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MALARIA
Presenter : Dr Nitish Kumar
Dr jaya
Moderator: Dr Alok hemal
OVERVIEW
• Introduction
• Etiology
• Epidemiology
• Pathogenesis
• Clinical manifestation
• Diagnosis
• Treatment
• Prevention
INTRODUCTION
• Malaria comes from Italian words “mal” and “aria”
meaning bad air.
• Mostly in developing country
• Death occur mostly in infant and children
• Malaria is curable if effective treatment is started
early.
• Chloroquine was effective for treating all cases but
recently chloroquine resistant pf malaria .
ETIOLOGY
• Malaria is a potentially life threatening parasitic
disease caused by P.vivax, P.falciparum, P.malariae,
P.ovale,
• After 2004, P.knowlesi (primate malaria ) southeast
Asia.
• Transmitted by the infective bite of female
Anopheles mosquito
• Transmitted through blood transfusion, use of
contaminated needles and trans placentally
ETIOLOGY
• Malaria is one of the major public health problems of
the India.
• India reports around one million malaria cases
annually.
• P. falciparum and P. vivax are the most common
species causing malaria
• P.vivax is more prevalent in the plain areas, while P.
falciparum predominates in forested and hilly
areas….
EPIDEMIOLOGY
• According to the latest WHO data, 216 million malaria
cases worldwide.
• 445 000 people died of malaria in 2016.
• With over 90% of these deaths occurring in sub-saharan
Africa.
• All the others occurring in south-east asia and south
america.
• Almost all malaria deaths are caused by plasmodium
falciparum.
• Most of these deaths occur in african children younger
than 5 years.
PREVALANCE OF PLASMODIUM
EPIDEMIOLOGICAL INDICATORS
OF MALARIA
• Annual Parasite Incidence (API)
• Annual Blood Examination Rate (ABER)
• Slide Positivity Rate (SPR)
• Slide Falciparum Rate (SFR)
• API : confirmed cases during one year X 1000
population under surveillance
• ABER: number of slides examined X 100
population
• SPR : % of slide +ve for malarial parasite irrespective
of species
• SFR : % of slide +ve for falciparum
TREND OF MALARIA
PARAMETERS (2001-2017)
SITUATION IN INDIA
• 0.8 million confirmed cases -(NVBDCP 2017)
• Out of which 533801 plasmodium falciparum 104
deaths
• 76238 cases of malaria till April 2018 ,42 thousand
falciparum cases, 3 deaths
TRENDS OF MALARIA IN INDIA
GEOGRAPHICAL DISTRIBUTION
OF ANOPHELES
PATHOGENESIS
• Complex life cycle of plasmodium
• Asexual life cycle in human (intermediate host)
Exoerythrocytic and erythrocytic
• Sexual life cycle in female anaphele(definitive host)
sporogonic cycle
LIFE CYCLE OF PLASMODIUM
PARASITE
SHOWING THE DIFFERENT STAGES IN THE MALARIA LIFE CYCLE
DIFFERENT STAGES OF PLASMODIUM
FOUR IMPORTANT PATHOLOGIC
PROCESS
• Fever ( erythrocytic rupture and release of
merozoites)
• Anemia( hemolysis ,sequestration of RBC in spleen ,
bone marrow suppression)
• Immunopathologic event(release of pro-
inflammatory event TNF
• Tissue anoxia ( cytoadherence )
• RBC containing Hb S resist malaria parasite growth
• RBC lacking Duffy blood group resist to P.vivax
• RBC containing Hb F and ovalocytes resistant to
p.falciparum.
CLINICAL MANIFESTATION
• Children are asymptomatic during initial phase-the
incubation period.
– P.falcirum :9-14 days
– P.vivax :12-17 days
– P.ovale :16-17 days
– P.malariae:18-40 days
PRODROMAL SYMPTOMS
• Headache
• Fatigue
• Anorexia
• Myalgia
• Pain abdomen
• Vomiting/diarrhea
CLINICAL FEATURES
• Fever is the cardinal symptom of malaria.
intermittent with or without periodicity or
continuous.
• Many cases have chills and rigors.
• Non-specific & mimic like viral , enteric fever.
• Suspected in patients residing in endemic
• Recently visited endemic
• All clinically suspected malaria cases should be
investigated immediately by microscopy
and/or Rapid Diagnostic Test (RDT).
CONGENITAL MALARIA
• By all four species
• In endemic areas important cause of abortion, still
birth, premature births and IUGR.
• Placenta may be black in colour d/t malaria pigment
• Maternal t/t is inadequate to cure fetus
Congenital malaria
• CLINICAL MANIFESTATIONS(mc b/w 10 and 30
days of age)
• Fever
• Irritability
• Poor feeding
• Vomiting
• FTT
• Pallor
• Jaundice
• Hepatosplenomegaly
Diagnosis
Malaria Diagnosis
1.Clinical Diagnosis
2. Microscopy
3.Antigen Detection
4.Malarial serology
5.Polymerase chain reaction
Clinical Diagnosis
• Signs and symptoms are nonspecific
• History of high grade fever with or without chills
• Headache, back pain, myalgia and abdominal pain
• Pallor, abnormal bleeding and Jaundice
• Respiratory distress, pulmonary edema and
circulatory collapse
• Impaired consciousness
• Splenomegaly (common), hepatomegaly
• Anemia, thrombocytopenia
Microscopy(peripheral smear)
• Microscopy of stained thick and thin blood
smears remains the gold standard for
confirmation of diagnosis of malaria
Parasite detection
Thick blood film
• Used for screening of parasites.
• 5-10 parasites/µL
Thin blood film
• Species & stages of parasites
• 200 parasites/µL
• Percentage of infected erythrocytes
The Malaria Parasite
• Three developmental
stages seen in blood
films:
– Trophozoite
– Schizont
– Gametocyte
Different stain for microscopy
• Giemsa stain ( superior stain )
• Leishman stain
• Field’s stain( quick method of staining thick
without fixation)
Microscopy
Advantages
• Low direct costs
• High sensitivity
• Differentiation between plasmodium species
• Determination of parasite densities
• Ability to monitor response to therapy
Microscopy
Disadvantages
• Accuracy depends on skilled staff
• Delay in providing results to patient
QUANTITATIVE BUFFY COAT TEST
(QBC)
• Involve staining of centrifuged and
compressed red cell layer with acridine
orange and examination under UV light
source.
