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MALARIA
Dr. Anand S M.D (AYU)
Assistant Professor
Department of Roga nidana evum Vikriti Vigyana
Global Institute of Ayurveda, Rajkot
Contents
 Introduction
 History
 Incidence and Prevalence
 Epidemiology
 Cause
 Pathophysiology
 Signs and symptoms
 Classification
 Diagnosis
 Risk factors
 Complications
 Articles and Publications
 References
2
Introduction
 Malaria is a mosquito-borne infectious disease affecting humans and other animals
caused by parasitic single-celled microorganisms belonging to the Plasmodium group.
 Malaria causes symptoms that typically include fever, tiredness, vomiting
and headache.
 In severe cases it can cause yellow skin, seizures, coma or death.
 Symptoms usually begin 10 to 15 days after being bitten by an infected mosquito.
3
 The disease is most commonly transmitted by an infected female Anopheles mosquito.
 The mosquito bite introduces the parasites from mosquito's saliva into a person's blood.
 The parasites travel to the liver where they mature and reproduce.
 If not properly treated, people may have recurrences of the disease months later.
 In those who have recently survived an infection, reinfection usually causes milder
symptoms.
4
 This partial resistance disappears over months to years if the person has no continuing
exposure to malaria.
 Five species of Plasmodium can infect and be spread by mosquitoes.
 Most deaths are caused by P. falciparum because P. vivax, P. ovale
and P. malariae generally cause a milder form of malaria.
 The species P. knowlesi rarely causes disease in humans.
5
 The parasite responsible for P. falciparum malaria has been in existence for 50,000 –
100,000 years, the population size of the parasite did not increase until about 10,000
years ago, concurrently with advances in agriculture and the development of human
settlements.
 Close relatives of the human malaria parasites remain common in chimpanzees.
 Some evidence suggests that the P. falciparum malaria may have originated in gorillas.
 References to the unique periodic fevers of malaria are found throughout recorded
history.
6
History
7
 Hippocrates described periodic fevers, labelling them tertian, quartan, subtertian and
quotidian.
 The term malaria originates from Medieval Italian: mala aria—"bad air"; the disease
was formerly called ague or marsh fever due to its association with swamps and
marshland.
 The term first appeared in the English literature about 1829.
 Malaria was once common in most of Europe and North America,where it is no longer
endemic, though imported cases do occur.
 Scientific studies on malaria made their first significant advance in 1880, when Charles
Louis Alphonse Laveran—a French army doctor working in the military hospital
of Constantine in Algeria—observed parasites inside the red blood cells of infected
people for the first time.
 He, therefore, proposed that malaria is caused by this organism, the first time
a protist was identified as causing disease.
8
Incidence and Prevalence
 Globally, an estimated 3.4 billion people in 91 countries and
territories are at risk of being infected with malaria and developing
disease and 1.1 billion are at high risk.
 According to the World Malaria Report 2016, there were 212 million
cases of malaria globally in 2015 and 429 000 malaria deaths (range
235 000–639 000), representing a decrease in malaria cases and
deaths of 22% and 50% since 2000 respectively.
 The burden was heaviest in the WHO African Region, where an
estimated 92% of all malaria deaths occurred and in children aged
under 5 years, who accounted for more than two thirds of all deaths.
9
 The disease is widespread in the tropical and subtropical regions that exist in a broad
band around the equator.
 This includes much of Sub-Saharan Africa, Asia and Latin America.
 In 2016, there were 216 million cases of malaria worldwide resulting in an estimated
445,000 to 731,000 deaths.
 Approximately 90% of both cases and deaths occurred in Africa.
 Rates of disease have decreased from 2000 to 2015 by 37%,but increased from 2014
during which there were 198 million cases.
10
 Malaria is prevalent in tropical and subtropical regions because of rainfall, consistent
high temperatures and high humidity, along with stagnant waters in which mosquito
larvae readily mature, providing them with the environment they need for continuous
breeding.
 In drier areas, outbreaks of malaria have been predicted with reasonable accuracy by
mapping rainfall.
11
Epidemiology
 The WHO estimates that in 2015 there were 214 million
new cases of malaria resulting in 438,000 deaths.
 Others have estimated the number of cases at between
350 and 550 million for falciparum malaria.
 The majority of cases (65%) occur in children under 15
years old.
 About 125 million pregnant women are at risk of infection
each year; across the world, maternal malaria is associated
with up to 200,000 estimated infant deaths yearly.
12
13
 The Malaria Atlas Project aims to map global endemic levels of malaria, providing a
means with which to determine the global spatial limits of the disease and to
assess disease burden.
Malarial Atlas Project
The Malaria Atlas Project, abbreviated as MAP, is a non-profit project funded primarily
by the Medical Research Council.
MAP aims to disseminate free, accurate and up-to-date information on malaria and
associated topics, organised on a geographical basis.
The MAP team have assembled a unique database derived from medical intelligence and
satellite-climate data.
It constrains the limits of malaria transmission and the largest archive of community-
based estimates of parasite prevalence.
14
Epidemiology in India
 During the latter parts of nineteenth and early twentieth centuries, nearly one-fourth of India’s
population suffered from malaria, particularly in the states like Punjab and Bengal.
 At the time of independence in 1947, of a population of 330 million, about 75 million people were
estimated to be infected with malaria every year, and the direct mortality due to the disease was
estimated at 0.8 million per annum.
 To combat this menace, the Govt. of India launched the National Malaria Control Programme in April
1953.
 Encouraged by this, the programme was changed to a more ambitious National Malaria Eradication
Programme in 1958.
World Malaria Report 2017
 According to the World Malaria Report 2017, in the year 2016, more than half of
the population (698 million) was at risk of malaria.
 According to the Report, India accounted for 6% of all malaria cases in the world,
6% of the deaths and 51% of the global P. vivax cases.
 The Report estimates the total cases in India at 1.31 million and deaths at 23990.
