite Detection
Level  100 g/ml
Very sensitive and
specific
Variable sensitivity and
specificity
Rs.100-200 / Rs.250-400/

131.  Malaria parasites can be identified by
examining under the microscope a drop of the
patient's blood, spread out as a "blood smear"
on a microscope slide. Prior to examination, the
specimen is stained (most often with the
Giemsa stain) to give to the parasites a
distinctive appearance. This technique remains
the gold standard for laboratory confirmation
of malaria

144.  Antigen Detection
 Various test kits are available to detect antigens
derived from malaria parasites. Such
immunologic ("immunochromatographic")
tests most often use a dipstick or cassette
format, and provide results in 2-15 minutes.
These "Rapid Diagnostic Tests" (RDTs) offer a
useful alternative to microscopy in situations
where reliable microscopic diagnosis is not
available. Malaria RDTs are currently used in
some clinical settings

145. Less sensitive than PBF.
Detects antigen not parasite ,remains +ve upto 2 weeks.
Doesn’t detect parasitemia or stage of parasite .

148. Slides
taken
MP positive
Plasmodium
Falciparum
Deaths
INDIA 5.172 crore 3.2 lacs 2.08 lacs 107
TRIPURA 1.9 lacs 13375 12945 33
Orrisa 26 lacs 1.3 lacs 1.12 lacs 20
Chandigarh 13035 29 0 0