This document provides information about malaria, including what it is, the species that cause it in humans, its prevalence and severity, symptoms, life cycle, transmission, immunity, diagnosis and treatment. Malaria is a mosquito-borne infectious disease caused by Plasmodium parasites. Four species infect humans: P. vivax, P. malariae, P. falciparum, and P. ovale. It is very common in developing countries, with 300-500 million cases and over 1 million deaths per year. Symptoms include periodic fevers, chills, sweating and flu-like illness. The parasite has stages in both humans and mosquitoes during its life cycle. Diagnosis is by blood smear microscopy

1. Malaria
Dr. Pendru Raghunath Reddy

2. What is malaria?
A mosquito-borne infectious disease caused by
protozoan parasites of the genus Plasmodium
Phylum: Apicomplexa
Class: Sporozoea
Order: Eucoccidea
Suborder: Haemosporina

3.  There
are 156 species of Plasmodium which infect various species
of vertebrates
 Of these only 4 species can infect human beings
1. Plasmodium vivax
2. Plasmodium malariae
3. Plasmodium falciparum
4. Plasmodium ovale
 Of these P. vivax and P. falciparum account for 95% of infections
 Some estimates indicate P. vivax may account for 80% of the
infections

4. The genus Plasmodium is divided into two subgenera
 P. vivax, P. malariae and P. ovale belonging to subgenus
Plasmodium while P. falciparum is allocated to the subgenus
Laverania

5. Is malaria a common disease?
Yes. The World Health Organization
estimates that each year 300-500 million
cases of malaria occur and more than 1
million people die of malaria.

6. Is malaria a serious disease?
Yes. Malaria is a leading cause of death and disease
worldwide, especially in developing countries
Most deaths occur in young children. For example, in
Africa, a child dies from malaria every 30 seconds

7. It’s especially hard on kids
75% of the deaths are among African children

8. 2.1 billion people live in MALARIOUS areas

9. 1907 Nobel Prize for Physiology
or Medicine!
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
www.uhhg.org/mcrh/resources/video/malariappt.pdf

10. Habitat
After passing through the hepatic parenchymal cells, the parasites
reside within RBCs and are carried by blood to various organs
Life cycle
All species of Plasmodium have a life cycle both in man and
various species of anopheline mosquitoes
1. Human cycle (Schizogony)
2. Mosquito cycle (Sporogony)

11. 1. Human cycle
 The parasites in the liver and RBCs multiply asexually
 Man therefore represents the intermediate host
 Human cycle can be divided into three phases
a) Exo-erythrocytic (tissue) phase
b) Erythrocytic phase
c) Gametogony
2. Mosquito cycle
 Sporogony takes place in female anopheline mosquitoes
 Therefore represents the definitive host

12. Malaria Life Cycle
Sporogony
Oocyst
Sporozoites
Mosquito Salivary
Gland
Zygote
Exoerythrocytic
(hepatic) cycle
Gametocytes
Erythrocytic
Cycle
Schizogony
Hypnozoites
(for P. vivax
and P. ovale)

13. Life cycle

14. Morphological features of P. vivax
Early trophozoite (ring form)
Red nucleus on the ring-like light blue cytoplasm
(large, 2.5 µm)

15. Late trophozoite
 It is irregular shape like ameboid form with pseudopodia; within
cytoplasm ,brown pigment granules (malarial pigment--haemozoin) appear
 Infected RBCs are pale in color,and have schuffner’s dots in it
(fine red granules)

16. Immature schizont
 Oval in shape , nucleus divided into 2-4 or
more , malarial pigment begins to concentrate in
a mass
Mature schizont
 Nucleus divided into 12-24 ;and cytoplasm
also divided, each nucleus surrounded by a
portion of cytoplasm to form merozoites,
malarial pigment clumped.

