Epidemiology of Malaria,

clinical features, treatment

and its control

Dr.J.Nuchin. M.D.,M.B.A.,D.C.A.
Epidemiologist
16-03-2011
 By the end of session, you would be
expected to be able to describe:

vProblem statement
vLife cycle of parasite
vType of vector
vClinical features
v8 important CFs of severe
complicated malaria
vTreatment
vDiagnosis
vControl measures
v
Sir Ronald Ross (1857-1932)

•
• 1897: role of
the mosquito.
•
•
• Nobel prize:
1902
 Introduction…
Ø A protozoan disease caused by a parasite
plasmodium
Ø A major parasitic cause of death in man
Ø One of the oldest recorded diseases
Ø Egyptian mummies with enlarged spleens (1000
BC).
Ø Hippocrates (460-370 B.C.)-Clear discussion of
quartan and tertian fevers made by in his Book of
Epidemics, Noted relationship between enlarged
spleens and marshes.
Ø Region between Tigris and Euphrates was
malarious (2000 BC).
Ø Malaria was well known to the Ancient Greeks and
Romans.
Problem statement-World
§ Has been a scourge of
mankind for the
centuries
§ Total death toll due to
malaria is more than
that due to any
other diseases or
even wars
§ Endemic in 109 (in
2006) countries
covering about 45%
of global population
§ Burden – 300-500
million cases and 2-3
million deaths
• Kills a child every 15 to 20 seconds or 8000
children per day
• Nine of 10 deaths globally are among sub-
Saharan children under age 5.
• Responsible for 25% total child mortality in
Africa
• 90 percent of global incidence of malaria
occurs in 13 countries of Africa.
• Out of this more than 50% of cases are from
Nigeria, Congo, Ethiopia, Tanzania and
Kenya.
• In pregnant women, it causes abortion, still
births, LBWs and neonatal deaths globally.
•
•


•
 Indian scenario
§ Has always been a home ground for
malaria
§ Before 1947 (preDDT era)- malaria was a
major cause of death
§ In 1908, an outbreak in UP and Punjab
killed more than 3 lakh people in just a
span of 2 months
§ In 1947, India had about 75 million cases
and >50% of total deaths were due to
Malaria alone
• All the aspects of life were affected
directly or indirectly
In 1950s, India used to report about
75 million every year with around 7.5
million deaths
 Major malaria ecotypes found in
India
• Rural malaria-
• Urban malaria-
• Forest malaria
• Irrigation malaria
• Project malaria
• Migration malaria
• Border malaria
•
 Factors responsible for the
increase in VBDs
ü
ü Poverty and rapid population growth
ü Irrigation
ü Urbanization and improper sanitation
ü Industrialization
ü Migration and rapid population movement
ü Natural disasters
ü Resistance
ü Global warming
ü Political instability
ü Inadequate health infrastructure
1.1 billion people live on
less than $1 a day.

2.7 billion people live on

less than $2 a day.
 IRRIGATION IN INDIA
100

91.02
80
78.12
Million Hectares

60
56.81
52.02
40
41.21
37.1
29.12 30.57
20 22.6
26.25

0
P re 1st IInd IIIrd Annual IVth Vth Annual VIth VIIth
1951-56 1956-61 1961-66 1966-69 1969-74 1974-78 1978-80 1985-90 1990-95
 Karnataka
§ A major CMD in the state.
§ 7 districts namely DK,G,R,K,T,Bijapur and
Bagalkot together contributed >65% of
the total burden in the state in 2010
§ The P.f cases are being decreased in
Karnataka and not so in other parts of
the country.
§ Double resistance has been recorded
§
MALARIA CASES IN Karnataka
since 2006 to 2010
Karnataka in 2006- 62864 cases

Dakshina
kannada
21%
Others
32%

Kolar
13%
Belgaum
7%
Raichur
Tumkur Gulbarga 12%
7% 8%
85% of the cases in the state were due to these 11
districts with 2 deaths in the year 2008

85
% o
ft
he c
a
se
si
n t
hes
t
at
e w
e
re

d
ue
to
th
es
e1
1d
i
str
i
cts
wi
th2
de
at
hs
Contribution of malaria cases in the year 2009 in 10
districts of Karnataka- Total no of cases-36859.

85% of the total cases in the year contributed by these 10 districts

 No. of cases in 2010-
Karnataka->85% of cases were due to
these10 districts
• Malaria status in
Belgaum
 Geographically the district has
been divided into 3 parts
1)Hilly region-
Khanapur
2)(South) Semi
Malnad –
Savdatti,
Hukkeri,
Bailhongal and
Belgaum
3)(North) Tropical
Region- Athani,
Raibagh, Gokak,
Ramdurga and
 Belgaum district
• Taluks-10
• GHs-9
• CHCs-16
• PHCs-140
• SCs-660
• M.O.s-165, HWs-745,LTs-121
• Villages-1160
• Rural population-3201814 (2001 census)
• Urban population-1012691
• Total population-4214505
• Density-314 per sq mtr
• The average rain fall in the district is
808mm every year.
• Krishna, Malaprabha and Ghata prabha
being the major rivers in the districts, it
also has five small rivers namely
Markhandeya, Hiranyakeshi, Mahadaayi,
Vedaganga and Dudhaganga. Navilu
Tirtha dam is built for Malaprabha river
in Savadatti taluka and Hidkal dam for
Ghataprabha river in Hukkeri taluka.
These two huge dams provide irrigation
facilities through canals for the 8 taluks
of the district
• With many historical places to its
credit and plenty of Jatraas, the
district attracts travelers from the
near by districts and neighboring
states all through the year
 Talukwise malaria incidence-2007

