Malaria advocacy

ADVOCACY ON MALARIA
General Purpose and inclusive of all
important subject areas

BY

DR. G. C. SAHU
REGIONAL DIRECTOR (I/C)
R O H & F W
(G o I)
AHMEDABAD

Dr. G. C. Sahu/ ROH&FW/
10/2/2010 A'bad/gcsahu61@gmail.com 1

IN THIS PRESENTATION………..
CAUSE OF MALARIA
CAUSE OF MALARIA

SIGNS AND SYMPTOMS
SIGNS AND SYMPTOMS

HUMAN MAL.PARASITES-TYPES
HUMAN MAL.PARASITES-TYPES

EPIDEMIOLOGICAL ASPECTS.
EPIDEMIOLOGICAL ASPECTS.

LIFE CYCLE IN MAN & THE VECTOR
LIFE CYCLE IN MAN & THE VECTOR

SOME HIGHLIGHTS OF ANTI MALARIAL DRUGS.
SOME HIGHLIGHTS OF ANTI MALARIAL DRUGS.

PARASITES AND VECTORS-DIFFICULT AREAS
PARASITES AND VECTORS-DIFFICULT AREAS

A PICTORIAL SOJOURN THROUGH MALARIA
A PICTORIAL SOJOURN THROUGH MALARIA
PARASITES,VECTOR MOSQUITOS, DRUG
PARASITES,VECTOR MOSQUITOS, DRUG
RESISTANCE ETC.
RESISTANCE ETC.

CONTROL ASPECTS.
CONTROL ASPECTS.

VACCINS, OTHER NEW DEVELOPMENTS ETC.
VACCINS, OTHER NEW DEVELOPMENTS ETC.


MALARIA!!
AN ENVIRONMENTAL ISSUE ??

IN A WAY YES !! ….
ALL DISEASES ARE CAUSED BY CONTINUOUS INTERACTION
BETWEEN A PERSON AND THE ENVIRONMENT [Macro + Micro]

THIS IS MORE RELAVENT IN MALARIA WHERE THREE LIVING
SYSTEMS “MAN, MALARIA PARASITE AND MOSQUITO VECTOR”
HAVING INTIMATE RELATIONSHIP WITH THE ENVIRONMENT
INTIMATELY INTERACT WITH EACH OTHER.

THEREFORE THE PREVALENCE, PERIODICITY AND INTENSITY OF
MALARIA IN THE COMMUNITY DEPENDS ON HOW THE
ENVIRONMENTAL FACTORS INFLUENCES THE PARASITE,THE
MOSQUITO VECTOR AND THE MAN .


Estimated global annual cost(in 1995)
for malaria: US $ 2 billion which includes
direct indirect and loss of labour.

Estimated worldwide expenditure on
malaria research is only US $ 58 which is
one thousandth of the US $ 56 billion spent
globally on health research annualy.
annualy.

Estimated annual cost on prevention
and treatment US $ 84 million only.

Malaria kills in one year what AIDS
killed in 15 years. In 15 years, if 5 million
have died of AIDS 50 million have died of
malaria. That is to say, one HIV/AIDS
death is equal to about 50 malaria deaths.

Malaria accounts for 2.6 percent of
the total disease burden of the world.
And currently being reported from 100
countries around the world.

It is responsible for the loss of more
than 35 million Disability-Adjusted-
Life-years(DALY) each year.

Basing on the current trend, WHO
forecasts a 16 % growth in malaria
cases annually. ! ! !


♥WHAT IS MALARIA? THE CAUSES:
MALARIA IS CAUSED BY THE TINY
PARASITE WHICH DWELLS INSIDE THE
RBC OF A PERSON
THERE EACH PARASITE DEVELOPS
AND PRODUCES 12 TO 24 DAUGHTER
PARASITES .
ON EVERY ALTERNATE DAY, NEW
BROODS OF PARASITES INVADE FRESH
RBCs AFTER DESTROYING THE OLD
ONES …….

Ψ SIGNS AND SYMPOTMS

PATIENTS GET CHILL OR SHIVERING FOR ½ TO 2
HOURS FOLLOWED BY HIGH FEVER FOR 8 TO 12
HOURS .
THE FEVER MAY BE ON ALTERNATE DAYS OR
SOMETIMES DAILY .
PATIENTS COMPLAINS OF HEAD ACHE, BODY ACHE,
VOMITING FEVER GOES DOWN WITH PROFUSE
SWEATING
UNTREATED CASES MAY HAVE SPLEEN
ENLARGEMENT, ANAEMIA, AND WEAKNESS .
IF MALARIA PARASITE AFFECTS BRAIN, IT CAUSES
CEREBRAL MALARIA WHICH MAY LEAD TO
UNCONSCIOUSNESS FOLLOWED BY DEATH,
ESPECIALLY IN CHILDREN AND PREGNANT WOMEN .
IN CHILDREN AND PREGNANT WOMEN .


MALARIA PARASITES
IN INDIA, IN ORDER OF PREVALENCE THE
FOLLOWING S ARE FOUND .
PLASMODIUM VIVAX .
PLASMODIUM FALCIPARUM .
PLASMODIUM MALARIAE .
AND….
⌦ AROUND 60% OF TOTAL INFECTION
REPORTED IN INDIA ARE CAUSED BY P.
VIVAX AND AROUND 40 % ARE DUE TO P.
FALCIPARUM. P. MALARIAE IS NOT A
PUBLIC HEALTH PROBLEM IN INDIA.
P. FALCIPARUM IS RESPONSIBLE FOR THE
DREADED AND FATAL CEREBRAL MALARIA .