15
Structure and Stages of Plasmodium Larva
16
17
Nucleus
Nuclear coated
vesicles
Dense
granules
Rough
endoplasmic
Reticulum
Microtubule
Micronemes
Rhoptry
Polar
rings
Apicoplast
Stages of Larva
18
Sporozoites Schizont
Merozoite Trophozoite
Gametocyte
Species of Larva
19
Sl. No. Species Ring form Trophozoite Schizont Gametocyte Change in
RBCs
1. P. vivax Single Irregular Larger
than RBC
Round Enlarged,
pale
2. P. malariae Single Band
shaped
Smaller
than RBC
Round,
small
Not
enlarged,
fine pink
granules
3. P. falciparum More than
one ring in
red cell
Not seen Not seen Crescent
shaped
Normal
size
4. P. ovale Single ----- Smaller
than RBC
Oval, small Enlarged,
oval
Causes
 Malaria parasites belong to the genus Plasmodium (phylum Apicomplexa).
 In humans, malaria is caused by P. falciparum, P. malariae, P. ovale, P. vivax and P. knowlesi.
 Among those infected, P. falciparum is the most common species identified (~75%)
followed by P. vivax (~20%).
 Although P. falciparum traditionally accounts for the majority of deaths, recent evidence
suggests that P. vivax malaria is associated with potentially life-threatening conditions
about as often as with a diagnosis of P. falciparum infection.
 P. vivax proportionally is more common outside Africa.
 There have been documented human infections with several species
of Plasmodium from higher apes; however, except for P. knowlesi—a zoonotic species that
causes malaria in macaques.
20
21
Life cycle
Recurrent
malaria
Climate change
Life of larva 22
Sexual Cycle
Female
Anopheles
mosquito
Asexual Cycle
In human
beings
Definitive
host
Intermediate
host
23
Blood stage
Liver
stage
Mosquito
stage
24
Sporozoites
Liver
Merozoites
Trophozoites
Male & Female
gametocytes Gametes
Infected
female
Anopheles
mosquito
Schizont
25
Zygote
Oocyst
1
Microgametocyte
Ookinete
Increase in size
26
Midgut
sporozoites
Transmission
to human
beings
Salivary
sporozoites
27
First vector
Liver
infection
Initial
human
host
Blood
infection
Second
vector
Next
human
host
In utero
transmission
Recurrent malaria
 Symptoms of malaria can recur after varying symptom-free periods.
 Depending upon the cause, recurrence can be classified as
either recrudescence, relapse or reinfection.
 Recrudescence is when symptoms return after a symptom-free period.
 It is caused by parasites surviving in the blood as a result of inadequate or ineffective
treatment.
28
29
 Relapse is when symptoms reappear after the parasites have been eliminated from blood
but persist as dormant hypnozoites in liver cells.
 Relapse commonly occurs between 8–24 weeks and is often seen
in P. vivax and P. ovale infections.
 However, relapse-like P. vivax recurrences are probably being over-attributed to
hypnozoite activation.
 Some of them might have an extra-vascular merozoite origin, making these recurrences,
recrudescences not relapses.
30
 Reinfection means the parasite that caused the past infection was eliminated from the
body but a new parasite was introduced.
 Reinfection cannot readily be distinguished from recrudescence, although recurrence
of infection within two weeks of treatment for the initial infection is typically attributed
to treatment failure.
 People may develop some immunity when exposed to frequent infections.
Climate change
 Global climate change is likely to affect malaria transmission, but the degree of effect
and the areas effected is uncertain.
 Greater rainfall in certain areas of India and following an El Nino event is associated
with increased mosquito numbers.
31
Pathophysiology
32
• involves the liver
Exoerythrocytic
phase
• involves red blood
cells or erythrocytes
Erythrocytic
phase
2 Phases
33
Sporozoites
Beginning of
Exoerythrocytic phase
34
Merozoites
Merozoites
Merozoites
Merozoites
Rupture
of host
cells
Beginning of Erythrocytic
phase
35
 The parasite escapes from the liver undetected by wrapping itself in
the cell membrane of the infected host liver cell.
 Within the red blood cells, the parasites multiply further, again asexually,
periodically breaking out of their host cells to invade fresh red blood cells.
Several such amplification cycles occur.
 Thus, classical descriptions of waves of fever arise from simultaneous
waves of merozoites escaping and infecting red blood cells.
 Some P. vivax sporozoites do not immediately develop into
exoerythrocytic-phase merozoites, but instead, produce hypnozoites
that remain dormant for periods ranging from several months (7–10
months is typical) to several years.
 After a period of dormancy, they reactivate and produce merozoites.
 Hypnozoites are responsible for long incubation and late relapses
in P. vivax infections, although their existence in P. ovale is uncertain.
 The parasite is relatively protected from attack by the
body's immune system because for most of its human life cycle it
resides within the liver and blood cells and is relatively invisible to
immune surveillance.
36
 However, circulating infected blood cells are destroyed in the spleen.
 To avoid this fate, the P. falciparum parasite displays
adhesive proteins on the surface of the infected blood cells, causing
the blood cells to stick to the walls of small blood vessels, thereby
sequestering the parasite from passage through the general circulation
and the spleen.
 The blockage of the microvasculature causes symptoms such as in
placental malaria.
 Sequestered red blood cells can breach the blood–brain barrier and
cause cerebral malaria.
37
Genetic resistance
 The high levels of mortality and morbidity caused by malaria especially
the P. falciparum species, it has placed the greatest selective pressure on the human
genome in recent history.
 Several genetic factors provide some resistance to it including sickle cell
trait, thalassaemia traits, glucose-6-phosphate dehydrogenase deficiency and the
absence of Duffy antigens on red blood cells.
 The impact of sickle cell trait on malaria immunity illustrates some evolutionary trade-
offs that have occurred because of endemic malaria.
 Sickle cell trait causes a change in the haemoglobin molecule in the blood.
38
 Normally, red blood cells have a very flexible, biconcave shape that allows them to move
through narrow capillaries; however, when the modified haemoglobin S molecules are
exposed to low amounts of oxygen or crowd together due to dehydration, they can stick
together forming strands that cause the cell to sickle or distort into a curved shape.
 In these strands the molecule is not as effective in taking or releasing oxygen, and the
cell is not flexible enough to circulate freely.
