Malaria Etiology, Pathogenesis, Clinical features, Diagnosis, Management

1. MALARIA
1
DR SHAHNAWAZ F SHAH
MD, FPM, FIAPM,FCPM (MUHS)
Interventional Spine & Pain Physician
Surat

2. ROLE OF PHYSIOTHERAPIST
in MALARIA
Having the knowledge about Malaria
Awareness about Malaria, its types, classification, about
cerebral malaria which can lead to neurological symptoms and
seizures, diagnosis, management and prevention
If while taking history you figure it to be Malaria, refer the
patient to the physician
Also make sure you make the patient aware about the
condition and consequences of not undergoing the medical
management.

3. What does Malaria mean?
T h e word “malaria” comes from the
Italian word
Mal = “bad”
Aria = “air”
When the term was coined, it was
commonly believed that malaria was
caused by breathing in bad air.

4. Overview
 Malaria is a mosquito-borne parasitic disease caused by
genus Plasmodium, affecting over 100 countries of the
tropical and subtropical regions of the world.
 Around 400-900 million people are affected
 At least 2.7 million deaths annually
 It is one of the major public health concerns

5. Epidemiology
 Around 300-500 million clinical cases of malaria are reported
every year, of which more than a million die of severe and
complicated cases of malaria.
 Malaria is known to kill one child every 30 sec, 3000
children per day under the age of 5 years.
 Major infectious diseases in causing deaths:
1. Pneumococcal acute respiratory infections
2. Tuberculosis
3. Malaria
 Accounts for approximately 2.6% of the total disease burden of
the world.

6. It was discovered
more than 100 years ago
6
A French army doctor in
Algeria observed
parasites inside red
blood cells of malaria
patients and proposed
for the first time that a
protozoan caused
disease
Charles Louis Alphonse
Laveran

7. • Ronald Ross
discovered that
mosquitoes transmitted
malaria in 1898.
RONALD ROSS DISCOVERS THE ROLE OF
MOSQUITOS AND TRANSMISSION
7

8. MALARIA – HOT SPOTS
GEOGRAPHIC DISTRIBUTION
8

9. Causative Agent
 Malaria is caused by species of Plasmodium, protozoan
parasite
 The genus Plasmodium contains over 200 species
 Most important are:
 Plasmodium falciparum
 Plasmodium malariae
 Plasmodium ovale
 Plasmodium vivax
 Plasmodium knowlesi (2004)
 Plasmodium parasites are highly specific with female
Anopheles mosquitoes

10. Vector
FEMALE mosquitos of genus ANOPHELES
are primary hosts and transmission vectors.
There are approximately 460 recognized species
 Only 30–40 commonly transmit parasites of the genus
Plasmodium
 Anopheles gambiae is one of the best known which
transmits Plasmodium falciparum

11. Vector
 O n l y f e m a l e mosquitoes feed on blood
while the males feed on plant nectar and do not
transmit the disease.
 T h e females of Anopheles genus preferto
feed at night
 T h e y start searching for a meal at dusk &
continue throughout the night until they take a
meal

12. WHAT DETERMINES THE SPREAD
OF MALARIA?
12
Malaria spread
depends on:
 Rainfall pattern
(How does this affect mosquito breeding?)
 Types of mosquitoes in the area
 How close are people to the breeding sites? Some
areas constantly have a high rate of malaria.
 Other areas have “malaria seasons” or occasional
epidemics of malaria.

13. MALARIA – VECTORS
13
Anopheles balabacensis
A. freeborni
A. gambiae
A. stephensi

14. MOSQUITOES AND MALARIA
14
• The spread of malaria depends
on the life cycle of the
mosquito.
• Adult mosquitoes lay their eggs
on water.
• The eggs hatch to become
larvae and then pupae, before
turning into adults.
• Adult females mosquitoes only
live 2 to 4 weeks.
• So you can reduce malaria by
attacking any of these four
stages of the mosquito.