Soundatti Bailhongal
10% 5%
Ramdurg
13%

Gokak
68%

Ta
luk
w is
eMa
lariain
cid
enc
e -2
008
B
ailhonngal
4%
Sav
d atti B
elgaum
18% 4%

R
amdurg
13 %

Gok
ak
59%
 M a la ria c a s-2e s0 0 6m o n th w is-To
e ta l C a s -e s
4149
678

Note the 2nd

589 peak of
551
disease

386 392 374

363
M
alricse

246 237

160

93
80

Ja n to D ec
 M o n t h w is e n o . o f M a-2l 0a 0r i7a c a
Note the 2nd
560 peak of
disease

421 429
401419
299 305
279
250
210
181
154

Jan Feb M ar Apr M ay J u n e J u ly Aug Sept O ct Nov D ec

 Note the 2nd
M o n t h w i s e n-2 o0 . 0 o4 f tc oa s2 e0 s0 7 peak of
disease

2000 1849

1500
1498 1483 1 3 51 83 3 4
1 0 7 29 6 0
1000 776 836
643
408373
500

J a n u a r y to D e c e m b e r
 Monthwise Malaria Cases-2007

560

421 429
401 419
299 305
279
250
210
181
154

Jan Feb Mar Apr May June July Aug Sept Oct Nov Dec

Monthwise Malaria Cases -2008

355
332

242
208 208
183 175
127 139 124
76 57

Jan Feb Mar Apr May June July Aug Sept Oct Nov Dec
 What’s the Good News?

• Every one of these deaths is

preventable!!!
• Just a 3 day course of treatment can cure
the disease
• No stigma associated with malaria
• No “Save the Mosquito” groups
•
 Endemicity and immunity to
malaria
Ø
 Endemicity
 Malaria is said to be endemic when there is a
constant incidence of cases over a period of many
successive years.
 Endemic malaria may be present in various degrees.
There are four grades

 A. Hypoendemicity – There is a little transmission

and the disease has little effect on the population.
 B. Mesoendemicity - varying intensity of
transmission; typically found in the small, rural
communities of the sub-tropics.
 C. Hyperendemicity - intense but seasonal
transmission; immunity is insufficient to prevent the
effects of malaria on all age groups.



 contnd…


 D. Holoendemicity - intense transmission

occurs throughout the year.
- As people are continuously exposed to
malaria parasites, they gradually develop
immunity to the disease.
 - In these areas, severe malaria is mainly a
disease of children from the first few months of
life to age 5 years.
 - Pregnant women are also highly susceptible
Although seasonal variations in transmission may occur


in holoendemic areas, malaria transmission occurs all

year round. Therefore, people acquire natural immunity
and epidemics are unlikely.

 Contnd…
 Depending on the intensity of transmission,
malaria can be stable or unstable, reflecting different
epidemic scenarios.
 Stable malaria: Sustained incidence over several
years. Seasonal fluctuations in transmission may occur
but epidemics are unlikely.


 Unstable malaria: Marked variations in the

incidence of malaria over time. Population does not
develop immunity and people of all ages are
susceptible to severe disease when transmission
increases.
•
•
 Agent –Parasite-Plasmodium
• Unicellular
• 140 types are there of which only 4 can
infect man(P.vivax, falciparum, ovale
and malariae)
• Malaria also affects other animals like
primates, rodents, birds, bats and even
cold blooded animals like lizards
• Some parasites infecting primates can
also infect man- eg,-P.knowelesi,
P.brasilianum and P.cyanomalgi
• Monkey malaria
Figure 11.30

Plasmodium Sporozoite
 Different species
P.vivax- all over 60-70% BTM Mild
world-less Anaemia, splenic
common in rupture rarely
Africa

P.falciparum- 25-35% MTM High degree

tropics and sub- parasitaemia, all
tropics deaths

P.malariae <1% BQM NS, found in

Karnataka

P.ovale-very NF BTM OM, in Africa

rare
 Mode of transmission

1.By bite of female anopheles mosquitoes

2.By blood- Blood transfusion and
contaminated syringes and needles
3.Mother to foetus.
 Congenital malaria
• Occurs in 5% of the babies borne to mothers
who were MP positive during pregnancy
• Transplacental infection
– Can occur in all 4 species
– Commonly seen P.v. and P.f. in endemic areas
– P.m.infections in nonendemic areas due to long
persistence of species
• Neonate can be diagnosed with parasitemia
within 7 days of birth
• Fever, irritability, feeding problems, anemia,
hepatosplenomegaly, and jaundice
•
 Life cycle of plasmodia
• The parasite 2 cycles of development- the
Human cycle (asexual cycle) and
Mosquito cycle (sexual cycle)


• Man is the intermediate host harbouring

the larval stages


• Mosquito is the definitive host harbouring

the adult stages
 Asexual cycle or Human cycle
• Begins with the injection
of sporozoites following
the bite of infected
mosquito
• Three phases are
observed
 Phase 1-Hepatic phase
(pre or exo erythrocytic
or tissue)-
Ø Sporozoites disappear
from the circulation
Ø Many of them are Hepatic Cells with
plasmodia
destroyed by
phagocytes and
some reach the
liver cells
Ø After 1-2 weeks of
development

(depending upon
the species) they
become hepatic
schizonts
•
 Hepatic schizoint- The actively dividing,
multinucleated, parasite form in hepatocytes; produces
no inflammatory response.