• Fast, easy, more sensitive
• Need special equipment, costly, more false
positivity d/t staining artifacts, not able to
differciate the parasite
Rapid Diagnostic Tests
• Immunochromatographic tests that detect
parasite specific antigen in a finger prick blood
sample
• NVBDCP supplies RDT kits for detection of P.
falciparum at locations where microscopy
results are not obtainable within 24 hours of
sample collection
Type of RDT-
• Based on
1. Histidine-Rich Protein 2 (HRP2)
2. Parasite specific lactate dehydrogenase
(pLDH)
3. Aldolase ( not used )
Criteria for selection of RDT
Recommendations are
i. For Pf:
Sensitivity and Specificity should be minimum
95% at parasite density level of 200 asexual
parasites/ul of blood
ii. For Pv:
Sensitivity: ≥75% at density of 200 parasites/ul
Specificity : ≥ 90%
Rapid Diagnostic Tests
Advantages
• Quick to perform (in practice, about 20 minutes)
• Sensitive in detecting P.falciparum, which causes
severe malaria
• Does not require skilled laboratory technicians
and can be used by health workers and non
health personnel after a few hours of training
• Does not require electricity or laboratory
equipment
False Negative result
– Insufficient parasites to register a positive result
– RDT kit damaged
– Illness by another species of malaria parasite
which RDT is not designed to detect
False Positive Result
– Dead parasite
– persistence of malaria gametocytes
– individuals with high immunity
Rapid Diagnostic Test
• Negative RDT should not preclude treatment
in a strongly suspected case, especially in
severe clinical disease
• RDTs do not quantitate P. falciparum
parasitemia
• Pf HRP-2 based kits may show positive result
up to three weeks after successful treatment
and parasite clearance.
Malaria Serology – antibody detection
Immunologic assays to detect host response
• Antibodies to asexual parasites appear some
days after invasion of RBCs and may persist
for months
• Positive test indicates past infection
• Not useful for treatment decisions
Polymerase Chain Reaction
• Detect parasite DNA
• Highly sensitive
• Very useful for detecting mixed infection,
particularly at low parasite density
• Identify drug resistance
• May have use in epidemiological investigations
• Not routinely available
• Differentiate b/w p.knowlesi and p.malaria , cant
be done by microscopy.
Treatment
CLASSIFICATION ON BASIS OF SEVERITY
• Uncomplicated malaria
• Complicated malaria
Uncomplicated malaria
• Defined as symptomatic malaria without signs
of severity or evidence (clinical or lab) of vital
organ dysfunction.
• Signs and symptom nonspecific
• Suspected clinically on basis of fever or history
of fever
TREATMENT
• Treatment of P. vivax malaria :
• Confirmed P. vivax cases should be treated with
chloroquine in full therapeutic dose of 25 mg/kg as
per the age-wise dosage schedule :
NO. OF TABLETS
AGE DAY 1
(10 mg /Kg)
DAY 2
(10 mg/Kg)
DAY 3
(5 mg/Kg)
< 1 YEARS 1/2 1/2 1/4
1-4 YEARS 1 1 1/2
5-8 YEARS 2 2 1
9-14 YEARS 3 3 1 1/2
>15 YEARS 4 4 2
Prevention of relapse
• P. vivax or P. ovale parasites remain
dormant in the liver cells in the form of
hypnozoites which can later cause a
relapse.
• For its prevention, primaquine should be
given at a dose of 0.25 mg/kg body
weight daily for 14 days under
supervision.
• Primaquine is contraindicated in
pregnant women, infants and known
G6PD deficient patients.
• Primaquine can lead to hemolysis in G6PD deficiency. Caution
should be exercised before administering primaquine in areas
known to have high prevalence of G6PD deficiency. Patient
should be advised to stop primaquine immediately if develops any
of the following symptoms and should report to the doctor
immediately:
(i) dark coloured urine
(ii) yellow conjunctiva
(iii) bluish discolouration of lips
(iv) abdominal pain
(v) nausea
(vi) vomiting
(vii) breathlessness
Treatment of Uncomplicated P. falciparum
malaria
• Artemisinin Combination Therapy (ACT) should be given to all the
confirmed P. falciparum cases found positive by microscopy or RDT.
• This is to be accompanied by single dose of primaquine (0.75 mg/kg
body weight) on Day 2.(0.25 mg/kg –WHO, G-6PD screening not
required)
• ACT consists of an artemisinin derivative combined with a
longacting antimalarial (amodiaquine, lumefantrine, mefloquine,
piperaquine or sulfadoxine-pyrimethamine).
• The ACT recommended in the National Programme all over India
except northeastern states is artesunate (4 mg/kg body weight)
daily for 3 days and sulfadoxine (25 mg/kg body weight) –
pyrimethamine (1.25 mg/kg body weight) [AS+SP] on Day 0.
• In the northeastern states (Arunachal Pradesh, Asom,Manipur,
Meghalaya, Mizoram, Nagaland, and Tripura), due to the recent
reports of late treatment failures to the current combination of AS+SP
in P. falciparum malaria, the presently recommended ACT in national
drug policy is fixed dose combination (FDC) of Artemether-
lumefantrine (AL).
• Although the ACT used in the national programme in NE states
is AL and rest of India is AS+SP, the other fixed dose combinations
registered for marketing in India are artesunate-amodiaquine,
artesunate-mefloquine and arterolane-piperaquine (for adults
only) and can be used for treatment of uncomplicated P. falciparum
or mixed infections.
Treatment of malaria in pregnancy
The ACT should be given for treatment of P. falciparum malaria
in second and third trimesters of pregnancy, while quinine is
recommended in the first trimester. Plasmodium vivax malaria
can be treated with chloroquine.