Geographical Distributions
P.vivax
Widespread in tropical and subtropical areas
Widespread in tropical and subtropical areas
range extends into temperate areas
range extends into temperate areas
relatively uncommon in Africa
relatively uncommon in Africa
P.falciparum

Widespread, but primarily in tropics and subtropics
Widespread, but primarily in tropics and subtropics

P.Malaria

Broad, but spotty geographical distribution
Broad, but spotty geographical distribution

P.ovale
Primarily tropical Africa, especially western
Primarily tropical Africa, especially western
coast
coast


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THE GENUS PLASMODIUM—THE MALARIA PARASITE
φ THE GENUS OF PARASITE: PROTOZOA
φ THE PHYLLUM: AN APICAL COMPLEX [AN INTRACELLULAR
PRESENCE OF
APICOMPLEXA: DISTINGUISHED BY THE
APPARATUS, USED IN THE INVASION OF THE HOST CELL]
SOME OF THE IMPORTANT CHARECTERSTICS ARE AS
FOLLOWS:
φ IN THE LIFE CYCLE, ONE SEXUAL PHASE IS FOLLOWED BY
THREE PHASES OF ASEXUAL MULTIPLICATION.
φ THE ONLY SEXUAL PHASE AND FIRST ASEXUAL PHASE
OCCUR IN THE ANOPHELES MOSQUITO.
φ THE SECOND AND THIRD ASEXUAL PHASE OCCUR IN A
VERTEBRATE SPECIES. THE SECOND IN THE LIVER, THE THIRD
IN THE BLOOD (RBC).


♣NATURALLYPHASE, IF ALLOWEDMANY
THE THIRD
MAY BE REPEATED
TIMES.

♣ERYTHROCYTESARETHE VERTEBRATE
GAMETOCYTES
OF
PRODUCED IN THE
HOST AND MATURE INTO MALE AND
FEMALE SEX CELLS (GAMETS) IN THE
STOMACH OF A VECTOR MOSQUITO
WHICH HAS FED ON THE HOST.

♣MALARIA THE PROCESS A SPECIFIC THE
DURING
PIGMENT IS PRODUCED IN
SOME STAGES OF THE PARASITE. THIS
PIGMENT (HAEMOZOINE) IS PRODUCED
DURING THE DIGESTION OF
HAEMOGLOBIN BY THE PARASITE


LIFE CYCLE OF MALARIA PARASITE AS IT PROCEEDS IN HUMAN & VECTOR
MOSQUITO

Life Cycle
Of Pf

LIFE CYCLE OF MAL.PARASITE—PF.
MAL.PARASITE—
Dr.G.C.Sahu/ROH&FW/GoI/A'bad 28
LIFE CYCLE OF MAL.PARASITE—P.VIVAX
MAL.PARASITE—


¥ LIFE CYCLE OF MALARIA PARASITE
THE LIFE CYCLE REQUIRES
TWO PHASES NAMELY ‘ASEXUAL
AND SEXUAL'
AND ………
TWO HOSTS FOR ITS
COMPLETION NAMELY ‘FEMALE
ANOPHELINE MOSQUITOS AND
HUMAN BEINGS’


SEXUAL CYCLE OCCURES IN AN.
MOSQUITO AND ASEXUAL CYCLE OCCURES
IN HUMAN BEINGS

☯ IN NATURE MAN GETS MALARIA“AFTER RECEIVING THE WITH
INFECTIVE STAGES OF PARASITE “SPOROZOITE” ALONG
SPOROZOITE”
THE SALIVA INJECTED BY AN INFECTIVE FEMALE ANOPHELINE
MOSQUITO

☯ SPOROZOITE INVADE LIVER ,, GROWS UPTO SCHIZONTS
GROWS UPTO SCHIZONTS
RELEASUNG MEROZOITES WHICH ATTACKS RBC AT
REPEATATEDLY REGULAR INTERVALS , CAUSING ALL THE
SIGNS AND SYMPTOMS, AND EVENTUALLY GIVING RISE TO
GAMETOCYTES STAGES WHICH ARE PICKED UP BY VECTOR
MOSQUITOS FOR TRANSFER TO NEXT PERSON

☯ THUS GAMETOCYTES ARE RESPONSIBLE FOR SPREAD OF
MALARIA .
CONTD…….
CONTD…….


THE FEMALE ANOPHELINE MOSQUITO IS DRIVEN BY AN URGE
TO OBTAIN A BLOOD MEAL FOR MATURATION OF HER EGGS,
WHICH THE VECTOR MOSQUITO OBTAINS BY BITING A WARM
BLOODED ANIMAL .IN CASE IT BITES AN INFECTED PERSON
HAVING GAMETOCYTES, THEY ENTER THE STOMACH OF THE
MOSQUITO AND DEVELOP FURTHER TO START THE SEXUAL
CYCLE .