Pre-erythrocytic schizoints
Ø
Ø These hepatic schizoints eventually rupture, Contnd…
releasing showers of merozoites which attack
RBCs.

Ø Erythrocytic schizont: It is a multinucleated

stage in a RBC resulting from asexual
multiplication of trophozoite. Each schizont
contains a species determined number of
meroziotes.

Ø Merozoite: is a protozoan cell that arises from

the schizogony of a parent sporozoan and
may enter either the asexual or sexual phase
of the life cycle. Infective to other fresh
RBCs.

Ø The number of meroziotes released vary

Ø In case of P.f, as many as 40,000 and in others 2000-
15,000 merozoites are released


Ø Trophozoite: Metabolically active form of the malaria

parasite living within the RBC; sometimes called the
ring form.
Ø In case of P.f, the intrahepatic schizoints rupture almost
simultaneously and there is no persistent tissue- no
secondary exo erythrocytic stage
•
Ø
Ø On the contrary, the intrahepatic schizonts of
other plasmodia do not burst all at the same
time.


Ø Some intrahepatic schizonts persist and remain

dormant (hypnozoites) for considerable
periods and later they cause relapses


Ø Once the parasites enter RBCs, they do not

reinvade the hepatic cells
Phase 2- Erythrocytic
 Malaria parasites
invading an RBC
phase (erythrocytic
schizogony)


Ø Many of the merozoites are

quickly destroyed and
Malaria parasites in the
significant number of RBCs
merozoites bind and enter
the RBCs
Ø Then they pass through the
stages of trophozoites and
schizonts
Ø Each parasite spends two
days in a red blood cell
consuming the
Erythrocytic Schizogony
•nuclear division =
begin schizont stage
•6-40 nuclei
•budding merozoites =
segmenter
•erythrocyte rupture
releases merozoites
erythrocytic schizogony
•48 hr in Pf, Pv, Po
•72 hr in Pm

gametocytes
Erythrocytic forms (signet)

Young ring form trophozoites

Ø RBCs rupture releasing merozoites which
infect the fresh RBCs
Ø
Ø 16 new parasites burst out to infect other
red blood cells from each merozoite
Ø
Ø The sporozoites first invade liver cells and
asexually reproduce to produce huge
numbers of merozoites which spread
to red blood cells where more
merozoites are produced through more
asexual reproduction.
•
Ø Duration of erythrocytic phase is constant
for species to species
Ø It is 48 hrs in case of P.v, P.f and P.o
whereas 72 hrs in P.m
Ø The cycle may be repeated many times
and may end with complications or be
slowed down by immunity of the host
Phase 3- Gametogony


Ø Some of the
erythrocytic forms
do not divide but
become male
(smaller) and
female (longer)
gametocytes
Ø These are infective to
mosquitoes
Ø Gametocytes always
circulate in the
subcutaneous
capillaries
 Characteristics of different species
Species Duration of Incubation Number of Red cells
tissue period (days) merozoites / invaded
phase (days) cell

P. falciparum 5.5 – 7 8 - 11 40,000 cells of all ages

P. vivax 6-8 10 - 17 10,000 reticulocytes

P. ovale 9 10 – 17 15,000 reticulocytes

P. malariae 12-16 18 - 40 2,000 mature

cells
 Sexual or mosquito cycle
Ø These infective gametocytes
are ingested by the
anopheles mosquitoes
Ø Then develop and undergo
stages of fertilisation-
zygote, ookinate, oocyst
and sporozoites
Ø Sporozoites enter the
salivary gland from the
gut and are infective to
man
Ø Once in the mosquito,
Plasmodium needs about
8-10 days to produce
Plasmodia in Anopheles
 Vector-Anopheles
• Anopheles mosquitoes
Life Cycle- 7days at 310c,20 days at 200c
Egg
2 Days

Complete
Metamorphosis 6–8
Total = 10 – 12 Days
days

2 Days
65
Sl. Common Malaria vector Features
No. geographical area

1 Urban area A.stephensi Breeds in used wells, overhead tanks

2 Rural area A.culicifacie Zoophilic, wide distribution, high
s density required for transmission, breeds
in stagnant water, found in plains
3 Hilly area A.fluvitalis More anthrophilic, less density required
for transmission, breeds in slow running
4 Coastal area A.sundaicus Breeds
water in salt water,exophilic
5 Plantation A.minimus Breeds in slow running water
area/Malnad
area
6 In water A.Philippensi Breeds in high level subsoil water, found
logging area s in plains