 In the early stages of malaria, the parasite can cause infected red cells to sickle, and so
they are removed from circulation soon.
39
 This reduces the frequency with which malaria parasites complete their life cycle in the
cell.
 Individuals who are homozygous (with two copies of the abnormal hemoglobin
beta allele) have sickle-cell anaemia, while those who are heterozygous (with one
abnormal allele and one normal allele) experience resistance to malaria without severe
anemia.
 Although the shorter life expectancy for those with the homozygous condition would
tend to disfavour the trait's survival, the trait is preserved in malaria-prone regions
because of the benefits provided by the heterozygous form.
40
Signs & Symptoms
 Initial manifestations of the disease (common to all malaria
species) are similar to flu-like symptoms and can resemble other
conditions such as sepsis, gastroenteritis and viral diseases.
 The classic symptom of malaria is paroxysm
 P. falciparum infection can cause recurrent fever every 36–48
hours or a less pronounced and almost continuous fever.
41
 Severe malaria is usually caused by P. falciparum (often referred to as
falciparum malaria).
 Symptoms of falciparum malaria arise 9–30 days after infection.
 Individuals with cerebral malaria frequently exhibit neurological symptoms,
including abnormal posturing, nystagmus, conjugate gaze palsy (failure of the
eyes to turn together in the same direction), opisthotonus, seizures or coma.
42
43
Paroxysm
General Signs & Symptoms
44
Headache
Vomiting
Fever
Joint pain
Jaundice
Haemolytic
anemia
Spleenomegaly
Hb in urine
Chills &
Shivering
Retinal
damage
Convulsions
45
3 Stages of
Fever
Cold
Stage
Hot
Stage
Sweating
Stage
Rigor and headache
Intense heat, Dry
burning skin,
Throbbing headache.
Lasts for 2-6 hours
Profuse sweating,
Declining
temperature, weak.
Last for 2-4 hours
Differential Clinical Features of Species of Plasmodium 46
Name Pathogen Notes
Algid malaria Plasmodium falciparum
severe malaria affecting
the cardiovascular system and
causing chills, circulatory shock
Bilious malaria Plasmodium falciparum
severe malaria affecting the liver and
causing vomiting, jaundice
Cerebral malaria Plasmodium falciparum
severe malaria affecting
the cerebrum
Congenital malaria various plasmodia
plasmodium introduced from the
mother via the fetal circulation
Falciparum
malaria, Plasmodium
falciparum malaria, Pernicious
malaria
Plasmodium falciparum
47
Ovale malaria, Plasmodium
ovale malaria
Plasmodium ovale
Quartan malaria, malariae
malaria, Plasmodium
malariae malaria
Plasmodium malariae
paroxysms every fourth day
(quartan), counting the day of
occurrence as the first day
Quotidian malaria
Plasmodium
falciparum, Plasmodium vivax
paroxysms daily (quotidian)
Tertian malaria
Plasmodium
falciparum, Plasmodium
ovale, Plasmodium vivax
paroxysms every third day (tertian),
counting the day of occurrence as
the first
Transfusion malaria various plasmodia
plasmodium introduced by blood
transfusion, needle sharing,
or needle stick injury
Vivax malaria, Plasmodium
vivax malaria
Plasmodium vivax
Classification
 Malaria is classified into either "severe" or "uncomplicated" by
the World Health Organization (WHO).
 It is deemed severe when any of the following criteria are present,
otherwise it is considered uncomplicated.
 Decreased consciousness
 Significant weakness such that the person is unable to walk
 Inability to feed
 Two or more convulsions
48
 Low blood pressure (less than 70 mmHg in adults and 50 mmHg in
children)
 Breathing problems
 Circulatory shock
 Kidney failure or haemoglobin in the urine
 Bleeding problems or haemoglobin less than 50 g/L (5 g/dL)
49
 Pulmonary oedema
 Blood glucose less than 2.2 mmol/L (40 mg/dL)
 Acidosis or lactate levels of greater than 5 mmol/L
 A parasite level in the blood of greater than 100,000 per microlitre (µL)
in low-intensity transmission areas, or 250,000 per µL in high-intensity
transmission areas
Cerebral malaria is defined as a severe P. falciparum-malaria presenting
with neurological symptoms, including coma (with a Glasgow coma
scale less than 11, or a Blantyre coma scale less than 3) or with a coma
that lasts longer than 30 minutes after a seizure.
50
Diagnosis
 In cases like non-specific nature of the presentation of symptoms, diagnosis of malaria might be elicited by
any of the following:
 Recent travel history, enlarged spleen, fever, low number of platelets in the blood and higher-than-normal
levels of bilirubin in the blood combined with a normal level of white blood cells.
 Incubation period : 10 – 14 days (P. ovale, P. vivax, P. falciparum)
28 – 30 days (P. malariae)
 Symptoms may appear in cycles.
 The time between episodes of fever and other symptoms varies with species.
 Episodes of symptoms may occur ;
 Every 48 hours – if infected with P. ovale and P. vivax
 Every 72 hours – if infected with P. malariae
51
Lab diagnosis
 Microscopic Diagnosis
 Blood smear
 Fluorescent microscopy
 Quantitative Buffy Coat (QBC)
 Antigen Detection
 Immuno chromatographic Dipstick : RDT
52
53
 Serology
 IFA
 ELISA
 Molecular Diagnosis
 PCR
Real time PCR
 CBC
 Leukopenia
 Thrombocytopenia
 Monocytosis
 Elevated ESR
54
55
RDT
 Malaria is usually confirmed by the microscopic examination
of blood films or by antigen-based rapid diagnostic
tests (RDT).
 In some areas, RDTs need to be able to distinguish whether
the malaria symptoms are caused by Plasmodium
falciparum or by other species of parasites since treatment
strategies could differ for non-P. falciparum infections.
56
Antigen capture test
 To detect trophozoite - derived protein can be used for
rapid diagnosis without need for microscopic examination.
 Malaria antigen detection tests are a group of
commercially available rapid diagnostic tests of the rapid
antigen test type that allow quick diagnosis of malaria by
people.
 There are currently over 20 such tests commercially
available (WHO product testing 2008).