Treatment of mixed infections
Mixed infections with P. falciparum should be treated as
falciparum malaria. Since AS+SP is not effective in vivax malaria,
other ACT should be used. However, anti-relapse treatment
with
primaquine can be given for 14 days, if indicated.
Few available fixed dose combinations
• CHLOROQUINE –TABLETS-100 ,150 ,300 mg BASE (150 mg
base=250 mg phosphate salt or 200 mg sulfate salt)
⮚ Syrup- 50 mg base=5ml
• ACT combinations available :
⮚ Falcigo plus kit –artesunate 50 mg + mefloquine 250 mg
⮚ Larinate 200 kit- artesunate 200 mg + sulphadoxine 500
mg+pyrimethamine 25 mg (larinate 50,100 also avialable)
⮚ Larinate –MF :artesunate 200 mg +mefloquine 250 mg
⮚ Tab. Lumerax-20 DT, Combither ,,ARH-L (Artemether 20 mg +
lumefantrine120 mg) , lumerax -40 and 80 also available.
⮚ Syp- lumerax-20/120/ 5 ml
⮚ Syp- lumether-40/240/ 5 ml
• Primaquine –tablets;7.5 and 15 mg
Treatment based on clinical criteria without
laboratory confirmation
All the efforts should be made to diagnose malaria either by
microscopy or RDT. However, special circumstances should be
addressed as mentioned below:
● If RDT for only P. falciparum is used, negative cases showing
signs and symptoms of malaria without any other obvious
cause for fever should be considered as ‘clinical malaria’ and
treated with chloroquine in full therapeutic dose of 25 mg/kg
body weight over three days. If a slide result is obtained later,
the treatment should be completed according to species.
● Suspected malaria cases not confirmed by RDT or microscopy
should be treated with chloroquine in full therapeutic dose.
General recommendations for the management of
uncomplicated malaria
• Avoid starting treatment on an empty stomach. The first
dose should be given under observation.
• Dose should be repeated if vomiting occurs within half an
hour of antimalarial intake.
• The patient should be asked to report back, if there is no
improvement after 48 hours or if the situation deteriorates.
• The patient should also be examined and investigated for
concomitant illnesses.
TREATMENT FAILURE/DRUG RESISTANCE
• After treatment patient is considered cured if
he/she does not have fever or parasitaemia till
Day 28.
• Some patients may not respond to treatment
which may be due to drug resistance or
treatment failure, especially in falciparum
malaria.
Early treatment failure (ETF):
Development of danger signs or severe malaria
on Day 1, 2 or 3, in the presence of
parasitaemia;
⮚ Parasitaemia on Day 2 higher than on Day 0,
irrespective of axillary temperature;
⮚ Parasitaemia on Day 3 with axillary
temperature >37.5°C;
⮚ and Parasitaemia on Day 3, >25% of count on
Day 0.
Late clinical failure (LCF):LATE TRAETMENT FAILURE
Development of danger signs or severe malaria in the presence
of parasitaemia on any day between Day 4 and Day 28 (Day
42) in patients who did not previously meet any of the criteria
of early treatment failure;
The presence of parasitaemia on any day between Day 4 and
Day 28 (Day 42) with axillary temperature >37°C in patients who
did not previously meet any of the criteria of early treatment
failure.
Late parasitological failure (LPF):
Presence of parasitaemia on any day between Day 7 and Day
28 with axillary temperature <37.5°C in patients who did not
previously meet any of the criteria of early treatment failure or
late clinical failure.
Such cases of falciparum malaria should be given alternative
ACT or quinine with Doxycycline.
Doxycycline is contraindicated in pregnancy, lactation and in
children up to 8 years.
Treatment failure with chloroquine in P. vivax malaria is rare in
India.
Algorithm for diagnosis and treatment
of malaria
SEVERE MALARIA
Severe malaria is characterized by one or more of the following
features :
• Impaired consciousness/coma
• Repeated generalized convulsions
• Renal failure (Serum Creatinine >3 mg/dl)
• Jaundice (Serum Bilirubin >3 mg/dl)
• Severe anaemia (Hb <5 g/dl) ,In > 12 years old patients < 7 gm %
• Pulmonary oedema/acute respiratory distress syndrome
• Hypoglycaemia (Plasma Glucose <40 mg/dl , treatment threshold
for < 5 year-54 mg/dl)
Severe malaria
• Metabolic acidosis
• Circulatory collapse/shock (Systolic BP <80 mm Hg, <70 mmHg in
children)
• Abnormal bleeding and Disseminated intravascular coagulation (DIC)/
Haemoglobinuria
• Hyperpyrexia (Temperature >106°F or >42°C) (NVBDCP)
• Hyperparasitaemia (>5% parasitized RBCs , WHO- > 10 %)
• Prostration (WHO)
Diagnosis of severe malaria cases negative on microscopy
Microscopic evidence may be negative for asexual parasites in
patients with severe infections due to sequestration and partial
treatment. Efforts should be made to confirm these cases by
RDT
or repeat microscopy. However, if clinical presentation
indicates
severe malaria and there is no alternative explanation these
patients should be treated accordingly.
Specific antimalarial treatment of severe
malaria
• Artesunate: 2.4 mg/kg body weight i.v. or i.m. given on
admission (time=0), then at 12 and 24 hours, then once a
day(Care should be taken to dilute artesunate powder in
5%Sodium bi-carbonate provided in the pack).
• Artemether: 3.2 mg/kg body weight i.m. given on admission
then 1.6 mg/kg body weight per day.
• Quinine: 20 mg quinine salt/kg body weight on admission
(i.v. infusion in 5% dextrose/dextrose saline over a period
of 4 hours) followed by maintenance dose of 10 mg/kg body
weight 8 hourly; infusion rate should not exceed 5 mg/kg
body weight per hour.
Loading dose of 20 mg/kg body weight should not be given, if the
patient has already received quinine.
NEVER GIVE BOLUS INJECTION OF QUININE.
If parenteral quinine therapy needs to be continued beyond 48
hours, dose should be reduced to 7 mg/ kg body weight 8 hourly.