Disease Potential is high in An. Minimus, An. Dirus, An. Fluviatilis, medium in
An. stephensi
An. sundaicus and low in An. culicifacies
An.culicifacies Breeding Sites
 Host factors
Ø Malaria affects all ages, but rare in newborn
due to presence of foetal haemoglobin and
maternal immunity
Ø Common in males because of outdoor activities
and clothing pattern (816 F -45% and 1014
M-55% out of 1830 in Belgaum till JAN 1998 to
August 2008)
Ø Duffy negative people are resistant to P.v. Most
of the Africans are Duffy negative, this
explains why P.v is not so common in Africa
Ø Patients of SC trait ( Hb AS), G6PD and
thalasseamia are less likely to be affected by
 High risk group
 Pregnant mothers- have an increased risk of severe
malaria especially in primigravidae, as the immunity to
the malaria is impaired in pregnancy.
Pregnant women attract twice the number of mosquitoes
than non-pregnant women
There is a greater susceptibility to P. falciparum than P.
vivax during pregnancy
•
 Children - Malaria affects cognitive development and
learning abilities of children.
• Malaria is a risk factor of neuro-sensory and behavioral
development in children
•
 Immigrants from Europe- as they lack natural
immunity

 Immunity

• Occurs only after repeated exposure to the disease

• Influenced by
– Genetics
– Age
– Health condition
– Pregnancy status
– Intensity of transmission in region
– Length of exposure
– Maintenance of exposure
–


Incubation period
It is the length of time between the bite of


infected mosquito and appearance of first

clinical feature (ie,fever). It is about 10-12
days in P.f and 10-14 days in other
species



Prepatent period
This is the length of time between the bite


of infected mosquito and appearance of

parasites in peripheral blood
•
 Clinical course

• Following a bite by an infected mosquito,

many people do not develop any signs
of infection. If infection does progress,
the outcome is one of three depending
on the host and parasite factors
enumerated in the previous slides:
– Asymptomatic parasitaemia (“clinical
immunity”)
– Acute,(Simple) uncomplicated malaria
– Severe malaria
•
 Asymptomatic parasitaemia

•
• This is usually seen in older children and adults
who have acquired natural immunity to
clinical disease as a consequence of living in
areas with high malaria endemicity.
• There are malaria parasites in the peripheral
blood but no symptoms.
• These individuals may be important reservoirs
for disease transmission.
•
• Some individuals may even develop anti-
parasite immunity so that they do not
develop parasitaemia following infection.
 Simple, uncomplicated malaria

• This can occur at any age but it is more likely to

be seen in individuals with some degree of
immunity to malaria. The affected person,
though ill, does not manifest life-threatening
disease.
•
• Fever is the most constant symptom of
malaria. It may occur in paroxysms when lysis
of red cells releases merozoites resulting in
fever, chills and rigors (uncontrollable
shivering).
 The periodicity of
malaria fever
• The first febrile attack corresponds to
 the development of parasites in the RBCs.
• The fever may be continuous or remittent
before it becomes classically intermittent
• Intermittent nature of the fever is due to
cyclical release of merozoites following
rupture of infected RBCs
• It is once in 48 hours in case of P.v, P.f (36 hrs-
sub-tertian) and P.o whereas 72 hours in P.m
 (erythrocytic schizogony is the time taken
for trophozoites to mature into merozoites
before release when the cell ruptures).
•

 Contnd…
• A typical attack involves 3 distinct stages
(in a person from non-endemic area).
 Cold stage
Ø Begins with feeling of cold, shivering and
headache
Ø Patient covers himself with blankets, BT
reaches 39-410C
Ø It may continue for 15 mins to 1 hour


 Parasites are demonstrable in the blood

Contnd
…

 Hot stage
Ø The fever raises so high so the
patient feels burning hot and takes off
the clothes
Ø The patient feels intense headache with
nausea and vomiting
Ø Pulse is of bounding type, patient feels
 Sweat stage
Ø Fever comes down with profuse sweating
Ø He goes usually into deep sleep
Ø Lasts for 2-4 hours
Ø Febrile herpes is very common
 Malaria- one clinical febrile
episode of malaria consumes 5,000 k
Cal.
Ø
 Note how the frequency of spikes of fever differ
according to the Plasmodium species.
In practice, spikes of fever in P. falciparum, occur
irregularly - probably because of the presence of
parasites at various stages of development.
 Other features of simple,
uncomplicated malaria include:


 Malaria is a multisystem disease. Other common

clinical features are:
v Vomiting
v
v Diarrhoea – more commonly seen in young children
and, when vomiting also occurs, may be
misdiagnosed as viral gastroenteritis
v
v Convulsions – commonly seen in young children. In an
endemic area, cerebral malaria should be ruled out if
any child fails to regain consciousness within an hour
after an episode of febrile convulsion.
v
v Pallor – resulting mainly from the lysis of RBCs. Malaria
also reduces the synthesis of red blood cells in the
bone marrow.
 Contnd…


v Anorexia
v Cough
v Headache
v Malaise
v Muscle aches
v Splenomegaly
v Tender hepatomegaly


These clinical features occur in “mild” malaria.



However, the infection requires urgent diagnosis

and management to prevent progression to
severe disease.
•
Hepatosplenomegaly
 Severe and complicated malaria
Although severe malaria is both
preventable and treatable, it is
frequently a fatal disease.

0.5 -2% of the total P.f malaria develop

complications and of which 50% are
fatal

The following are 8 important severe

manifestations of malaria
•
1.Severe malaria anaemia
2.Cerebral malaria
3.Hypoglycaemia
4.Metabolic acidosis
5.Acute renal failure
6.Pulmonary oedema
7.Circulatory collapse, shock or “algid malaria”
8.Blackwater fever


 Note: It is common for an individual

patient to have more than one
severe manifestation of malaria!