IN MOSQUITO BODY BOTH MALE AND FEMALE
GAMETOCYTES AFTER GOING THROUGH A SEXUAL AND AN
ASEXUAL PHASE GIVE RISE TO “SPOROZOITES” THAT FIND
THEIR WAY TO MOSQUITO SALIVARY GLANDS TO RENDER IT
INFECTIVE.IN HER NEXT BITE VECTOR MOSQUITO TRANSFERS
THE SPOROZOITES THE HEALTHY PERSON TO CONTINUE THE
CYCLE .

☺ BUT THE MOSQUITOES NEVER SUFFER FROM MALARIA ! ! !


Human dynamics
Age
Pregnancy
Immunity
Haemoglobinopathies
Asymptomatic malaria case load.
Type of housing
Cultural factors like clothing
Sleeping habits
Occupation
Migration

Disease transmission dynamics

• Human

• Parasites

• Vector

• Environment

Parasite dynamics

Predominant P. vivax: > 60%

Rapidly increasing P. falciparum: < 40%


Factors related to Gametocytes
Density and viability in the circulation:
Higher in primary attack
Appear simultaneously with other
stages in P. vivax [viable for 2- 4 days]
2-
P. falciparum appear 7- 8 days later or
7-
more [viable for a longer period]
Higher density in P. falciparum as
compared to P. vivax at the same level
of asexual parasitemia.


Vector dynamics
Greater the frequency of man vector
contact higher will be the transmission
potential of the area. This contact is
influenced by
Vector density
Flight range
Feeding habit (Frequency of blood meal)
Biting habit (Anthropophilic/ Zoophilic)
(Anthropophilic/ Zoophilic)
Resting habit (Indoor-outdoor)
(Indoor-outdoor)
Biting time

TEMPERATURE
TEMPERATURE AFFECTS THE TRANSMISSION OF MALARIA
TEMPERATURE AFFECTS THE TRANSMISSION OF MALARIA
PRINCIPALLY ON ITS IMPACT ON SPOROGONY CYCLE OF MP
PRINCIPALLY ON ITS IMPACT ON SPOROGONY CYCLE OF MP
IN VECTOR MOSQUITO.
IN VECTOR MOSQUITO.

THE IDEAL TEMPERATURE RANGE IS 20 DEGREE CENT TO
THE IDEAL TEMPERATURE RANGE IS 20 DEGREE CENT TO
33 DEGREE CENT.BETWEEN THE LIMITS THE SPEED OF
33 DEGREE CENT.BETWEEN THE LIMITS THE SPEED OF
SPOROGONY IS THE FUNCTION OF TEMPERATURE i.e THE
SPOROGONY IS THE FUNCTION OF TEMPERATURE i.e THE
HIGHERTHE TEMPERATURE FASTER THE DEVELOPMENT OF
HIGHERTHE TEMPERATURE FASTER THE DEVELOPMENT OF
SPOROZOITES.
SPOROZOITES.

TEMPERATURE BELOW 20 DEGREE C INDEFINITELY DELAY
TEMPERATURE BELOW 20 DEGREE C INDEFINITELY DELAY
THE COMLETION OF SPOROGONY CYCLE AND ABOVE 33
THE COMLETION OF SPOROGONY CYCLE AND ABOVE 33
DEGREE C IS LETHAL TO MOSQUITO.
DEGREE C IS LETHAL TO MOSQUITO.

TEMPERATURE HAS ALSO A BEARING ON THE LARVAL
TEMPERATURE HAS ALSO A BEARING ON THE LARVAL
DEVELOPMENT IN WATER.THE OPTIMAL DEVELOPMENTAL
DEVELOPMENT IN WATER.THE OPTIMAL DEVELOPMENTAL
WATER TEMPERATURE FOR AQUATIC STAGE IS ABOUT 31
WATER TEMPERATURE FOR AQUATIC STAGE IS ABOUT 31
DEGREE CENTIGRADE.
DEGREE CENTIGRADE.


RELATIVE HUMIDITY.
IT IS THE DRYING POWER OF THE ATMOSPHERE
WHICH IS IMPORTANT WHICH IS EXPRESSED AS
THE NUMBER OF GRAMMES OF WATER ADDED TO
CUBIC METERS OF AIR,TEMPERATUREREMAINING
NORMAL.

THE RELATIVE HUMIDITY REQURED FOR
TRANSMISSION IS AROUND 60 to 65.

RELATIVE HUMIDITY INFLUENCES THE BITING
HABIT OF THE MOSQUITO AND AT RELATIVE
HUMIDITY LESS THAN 50 BITING DOES NOT
OCCUR.


RAINFALL.

RAINFALL AFFECTS LARVAE AND THEIR
BREEDING PLACES.
TORRENTIAL RAINS MAY FLUSH OUT EXISTING
BREEDING SITES RENDERING A POSITIVE
IMPACTAND SLOW RAIN MAY ADD TO THE
BREEDING SITES.
IT ALSO INFLUENCES THE RELATIVE HUMIDITY.
DEGREE OF WETNESS i.e THE NUMBER OF RAINY
DAYS IS MORE IMPORTANT THAN THE AMOUNT
OF RAINS.


Classical Epidemiological Triad of Malaria

Environment

Agent Host


Classical Epidemiological Triad of Malaria-Variables

Environment*
(biophysical, psycho-social, etc.)