16. Sporozoites
injected
Invade liver cells
(exoerythrocytic
schizogony)
Merozoites
Invade RBCs
(erythrocytic
schizogony)
Gametocytes
(infective for
mosquito)

17. gametocytes entry while
feeding
fusion of gametes in gut
sporogony on gut wall in
hemocoel
sporozoites invade salivary
glands
Ready for spread

18. CHARACTERISTIC OF LIFE CYCLE
18
• Intermediate host : human
• Final host : mosquito
• Infective stage : sporozoite
• Infective way : mosquito bite skin of human
• Parasitic position : liver and red blood cells
• Transmitted stage : gametocytes

19. MORPHOLOGY
19
• Malarial parasite trophozoites are generally
ring shaped, 1-2 microns in size, although
other forms (ameboid and band) may also
exist.
• The sexual forms of the parasite
(gametocytes) are much larger and 7-14
microns in size.
• P.falciparum is the largest and is banana
shaped, while others are smaller and
round.

20. Hyponozoite Forms
20
• Hypnozoites are dormant forms in the life
cycles of certain parasitic protozoa
• some EE forms exhibit delayed replication
(ie, dormant)
• merozoites produced months after initial
infection
• only P.vivax and P.ovale
relapse = hypnozoite

21. INCUBATION PERIOD
21
 Following the infective bite by the Anopheles
mosquito a period of time (the "incubation
period") goes by before the first symptoms appear.
 The incubation period in most cases varies from
7 to 30 days.
 The shorter periods are observed most
frequently with P.falciparum and the longer ones
with P. malariae.

22. Clinical Features
22
 Characterized by acute febrile attacks (malaria
paroxysms)
• periodic episodes of fever alternating with
symptom-free periods
 Manifestations and severity depend on species and host
status
• immunity, general health, nutritional state, genetics
 Recrudescences and relapses can occur over months or
years
 can develop severe complications (especially P.
falciparum)

23. SIGNS AND SYMPTOMS OF
MALARIA
23
Fever and flu-like illness
Shaking chills
Headache
Muscle aches and tiredness.
Nausea, Vomiting, and Diarrhea
Anemia and jaundice

24. 

25. UNCOMPLICATED MALARIA
25
The classical malaria attack lasts 6-10
hours.
It consists of:
1. COLD STAGE (sensation of cold,
shivering)
2. HOT STAGE (fever, headaches,
vomiting; seizures in young children)
3. SWEATING STAGE (sweats, return to
normal temperature, tiredness)

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

27. Clinical Features

P. vivax & P. ovale (benign tertian)
 Starts with several days of continued fever before the
development of classical bouts of fever on alternate days.
 Fever starts with a rigor.
 The patient feels cold and the temperature rises to about
40 C.
 After an hour hot or flush phase begins.
 It lasts several hours and gives way to profuse
perspiration and a gradual fall in temperature.
 The cycle is repeated 48 hours later.
 Anemia develops slowly

28. Clinical Features

P. Malariae infection (quartan)
 This is usually associated with mild symptoms a
n
d
bouts
of fever every third day.
 Parasitemia may persist for many years with the
occasional recurrence of fever, or without producing
any symptoms.

29. Clinical Features

P. Falciparum (malignant tertian)
 It is the most dangerous of the malarias
 Onset is insidious, with malaise, headache and
vomiting… commonly mistaken for influenza
 The fever has no particular pattern.
 Jaundice is common due to hemolysis & hepatic
dysfunction
 There is hepato-splenomegaly
 Anemia develops rapidly

30. P. Falciparum complications:
 Cerebral Malaria: the most grave complication,
causing either confusion or coma without localizing
signs.
 Convulsions
 Hypoglycemia
 Acute pulmonary edema
 Acute renal failure (Blackwater fever )
 Metabolic acidosis
 Aspiration pneumonia
 Severe anemia
 Coagulopathy/Spontaneous bleeding
Clinical Features


31. IS IT FALCIPARUM?
31
• WHAT DOES THE SMEAR SHOW?
• >3% PARASITEMIA
• MONOTONOUS SMALL RINGS
• NO TROPHOZOITES OR SCHIZONTS
• BANANA SHAPED GAMETOCYTES
• MULTIPLY INFECTED CELLS
• APPLIQUE FORMS
• CELLS OF ALL SIZES INFECTED