Anaemia in malaria-
Severe anaemia(haematocirt < 15%
or haemoglobin < 5 g/dl).
Ø It is severe in P.f infections as it
attacks 20-35% of total RBCs
whereas only 1% is affected in
other plasmodia
Causes

ü Haemolysis of infected RBCs

ü Haemolysis of uninfected RBCs
ü Dyserythropoiesis (Bone marrow)
ü Splenomegaly-erythrocyte
sequestration
ü Depletion of folate stores
Ø
Immediate blood transfusion is
 Cerebral malaria
• The most well-known severe
manifestation of malaria.
Responsible for 80% of the total
malaria deaths.
• Defined as:
– unarousable coma persisting
for more than one hour
– with asexual forms of P.
falciparum in the peripheral
blood
– other common causes of
encephalopathy excluded
(WHO1999)
Common in P.f infections where the
erythrocytic schizogony takes place
in the smaller capillaries of the
internal organs
Results in the blockage of capillaries
by parasitized RBCs.
• reduced cerebral blood flow
A young girl with cerebral malaria. Note the abnormal,
decerebrate posturing

Occurs most commonly in young children although non-

immune adults are also at risk.
Cerebral malaria can rapidly progress to death, even with
appropriate treatment. Case fatality is between 20-50%.

The illness may start with drowsiness and

confusion and then progress to coma.
The loss of consciousness is often preceded by
repeated convulsions.
Retinal haemorrhages may be seen on
fundoscopy.
In survivors, resolution of coma usually occurs
within 1-2 days in children and within 2-4 days in
adults but may be complicated by neurological
sequelae in ~5% adults and >10% of children.

A 4 year old boy who was



deeply comatose and

had persistent deviation
 3. Hypoglycaemia

Blood sugar <2.5 mmol/L (i.e.,<40 mg/dl).



•
• Increases the risk of mortality and sequelae in
children with cerebral malaria; may present
with convulsions or a deterioration in level of
consciousness.
• Results from a combination of factors:
– reduced glycogen stores because of
reduced food intake
– increased metabolism due to fever and
repeated convulsions
– glucose consumption by malaria parasites
– cytokine or quinine-stimulated
 4. Metabolic acidosis
• Lactic acidosis is a major contributor and
probably results from tissue anoxia and
anaerobic glycolysis
Presents with deep, rapid respirations (as in

diabetic ketoacidosis)
Acidaemia (arterial pH < 7.25) or Acidosis

 (plasma bicarbonate < 15 mmol/1).

•
 Lactic acidosis results from :
Anaerobic glycolysis due to microvascular obstruction.
Failure of hepatic and renal lactate clearance.
Production of lactate by the parasite.
Lactate levels rise after generalized convulsions.
 5. Acute renal failure

• Occurs almost exclusively in adults and older children

in areas of unstable malaria
• The kidneys are often slightly swollen. Tubular
abnormalities consistent with acute tubular
necrosis (ATN) are seen.
• Sequestration in glomerular capillaries,mesangial
endothelial cell proliferation, and immunoglobulin
deposits may be seen.
• Cortical necrosis never occurs.
• Affected patients are usually oliguric (urinary output
<400 ml/day) or anuric (<50 ml/day)
• Renal failure may be associated with haemoglobinuria (Black water
fever).
• Serum creatinine levels are elevated >3 mg/dl
 Nephro Hyperparasitaemia>5% of
sis RBCs are affected-P.falciparum

P. Malariae
quarten nephrosis
 6. Acute pulmonary oedema
This is a grave and usually
fatal manifestation of severe
falciparum malaria and
occurs mainly in adults.
Hyperparasitaemia (>5% of
RBCs are parasitized), renal
failure and pregnancy are
recognised predisposing
factors and the condition is
commonly associated with
hypoglycaemia and
metabolic acidosis.
 7. Circulatory collapse, shock,
“algid malaria”
Systolic BP < 50 mmHg in children and < 80 mmHg in
adults defines hypotension/shock.
Patient with severe malaria can develop sudden
hypotension & become shocked. This is “Algid
Malaria”.
Features of circulatory collapse-
cold/clammy skin, weak/ thready pulses,
hypotension, peripheral cyanosis, peripheral
vasoconstriction, and rapid feeble pulse with core/skin
temperature difference of ≥ 10° C.
“Algid malaria” is characterised by
hypotension, vomiting, diarrhoea, rapid
respiration and oliguria. This condition is
associated with a poor prognosis.
 8. Haemoglobinuria or
“Blackwater Fever”
Characterized by rapid, severe, massive
intravascular haemolysis.
It is associated with infection by P.f, most
commonly seen in a non-immune person
who has resided in the endemic country
for the last 6 months to 1 year and
inadequately treated by quinine.
In these cases, quinine is a precipitating
factor.
It is triggered by exposure to cold, sun,
fatigue, trauma, pregnancy, X-rays etc,.
The condition presents with severe pallor,
A 3 year old boy with
severe anaemia (Hb%
3.3 g/dl) and dark
urine (shown in the
container)

Typical dark urine of

Haemoglobinuria on Day 0 and
cleared by Day3
 in the clinical features of severe Summary
of differences malaria in adults and children
Frequency of
occurrence

Clinical Manifestation Children Adults

Similar in adults and children
Prostration +++ +++
Circulatory collapse + +

More common in children

Cerebral malaria +++ ++
Severe anaemia +++ +
Multiple convulsions +++ +
Metabolic acidosis +++ +
Hypoglycaemia ++ +/-

