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
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
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
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
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
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