( WHO -10mg/kg 12 hrly )
FOLLOW ON TREATMENT
• Once the patient can tolerate oral therapy or
after at least 24 hours of parenteral therapy,
further follow-uptreatment should be as
below:
• Patients receiving artemisinin derivatives
should get full course of oral ACT. However,
ACT containing mefloquine should be avoided
in cerebral malaria due to neuropsychiatric
complications.
• Patients receiving parenteral quinine should
also betreated with full course of oral ACT.
• In first trimester of pregnancy, parenteral
quinine is the drug of choice.
• If quinine is not available, artemisinin derivatives
may be given to save the life of mother. In second
and third trimester, parenteral artemisinin
derivatives are preferred
Change in recommendations to treat severe
malaria (WHO 3RD EDITION-2015)
Severe malaria due to P. vivax
• In recent years, increased attention has been
drawn to severe malaria caused by P. vivax.
• Some cases have been reported in India,
and there is reason to fear that this problem may
become more common in the coming years.
• Severe malaria caused by P. vivax
should be treated like severe P. falciparum
malaria, however, primaquine should be given for
14 days for preventing relapse as per guidelines
after the patient recovers from acute illness and
can tolerate primaquine.
SIDE EFFECTS OF ANTIMALARIALS
• Artemether:
– Dizziness, reticulocytopenia, neutropenia, elevated
liver enzymes, prolonged QT interval, bradycardia
• Artesunate:
– GI disturbances, cough, rash, arthralgia, delayed
hemolysis
• Chloroquine:
– Pleuritis, headache, hepatitis, widening of QRS and QT
interval, nausea, vomiting, retinopathy, keratopathy,
hair loss
SIDE EFFECTS OF ANTIMALARIALS
• Mefloquine:
– Hepatitis, polyneuropathy, skin rashes, C/I in
cerebral malaria
• Primaquine:
– Hypertension, cardiac arrythmia
• Sulfadoxine-pyrimethamine:
– SJS, TEN, Erythema multiforme, C/I in
documented megaloblastic anaemia d/t folate
deficiency
Prevention
CHEMOPROPHYLAXIS
• Chemoprophylaxis is recommended for travellers,
migrant labourers and military personnel exposed to
malaria in highly endemic areas.
• Short-term chemoprophylaxis (less than 6 weeks)
Doxycycline: 100 mg daily in adults and 1.5 mg/kg
body weight for children more than 8 years old. The
drug should be started 2 days before travel and
continued for 4 weeks after leaving the malarious
area
Long-term chemoprophylaxis (more than 6 weeks)
• Mefloquine: 5 mg/kg body weight (up to 250 mg) weekly and
should be administered two weeks before, during and four weeks
after leaving the area.
Mefloquine is contraindicated in cases with history of convulsions,
neuropsychiatric problems and cardiac conditions
Malaria control strategies
1. Early case Detection and Prompt Treatment
(EDPT)
2. Vector Control
3. Community Participation
4. Environmental Management & Source
Reduction Methods
Early case Detection and Prompt
Treatment
• EDPT is the main strategy of malaria control - radical
treatment is necessary for all the cases of malaria to
prevent transmission of malaria.
• Chloroquine is the main anti-malaria drug for
uncomplicated malaria.
• Drug Distribution Centres (DDCs) and Fever Treatment
Depots (FTDs) have been established in the rural areas
for providing easy access to anti-malarial drugs to the
community.
• Alternative drugs for chloroquine resistant malaria are
recommended as per the drug policy of malaria
Vector Control
• Chemical Control
– Use of Indoor Residual Spray (IRS) with insecticides
recommended under the programnme
– Use of chemical larvicides like Abate in potable water
– Aerosol space spray during day time
– Malathion fogging during outbreaks
• Biological Control
– Use of larvivorous fish in ornamental tanks, fountains
etc.
Mosquito control
measures
Anti larval
environmental
Chemical
(mineral oil,paris green,
fenthion,chlorpyrifos
Biological
Antiadult
Residual spray
(DDT,
malathion,lindane,OMX##
)
Space
spray(pyrithrim)
Genetic control
Personal
protection
Mosquito net
Repellant.(DEET)
Screening with
copper and
bronze
Personal Prophylatic Measures
• Use of mosquito repellent creams, liquids,
coils, mats etc.
• Screening of the houses with wire mesh
• Use of bednets treated with insecticide
• Wearing clothes that cover maximum surface
area of the body
Community Participation
• Sensitizing and involving the community for
detection of Anopheles breeding places and
their elimination
• NGO schemes involving them in programme
strategies
Environmental Management &
Source Reduction Methods
• Source reduction i.e. filling of the breeding
places
• Proper covering of stored water
• Channelization of breeding source
Resistance of Anopheles culicifacies,
to commonly used insecticides in India
Malaria vaccine
• More than 30 P. falciparum malaria vaccine
candidates are at either advanced preclinical or
clinical stages of evaluation.
• Only the RTS,S/AS01 vaccine has completed Phase
3 evaluation and received a positive regulatory
assessment.
• WHO has developed a set of principles to ensure
the quality, safety, and efficacy of recombinant
vaccines targeting pre-erythrocytic and blood
stage malaria parasites.
• The vaccine has been recommended by WHO
for pilot introduction in selected areas of 3
African countries
• The vaccine will be made available through
routine immunization programmes to young
children living in selected areas in Ghana,
Kenya and Malawi. At least 360 000 children
in the selected areas will be vaccinated.
TAKE HOME MESSAGE
• Malaria is a potentially life threatening parasitic
disease and fortunately treatable.
• Acc to WHO 216 million malaria cases reported and
about 4.5 lakh deaths.
• India .8 million confirmed cases & 104 death in 2017.
• Classical sign & symptom may not be present
paediatric age group.
• All suspected malaria cases should promptly
investigated by RDT & microscopy.
• Empirical treatment should only be given if
illness could not be explained by any cause
and if high index of suspicion of malaria
• Anti malarial treatment once started should
be completed.