More common in adults

Jaundice + +++
Pulmonary oedema +/- ++
Haemoglobinuria +/- +
Abnormal bleeding +/- +
Renal failure +/- +
 Diagnosis
Ø Malaria is a multisystem disease.
Ø It presents with a wide variety of non-
specific clinical features.
Ø None of the clinical features are
pathognomonic.
Ø Many patients have fever, general aches
and pains and malaise and are initially
misdiagnosed as having “flu”.
Ø P. falciparum malaria can be rapidly
progressive and fatal.
 Diagnosis
• A good history
– Residence or a recent visit (in the preceding 3
months) to a malaria endemic area
– History of fever
– Recognise significance of non-specific clinical
features such as vomiting, diarrhoea, headache,
malaise
• Physical examination
– Identify signs consistent with malaria: fever,
pallor, jaundice, Splenomegaly
– Exclude other possible causes of fever (e.g. signs
of viral and bacterial infections)


 The diagnosis of malaria should be

considered in any unwell person who
has been in a malarious area
recently
 Thick and thin blood films (or “smears”)
have remained the gold standard for the
diagnosis of malaria. The films are stained
and examined by microscopy.
v Thick blood film - v Thin blood film –
Used for detecting Gives more
malaria: a larger information about
volume of blood is the parasite
examined allowing morphology and,
detection of even low therefore, is used to
levels of parasitaemia. identify the
Also used for particular infecting
determining parasite species of
density and monitoring Plasmodium.
the response to
treatment.
•
•
 Appearance of P. falciparum in thin blood
films. Ring forms or trophozoites; many red cells
infected – some with more than one parasite
 Other methods of diagnosis of malaria
These are not routinely used in clinical


practice.
a)Antigen capture kits. Uses a dipstick and a
finger prick blood sample. Rapid test - results are
available in 10-15 minutes. Expensive and
sensitivity drops with decreasing parasitaemia.
b)
c)PCR based techniques. Detects DNA or
mRNA sequences specific to Plasmodium.
Sensitivity and specificity high but test is
expensive, takes several hours and requires
technical expertise.
d)
 c) Fluorescent techniques- Relatively low
specificity and sensitivity. Cannot identify the parasite
species. Expensive and requires skilled personnel.

The treatment of


malaria depends on a Treatment

number of factors
1.Severity of the infection:
whether simple,
uncomplicated or severe,
complicated malaria.
2.Parasite factors: species,
drug sensitivity
3.Patient factors: age,
pregnancy, prior
chemoprophylaxis, known
allergies, likelihood of
 Drugs under NVBDCP- Malaria drug
policy 2010
1. Chloroquine
2. Primaquine
3. ACT- Artesunte +Sulphadoxine /Sulfalene + Pyrimethamine
4. Quinine
5. Doxycycline
6. Artesunate
7. Artemether
8. Arteether
 Treatment of uncomplicated
malaria
Presumptive treatment: It is given to


1. All fever cases with H/O fever during past 15 days

2. All fever cases irrespective of age and sex
3. No Primaquine to infants and pregnant women.
4. Each Chloroquine tab available as 150 mg and Primaquine
tab as 2.5 mg & 7.5 mg.
Radical Treatment:


1. Given after microscopic confirmation

2. No Primaquine to infants and pregnant women.
3. Each Chloroquine tab available as 150 mg and Primaquine
tab as 2.5 mg & 7.5 mg.
4.
 PRESUMPTIVE YREATMENT – All fever cases
are given tabs even before microscopic confirmation.(No
more recommended under MDP-2010-NVBDCP)
No Primaquine to infants and pregnant women. Each
Chloroquine tab available as 150 mg and Primaquine tab
as 2.5 mg
Age LRA HRA
(Yr)
Chloroquine( Chloroquine(mg) Primaquine
mg) (mg)

Base in mg. Day 1 Day 2 Day 3 Day 1

0-1 75 75 75 37.5 -
1-4 150 150 150 75 7.5
4-8 300 300 300 150 15
8-14 450 450 450 225 30
>14 600 600 600 300 45
 RADICAL TREATMENT- After microscopic
confirmation
No Primaquine to infants and pregnant women. Each
Chloroquine tab available as 150 mg and Primaquine
tab as 2.5 mg
Age (Yr) P.vivax P.falciparum
Chloroqui Primaquin Chloroquine(mg) Primaquin
ne e e
(mg) (mg) (mg)
14 days Day1 Day2 Day3

0-1 75 - 75 75 37.5 -
1-4 150 2.5 150 150 75 7.5
4-8 300 5 300 300 150 15
8-14 450 10 450 450 225 30
>14 600 15 600 600 300 45
Site of Action

Primaquine

Chloroquine
Quinine, SP
Artemisinin

Quinine &
Chloroquine in P.V.
and Primaquine in
P.F.
Drug Drugs
Class
Blood Chloroquine, Quinine, Quinidine, Mefloquine, Halofantrine,
Schizon Sulfonamides, Tetracyclines, Atovaquone, Artemisinin
tocidal compounds

Tissue Primaquine, Proguanil, Pyrimethamine,

Schizon
tocidal

Gametoc Primaquine
idal

Hypnozo Primaquine
itocida
l

109
Drug Sporozoites Primary Asexual Gametocyte Hypnozoite
tissue phase parasite

Quinine NA NA A A-P.v NA

Chloroquine NA NA A A-P.v NA

Primaquine A A A A A
in toxic dose
SP Less A Little A on Incomplete NA NA
P.f
Mefloquine NA NA A NA NA