Agent Host
(diverse exposures, (animal, plant,
including non- ultimately human)
contagious )

*CLIMATE is an Environmental Influence


Classical Epidemiological Triad of Malaria-Interplay of factors

Environment

Agent Host


Complex interplay of factors……
Examples of other Infectious Diseases (malaria included)
Environment
longevity & infectivity nutrition
outside host
hygiene
host distribution, treatment
abundance, infection
housing
e.g. cholera e.g. TB, HIV/AIDS,
hantaviral disease diarrheal diseases,
hookworm acute respiratory
schistosomiasis infections

Agent Host
tissue tropisms, e.g. rabies,
pathogenicity, Lyme disease,
malaria,
immune response, cryptosporidiosi.
host specificity


Complex interactions of each factor with rest occur all the time...

Environment

Altered hygiene
Improved irrigation
Redesigned housing
Better nutrition

Agent Host



Environment
Agent transport to new areas
New antibiotics, pesticides

Labor actions affecting toxin exposure

Agent Host



Environment

Agent Host
Exposure probability, host immunity,
support networks, availability of supportive care


Environmental Determinants of Malaria
Social and Economic Policies
Institutions (including medical care)

Living Conditions
Social Relationships
Individual Risk Factors
Genetic/Constitutional
Factors

ent
Pathophysiologic
pathways m
on
nvir
Individual/Population c a lE
ysi
Health
Ph
Modified from Kaplan, 2002

Research Challenge – Analyze and understand interactions!

Social and Economic Policies
Institutions (including medical care)

Living Conditions
Social Relationships
Individual Risk Factors
Genetic/Constitutional
Factors
Pathophysiologic
pathways

Individual/Population a te?
Health
C lim

Malaria Paradigms
Irrigation malaria
Tribal-forest malaria
Urban malaria
Industrial/ Project malaria
Epidemic prone areas
Border malaria
Desert Malaria

Aims Of Treatment of a malaria case.

Aims Causation Therapy Drugs

To Symptoms are caused by Blood schizonticidal Chloroquine, quinine,
alleviate blood forms of the parasite drugs pyrimethamine/sulphadoxin
symptoms
, artemisinin

To Relapses are due to Tissue schizonticidal Primaquine
prevent hypnozoites of P. vivax/ P. drugs
relapses ovale

To Spread is through the Gametocytocidal drugs Primaquine
prevent gametocytes
spread

Thus, in effect, a blood schizonticidal drug and primaquine should be
Thus, in effect, a blood schizonticidal drug and primaquine should be
administered to ALL types of malaria.
administered to ALL types of malaria.

SITE OF ACTION
SITE OF ACTION
OF ANTI-MALARIALS
OF ANTI-
ANTI-MALARIALS
UNDER USE.
UNDER USE.


DRUG RESISTANCE-HYPOTHESIS
OF POSSIBLE WESTWARD SPREAD.


DRUG RESISTANCE—R I , R I I AND R I I I.


Treatment of P. vivax malaria: A flow chart
Chloroquine + Primaquine
After 48 hours

Clinical Recovery Status quo / worse
Continue the treatment Suspect P. falciparum, repeat M.P. test at 48
Repeat the M.P. test on hrs.
(A thin smear examination is better for species
the 6th day identification and for assessing parasite count)

NEGATIVE
POSITIVE POSITIVE NEGATIVE
Cured
Consider
other causes
P. Falciparum P. Vivax of fever, may
Treat as possibly If the patient has be in
typical malarial association
chloroquine resistant
complications, treat as with malaria
P. falciparum;
otherwise, wait.

Treatment of P. falciparum malaria - A flow chart
Complicated and
Uncomplicated and chloroquine
chloroquine sensitive
sensitive
Tab. Chloroquine + Primaquine Inj. Chloroquine +
Inj.
single dose Primaquine single dose

Status quo/ worse;
Better; parasite count reduced by
parasite count reduced
> 75%
by < 75%

Continue Consider resistance


Drugs for chloroquine resistant malaria
Complicated
and
Uncomplicated and
Chloroquine
Chloroquine resistant
resistant
1. Inj.Quinine +
Use any one of the following combinations: Pyrimethamine/Sulphadoxine
Pyrimethamine/Sulphadoxine
1. Tab.Quinine + Tab. Pyrimethamine/
+ Tab. Pyrimethamine/ 2. Inj. Quinine + Tetracycline
Inj.
Sulfa. // Doxycycline
Doxycycline
2. Tab. Quinine + Tetracycline //doxycycline
doxycycline 3. Inj. Artemether / Arteether
Inj.
3. Tab. Artesunate + Tab. Mefloquine // Artesunate + Mefloquine.
Artesunate + Mefloquine.
4.Tab.Mefloquine + Pyrimethamine/Sulpha.
Pyrimethamine/Sulpha.