• Test using ab detection & PCR are not useful
for diagnosis
• Antibody detecting rapid diagnostic tests are
banned in India.
• Suspected severe malaria cases should receive
pre referral treatment depending upon the
availability
• Children < 20 kg BW should receive high dose
artesunate( 3mg/kg BW)
THANK YOU

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Malaria ppt final

  • 1. MALARIA Presenter : Dr Nitish Kumar Dr jaya Moderator: Dr Alok hemal
  • 2. OVERVIEW • Introduction • Etiology • Epidemiology • Pathogenesis • Clinical manifestation • Diagnosis • Treatment • Prevention
  • 3. INTRODUCTION • Malaria comes from Italian words “mal” and “aria” meaning bad air. • Mostly in developing country • Death occur mostly in infant and children • Malaria is curable if effective treatment is started early. • Chloroquine was effective for treating all cases but recently chloroquine resistant pf malaria .
  • 4. ETIOLOGY • Malaria is a potentially life threatening parasitic disease caused by P.vivax, P.falciparum, P.malariae, P.ovale, • After 2004, P.knowlesi (primate malaria ) southeast Asia. • Transmitted by the infective bite of female Anopheles mosquito • Transmitted through blood transfusion, use of contaminated needles and trans placentally
  • 5. ETIOLOGY • Malaria is one of the major public health problems of the India. • India reports around one million malaria cases annually. • P. falciparum and P. vivax are the most common species causing malaria • P.vivax is more prevalent in the plain areas, while P. falciparum predominates in forested and hilly areas….
  • 6. EPIDEMIOLOGY • According to the latest WHO data, 216 million malaria cases worldwide. • 445 000 people died of malaria in 2016. • With over 90% of these deaths occurring in sub-saharan Africa. • All the others occurring in south-east asia and south america. • Almost all malaria deaths are caused by plasmodium falciparum. • Most of these deaths occur in african children younger than 5 years.
  • 8. EPIDEMIOLOGICAL INDICATORS OF MALARIA • Annual Parasite Incidence (API) • Annual Blood Examination Rate (ABER) • Slide Positivity Rate (SPR) • Slide Falciparum Rate (SFR)
  • 9. • API : confirmed cases during one year X 1000 population under surveillance • ABER: number of slides examined X 100 population • SPR : % of slide +ve for malarial parasite irrespective of species • SFR : % of slide +ve for falciparum
  • 11. SITUATION IN INDIA • 0.8 million confirmed cases -(NVBDCP 2017) • Out of which 533801 plasmodium falciparum 104 deaths • 76238 cases of malaria till April 2018 ,42 thousand falciparum cases, 3 deaths
  • 12. TRENDS OF MALARIA IN INDIA
  • 14. PATHOGENESIS • Complex life cycle of plasmodium • Asexual life cycle in human (intermediate host) Exoerythrocytic and erythrocytic • Sexual life cycle in female anaphele(definitive host) sporogonic cycle
  • 15. LIFE CYCLE OF PLASMODIUM PARASITE SHOWING THE DIFFERENT STAGES IN THE MALARIA LIFE CYCLE
  • 16. DIFFERENT STAGES OF PLASMODIUM
  • 17. FOUR IMPORTANT PATHOLOGIC PROCESS • Fever ( erythrocytic rupture and release of merozoites) • Anemia( hemolysis ,sequestration of RBC in spleen , bone marrow suppression) • Immunopathologic event(release of pro- inflammatory event TNF • Tissue anoxia ( cytoadherence )
  • 18. • RBC containing Hb S resist malaria parasite growth • RBC lacking Duffy blood group resist to P.vivax • RBC containing Hb F and ovalocytes resistant to p.falciparum.
  • 19. CLINICAL MANIFESTATION • Children are asymptomatic during initial phase-the incubation period. – P.falcirum :9-14 days – P.vivax :12-17 days – P.ovale :16-17 days – P.malariae:18-40 days
  • 20. PRODROMAL SYMPTOMS • Headache • Fatigue • Anorexia • Myalgia • Pain abdomen • Vomiting/diarrhea
  • 21. CLINICAL FEATURES • Fever is the cardinal symptom of malaria. intermittent with or without periodicity or continuous. • Many cases have chills and rigors. • Non-specific & mimic like viral , enteric fever. • Suspected in patients residing in endemic • Recently visited endemic
  • 22. • All clinically suspected malaria cases should be investigated immediately by microscopy and/or Rapid Diagnostic Test (RDT).