NA-not active, A-active,

-236 PHCs in 19 states are identified as Chloroquine resistant.
 Avoid these combinations
• Most antimalarial drugs have a long plasma half-life.
Therefore, adding similar drugs half way through the
treatment will only add to the adverse effects and not
to the therapeutic benefit. The following
combinations should therefore be avoided,
concurrently or within
(1) Chloroquine + Quininea short interval:

(2) Chloroquine + Mefloquine


(3) Quinine + Mefloquine


 (4) Quinine + Primaquine

 (5) Quinine + Halofantrine

(6) Mefloquine + Primaquine


Both sulpha and primaquine can precipitate hemolytic



crisis in patients with Glucose 6-phosphate

dehydrogenase deficiency.
• National drug Policy on
Malaria-2010-NVBDCP
 National drug Policy on Malaria-
2010-NVBDCP
1)Treatment of P.v infections- As discussed
earlier
2)Treatment of uncomplicated P.f. cases.
 a) Artemesinin based Combination
Therapy-ACT
 Artesunate 4mg/kgBW daily for 3
days
 + sulfadoxine(25mg/kgBW)-
Pyrimethamine (1.25mg/kgBW) on 1st
day
st
 Age-wise dosage for treatment of P.f cases

3) Treatment of uncomplicated P.f cases in pregnancy:

1st trimester-Quinine salt 10mg/kgBW to be given 3 times daily for 7 days
II and III trimester: ACT as per dosage above
4)Treatment of mixed infections: All mixed


infections should be treated with full course of ACT

and Primaquine 0.25mg/kgBW daily for 14 days
5) Treatment of severe malaria cases:
 a) Artesunate: 2.4mg/kgBW IV or IM given
on admission, then at 12 hour and 24 hour
and then once daily. OR
 b) Artemether: 3.2mg/kgBW IM given on
admission and then 1.6mg/kgBW per day.
OR
 c) Arteether: 150mg/kgBw IM daily for 3
daysin adults only (not to be given in
children) OR
 d) Quinine: 20mg/kgBW on admission (IV
 Mass drug administration
• Recommended in API>5 per 1000 popn (WHO)
• Not for under 5 children
 Chemoprophylaxis
- Use of anti-malarial drugs to prevent the
development of malaria is known as
chemoprophylaxis.
- Unreliable with development of drug resistance
- Started 1 week before arrival in the malarious
area and continued for atleast 4 weeks,
preferably 6 weeks after leaving a HRA.
- Should be complemented by personal
protection and other VCMs
 Chemoprophylaxis


- Recommended for
1.Travellers from non endemic areas
2.As a short measure for soldiers,
police and labours serving in highly
endemic areas
3.All ANCs in HRAs- initiated in II
semester
•
 MALARIA TREATMENT COST OF

AN ADULT IN INDIA
Drugs Cost (Rs.)
Chloroquine 3.50-10.00
Chloroquine injection + fluids 200.00
Sulfadoxine Pyrimethamine 7.00-30.00
Mefloquine 240.00-300.00
Artemether injections 390.00-1000.00
Arteether injections 275.00
Artesunate injections 1120.00
Quinine tables + Tetracycline 270.00-210.00
Quinine injections+IV fluid+Tetracycline 800-910
*Antipyretics @ Rs. 5.00-10.00 per treatment
I/V fluid may be required during Artemisinin treatment
 HIV,Pregnant women and their
fetus/newborn
• HIV does make malaria in pregnancy
worse
– More and higher density malaria, more
illness, more anemia, more low birth
weight
• Malaria may make HIV worse
– Higher HIV viral load
– ? impact on Mother-to-Child Transmission
(MTCT)
 The Worlds Priorities? Annual Expenditure
Global Reduction in Malaria $ 1 billion
Basic education for all $ 6 billion
Cosmetics in the US $ 8 billion
Safe water and sanitation $ 9 billion
Ice cream in Europe $ 11 billion
Reproductive health for all women $ 12 billion
Perfumes in Europe and the US $ 12 billion
Basic health and nutrition $ 13 billion
Pet food in Europe and the US $ 17 billion
Business entertainment in Japan $ 35 billion
Cigarettes in Europe $ 50 billion
Alcoholic drinks in Europe $ 105 billion
Narcotic drugs in the world $ 400 billion
Military spending in the world $ 780 billion

Source-Favaloro et al Circulation 1999

Prevention and Control of
Malaria
 Malaria vaccine
A burning issue
Several vaccine candidates are now
being tested in Africa, Asia and USA.
Vaccines such as SPf66, RTs, S/AS02
developed by some countries failed to
show required efficacy.
Unlike other vaccines, a malaria vaccine
even with only 50% efficacy would still
be a very useful in controlling the
disease.
An effective vaccine is thought to be at
least 10 years away (Park’s TB of PSM,20th edition)
 Developing any vaccine is hard

Laboratory Pre-clinical
Phase 1a, 2a

Phase 1b
Phase 2b
Phase 3

Can take 10-20 years to develop a product and

cost hundreds of millions of dollars.
Integrated Vector Control Management: Appropriate
combination of one or more methods