Established antimalarial drugs
Drug Role Best features(s)
Best features(s) Limitation
Chloroquine TX of and CP against non-Pf
TX of and CP against non-Pf Very safe; low cost;
Very safe; low cost; Widespread R
Widespread R
and sensitive Pf parasites
and sensitive Pf parasites long half-life
long half-life

Quinine/quinidine
Quinine/quinidine Best TX for Pf malaria; low
Best TX for Pf malaria; low Limited R; rapidly
Limited R; rapidly Fairly toxic ((cinchonism,
Fairly toxic cinchonism,
cost
cost acting
acting cardiac)
cardiac)
Amodiaquine TX of R Pf malaria
TX of R Pf malaria Low cost
Low cost Toxicity (bone marrow,
Toxicity (bone marrow,
liver); R Common
liver); R Common
Mefloquine CP against R malaria; not
CP against R malaria; not Relatively little R,
Relatively little R, Moderately toxic (mostly
Moderately toxic (mostly
approved for TX in United
approved for TX in United though increasing;
though increasing; CNS); high cost; R in SE
CNS); high cost; R in SE
State
State long half-life
long half-life Asia
Asia
Fansidar TX of Pf malaria; no longer
TX of Pf malaria; no longer Relatively low cost;
Relatively low cost; Skin toxicity (can be fatal);
Skin toxicity (can be fatal);
recommended for CP
recommended for CP long half-life
long half-life increasing R
increasing R
Primaquine Eradication of chronic liver
Eradication of chronic liver Only drug for this
Only drug for this Hemolysis with G6Pd
Hemolysis with G6Pd
stage Pv,Po malaria
stage Pv,Po malaria indication
indication deficiency; increasing R
deficiency; increasing R
Progunil CP only (often with
CP only (often with Low cost; nontoxic
Low cost; nontoxic R common
R common
Chloroquine)
Chloroquine)
S-P Combinations
S-P Combinations CP only (often with
CP only (often with Low cost
Low cost R Common; skin rashes
R Common; skin rashes
Chloroquine)
Chloroquine)

Tetracycline Cp; TX of Pf malaria in
Cp; TX of Pf malaria in Low cost
Low cost Skin and gastrointestinal
Skin and gastrointestinal
Combination with quinine
Combination with quinine


New antimalarial drugs
Drug Role Best Feature(s) Limitations
Halofantriine TX of Pf malaria; not
TX of Pf malaria; not Usually effective against R
Usually effective against R Variable bioavailability,
Variable bioavailability,
approved for CP
approved for CP Pf malaria
Pf malaria cardiac toxicity
cardiac toxicity

Artemisinin and
Artemisinin and TX of Pf malaria
TX of Pf malaria Rapidly acting; effective
Rapidly acting; effective Recurrence after TX fairly
Recurrence after TX fairly
related compounds
related compounds against multidrug-R
against multidrug-R common
common

Atovaquone ? TX of Pf malaria?
? TX of Pf malaria? Limited toxicity
Limited toxicity Limited studies so far
Limited studies so far
CP (Probably in
CP (Probably in show frequent recurrence
show frequent recurrence
combination with
combination with after TX
after TX
proguanil
proguanil

Pyronaridine ? TX of malaria
? TX of malaria Effective against R strains
Effective against R strains Studies limited to date
Studies limited to date

Desferrioxamine ? TX of severe Pf
? TX of severe Pf Well tolerated when used
Well tolerated when used Studies limited to date
malaria
malaria for iron overload
for iron overload

Azithromycin ? CP
? CP Limited toxicity
Limited toxicity Studies limited to date


Compatibility of Anti-Malaria Drugs
Pregnan Breast Scuba
Epilepsy Psoriasis Altitude
cy Feeding Diving

OK OK NO NO OK OK
Chloroquine
OK OK OK OK OK OK
Paludrine
OK* OK OK OK OK OK
Maloprim
OK* NO NO OK NO NO
Mefloquine
NO NO OK OK OK OK
Doxycycline
NO NO OK OK OK OK
Malarone

* These drugs are not suitable during the first trimester of pregnancy.


Sign or Symptom Percent with
Finding
· Fever & Chills 96

· Headache
79
· Muscle Pain
60
· Palpable Liver
33
· Palpable Spleen
28
· Nausea & Vomiting
23
· Abdominal Cramps/Diarrhea 6


Some Laboratory Findings………..
Percent with
Finding Normal Range
Abnormal Findings
· Reticulocytosis 3 - 18% 42

· Thrombocytopenia 12K-150K 36
· Bilirubin Increased 1 - 1.8 33

· VDRL Positive (-) 28 (+)

· Anemia 5.8 - 12 (Hgb) 28

· Leukopenia 3,000 - 4,700 26

· Alk. Phos. Increased 11-27 17

· SGOT Increased 40 - 108 10


G-6 P D Deficiency-Four most common variants out of
300+ known

All World
GdB Normal Activity Populations

Normal Activity; Acetic acid substituted for Africa (most
GdA asparagine at position 126, Guanine for common
adenine at DNA position 376 variant)

8 - 20% Normal Activity; Methionine for Valine at
position 67 and Aspartic Acid for Asparagine at
GdA- position 126, Adenine for Guanine at position 202
Africa
and Guanine for Adenine at position 376

< 5% Normal Activity; Phenylalanine for Iran, Iraq, India,
GdMed Serine at position 188; Thymine for Cytosine Pakistan,
at position 563 Greece, Sardinia


Primaquine Treatment Regimens
Adult-1 tablet* per day x 14
days
G-6-PD NORMAL
* The Indian programme recommends
14 days RT regime to all P.vivax cases.