 The first malaria antigen suitable as target for such a test
was a soluble glycolytic enzyme Glutamate dehydrogenase.
 A major drawback in the use of all current dipstick methods
is that the result is essentially qualitative.
57
QBC tube test
 The method which acridine orange staining in the
quantitative buffy coat tube system.
 For identifying malarial parasite in peripheral blood.
 It is provided with a simple fluorescence microscope
system, consisting of a battery-powered and a special
ultraviolet lens and a battery powered centrifuge.
 Fluorescence microscopy – based malaria diagnostic test.
 More than 90% of cases, species of organism can be
identified.
 Fill the capillary tube with patient sample – coat with
Acridine orange (fluorescent dye) – centrifuge – observe
under fluorescent microscope.
58
59
Gene amplification by PCR
Methods that use the polymerase chain reaction to detect the
parasite's DNA have been developed, but are not widely used in areas where
malaria is common due to their cost and complexity.
Immunological diagnosis
 Immunological diagnosis is possible by looking for malarial antibodies using
Immuno Fluorescent Antibody (IFA) in addition to ELISA methods.
 IFA is sensitive and relatively simple but cannot be automated.
 ELISA is also sensitive, simple, cost effective and can be automated.
60
Risk factors
 Immune System Deficiency
 People who have immune system deficiencies including HIV are more likely to experience
severe effects of the infection.
 Pregnancy
 Women who are pregnant are at increased risk of malaria infection.
 There are several proposed reasons for this, including a lowered immune system which can
reactivate previous infection or a lowered immune system which makes it more likely for
pregnant women to develop the illness.
 Newborn Babies- Transmission From Their Mother
 Some babies may be born with malaria infection, acquiring the parasite from the mother
and not from a mosquito vector.
61
 Blood Transfusion
 There have been reports of malaria infection that have spread from one person to
another through blood transfusions.
 In these instances, a blood donor who has acquired an infection, usually from a mosquito
vector typically has not yet developed symptoms of the illness.
 The transfer of blood cells, which are infected with the parasitic organism can then allow
the parasite to thrive inside the body of the recipient of the blood transfusion.
 Lifestyle Factors
 Malaria is an infection that is predominantly spread in certain geographic regions with a
tropical climate and an abundance of still water, where the mosquito vector that carries
the parasite can survive.
62
 Living in a Region With a High Rate of Malaria
 Living in a region that is known for malaria substantially increases the risk of becoming
infected.
 While it has been noted that some people living in regions with a high rate of malaria may
become immune, many otherwise healthy people with normal immune systems
experience serious complications and may die from the infection.
 Visiting a Region With a High Rate of Malaria
 Travellers who visit regions with a high rate of malaria may become infected, particularly
because travellers who have not been exposed to the infection before have not developed
immunity to the condition.
 Environmental Factors
 Some factors increase exposure to malaria, including a lack of protective clothing, exposed
sleeping accommodations, lack of insect repellent and lack of immunization.
63
Complications
 Among several serious complications, development of respiratory
distress, which occurs in up to 25% of adults and 40% of children with
severe P. falciparum malaria.
 Acute respiratory distress syndrome occurs in 5–25% of adults and up to
29% of pregnant women.
 Coinfection of HIV with malaria increases mortality.
 Malaria in pregnant women is an important cause of stillbirths, infant
mortality, abortion and low birth weight, particularly
in P. falciparum infection but also with P. vivax.
64
 Infection with P. falciparum may result in cerebral malaria, a form of
severe malaria that involves encephalopathy.
 It is associated with retinal whitening, which may be a useful clinical
sign in distinguishing malaria from other causes of fever.
 Enlarged spleen, enlarged liver or both of these, severe headache, low
blood sugar and hemoglobin in the urine with renal failure may occur.
 Complications may include spontaneous bleeding, coagulopathy,
and shock.
65
66
Articles and Publications
67
 Among the Agantuja Nidana (external factors), it was identified that all the patients of
Vishama Jvara (irregular or intermittent fever) were affected by Bhootabhishanga
(plasmodium species in case of malaria).
 Various other Viharaja Nidanas (routine activities), Manasika Nidanas (mental factors), and
Anya Nidanas (other aetiological factors) considered in the study also show that certain
societal and climatic changes play a major role in the onset of vishama jvara(irregular or
intermittent fever).
 From the data obtained from the observational study, it can be inferred that apart from
Bhootabhishanga(microbes/plasmodium species in case of Malarial fever) which is the
Agantuja(external) cause for VishamaJvara(irregular/ intermittent fever),many other
factors such as Aharaja (dietary), Viharaja (routine activities), Manasika (mental factors)
and Anya Nidanas(other aetiological factors) may precipitate the onset of Vishama
Jvara(irregular or intermittent fever).
68
69
 According to gender and age distribution, males were more prone
to disease than females because of daily ambulation at different
places.
 P. vivax showed more prevalence rate among the patients.
 High parasite index, thrombocytopenia and less Hb concentration
are as main prognostic factors.
70
71
Additional Information
National Malaria Eradication Programme (NMEP)
 National Malaria Eradication Programme (NMEP) was launched in
United States on 1 July 1947.
 This federal program had succeeded in eradicating malaria in the
United States by 1951.
 By the 1930s, it had become concentrated in 13 south eastern states.
 National malaria eradication effort was originally proposed by Louis
Laval Williams.
 The NMEP was directed by the federal Communicable Disease Center.
 DDT was applied to the interior surfaces of rural homes or entire
premises in counties where malaria was reported to have been
prevalent in recent years.
72
 In addition, wetland drainage, removal of mosquito breeding sites and DDT spraying
(occasionally from aircraft) were all pursued.
 By 1951, malaria was considered eliminated altogether from the country and the CDC
gradually withdrew from active participation in the operational phases of the program
shifting its interest to surveillance.
 In 1952, CDC participation in eradication operations ceased altogether.
73
World Malaria Day
74
 World Malaria Day (WMD) is an international observance commemorated every
year on 25 April and recognizes global efforts to control malaria.
 World Malaria Day sprung out of the efforts taking place across the African
continent to commemorate Africa Malaria Day.