17. Male gametocyte
 Oval in shape; 1 loose nucleus in centre of it ;
malarial pigments diffuse
Female gametocyte
 Oval in shape ; 1 compact nucleus not in centre of it

18. Morphological features of P. falciparum
Early trophozoite (ring form)
 1or 2 red nuclei on the ring-like light blue cytoplasm ; multiple
infection in a cell
P. falciparum: Only the early trophozoites and
gametocytes can be seen in the peripheral blood

19. Male gametocyte
 Sausage in shape; 1 loose nucleus in centre
of it ; malarial pigment diffuse
Female gametocyte
 Crescentic in shape ; 1 compact nucleus in
centre of it

20. Differential characters of malaria parasites
P. vivax
P. falciparum
P. malariae
P. ovale
Hypnozoites
Yes
No
No
Yes
Erythrocyte
preference
Reticulocytes
Young
erythrocytes
Old
erythrocytes
Reticulocytes
As in vivax
As in vivax
Stages found
in blood
Rings,
Only rings
trophozoites,
and
schizonts and gametocytes
gametocytes
Duration of
erythrocytic
schizogony
48 h
48 h
72 h
48 h
Prepatent
period (days)
8
5
13
9
Average
incubation
period (days)
14
12
30
14

21. Schizogenic periodicity and fever patterns
Schizogonic periodicity is length of asexual erythrocytic phase
– 48 hours in P. falciparum, P. vivax and P. ovale (tertian)
– 72 hours in P. malariae (quartan)
Initially may not see characteristic fever pattern if schizogony not
synchronous
With synchrony, periods of fever or febrile paroxsyms assume a
more definite 3 (tertian)- or 4 (quartan)- day pattern

22. Extrinsic Incubation Period
Time required for the development of sexual cycle in mosquitoes
at a given temperature
Pre-patent period
It is the time required for the malaria parasite to appear in the blood
after the bite of infective mosquito
Incubation period
This is an interval between the infective mosquito bite and the first
appearance of clinical symptoms, of which fever is most common
The incubation period varies usually from 8 – 40 days

23. Reservoirs of infection
 Human species of malarial parasites are not harboured by any of the
lower animals
 Hence man, particularly the children in an endemic area act as the
only reservoir of infection
Method of transmission: Infected mosquito bite (Inoculative method)
Transmitting agent: Female anopheles
Infective forms: Sporozoites
Portal of entry: Skin
Site of localisation: First in liver cells, then in erythrocytes

24. Other methods of transmission
1. Trophozoite - induced malaria
Injection of blood from malarial patient containing the asexual forms
of erythrocytic schizogony will also induce malaria in man
a) Transfusion malaria
b) Congenital malaria
c) Malaria in drug addicts
2. Therapeutic malaria

25. Pathogenesis
Infection with Plasmodia causes intermittent fevers which are known
as malaria
Each of the four species causes a characteristic fever and the
disease are designated as follows
P. vivax – Benign tertian malaria (Vivax malaria)
P. malariae – Quartan malaria (Malariae malaria)
P. falciparum – Malignant tertian malaria (Falciparum malaria)
P. ovlae – Ovale tertian malaria (Ovale malaria)

26. Clinical features
The main clinical manifestations in a typical case, are a series of
febrile paroxysms (periodic bouts of fever) with rigor followed by
anaemia and splenic enlargement
Febrile paroxysm
 The malarial fever starts generally in the early afternoon
 The febrile paroxysm comprises three successive stages
1. The cold stage
2. The hot stage
3. The sweating stage

27. 1. The cold stage
 Lasts for 15 – 60 minutes
 The patient experiences intense cold and uncontrollable shivering
2. The hot stage
 Lasts for 2 to 6 hours
 The fever mounts to 410C or higher and the patient feels
intensely hot
 Severe headache, nausea, and vomiting are common

28. 3. The sweating stage
 The patient is drenched in profuse sweat
 The temperature drops rapidly and the patient usually falls into
deep sleep, to wake up refreshed
 The total duration of the febrile cycle is from 8 to 12 hours

29. All clinical manifestations in malaria are due to the products of
erythrocytic schizogony and the host’s reactions to them
The exoerythrocytic liver cycle and gametogony do not appear to
contribute to clinical illness
At the end of erythrocytic schizogony, mature schizont ruptures
and merozoites, malarial pigment and other parasitic debris
will be released
Macrophages and polymorphs phagocytose these and release
large quantities of endogenous pyrogens, leading to elevation of
temperature

30. Recrudescence
 In P. falciparum and P. malariae infections, the parasites are not
completely eliminated after recovery from primary infection
 Erythrocytic schizogony continues in the body at low levels and
gradually the numbers of parasites build up to cross the fever
- threshold
 These new malarial attacks that appear after a period of latency
usually within 8 weeks after the culmination of the primary attack
are called recrudescences