3 tablets per week for 8
G-6-PD deficiency weeks
(Mild African form)

2 tablets per week for 30
G-6-PD deficiency
weeks
(More severe Mediterranean
variety)

* Primaquine – Not an absolute contraindication in G-6-PD deficient persons
* 1 tablet consists of 26.3 mg pimaquine phosphate, 15 mg primaquine base.


Malaria in Pregnancy : Double Trouble
Malaria is more common in pregnancy compared to the general
More common population. Immuno suppression and loss of acquired immunity to
malaria could be the causes.

In pregnancy, malaria tends to be more atypical in presentation. This
More atypical could be due to the hormonal, immunological and hematological changes
of pregnancy.

Due to the hormonal and immunological changes, the parasitemia tends
to be 10 times higher and as a result, all the complications of falciparum
More severe malaria are more common in pregnancy compared to the non-pregnant
population.
P. falciparum malaria in pregnancy being more severe, the mortality is
More fatal also double (13 % ) compared to the non-pregnant population (6.5%).

Some anti malarials are contra indicated in pregnancy and some may
Selective treatment cause severe adverse effects. Therefore the treatment may become
difficult, particularly in cases of severe P. falciparum malaria.

Management of complications of malaria may be difficult due to the
various physiological changes of pregnancy. Careful attention has to be
Other problems paid towards fluid management, temperature control, etc. Also decisions
regarding induction of labour may be difficult and complex. Foetal loss,
IUGR, and premature labour are common.


Potential Vaccines in Malaria.

Target Protection
sporozoite anti-infection

merozoite anti-parasite

infected RBC anti-parasite

exoantigens anti-disease

sexual stages anti-transmission

Malaria is a preventable infection that can be fatal if left untreated.
Malaria is a preventable infection that can be fatal if left untreated.
Currently, you cannot be vaccinate against malaria, but you can protect yourself
Currently, you cannot be vaccinate against malaria, but you can protect yourself


MALARIA---BEYOND CLINICAL CURE
SOME POINTS TO PONDER FOR PHYSICIANS
Ø CLINICAL CURE WITH APPROPRIATE BLOOD
SCHIZONTICIDALS

Ø GAMETOCYTES,WHEN LATER SUCKED BY THE VECTOR
MOSQUITOS,DEVELOP IN THEIR BODY INTO DISEASE CAUSING
SPOROZOITES WHICH ARE TRANSMITTED AGAIN TO THE NEXT
HEALTHY PERSON BY THE MOSQUITO BITE –THUS ANOTHER
HUMAN BEING FALLS VICTIM TO THE DEADLY MALARIA .

Ø THIS TRANSMISSION OF MALARIA CAN BE PREVENTED BY
ADMINISTERING GAMETOCIDAL DRUGS LIKE PRIMAQUINE AFTER
CONTROLLING THE ACUTE STAGES OF THE DISEASE .

Ø THE PRACTICE OF USING GAMETOCIDAL DRUGS SHOULD BE
CONSIDERED AS IMPORTANT AND SHOULD BECOME A PART OF
STANDARD TREATEMENT STRATEGY WHENEVER A CASE OF
P.FALCIPARUM IS ENCOUNTERED. ……contd


Manifestations of the Malaria Burden
Anemia
Anemia
Long-term
Long-
Long-term
Hypoglycemia sequelae
sequelae
Hypoglycemia
Acute
Acute Severe illness
Severe illness Respiratory
Respiratory
febrile
febrile distress
distress Death
Death
illness
illness
Hypovolemia
Hypovolemia
Infected
Infected Cerebral malaria
Cerebral malaria
Mosquito
Mosquito

Anemia
Anemia
Chronic
Chronic Impaired
Impaired
Infected Neurologic
Neurologic Malnutrition
Malnutrition
Infected effects growth and
growth and
Human
Human
effects Cognitive
Cognitive development
development
Developmental
Developmental

Low birth weight
Low birth weight
Fetus Infant and fetal
Infant and fetal
Fetus Abortion, stillbirth
Abortion, stillbirth
mortality
mortality
Pregnancy
Pregnancy
Acute illness
Acute illness
Maternal
Maternal Long-term
Long-
Long-term
Anemia
Anemia sequelae
sequelae

Prognosis:

Uncomplicated malaria due to P vivax, P malariae, and P ovale has an
excellent prognosis. Most patients have a full recovery with no sequelae.

Malaria due to P falciparum is dangerous. If not treated quickly and
completely, complicated and severe malaria can result, which carries a grave
prognosis.

Malaria in children younger than 5 years carries the worst prognosis in
endemic areas. In a nonimmune population, malaria is equally deadly at all
ages.

Cerebral malaria has a mortality rate of 25%, even with the best treatment.
Survivors may have sequelae (e.g., hemi paresis, cerebellar ataxia, aphasia,
spasticity).

Repeated attacks of malaria can lead to chronic anemia, malnutrition, and
stunted growth.

Pregnancy: Malaria can be severe in pregnancy(Special Concerns). This is a
major problem because many anti-malarial drugs are considered unsafe during
pregnancy.


Malaria the disease --I
--I

9-14 day
incubation
period
Fever, chills,
headache, back
and joint pain
Gastrointestinal
symptoms
(nausea,
vomiting, etc.)