 WMD is one of eight official global public health campaigns currently marked by
the World Health Organization (WHO) along with World Health Day, World
Tuberculosis Day, World AIDS Day….etc
References
 Davidson’s Principles and Practices of Medicine
 Articles – Medi.net
 Internet Sources
75
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Thankyou

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Malaria

  • 1. 1 MALARIA Dr. Anand S M.D (AYU) Assistant Professor Department of Roga nidana evum Vikriti Vigyana Global Institute of Ayurveda, Rajkot
  • 2. Contents  Introduction  History  Incidence and Prevalence  Epidemiology  Cause  Pathophysiology  Signs and symptoms  Classification  Diagnosis  Risk factors  Complications  Articles and Publications  References 2
  • 3. Introduction  Malaria is a mosquito-borne infectious disease affecting humans and other animals caused by parasitic single-celled microorganisms belonging to the Plasmodium group.  Malaria causes symptoms that typically include fever, tiredness, vomiting and headache.  In severe cases it can cause yellow skin, seizures, coma or death.  Symptoms usually begin 10 to 15 days after being bitten by an infected mosquito. 3
  • 4.  The disease is most commonly transmitted by an infected female Anopheles mosquito.  The mosquito bite introduces the parasites from mosquito's saliva into a person's blood.  The parasites travel to the liver where they mature and reproduce.  If not properly treated, people may have recurrences of the disease months later.  In those who have recently survived an infection, reinfection usually causes milder symptoms. 4
  • 5.  This partial resistance disappears over months to years if the person has no continuing exposure to malaria.  Five species of Plasmodium can infect and be spread by mosquitoes.  Most deaths are caused by P. falciparum because P. vivax, P. ovale and P. malariae generally cause a milder form of malaria.  The species P. knowlesi rarely causes disease in humans. 5
  • 6.  The parasite responsible for P. falciparum malaria has been in existence for 50,000 – 100,000 years, the population size of the parasite did not increase until about 10,000 years ago, concurrently with advances in agriculture and the development of human settlements.  Close relatives of the human malaria parasites remain common in chimpanzees.  Some evidence suggests that the P. falciparum malaria may have originated in gorillas.  References to the unique periodic fevers of malaria are found throughout recorded history. 6 History
  • 7. 7  Hippocrates described periodic fevers, labelling them tertian, quartan, subtertian and quotidian.  The term malaria originates from Medieval Italian: mala aria—"bad air"; the disease was formerly called ague or marsh fever due to its association with swamps and marshland.  The term first appeared in the English literature about 1829.  Malaria was once common in most of Europe and North America,where it is no longer endemic, though imported cases do occur.
  • 8.  Scientific studies on malaria made their first significant advance in 1880, when Charles Louis Alphonse Laveran—a French army doctor working in the military hospital of Constantine in Algeria—observed parasites inside the red blood cells of infected people for the first time.  He, therefore, proposed that malaria is caused by this organism, the first time a protist was identified as causing disease. 8
  • 9. Incidence and Prevalence  Globally, an estimated 3.4 billion people in 91 countries and territories are at risk of being infected with malaria and developing disease and 1.1 billion are at high risk.  According to the World Malaria Report 2016, there were 212 million cases of malaria globally in 2015 and 429 000 malaria deaths (range 235 000–639 000), representing a decrease in malaria cases and deaths of 22% and 50% since 2000 respectively.  The burden was heaviest in the WHO African Region, where an estimated 92% of all malaria deaths occurred and in children aged under 5 years, who accounted for more than two thirds of all deaths. 9
  • 10.  The disease is widespread in the tropical and subtropical regions that exist in a broad band around the equator.  This includes much of Sub-Saharan Africa, Asia and Latin America.  In 2016, there were 216 million cases of malaria worldwide resulting in an estimated 445,000 to 731,000 deaths.  Approximately 90% of both cases and deaths occurred in Africa.  Rates of disease have decreased from 2000 to 2015 by 37%,but increased from 2014 during which there were 198 million cases. 10
  • 11.  Malaria is prevalent in tropical and subtropical regions because of rainfall, consistent high temperatures and high humidity, along with stagnant waters in which mosquito larvae readily mature, providing them with the environment they need for continuous breeding.  In drier areas, outbreaks of malaria have been predicted with reasonable accuracy by mapping rainfall. 11
  • 12. Epidemiology  The WHO estimates that in 2015 there were 214 million new cases of malaria resulting in 438,000 deaths.  Others have estimated the number of cases at between 350 and 550 million for falciparum malaria.  The majority of cases (65%) occur in children under 15 years old.  About 125 million pregnant women are at risk of infection each year; across the world, maternal malaria is associated with up to 200,000 estimated infant deaths yearly. 12
  • 13. 13  The Malaria Atlas Project aims to map global endemic levels of malaria, providing a means with which to determine the global spatial limits of the disease and to assess disease burden. Malarial Atlas Project The Malaria Atlas Project, abbreviated as MAP, is a non-profit project funded primarily by the Medical Research Council. MAP aims to disseminate free, accurate and up-to-date information on malaria and associated topics, organised on a geographical basis. The MAP team have assembled a unique database derived from medical intelligence and satellite-climate data. It constrains the limits of malaria transmission and the largest archive of community- based estimates of parasite prevalence.
  • 14. 14 Epidemiology in India  During the latter parts of nineteenth and early twentieth centuries, nearly one-fourth of India’s population suffered from malaria, particularly in the states like Punjab and Bengal.  At the time of independence in 1947, of a population of 330 million, about 75 million people were estimated to be infected with malaria every year, and the direct mortality due to the disease was estimated at 0.8 million per annum.  To combat this menace, the Govt. of India launched the National Malaria Control Programme in April 1953.  Encouraged by this, the programme was changed to a more ambitious National Malaria Eradication Programme in 1958.