31. Relapse
 In P. vivax and P. ovale infections, the parasite may survive for
long periods in a dormant exoerythrocytic phase as hypnozoites
in liver cells
 Reactivation of those hypnozoites leads to initiation of fresh
erythrocytic cycles, and leads to new attacks of malarial fever
known as relapses
 Relapses occur after long periods, usually from 24 weeks to 5 years
after the primary attack

32. Anaemia
 Anaemia occurs in all types of malaria, but is most pronounced in
falciparum infections
 The type of anaemia is haemolytic, normocytic, normochromic
 Anaemia occurs due to a variety of reasons such as
1. Destruction of parasitised RBCs
2. Hypersplenism
3. Autoimmune lysis of coated infected and uninfected RBCs
4. Decreased RBC production from bone-marrow supression

33. Splenomegaly
 The spleen is invariably affected, being always enlarged in malaria
 Spleen becomes palpable after the second week of fever
 Accumulation of macrophages leads to enlargement of spleen,
which becomes hard due to fibrosis
Malaria in pregnancy
 Malaria of any form may precipitate miscarriage or abortion
 May complicate pregnancy by causing severe anaemia
 Pregnancy also appears to impair immunity and may lead to
a relapse

34. Malaria in children
 Malaria usually does not occur in a classical way in children
 Children commonly develop high fever even from relatively
mild infections
 They may develop convulsions during malarial attack
 Anaemia in children is more marked than in adults
 Dehydration in them develops with greater rapidity as a result of
vomiting and sweating

35. Complications of malaria
The complications are more common due to P. falciparum infection
than due to other three species
Complications of P. falciparum infection
Blackwater fever
 It is seen in patients who have experienced repeated falciparum
malaria infections and inadequately treated with quinine
 Clinical manifestations include bilious vomiting and prostration with
passage of dark red or blackish urine (black water)
 The pathogenesis is believed to be massive intravascular hemolysis
caused by antierythrocyte autoantibodies, leading to
haemoglobinaemia and haemoglobinuria

36. Malignant Tertian Malaria
 The most serious and fatal type of malaria
 Caused by P. falciparum
 When not treated promptly and adequately, dangerous
complications develop

37. Pernicious malaria
 Refers to a complex of life-threatening complications that
sometimes supervenes in acute falciparum malaria
 It results from anoxia due to obstruction of capillaries in various
organs followed by necrosis (death) of tissues
 The symptoms appearing depend on the site where the injury occurs
without immunity to the parasite
 In endemic conditions it is always due to P. falciparum infection

38. Clinical types
 According to the organs affected pernicious malaria may be broadly
divided into three groups
1. Cerebral malaria
 Manifested by hyperpyrexia, coma, paralysis
2. Algid malaria
 Resembles surgical shock, characterised by cold and clammy skin
with vascular collapse leading to peripheral circulatory failure and
profound hypotension
 Gastro-intestinal system may be involved leading to vomiting
(gastric type) or watery diarrhoea (choleraic type) or passage of
blood in faceces (dysenteric type)

39. 3. Septicaemic malaria
 Characterised by high continued temperature (resembling typhoid
-fever), high degree of prostration, bilious remittent fever,
and pneumonia
 Acute renal failure and acute pulmonary oedema are other
serious complications

40. Tropical splenomegaly syndrome
 Also known as hyper-reactive malarial splenomegaly (HMS) is
a chronic benign condition seen in some adults in endemic areas
 This results from an abnormal immunological response to malaria
and is characterised by
1. Enormous splenomegaly
2. High titres of circulating antimalaria antibody
3. Absence of malaria parasites in peripheral blood smears
4. Reduced C3 and presence of rheumatoid factor without arthritis
5. Normocytic, normochromic anaemia is present, not responding to
haematinics or anthelmentics

41. Immunity
 Immunity in malaria may be classified into innate immunity
and acquired immunity
1. Innate immunity
2. Acquired immunity
Innate immunity
 Only little is known about innate immunity in malaria

42. But a few naturally occuring examples illustrate its importance
 Persons who lack the Duffy blood group antigen (Fya FyB)
are refractory to infection by P. vivax
 P. falciparum does not multiply properly in sickle red cells containing
abnormal haemoglobin S
 G6PDH deficiency and HLA-B53 is associated with protection from
falciparum malaria
 There is some evidence that severe malnutrition and iron deficiency
may confer some protection against malaria