  • 23. CONGENITAL MALARIA • By all four species • In endemic areas important cause of abortion, still birth, premature births and IUGR. • Placenta may be black in colour d/t malaria pigment • Maternal t/t is inadequate to cure fetus
  • 24. Congenital malaria • CLINICAL MANIFESTATIONS(mc b/w 10 and 30 days of age) • Fever • Irritability • Poor feeding • Vomiting • FTT • Pallor • Jaundice • Hepatosplenomegaly
  • 26. Malaria Diagnosis 1.Clinical Diagnosis 2. Microscopy 3.Antigen Detection 4.Malarial serology 5.Polymerase chain reaction
  • 27. Clinical Diagnosis • Signs and symptoms are nonspecific • History of high grade fever with or without chills • Headache, back pain, myalgia and abdominal pain • Pallor, abnormal bleeding and Jaundice • Respiratory distress, pulmonary edema and circulatory collapse • Impaired consciousness • Splenomegaly (common), hepatomegaly • Anemia, thrombocytopenia
  • 28. Microscopy(peripheral smear) • Microscopy of stained thick and thin blood smears remains the gold standard for confirmation of diagnosis of malaria
  • 29. Parasite detection Thick blood film • Used for screening of parasites. • 5-10 parasites/µL Thin blood film • Species & stages of parasites • 200 parasites/µL • Percentage of infected erythrocytes
  • 30. The Malaria Parasite • Three developmental stages seen in blood films: – Trophozoite – Schizont – Gametocyte
  • 31. Different stain for microscopy • Giemsa stain ( superior stain ) • Leishman stain • Field’s stain( quick method of staining thick without fixation)
  • 32. Microscopy Advantages • Low direct costs • High sensitivity • Differentiation between plasmodium species • Determination of parasite densities • Ability to monitor response to therapy
  • 33. Microscopy Disadvantages • Accuracy depends on skilled staff • Delay in providing results to patient
  • 34. QUANTITATIVE BUFFY COAT TEST (QBC) • Involve staining of centrifuged and compressed red cell layer with acridine orange and examination under UV light source. • Fast, easy, more sensitive • Need special equipment, costly, more false positivity d/t staining artifacts, not able to differciate the parasite
  • 35. Rapid Diagnostic Tests • Immunochromatographic tests that detect parasite specific antigen in a finger prick blood sample • NVBDCP supplies RDT kits for detection of P. falciparum at locations where microscopy results are not obtainable within 24 hours of sample collection
  • 36. Type of RDT- • Based on 1. Histidine-Rich Protein 2 (HRP2) 2. Parasite specific lactate dehydrogenase (pLDH) 3. Aldolase ( not used )
  • 37. Criteria for selection of RDT Recommendations are i. For Pf: Sensitivity and Specificity should be minimum 95% at parasite density level of 200 asexual parasites/ul of blood ii. For Pv: Sensitivity: ≥75% at density of 200 parasites/ul Specificity : ≥ 90%
  • 39. Advantages • Quick to perform (in practice, about 20 minutes) • Sensitive in detecting P.falciparum, which causes severe malaria • Does not require skilled laboratory technicians and can be used by health workers and non health personnel after a few hours of training • Does not require electricity or laboratory equipment
  • 40. False Negative result – Insufficient parasites to register a positive result – RDT kit damaged – Illness by another species of malaria parasite which RDT is not designed to detect
  • 41. False Positive Result – Dead parasite – persistence of malaria gametocytes – individuals with high immunity
  • 42. Rapid Diagnostic Test • Negative RDT should not preclude treatment in a strongly suspected case, especially in severe clinical disease • RDTs do not quantitate P. falciparum parasitemia • Pf HRP-2 based kits may show positive result up to three weeks after successful treatment and parasite clearance.
  • 43. Malaria Serology – antibody detection Immunologic assays to detect host response • Antibodies to asexual parasites appear some days after invasion of RBCs and may persist for months • Positive test indicates past infection • Not useful for treatment decisions
  • 44. Polymerase Chain Reaction • Detect parasite DNA • Highly sensitive • Very useful for detecting mixed infection, particularly at low parasite density • Identify drug resistance • May have use in epidemiological investigations • Not routinely available • Differentiate b/w p.knowlesi and p.malaria , cant be done by microscopy.
  • 46. CLASSIFICATION ON BASIS OF SEVERITY • Uncomplicated malaria • Complicated malaria
  • 47. Uncomplicated malaria • Defined as symptomatic malaria without signs of severity or evidence (clinical or lab) of vital organ dysfunction. • Signs and symptom nonspecific • Suspected clinically on basis of fever or history of fever
  • 48. TREATMENT • Treatment of P. vivax malaria : • Confirmed P. vivax cases should be treated with chloroquine in full therapeutic dose of 25 mg/kg as per the age-wise dosage schedule : NO. OF TABLETS AGE DAY 1 (10 mg /Kg) DAY 2 (10 mg/Kg) DAY 3 (5 mg/Kg) < 1 YEARS 1/2 1/2 1/4 1-4 YEARS 1 1 1/2 5-8 YEARS 2 2 1 9-14 YEARS 3 3 1 1/2 >15 YEARS 4 4 2
  • 49. Prevention of relapse • P. vivax or P. ovale parasites remain dormant in the liver cells in the form of hypnozoites which can later cause a relapse. • For its prevention, primaquine should be given at a dose of 0.25 mg/kg body weight daily for 14 days under supervision. • Primaquine is contraindicated in pregnant women, infants and known G6PD deficient patients.
  • 50. • Primaquine can lead to hemolysis in G6PD deficiency. Caution should be exercised before administering primaquine in areas known to have high prevalence of G6PD deficiency. Patient should be advised to stop primaquine immediately if develops any of the following symptoms and should report to the doctor immediately: (i) dark coloured urine (ii) yellow conjunctiva (iii) bluish discolouration of lips (iv) abdominal pain (v) nausea (vi) vomiting (vii) breathlessness
  • 51. Treatment of Uncomplicated P. falciparum malaria • Artemisinin Combination Therapy (ACT) should be given to all the confirmed P. falciparum cases found positive by microscopy or RDT. • This is to be accompanied by single dose of primaquine (0.75 mg/kg body weight) on Day 2.(0.25 mg/kg –WHO, G-6PD screening not required) • ACT consists of an artemisinin derivative combined with a longacting antimalarial (amodiaquine, lumefantrine, mefloquine, piperaquine or sulfadoxine-pyrimethamine). • The ACT recommended in the National Programme all over India except northeastern states is artesunate (4 mg/kg body weight) daily for 3 days and sulfadoxine (25 mg/kg body weight) – pyrimethamine (1.25 mg/kg body weight) [AS+SP] on Day 0.
  • 52.
  • 53. • In the northeastern states (Arunachal Pradesh, Asom,Manipur, Meghalaya, Mizoram, Nagaland, and Tripura), due to the recent reports of late treatment failures to the current combination of AS+SP in P. falciparum malaria, the presently recommended ACT in national drug policy is fixed dose combination (FDC) of Artemether- lumefantrine (AL). • Although the ACT used in the national programme in NE states is AL and rest of India is AS+SP, the other fixed dose combinations registered for marketing in India are artesunate-amodiaquine, artesunate-mefloquine and arterolane-piperaquine (for adults only) and can be used for treatment of uncomplicated P. falciparum or mixed infections.
  • 54.
  • 55. Treatment of malaria in pregnancy The ACT should be given for treatment of P. falciparum malaria in second and third trimesters of pregnancy, while quinine is recommended in the first trimester. Plasmodium vivax malaria can be treated with chloroquine. Treatment of mixed infections Mixed infections with P. falciparum should be treated as falciparum malaria. Since AS+SP is not effective in vivax malaria, other ACT should be used. However, anti-relapse treatment with primaquine can be given for 14 days, if indicated.