  • 15. World Malaria Report 2017  According to the World Malaria Report 2017, in the year 2016, more than half of the population (698 million) was at risk of malaria.  According to the Report, India accounted for 6% of all malaria cases in the world, 6% of the deaths and 51% of the global P. vivax cases.  The Report estimates the total cases in India at 1.31 million and deaths at 23990. 15
  • 16. Structure and Stages of Plasmodium Larva 16
  • 18. Stages of Larva 18 Sporozoites Schizont Merozoite Trophozoite Gametocyte
  • 19. Species of Larva 19 Sl. No. Species Ring form Trophozoite Schizont Gametocyte Change in RBCs 1. P. vivax Single Irregular Larger than RBC Round Enlarged, pale 2. P. malariae Single Band shaped Smaller than RBC Round, small Not enlarged, fine pink granules 3. P. falciparum More than one ring in red cell Not seen Not seen Crescent shaped Normal size 4. P. ovale Single ----- Smaller than RBC Oval, small Enlarged, oval
  • 20. Causes  Malaria parasites belong to the genus Plasmodium (phylum Apicomplexa).  In humans, malaria is caused by P. falciparum, P. malariae, P. ovale, P. vivax and P. knowlesi.  Among those infected, P. falciparum is the most common species identified (~75%) followed by P. vivax (~20%).  Although P. falciparum traditionally accounts for the majority of deaths, recent evidence suggests that P. vivax malaria is associated with potentially life-threatening conditions about as often as with a diagnosis of P. falciparum infection.  P. vivax proportionally is more common outside Africa.  There have been documented human infections with several species of Plasmodium from higher apes; however, except for P. knowlesi—a zoonotic species that causes malaria in macaques. 20
  • 22. Life of larva 22 Sexual Cycle Female Anopheles mosquito Asexual Cycle In human beings Definitive host Intermediate host
  • 24. 24 Sporozoites Liver Merozoites Trophozoites Male & Female gametocytes Gametes Infected female Anopheles mosquito Schizont
  • 28. Recurrent malaria  Symptoms of malaria can recur after varying symptom-free periods.  Depending upon the cause, recurrence can be classified as either recrudescence, relapse or reinfection.  Recrudescence is when symptoms return after a symptom-free period.  It is caused by parasites surviving in the blood as a result of inadequate or ineffective treatment. 28
  • 29. 29  Relapse is when symptoms reappear after the parasites have been eliminated from blood but persist as dormant hypnozoites in liver cells.  Relapse commonly occurs between 8–24 weeks and is often seen in P. vivax and P. ovale infections.  However, relapse-like P. vivax recurrences are probably being over-attributed to hypnozoite activation.  Some of them might have an extra-vascular merozoite origin, making these recurrences, recrudescences not relapses.
  • 30. 30  Reinfection means the parasite that caused the past infection was eliminated from the body but a new parasite was introduced.  Reinfection cannot readily be distinguished from recrudescence, although recurrence of infection within two weeks of treatment for the initial infection is typically attributed to treatment failure.  People may develop some immunity when exposed to frequent infections.
  • 31. Climate change  Global climate change is likely to affect malaria transmission, but the degree of effect and the areas effected is uncertain.  Greater rainfall in certain areas of India and following an El Nino event is associated with increased mosquito numbers. 31
  • 32. Pathophysiology 32 • involves the liver Exoerythrocytic phase • involves red blood cells or erythrocytes Erythrocytic phase 2 Phases
  • 35. 35  The parasite escapes from the liver undetected by wrapping itself in the cell membrane of the infected host liver cell.  Within the red blood cells, the parasites multiply further, again asexually, periodically breaking out of their host cells to invade fresh red blood cells. Several such amplification cycles occur.  Thus, classical descriptions of waves of fever arise from simultaneous waves of merozoites escaping and infecting red blood cells.
  • 36.  Some P. vivax sporozoites do not immediately develop into exoerythrocytic-phase merozoites, but instead, produce hypnozoites that remain dormant for periods ranging from several months (7–10 months is typical) to several years.  After a period of dormancy, they reactivate and produce merozoites.  Hypnozoites are responsible for long incubation and late relapses in P. vivax infections, although their existence in P. ovale is uncertain.  The parasite is relatively protected from attack by the body's immune system because for most of its human life cycle it resides within the liver and blood cells and is relatively invisible to immune surveillance. 36
  • 37.  However, circulating infected blood cells are destroyed in the spleen.  To avoid this fate, the P. falciparum parasite displays adhesive proteins on the surface of the infected blood cells, causing the blood cells to stick to the walls of small blood vessels, thereby sequestering the parasite from passage through the general circulation and the spleen.  The blockage of the microvasculature causes symptoms such as in placental malaria.  Sequestered red blood cells can breach the blood–brain barrier and cause cerebral malaria. 37
  • 38. Genetic resistance  The high levels of mortality and morbidity caused by malaria especially the P. falciparum species, it has placed the greatest selective pressure on the human genome in recent history.  Several genetic factors provide some resistance to it including sickle cell trait, thalassaemia traits, glucose-6-phosphate dehydrogenase deficiency and the absence of Duffy antigens on red blood cells.  The impact of sickle cell trait on malaria immunity illustrates some evolutionary trade- offs that have occurred because of endemic malaria.  Sickle cell trait causes a change in the haemoglobin molecule in the blood. 38
  • 39.  Normally, red blood cells have a very flexible, biconcave shape that allows them to move through narrow capillaries; however, when the modified haemoglobin S molecules are exposed to low amounts of oxygen or crowd together due to dehydration, they can stick together forming strands that cause the cell to sickle or distort into a curved shape.  In these strands the molecule is not as effective in taking or releasing oxygen, and the cell is not flexible enough to circulate freely.  In the early stages of malaria, the parasite can cause infected red cells to sickle, and so they are removed from circulation soon. 39
  • 40.  This reduces the frequency with which malaria parasites complete their life cycle in the cell.  Individuals who are homozygous (with two copies of the abnormal hemoglobin beta allele) have sickle-cell anaemia, while those who are heterozygous (with one abnormal allele and one normal allele) experience resistance to malaria without severe anemia.  Although the shorter life expectancy for those with the homozygous condition would tend to disfavour the trait's survival, the trait is preserved in malaria-prone regions because of the benefits provided by the heterozygous form. 40