32. Malaria caused by P.falciparum. is more severe
than that caused by other plasmodia.
The serious complication of P.falciparum involves
 cerebral malaria (involving the brain);
 massive haemoglobinuria (blackwater fever) in
which the urine becomes dark in color, because
of acute hemolysis of RBC;
 acute respiratory distress syndrome;
 severe gastrointestinal symptoms;
 shock and renal failure which may cause death.
32
MALIGNANT MALARIA

33. 
CLINICAL
 Fever, sweat, chills, headache and muscle pain
SEROLOGY
 PCR
 ELISA
BLOOD FILM (GOLD STANDARD)
 Banana-shaped intraerythrocytic gametocytes identify P.
falciparum
 Enlarged erythrocytes with Schuffner’s dots are
characteristics of P. vivax
 Schuffner’s dots in ovale-shaped red blood cells are
characteristic of P. ovale
 Band-form trophozoites are seen in P. malariae
Diagnosis

34. LABORATORY DIAGNOSIS
Laboratory diagnosis of malaria is confirmed by the
demonstration of malarial parasites in the
blood filmunder microscopic examination
• Thin film
• Thick film
34

35. 

36. HOW THE PARASITE APPEARS IN
BLOOD SMEAR
36

37. GAMETOCYTES
37
Male gametocyte Female gametocyte
Note: compact cytoplasm and absence of
nuclear division.

38. GAMETOCYTE OF P.
FALCIPARUM
38
banana shaped gametocyte ( P. falciparum)

39. Detects circulating
malaria antigens in
whole blood.
15 minute test
The only FDA
approved rapid
malaria test.
BinaxNOW® Malaria

ANTIGEN DETECTION METHODS

40. • Serology detects antibodies
against malaria parasites, using
either indirect
immunofluorescence (IFA) or
enzyme-linked immunosorbent
assay (ELISA).
• Serology does not detect current
infection but rather measures
past exposure.
SEROLOGY IN MALARIA
40

41. • Parasite nucleic acids are detected
using polymerase chain reaction
(PCR).
• More sensitive than smear
microscopy
• Limited utility for the diagnosis of
acutely ill patients in the standard
healthcare setting.
• PCR results are often not available
quickly enough to be of value in
establishing the diagnosis of malaria
infection.
MOLECULAR DIAGNOSIS OF MALARIA
41

42. • PCR is most useful
for confirming the
species of malarial
parasite after the
diagnosis has been
established by
either smear
microscopy or
RDT.
PCR IS USEFUL IN SPECIES
DETECTION
42

43. Currently registered antimalarial
drugs in India
2nd ed. New Delhi: NIMR; 2011. National Institute of Malaria Research (NIMR). Guidelines
for diagnosis and treatment of malaria in India.

44. Treatment of severe falciparum malaria
Preferred regime Alternative regime
IV Artesunate (60mg): 2.4mg/kg on
admission, followed by 2.4mg/kg at 12h &
24h, then once daily for 7 days.
Once the patient can tolerate oral therapy,
treatment should be switched to a complete
dosage of Riamet (artemether/lumefantrine)
for 3 day.
IV Quinine loading 7mg salt /kg over 1hr
followed by infusion quinine 10mg salt/kg over 4
hrs, then 10mg salt/kg Q8H or IV Quinine
20mg/kg over 4 hrs, then 10mg/kg Q8H.
Plus
Adult & child >8yrs old: Doxycycline (3.5mg/
kg once daily)
or
Pregnant women & child < 8yrs old:
Clindamycin (10mg/kg twice daily). Both drug
can be given for 7 days.
Reconstitute with 5% Sodium Bicarbonate &
shake 2-3min until clear solution obtained. Then
add 5ml of D5% or 0.9%NaCl to create total
volume of 6ml.
Slow IV injection with rate of 3-4ml/min or
IM injection to the anterior thigh.
The solution should be prepared freshly for
each administration & should not be stored.
Dilute injection quinine in 250ml od D5%
and infused over 4hrs.
Infusion rate should not exceed 5 mg salt/kg
per hour.