  • 56. Few available fixed dose combinations • CHLOROQUINE –TABLETS-100 ,150 ,300 mg BASE (150 mg base=250 mg phosphate salt or 200 mg sulfate salt) ⮚ Syrup- 50 mg base=5ml • ACT combinations available : ⮚ Falcigo plus kit –artesunate 50 mg + mefloquine 250 mg ⮚ Larinate 200 kit- artesunate 200 mg + sulphadoxine 500 mg+pyrimethamine 25 mg (larinate 50,100 also avialable) ⮚ Larinate –MF :artesunate 200 mg +mefloquine 250 mg ⮚ Tab. Lumerax-20 DT, Combither ,,ARH-L (Artemether 20 mg + lumefantrine120 mg) , lumerax -40 and 80 also available. ⮚ Syp- lumerax-20/120/ 5 ml ⮚ Syp- lumether-40/240/ 5 ml • Primaquine –tablets;7.5 and 15 mg
  • 57. Treatment based on clinical criteria without laboratory confirmation All the efforts should be made to diagnose malaria either by microscopy or RDT. However, special circumstances should be addressed as mentioned below: ● If RDT for only P. falciparum is used, negative cases showing signs and symptoms of malaria without any other obvious cause for fever should be considered as ‘clinical malaria’ and treated with chloroquine in full therapeutic dose of 25 mg/kg body weight over three days. If a slide result is obtained later, the treatment should be completed according to species. ● Suspected malaria cases not confirmed by RDT or microscopy should be treated with chloroquine in full therapeutic dose.
  • 58. General recommendations for the management of uncomplicated malaria • Avoid starting treatment on an empty stomach. The first dose should be given under observation. • Dose should be repeated if vomiting occurs within half an hour of antimalarial intake. • The patient should be asked to report back, if there is no improvement after 48 hours or if the situation deteriorates. • The patient should also be examined and investigated for concomitant illnesses.
  • 59. TREATMENT FAILURE/DRUG RESISTANCE • After treatment patient is considered cured if he/she does not have fever or parasitaemia till Day 28. • Some patients may not respond to treatment which may be due to drug resistance or treatment failure, especially in falciparum malaria.
  • 60. Early treatment failure (ETF): Development of danger signs or severe malaria on Day 1, 2 or 3, in the presence of parasitaemia; ⮚ Parasitaemia on Day 2 higher than on Day 0, irrespective of axillary temperature; ⮚ Parasitaemia on Day 3 with axillary temperature >37.5°C; ⮚ and Parasitaemia on Day 3, >25% of count on Day 0.
  • 61. Late clinical failure (LCF):LATE TRAETMENT FAILURE Development of danger signs or severe malaria in the presence of parasitaemia on any day between Day 4 and Day 28 (Day 42) in patients who did not previously meet any of the criteria of early treatment failure; The presence of parasitaemia on any day between Day 4 and Day 28 (Day 42) with axillary temperature >37°C in patients who did not previously meet any of the criteria of early treatment failure.
  • 62. Late parasitological failure (LPF): Presence of parasitaemia on any day between Day 7 and Day 28 with axillary temperature <37.5°C in patients who did not previously meet any of the criteria of early treatment failure or late clinical failure. Such cases of falciparum malaria should be given alternative ACT or quinine with Doxycycline. Doxycycline is contraindicated in pregnancy, lactation and in children up to 8 years. Treatment failure with chloroquine in P. vivax malaria is rare in India.
  • 63. Algorithm for diagnosis and treatment of malaria
  • 64. SEVERE MALARIA Severe malaria is characterized by one or more of the following features : • Impaired consciousness/coma • Repeated generalized convulsions • Renal failure (Serum Creatinine >3 mg/dl) • Jaundice (Serum Bilirubin >3 mg/dl) • Severe anaemia (Hb <5 g/dl) ,In > 12 years old patients < 7 gm % • Pulmonary oedema/acute respiratory distress syndrome • Hypoglycaemia (Plasma Glucose <40 mg/dl , treatment threshold for < 5 year-54 mg/dl)
  • 65. Severe malaria • Metabolic acidosis • Circulatory collapse/shock (Systolic BP <80 mm Hg, <70 mmHg in children) • Abnormal bleeding and Disseminated intravascular coagulation (DIC)/ Haemoglobinuria • Hyperpyrexia (Temperature >106°F or >42°C) (NVBDCP) • Hyperparasitaemia (>5% parasitized RBCs , WHO- > 10 %) • Prostration (WHO)
  • 66. Diagnosis of severe malaria cases negative on microscopy Microscopic evidence may be negative for asexual parasites in patients with severe infections due to sequestration and partial treatment. Efforts should be made to confirm these cases by RDT or repeat microscopy. However, if clinical presentation indicates severe malaria and there is no alternative explanation these patients should be treated accordingly.
  • 67. Specific antimalarial treatment of severe malaria • Artesunate: 2.4 mg/kg body weight i.v. or i.m. given on admission (time=0), then at 12 and 24 hours, then once a day(Care should be taken to dilute artesunate powder in 5%Sodium bi-carbonate provided in the pack). • Artemether: 3.2 mg/kg body weight i.m. given on admission then 1.6 mg/kg body weight per day.
  • 68. • Quinine: 20 mg quinine salt/kg body weight on admission (i.v. infusion in 5% dextrose/dextrose saline over a period of 4 hours) followed by maintenance dose of 10 mg/kg body weight 8 hourly; infusion rate should not exceed 5 mg/kg body weight per hour. Loading dose of 20 mg/kg body weight should not be given, if the patient has already received quinine. NEVER GIVE BOLUS INJECTION OF QUININE. If parenteral quinine therapy needs to be continued beyond 48 hours, dose should be reduced to 7 mg/ kg body weight 8 hourly. ( WHO -10mg/kg 12 hrly )
  • 69. FOLLOW ON TREATMENT • Once the patient can tolerate oral therapy or after at least 24 hours of parenteral therapy, further follow-uptreatment should be as below: • Patients receiving artemisinin derivatives should get full course of oral ACT. However, ACT containing mefloquine should be avoided in cerebral malaria due to neuropsychiatric complications. • Patients receiving parenteral quinine should also betreated with full course of oral ACT.