  • 41. Signs & Symptoms  Initial manifestations of the disease (common to all malaria species) are similar to flu-like symptoms and can resemble other conditions such as sepsis, gastroenteritis and viral diseases.  The classic symptom of malaria is paroxysm  P. falciparum infection can cause recurrent fever every 36–48 hours or a less pronounced and almost continuous fever. 41
  • 42.  Severe malaria is usually caused by P. falciparum (often referred to as falciparum malaria).  Symptoms of falciparum malaria arise 9–30 days after infection.  Individuals with cerebral malaria frequently exhibit neurological symptoms, including abnormal posturing, nystagmus, conjugate gaze palsy (failure of the eyes to turn together in the same direction), opisthotonus, seizures or coma. 42
  • 44. General Signs & Symptoms 44 Headache Vomiting Fever Joint pain Jaundice Haemolytic anemia Spleenomegaly Hb in urine Chills & Shivering Retinal damage Convulsions
  • 45. 45 3 Stages of Fever Cold Stage Hot Stage Sweating Stage Rigor and headache Intense heat, Dry burning skin, Throbbing headache. Lasts for 2-6 hours Profuse sweating, Declining temperature, weak. Last for 2-4 hours
  • 46. Differential Clinical Features of Species of Plasmodium 46 Name Pathogen Notes Algid malaria Plasmodium falciparum severe malaria affecting the cardiovascular system and causing chills, circulatory shock Bilious malaria Plasmodium falciparum severe malaria affecting the liver and causing vomiting, jaundice Cerebral malaria Plasmodium falciparum severe malaria affecting the cerebrum Congenital malaria various plasmodia plasmodium introduced from the mother via the fetal circulation Falciparum malaria, Plasmodium falciparum malaria, Pernicious malaria Plasmodium falciparum
  • 47. 47 Ovale malaria, Plasmodium ovale malaria Plasmodium ovale Quartan malaria, malariae malaria, Plasmodium malariae malaria Plasmodium malariae paroxysms every fourth day (quartan), counting the day of occurrence as the first day Quotidian malaria Plasmodium falciparum, Plasmodium vivax paroxysms daily (quotidian) Tertian malaria Plasmodium falciparum, Plasmodium ovale, Plasmodium vivax paroxysms every third day (tertian), counting the day of occurrence as the first Transfusion malaria various plasmodia plasmodium introduced by blood transfusion, needle sharing, or needle stick injury Vivax malaria, Plasmodium vivax malaria Plasmodium vivax
  • 48. Classification  Malaria is classified into either "severe" or "uncomplicated" by the World Health Organization (WHO).  It is deemed severe when any of the following criteria are present, otherwise it is considered uncomplicated.  Decreased consciousness  Significant weakness such that the person is unable to walk  Inability to feed  Two or more convulsions 48
  • 49.  Low blood pressure (less than 70 mmHg in adults and 50 mmHg in children)  Breathing problems  Circulatory shock  Kidney failure or haemoglobin in the urine  Bleeding problems or haemoglobin less than 50 g/L (5 g/dL) 49
  • 50.  Pulmonary oedema  Blood glucose less than 2.2 mmol/L (40 mg/dL)  Acidosis or lactate levels of greater than 5 mmol/L  A parasite level in the blood of greater than 100,000 per microlitre (µL) in low-intensity transmission areas, or 250,000 per µL in high-intensity transmission areas Cerebral malaria is defined as a severe P. falciparum-malaria presenting with neurological symptoms, including coma (with a Glasgow coma scale less than 11, or a Blantyre coma scale less than 3) or with a coma that lasts longer than 30 minutes after a seizure. 50
  • 51. Diagnosis  In cases like non-specific nature of the presentation of symptoms, diagnosis of malaria might be elicited by any of the following:  Recent travel history, enlarged spleen, fever, low number of platelets in the blood and higher-than-normal levels of bilirubin in the blood combined with a normal level of white blood cells.  Incubation period : 10 – 14 days (P. ovale, P. vivax, P. falciparum) 28 – 30 days (P. malariae)  Symptoms may appear in cycles.  The time between episodes of fever and other symptoms varies with species.  Episodes of symptoms may occur ;  Every 48 hours – if infected with P. ovale and P. vivax  Every 72 hours – if infected with P. malariae 51
  • 52. Lab diagnosis  Microscopic Diagnosis  Blood smear  Fluorescent microscopy  Quantitative Buffy Coat (QBC)  Antigen Detection  Immuno chromatographic Dipstick : RDT 52
  • 53. 53  Serology  IFA  ELISA  Molecular Diagnosis  PCR Real time PCR
  • 54.  CBC  Leukopenia  Thrombocytopenia  Monocytosis  Elevated ESR 54
  • 55. 55
  • 56. RDT  Malaria is usually confirmed by the microscopic examination of blood films or by antigen-based rapid diagnostic tests (RDT).  In some areas, RDTs need to be able to distinguish whether the malaria symptoms are caused by Plasmodium falciparum or by other species of parasites since treatment strategies could differ for non-P. falciparum infections. 56
  • 57. Antigen capture test  To detect trophozoite - derived protein can be used for rapid diagnosis without need for microscopic examination.  Malaria antigen detection tests are a group of commercially available rapid diagnostic tests of the rapid antigen test type that allow quick diagnosis of malaria by people.  There are currently over 20 such tests commercially available (WHO product testing 2008).  The first malaria antigen suitable as target for such a test was a soluble glycolytic enzyme Glutamate dehydrogenase.  A major drawback in the use of all current dipstick methods is that the result is essentially qualitative. 57
  • 58. QBC tube test  The method which acridine orange staining in the quantitative buffy coat tube system.  For identifying malarial parasite in peripheral blood.  It is provided with a simple fluorescence microscope system, consisting of a battery-powered and a special ultraviolet lens and a battery powered centrifuge.  Fluorescence microscopy – based malaria diagnostic test.  More than 90% of cases, species of organism can be identified.  Fill the capillary tube with patient sample – coat with Acridine orange (fluorescent dye) – centrifuge – observe under fluorescent microscope. 58
  • 59. 59
  • 60. Gene amplification by PCR Methods that use the polymerase chain reaction to detect the parasite's DNA have been developed, but are not widely used in areas where malaria is common due to their cost and complexity. Immunological diagnosis  Immunological diagnosis is possible by looking for malarial antibodies using Immuno Fluorescent Antibody (IFA) in addition to ELISA methods.  IFA is sensitive and relatively simple but cannot be automated.  ELISA is also sensitive, simple, cost effective and can be automated. 60