45. Treatment of uncomplicated p.falciparum

46. Treatment of malaria caused by P.Knowlesi
& mixed infection(P. Falciparum + P.Vivax)
Treat as p. falciparum

47. Treatment of of malaria caused by p.vivax, p. ovale or
p. malariae.
PRIMAQUINE
(7.5 mg
base/tab)
CHLOROQUINE
(150 mg base/tab) 25 mg
base/kg divided over 3 days
Day 1 Day 2 Day 3 Start concurrently with CHLOROQUINE
0.5 mg base/kg Q24H for 2 weeks
Take with food
Check G6PD status before start primaquine
In mild-to-moderate G6PD deficiency,
primaquine 0.75 mg base/kg body weight
given once a week for 8 weeks.
In severe G6PD deficiency, primaquine is
contraindicated and should not be used.
10mg
base/kg
stat,
then
5mg
base/kg
5mg
base/kg
Q24H
5mg base/
kg Q24H
1 tab of chloroquine phosphate 250mg equivalent to 150mg base. Calculation of
dose for chloroquine is based on BASE, not SALT form. 1 tab of primaquine
phosphate contains 7.5mg base.

48. Treatment in specific population & situations
Specific
populations
Preferred regime Alternative regime
Pregnancy Quinine plus clindamycin to be given for 7
day
Artesunate plus Clindamycin for 7
days is indicated if first line
treatment fails
Lactating
women
Should receive standard antimalarial treatment (including ACTs) except for
dapsone, primaquine and tetracyclines, which should be withheld during
lactation
Hepatic
impairment
Chloroquine: 30-50% is modified by liver, appropriate dosage adjustment is
needed, monitor closely.
Quinine : Mild to moderate hepatic impairment-no dosage adjustment,
monitor closely.
Artemisinins : No dosage adjustment
Renal
Impairment
Chloroquine : ClCr<10ml/min-50% of normal dose.
Hemodialysis, peritoneal dialysis: 50% of normal dose.
Continuous Renal Replacement Therapy(CRRT) :100% of normal dose.
Quinine : .ClCr 10-50ml/min : Administer Q8-12H, CLCr<10ml/min : administer
Q24H,Severe chronic renal failure not on dialysis : initial dose: 600mg followed
by 300mg Q12H, Hemo- or peritoneal dialysis: administer Q24H ,Continuous
arteriovenous or hemodialysis: Administer Q8-12H. Artemisinin : no dosage
adjustment.

49. Treatment of complications of malaria
• Severe & complicated falciparum or
knowlesi malaria is a medical
emergency that requires intervention
and intensive care as rapidly as
possible.
• Fluid, electolyte glucose & acid-base balance
must be monitored.Intake & output should be
carefully recorded.

50. Immediate clinical management of severe manifestations and
complications of P. falciparum malaria
Definitive clinical
features
Immediate management/treatment
Come (Cerebral malaria) Monitor & record level of consciousness using Glaslow
coma scale, temperature, respiratory, and depth, BP and
vital signs.
Hyperpyrexia (rectal
body temperature
>40°C)
Treated by sponging, fanning &with an antipyretic drug.
Rectal paracetamol is preferred over more nephrotoxic
drugs (e.g. NSAIDs)
Convulsions A slow IV injection of diazepam(0.15mg/kg, maximum
20mg for adults).
Hypoglycaemia
(glucose conc.
<2.8mmol/L)
Correct with 50% dextrose (as infusion fluids). Check
blood glucose Q4-6H in the first 48hrs.
Severe anaemia (hb
< 7g/dl)
Transfuse with packed cells. Monitor carefully to avoid fluid
overload. Give small IV dose of frusemide, 20mg, as
necessary during blood transfusion to avoid circulatory
overload.
Acute pulmonary oedema Prop patient upright (45°), give oxygen, give IV diuretic
(but most patient response poorly to diuretics), stop
intravenous fluids. Early mechanical ventilation should be
considered.