Malaria the disease -- II

Symptoms intensify
Irregular high fever
Anxiety, delirium and
other mental
problems
Sweating, increased
pulse rate, severe
exhaustion
Worsening GI
symptoms
Enlarged spleen and
liver


Malaria the disease -- III


MOSQUITO OF ANOPHELINE SPECIES


ANOPHELINE MOSQUITO SUCKING
BLOOD.


ANOPHELINE-DORSAL VIEW.


MOSQUITOS OF PUBLIC HEALTH IMPORTANCE

AEDES-- DENGUE ANOPHELES-MALARIA
ANOPHELES- CULEX--FILERIA

…….AND THE TYPE OF EGGS THEY LAY.

ANO. AED. CUL.

The mosquito goes
through four distinct
stages during its life
cycle:

egg - hatches when
exposed to water;

larva - (plural. -
larvae) lives in the
water; molts several
times; most species
surface to breathe air;

pupa - (plural - pupae)
does not feed; stage just
prior to emerging as
adult;

adult - flies short
time after emerging and
after its body parts have
hardened.


Examination of blood smear

Demonstration of the parasite in a smear of the blood definitely establishes the presence
Demonstration of the parasite in a smear of the blood definitely establishes the presence
of malaria.
of malaria.

A negative finding on examination does not rule out malaria.. Only 50% of
A negative finding on examination does not rule out malaria Only 50% of
children with malaria are smear positive, even on repeated examination.
children with malaria are smear positive, even on repeated examination.
examination.

A positive finding on examination does not confirm clinical malaria, especially
A positive finding on examination does not confirm clinical malaria, especially
in patients from an endemic area, in whom a symptomatic parasitemia often exists.
in patients from an endemic area, in whom a symptomatic parasitemia often exists.
parasitemia

Both thick and thin films are essential.. If the parasitemia is light, a thin film
Both thick and thin films are essential If the parasitemia is light, a thin film
examination may miss the diagnosis. Thick films save time in diagnosis of scanty infections
examination may miss the diagnosis. Thick films save time in diagnosis of scanty infections
diagnosis
but make species identification of the parasite difficult.
but make species identification of the parasite difficult.

At least 100-200 fields of a thick film should be scrutinized before a slide is
At least 100-200 fields of a thick film should be scrutinized before a slide is
reported as negative for malaria. In doubtful cases, the examination can be repeated
reported as negative for malaria. In doubtful cases, the examination can be repeated
after 4 hours.
after 4 hours.

Various techniques to enhance the diagnostic utility of the peripheral blood smear
Various techniques to enhance the diagnostic utility of the peripheral blood smear
peripheral
examination are in use. Fluorescent staining and microscopy, centrifugation, selective
centrifugation, selective
examination are in use. Fluorescent staining and microscopy, centrifugation,
magnetic separation techniques, and other techniques have been used but have only a
magnetic separation techniques, and other techniques have been used but have only a
used
moderate effect.
moderate effect.


….. AND P.VIVAX AS SEEN UNDER MICROSCOPE.


P.FALCIPARUM UNDER MICROSCOPE.


P.FALCIPARUM UNDER FLOUROCENT
MICROSCOPY


P.FALCIPARUM-GAMETOCYTES
P.FALCIPARUM-GAMETOCYTES
UNDER MICROSCOPE.


TROPHOZOITE STAGE OF
P.VIVAX.


P.VIVAX-
TROPHOZOITES,GAMETOCYTES.


P.VIVAX-TROPHOZOITES
P.VIVAX-TROPHOZOITES
in Thin Smear


P.VIVAX-GAMETOCYTE


P.VIVAX-MATURE SCHIZONT
P.VIVAX-MATURE
in Thin Smear.


P.VIVAX UNDER FLOURECENT
MICROSCOPY..


PF GAMETOCYTES-UNDER FLOUROCENT
GAMETOCYTES-UNDER
MICROSCOPY


PLASMODIUM SPOROZOITES OBTAINED
FROM AN ANOPHELINE MOSQUITO.


Clinical approach to cases of recurrent malaria

Recurrence Within 8- After 2 After 2
10 days weeks months

1st ?P. ?Re-infection ?Re-infection
possibility falciparum

2nd ?Compliance ?P. ?Relapse
possibility falciparum


OUTER WALL OF A FEM. AN.MOSQUITO GUT,-
GUT,-
INFESTED WITH OOCYSTS CONTAINING SPOROZOITES.


THE INVASION--MEROZOITE STAGE OF THE
INVASION--MEROZOITE
MALARIA PARASITE ATTACKING AN RBC.


Control of malaria is a complex chain of measures that often complement one another. The
complement
above diagram depicts this control chain: For example, by taking personal protective
taking
measures, three things can be achieved - prevention of malaria in the given individual, thus
reduced parasite load and reduction in spread, and by denying blood meal to the mosquito
blood
the egg laying is also hampered! In the recent years, more emphasis is being laid on early
hampered!
diagnosis and treatment, on personal protection especially with insecticide treated bednets
and on biological vector control. By these means, it is intended to minimise use of
potentially harmful chemical insecticides.