43. Acquired immunity
 Infection with malaria parasites induces specific immunity which can
bring about clinical cure but cannot lead to complete elimination of
parasites from the body
 It can prevent superinfection. This state of resistance in an infected
host, which is associated with continued asymptomatic parasitic
infection is called premunition
Protective immunity against malaria includes
1. Humoral immunity (IgM, IgG and IgA antibodies)
2. Cell Mediated Immunity (CMI)

44.  The immunity produced is species-specific, stage-specific and
strain-specific
 The mechanisms employed by the malarial parasite to persist in the
host are not known but may include
1. Antigenic variation
2. Sequestration in a protected site such as liver and/ or
3. Supression of host immune responses

45. Laboratory diagnosis of malaria
 Clinical diagnosis of malaria can be made with considerable
confidence in residents of endemic areas and recent visitors
but confirmation requires the finding of parasites in blood smear
The most important method for the diagnosis of malaria is the
demonstration of the parasite in blood
Site of sampling
 The concentration of malarial parasites is fairly homogenous
throughout circulatory system, so the sample can be taken either
from peripheral blood or internal blood

46. Two kinds of smears are prepared from the peripheral blood
1. Thin smear
2. Thick smear

47. Time of collection
Parasites are abundant in peripheral blood late in the febrile
paroxysm, a few hours after the peak of the fever
Fixation of the smear
Thin film is fixed in methanol for 30 seconds
Thick film is not fixed as it is to be dehaemoglobinised

48. Staining
The smears are stained by JSB stain, Field’s or Giemsa stain
Why make thin and thick smears?
 Thick smears have more quantity of blood in a smaller area, so that
the parasites are concentrated in this area, hence chances of
detection of malaria parasite are more in a thick smear
 But one disadvantage is that morphology of the parasite is not clear
 Thin smears are less sensitive for detection of malaria parasites but
better for species identification

49. Morphological features in thin films
 The cytoplasm of the parasite stained blue
 The nucleus, known as chromatin is stained red
 There is central unstained portion called vacuole in the early stages
 Pigment granules of different colours are found on the cytoplasm
and vacuole
 Stippling appears as pink dots. These are inside the RBC but lie on
the outside of the parasite

50. Some notable features in malaria morphology include:
 Enlargement of RBCs in P. vivax infection
 Multiple invasion of RBCs by ring forms is more common in
P. falciparum infection
 In P. falciparum, only ring stages and gametocytes are seen in the
peripheral blood
 Gametocytes of all other species are round except that of
P. falciparum where these are crescent shaped
 The pigment is black in P. malariae infection

51. P. vivax
P. ovale

52. P. malariae
P. falciparum

55.  It is recommended that 200 oil immersion fields should be examined
before a thick film is declared negative
 When parasites are found, an approximate quantitative estimate
may be given as follows
+ = 1-10 parasites per 100 thick film fields
++ = 11-100 parasites per 100 thick film fields
+++ = 1-10 parasites per each thick film field
++++ = More than 10 parasites per each thick film field

56. QBC (Quantitative Buffy Coat) technique

57. Immunodiagnosis
 Detection of parasite-specific antigens using monoclonal antibodies
 The Para Sight –F test (BD) is a dip-stick antigen capture test
targeting the “histidine-rich protein-2” (HRP-2), specific for
P. falciparum
 Dipstick tests are also available for vivax malaria
 Various serological tests such as IHA, IFA, ELISA, RIA and agar gel
-diffusion have been investigated or applied for the diagnosis of
malaria
 However, serological tests are not employed for routine diagnosis

58. Treatment
The various antimalarial drugs are grouped as follows
1. Essentially therapeutic (Clinical cure)
 Chloroquine, quinine, mefloquine
 To destroy exoerythrocytic parasites, a tissue schizonticidal drug
such as primaquine should be administered
2. Protective or prophylactic
 Proguanil, pyrimethamine and trimethoprim

59. Prophylaxis
1. Personal prophylaxis
2. Chemoprophylaxis
 The drugs recommended for chemoprophylaxis are chloroquine,
amodiaquin and fansidar in weekly doses or doxycycline daily
 No vaccine is now available
Control