  • 70. • In first trimester of pregnancy, parenteral quinine is the drug of choice. • If quinine is not available, artemisinin derivatives may be given to save the life of mother. In second and third trimester, parenteral artemisinin derivatives are preferred
  • 71. Change in recommendations to treat severe malaria (WHO 3RD EDITION-2015)
  • 72.
  • 73. Severe malaria due to P. vivax • In recent years, increased attention has been drawn to severe malaria caused by P. vivax. • Some cases have been reported in India, and there is reason to fear that this problem may become more common in the coming years. • Severe malaria caused by P. vivax should be treated like severe P. falciparum malaria, however, primaquine should be given for 14 days for preventing relapse as per guidelines after the patient recovers from acute illness and can tolerate primaquine.
  • 74. SIDE EFFECTS OF ANTIMALARIALS • Artemether: – Dizziness, reticulocytopenia, neutropenia, elevated liver enzymes, prolonged QT interval, bradycardia • Artesunate: – GI disturbances, cough, rash, arthralgia, delayed hemolysis • Chloroquine: – Pleuritis, headache, hepatitis, widening of QRS and QT interval, nausea, vomiting, retinopathy, keratopathy, hair loss
  • 75. SIDE EFFECTS OF ANTIMALARIALS • Mefloquine: – Hepatitis, polyneuropathy, skin rashes, C/I in cerebral malaria • Primaquine: – Hypertension, cardiac arrythmia • Sulfadoxine-pyrimethamine: – SJS, TEN, Erythema multiforme, C/I in documented megaloblastic anaemia d/t folate deficiency
  • 77. CHEMOPROPHYLAXIS • Chemoprophylaxis is recommended for travellers, migrant labourers and military personnel exposed to malaria in highly endemic areas. • Short-term chemoprophylaxis (less than 6 weeks) Doxycycline: 100 mg daily in adults and 1.5 mg/kg body weight for children more than 8 years old. The drug should be started 2 days before travel and continued for 4 weeks after leaving the malarious area
  • 78. Long-term chemoprophylaxis (more than 6 weeks) • Mefloquine: 5 mg/kg body weight (up to 250 mg) weekly and should be administered two weeks before, during and four weeks after leaving the area. Mefloquine is contraindicated in cases with history of convulsions, neuropsychiatric problems and cardiac conditions
  • 79. Malaria control strategies 1. Early case Detection and Prompt Treatment (EDPT) 2. Vector Control 3. Community Participation 4. Environmental Management & Source Reduction Methods
  • 80. Early case Detection and Prompt Treatment • EDPT is the main strategy of malaria control - radical treatment is necessary for all the cases of malaria to prevent transmission of malaria. • Chloroquine is the main anti-malaria drug for uncomplicated malaria. • Drug Distribution Centres (DDCs) and Fever Treatment Depots (FTDs) have been established in the rural areas for providing easy access to anti-malarial drugs to the community. • Alternative drugs for chloroquine resistant malaria are recommended as per the drug policy of malaria
  • 81. Vector Control • Chemical Control – Use of Indoor Residual Spray (IRS) with insecticides recommended under the programnme – Use of chemical larvicides like Abate in potable water – Aerosol space spray during day time – Malathion fogging during outbreaks • Biological Control – Use of larvivorous fish in ornamental tanks, fountains etc.
  • 82. Mosquito control measures Anti larval environmental Chemical (mineral oil,paris green, fenthion,chlorpyrifos Biological Antiadult Residual spray (DDT, malathion,lindane,OMX## ) Space spray(pyrithrim) Genetic control Personal protection Mosquito net Repellant.(DEET) Screening with copper and bronze
  • 83. Personal Prophylatic Measures • Use of mosquito repellent creams, liquids, coils, mats etc. • Screening of the houses with wire mesh • Use of bednets treated with insecticide • Wearing clothes that cover maximum surface area of the body
  • 84. Community Participation • Sensitizing and involving the community for detection of Anopheles breeding places and their elimination • NGO schemes involving them in programme strategies
  • 85. Environmental Management & Source Reduction Methods • Source reduction i.e. filling of the breeding places • Proper covering of stored water • Channelization of breeding source
  • 86. Resistance of Anopheles culicifacies, to commonly used insecticides in India
  • 87. Malaria vaccine • More than 30 P. falciparum malaria vaccine candidates are at either advanced preclinical or clinical stages of evaluation. • Only the RTS,S/AS01 vaccine has completed Phase 3 evaluation and received a positive regulatory assessment. • WHO has developed a set of principles to ensure the quality, safety, and efficacy of recombinant vaccines targeting pre-erythrocytic and blood stage malaria parasites.
  • 88. • The vaccine has been recommended by WHO for pilot introduction in selected areas of 3 African countries • The vaccine will be made available through routine immunization programmes to young children living in selected areas in Ghana, Kenya and Malawi. At least 360 000 children in the selected areas will be vaccinated.
  • 89. TAKE HOME MESSAGE • Malaria is a potentially life threatening parasitic disease and fortunately treatable. • Acc to WHO 216 million malaria cases reported and about 4.5 lakh deaths. • India .8 million confirmed cases & 104 death in 2017. • Classical sign & symptom may not be present paediatric age group. • All suspected malaria cases should promptly investigated by RDT & microscopy.
  • 90. • Empirical treatment should only be given if illness could not be explained by any cause and if high index of suspicion of malaria • Anti malarial treatment once started should be completed. • Test using ab detection & PCR are not useful for diagnosis • Antibody detecting rapid diagnostic tests are banned in India.
  • 91. • Suspected severe malaria cases should receive pre referral treatment depending upon the availability • Children < 20 kg BW should receive high dose artesunate( 3mg/kg BW)