VECTOR CONTROL MEASURES AT A GLANCE


Control of the Malaria Burden
Current Interventions

Drugs
(treatment,
prevention)
Protection Insecticides
(insecticide- (house
impregnated spraying,
materials) larvicides)
Environmental and
Behavioral
Modification
Vaccines Genetic
(preerythrocytic,
blood stage,
modification
transmission-
Future Interventions of vectors
blocking)

The Acts of Commissions And Omissions IN MALARIA.
1. Mis-diagnosis
1. Mis-diagnosis
In an endemic area, there may be a tendency to diagnose all cases of
In an endemic area, there may be a tendency to diagnose all cases of
fever as malaria, forgetting to even consider other causes. Whereas
fever as malaria, forgetting to even consider other causes. Whereas
Over-diagnosis presumptive treatment with chloroquine in cases of fever is well
presumptive treatment with chloroquine in cases of fever is well
Over-diagnosis
accepted, sometimes, doctors may go beyond that and indulge in
accepted, sometimes, doctors may go beyond that and indulge in
Obsession with
Obsession with presumptive treatment with newer drugs, (reserved for multi drug
presumptive treatment with newer drugs, (reserved for multi drug
malaria and
malaria and resistance falciparum malaria), even if the MP test is repeatedly
resistance falciparum malaria), even if the MP test is repeatedly
forgetting the
forgetting the negative. Most often such cases turn out to be non-malarial fevers.
negative. Most often such cases turn out to be non-malarial fevers.
OTHER causes of
OTHER causes of Therefore consider other causes of fever.
Therefore consider other causes of fever.
fever
fever

1. Malaria may not be considered as a possibility in places where iit
1. Malaria may not be considered as a possibility in places where t
is not common-history of travel to malarious area should be
is not common-history of travel to malarious area should be
elicited.
elicited.
2. It may not be considered in patients on chemoprophylaxis for
2. It may not be considered in patients on chemoprophylaxis for
malaria. Chemoprophylaxis does not offer 100% protection and
malaria. Chemoprophylaxis does not offer 100% protection and
Under-diagnosis
Under-diagnosis malaria should be therefore looked for in these patients.
malaria should be therefore looked for in these patients.
Forgetting malaria
Forgetting malaria 3. Malaria can always co-exist with other infections in an endemic
3. Malaria can always co-exist with other infections in an endemic
area. Therefore, it should be considered even in patients with other
area. Therefore, it should be considered even in patients with other
obvious infections causing fever.
obvious infections causing fever.


2. Mis-report
Mis-report
Artifacts may be read as malarial parasites on
peripheral smear as well as QBC test. Dirty
False positive slides, contaminated stains, inexperienced
microscopist, recycled QBC tubes may be the
microscopist,
causes.

Malarial parasites may be missed and the test
reported as negative. Inadequate smear, dirty
stains, contaminated/deteriorated stains,
wrong buffer pH, inexperienced technician,
False negative
incomplete examination of the slide, storage
of blood in anticoagulant before preparing
the smear etc. may contribute to this problem.


3. Mis-judgement of severity
Mis-judgement
Panic reaction to P. falciparum malaria is common among
Panic reaction to P. falciparum malaria is common among
patients and not uncommon among doctors, resulting in
patients and not uncommon among doctors, resulting in
over-reaction to the situation and over-treatment. Mild
over-reaction to the situation and over-treatment. Mild
anemia, mild icterus, headache etc. are common in
anemia, mild icterus, headache etc. are common in
falciparum malaria and need not necessarily imply severe
falciparum malaria and need not necessarily imply severe
Over-estimation
Over-estimation malaria. Such patients need not be treated with parenteral
malaria. Such patients need not be treated with parenteral
or second line antimalarial drugs. Also it should not be
or second line antimalarial drugs. Also it should not be
forgotten that some of the manifestations could be due to
forgotten that some of the manifestations could be due to
fever, drugs etc., and not necessarily due to severe malaria.
fever, drugs etc., and not necessarily due to severe malaria.

P. falciparum malaria can cause dramatic complications
P. falciparum malaria can cause dramatic complications
and therefore one should be always looking for them.
and therefore one should be always looking for them.
Patients who are at for development of complications
Patients who are at for development of complications
Under-estimation
Under-estimation should be ideally admitted for observation. Any indication
should be ideally admitted for observation. Any indication
of complication should be properly managed. Neglecting
of complication should be properly managed. Neglecting
the signs like high fever, prostration, significant pallor and
the signs like high fever, prostration, significant pallor and
jaundice, dehydration etc. may prove costly. Hypoglycemia
jaundice, dehydration etc. may prove costly. Hypoglycemia
may be easily missed.
may be easily missed.


MOSQUITO(MALARIA),YET TO BE CAGED---ALL
CAGED---ALL
THE GLOBAL EFFORTS GOING IN VAIN ??? !!


MALARIA BURDEN—ERADICATION IMPOSSIBLE,CONTROL
BURDEN—ERADICATION
PROSPECTS NOT PROMISING IN NEAR FUTURE--A SIGN OF
FUTURE--A
INCREASING GLOBAL HELPLESSNESS.

postal stamp
of
Cameroon.


MALARIA CONTROL-SUCCESS STRATEGY
CONTROL-SUCCESS
DEPENDS ON COORDINATED,MULTI
PRONGED,FOCUSSED AND RESULT ORIENTED
GLOBAL EFFORTS.


…..And


Have a nice…..and
nice…..and
a…. malaria free
a….
time folks !!!


Malaria advocacy

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