51. Immediate clinical management of severe manifestations and
complications of P. falciparum malaria (cont.)
Definitive clinical
features
Immediate management/treatment
Acute renal failure
(urine output <400ml in
24hrs in adults or
0.5ml/kg/hr, failing to
improve after
rehydration & a serum
creatinine of
>265μmol/L)
Exclude pre-renal causes by assessing hydration status.
Rule out urinary tract obstruction by abdominal
examination or ultrasound.
Give intravenous normal saline
If in established renal failure add haemofiltration
or haemodialysis, or if unavailable, peritoneal
dialysis.
Disseminated
intravascular
Coagulopathy
(DIVC)
Transfuse with packed cell, clotting factors or platelet.
Usual regime: Cryoprecipitate 10units,platelets 4-
8units, fresh frozen plasma(10-15ml/kg).
For prolonged PT, give vitamin K, 10mg by slow IV
injection.
metabolic acidosis Infuse sodium bicarbonate 8.4% 1mg/kg over 30min
and repeat if needed.
if severe, add haemodialysis.
Shock (hypotension
with systolic blood
Suspect septicaemia, take blood for cultures; give
parenteral broad-spectrum antimicrobials, correct

52. Monitoring & follow-up
• Blood smear should be repeated daily (twice daily
in severe infection).
• Within 48-72 hr after start of treatment, patients
usually become afebrile and improve clinically
except in complicated cases
• All patients should be investigated with repeated
blood film of malarial parasite one month upon
recovery of malarial infection, to ensure no
recrudescence.

53. • Use mosquito
repellants.
• Wear long pants
and long sleeves.
• Wear light-
colored clothes.
• Use window
screens
• Use bed nets.
WHAT ARE WAYS TO PREVENT
MOSQUITO BITES?
53

54. INSECTICIDE-TREATED NETS (ITNS)
ITNS estimated to be twice as effective as
untreated nets and offer greater than 70%
protection compared with no net.
54

55. ORIGINAL ERADICATION PLANS
( VECTOR CONTROL)
• Interruption of
transmission of main
species infecting
humans by DDT
spraying
• Malaria disappears
spontaneously in
under 3 years
5
6

56. OTHER WAYS TO PREVENT MALARIA
56
Who is at the highest risk of malaria?
• Travelers to an area high in malaria
• Travelers often take prophylactic
(preventive) medicines to prevent
malaria.
• Pregnant women (especially those with HIV)
• Pregnant women are given intermittent
preventive treatment. They are given at
least 2 doses of a malaria drug during their
pregnancy.
• Young children

57. 
Antimalarial tablets Adult prophylactic
dose
Regimen
Chloroquine resistance high
Mefloquine 250mg weekly Started 2-3 weeks before
travel and continued until
4 weeks after
or Doxycycline 100mg daily Started 1 week before
and continued until 4
weeks after travel
Or Malarone 1 tablet daily From 1-2 days before
travel until 1 week after
return
Chloroquine resistance absent
Chloroquine 300mg base weekly Started 1 week before
& continued until 4
weeks after travel
and proguanil 100-200mg daily
Chemoprophylaxis

58. MALARIA VACCINE
58
First proposed in 1960s, still nothing fully effective
Difficulties include :
 Intracellular parasites
 Polymorphism and clonal variation
 Parasite induced immunosuppression
 Antigenic variation
 Evaluation and trials difficult to interpret
 High level of parasite mutation

59. 
Education in recognizing the symptoms of
malaria has reduced the number of cases in
some areas of the developing world by as
much as 20%.
Recognizing the disease in the early stages
can also stop the disease from becoming a
killer.
Education

60.  Education can also inform people to cover over areas
of stagnant, still water which are ideal breeding
grounds for the parasite and mosquito, thus cutting
down the risk of the transmission between people.
 This is most put in practice in urban areas where
there are large centers of population in a confined
space and transmission would be most likely in these
areas.
Education

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