  • 61. Risk factors  Immune System Deficiency  People who have immune system deficiencies including HIV are more likely to experience severe effects of the infection.  Pregnancy  Women who are pregnant are at increased risk of malaria infection.  There are several proposed reasons for this, including a lowered immune system which can reactivate previous infection or a lowered immune system which makes it more likely for pregnant women to develop the illness.  Newborn Babies- Transmission From Their Mother  Some babies may be born with malaria infection, acquiring the parasite from the mother and not from a mosquito vector. 61
  • 62.  Blood Transfusion  There have been reports of malaria infection that have spread from one person to another through blood transfusions.  In these instances, a blood donor who has acquired an infection, usually from a mosquito vector typically has not yet developed symptoms of the illness.  The transfer of blood cells, which are infected with the parasitic organism can then allow the parasite to thrive inside the body of the recipient of the blood transfusion.  Lifestyle Factors  Malaria is an infection that is predominantly spread in certain geographic regions with a tropical climate and an abundance of still water, where the mosquito vector that carries the parasite can survive. 62
  • 63.  Living in a Region With a High Rate of Malaria  Living in a region that is known for malaria substantially increases the risk of becoming infected.  While it has been noted that some people living in regions with a high rate of malaria may become immune, many otherwise healthy people with normal immune systems experience serious complications and may die from the infection.  Visiting a Region With a High Rate of Malaria  Travellers who visit regions with a high rate of malaria may become infected, particularly because travellers who have not been exposed to the infection before have not developed immunity to the condition.  Environmental Factors  Some factors increase exposure to malaria, including a lack of protective clothing, exposed sleeping accommodations, lack of insect repellent and lack of immunization. 63
  • 64. Complications  Among several serious complications, development of respiratory distress, which occurs in up to 25% of adults and 40% of children with severe P. falciparum malaria.  Acute respiratory distress syndrome occurs in 5–25% of adults and up to 29% of pregnant women.  Coinfection of HIV with malaria increases mortality.  Malaria in pregnant women is an important cause of stillbirths, infant mortality, abortion and low birth weight, particularly in P. falciparum infection but also with P. vivax. 64
  • 65.  Infection with P. falciparum may result in cerebral malaria, a form of severe malaria that involves encephalopathy.  It is associated with retinal whitening, which may be a useful clinical sign in distinguishing malaria from other causes of fever.  Enlarged spleen, enlarged liver or both of these, severe headache, low blood sugar and hemoglobin in the urine with renal failure may occur.  Complications may include spontaneous bleeding, coagulopathy, and shock. 65
  • 67. 67
  • 68.  Among the Agantuja Nidana (external factors), it was identified that all the patients of Vishama Jvara (irregular or intermittent fever) were affected by Bhootabhishanga (plasmodium species in case of malaria).  Various other Viharaja Nidanas (routine activities), Manasika Nidanas (mental factors), and Anya Nidanas (other aetiological factors) considered in the study also show that certain societal and climatic changes play a major role in the onset of vishama jvara(irregular or intermittent fever).  From the data obtained from the observational study, it can be inferred that apart from Bhootabhishanga(microbes/plasmodium species in case of Malarial fever) which is the Agantuja(external) cause for VishamaJvara(irregular/ intermittent fever),many other factors such as Aharaja (dietary), Viharaja (routine activities), Manasika (mental factors) and Anya Nidanas(other aetiological factors) may precipitate the onset of Vishama Jvara(irregular or intermittent fever). 68
  • 69. 69
  • 70.  According to gender and age distribution, males were more prone to disease than females because of daily ambulation at different places.  P. vivax showed more prevalence rate among the patients.  High parasite index, thrombocytopenia and less Hb concentration are as main prognostic factors. 70
  • 72. National Malaria Eradication Programme (NMEP)  National Malaria Eradication Programme (NMEP) was launched in United States on 1 July 1947.  This federal program had succeeded in eradicating malaria in the United States by 1951.  By the 1930s, it had become concentrated in 13 south eastern states.  National malaria eradication effort was originally proposed by Louis Laval Williams.  The NMEP was directed by the federal Communicable Disease Center.  DDT was applied to the interior surfaces of rural homes or entire premises in counties where malaria was reported to have been prevalent in recent years. 72
  • 73.  In addition, wetland drainage, removal of mosquito breeding sites and DDT spraying (occasionally from aircraft) were all pursued.  By 1951, malaria was considered eliminated altogether from the country and the CDC gradually withdrew from active participation in the operational phases of the program shifting its interest to surveillance.  In 1952, CDC participation in eradication operations ceased altogether. 73
  • 74. World Malaria Day 74  World Malaria Day (WMD) is an international observance commemorated every year on 25 April and recognizes global efforts to control malaria.  World Malaria Day sprung out of the efforts taking place across the African continent to commemorate Africa Malaria Day.  WMD is one of eight official global public health campaigns currently marked by the World Health Organization (WHO) along with World Health Day, World Tuberculosis Day, World AIDS Day….etc
  • 75. References  Davidson’s Principles and Practices of Medicine  Articles – Medi.net  Internet Sources 75

Editor's Notes

  1. When an infected mosquito pierces a person's skin to take a blood meal sporozoites in the mosquito's saliva enter the bloodstream and migrate to the liver where they infect hepatocytes, multiplying asexually and asymptomatically for a period of 8–30 days.
  2. After a potential dormant period in the liver, these organisms differentiate to yield thousands of merozoites, which following rupture of their host cells, escape into the blood and infect red blood cells to begin the erythrocytic stage of the life cycle.
  3. Possible causes include respiratory compensation of metabolic acidosis, noncardiogenic pulmonary oedema, concomitant pneumonia, and severe anaemia.