Environmental
management

AL
I V C or
IC
OG
OL
BI

IDVC

IEC, community
CHEMICAL
participation,
Intersectoral
cooperation ,etc
 Integrated vector control
programme
vOne of the main strategy is to reduce the
man-mosquito contact.
vThere are many methods to curb the
mosquito nuisance
vNo single method of control is likely to
provide a solution in all situations.
vIntegrated approach is the present trend
to obtain maximum results with the
minimum effort and to avoid the
excessive use of any one method,
implement in an effective manner
simultaneously.
 Mosquito control measures
vVarious methods are classified as bellow
v
v

I.Anti-larval methods
II.Anti-adult measures
III.Protection against
mosquito bites




I. Anti-larval
methods
 i) Environmental control
 ii) Chemical control
 III) Biological control
 i) Environmental control
• Source reduction - elimination of
breeding sites by minor
engineering methods- yield
permanent results
a.Filling and levelling-the filling of
depressions holding water and the
levelling of ground
b.Drainage -Designed to remove and
dispose off excess or unwanted
water.

 Contd…
 If anopheles are a problem
• filling and drainage
 If Mansonia are a problem
• Removal of aquatic plants to which
larvae attach themselves
•
•
 Contnd…
 If Culex are a problem
• Abolish domestic and peri domestic
sources such as cesspools and open
ditches
• Adequate collection, removal and disposal
of sewage and waste water
 If Aedes are a problem
• Remove the water holding containers such
as discarded tins, empty pots, broken
bottles, coconut shells and similar other
artificial collections of water
•
 ii) Chemical control
 The commonly used larvicides are
§ Mineral oils
§ Paris green and
§ Synthetic insecticides

 Dosage
Larvicide Dosage

Temephos (Abate) 50-100 gm/ha

Fenthion (Baytex) 25-100 gm/ha

Chloropyrifos 10-15gm/ha
 Use and limitations
• Useful in control of urban mosquitoes
& in the presence of other
refractory situations .
• Important limitations :
Ø Larvae not killed develop into adult
mosquitoes.
Ø Repeated every 7 to 10 days
Ø Thorough knowledge about the
habitats and ecology of the target
species.
Ø Environmental contamination.
 III. Biological control
• Control of mosquito breeding by
application of biological control systems.
• An innovative approach to the problem of
mosquitoes and the diseases they
transmit.
• Cost effective, non-polluting, resistance
does not develop.
• Mosquitoes can be controlled by
employing their natural enemies viz.,
fishes, bugs, nematodes, bacteria and
fungi.
A female western
mosquitofish, Gambusia
affinis

Guppy fish

The guppy (Poecilia reticulata), also

known as the millionfish, one of the most
popular freshwater aquarium fish species
in the world.
 Contnd…

For maximum efficacy:
s Remove predacious fishes .
s Clean water of all vegetation.
s Shore line should be of clear grass
s Fishes should not be released in extremely
shallow water.
s Tie nylon or brass mesh at the submerged end of
inlet or outlet pipes.
 Biocides
• Bacillus sphaericus & Bacillus
thuringiensis
• Used only under special situations.
• Used to kill mosquito larvae.
• Breeding places:selective water
bodies in domestic and peri-
domestic areas.
• Should not be used for larval control
in potable water.
 II. Anti-adult measures
vVarious methods are classified as bellow
v
i. Indoor Residual sprays
ii.Space sprays-Fogging
iii.Environmental sanitation
iv.Genetic control


Daily mortality of 15 to 35% may be sufficient to cause

an interruption of transmission.
Imagiciding has gradually replaced larviciding.

i.
 Insecticidal dosage for IRS
Insecticide preparation Per sq. Rounds/ Area to be
mtr yr covered

DDT 50% 1 Kg/10ltr 1 gm 2 500sq.mtr

Malathion 2 Kg/10ltr 2gm 3 250sq.mtr

25%

Cyfluthrin 125 gm/10ltr 25mg 2 500sq.mtr

10%
III. Protection against mosquito
bites
vVarious methods are classified as bellow
v
i. Mosquito nets (Insecticide Treated bed
Nets-ITNs) are distributed in high risk
area
ii.Screening
iii.Repellents



 In and out door fogging

Portable fogging machines to combat mosquitoes

Different types of foggers

 Insecticide Resistance by
vectors
Defined (WHO) as “the development of an ability in
strain of insects to tolerate doses of toxicants”
This is considered as one of the main obstacles
to using insecticides which would prove lethal to the
majority of individual in normal population of the same
species”for vector control.
This is due to biochemical and genetic factors.
 III. Prersonal protection
1) Mosquito net
Ø Offers protection
during sleep.
Ø Material should be
white to allow easy
detection of
mosquitoes
Ø Top as well as sides of
the net should be of
netting
Ø Best pattern is
rectangular net
Ø Size of the hole should
not exceed 0.0475
inch in any diameter
Ø No. of holes in one
square inch is
Ø Screening of building
with copper or bronze 2)Screeni
gauge having 16 ng
meshes to the inch is
recommended
Ø Costly but gives
excellent results
Ø Hole should not exceed
0.0475 inch in any
diameter
•
 3) Repellents
• For application over the skin
• Diethyl tolbutamine (Deet) is used
• Found to be effective against C.fatigans
for 18-20 hours.
•
Biological Control for Adults
 Biological Control for Larvae
Predacaeous diving beetle

Dragonfly &
Damselfly larvae
Backswimmers

Water Striders
Thank you
Any ????