بسم هللا الرحمن الرحيم
Epidemiology &
Control of Infectious diseases
Malaria
Shahid Beheshti University of
medical sciences, 2004
By: Hatami H. MD. MPH 1
Definition
History
Etiology
2
Definition of Malaria
• Disease caused by a unicellular
protozoan Plasmodium
• The most important of the parasitic
diseases of humans
• Affecting > 1 billion people
• Transmission in 103 countries
• Causing 1-3 million deaths each year
3
World's Deadliest Scourges
Infectious disease Annual deaths
• Acute Respiratory Infections – 4,300,000
• Diarrheal Diseases – 3,200,000
• Tuberculosis – 3,000,000
• Hepatitis B – 1-2,000,000
• Malaria – 1,000,000
• Measles – 880,000
• Neonatal Tetanus – 600,000
• AIDS – 550,000
4
History
Latin: “mal aria” = Bad air
association with swamp and
marshland
500_BC Hippocrates Clinical Symptoms
1880 Laveran Blood Stage
1898 Ross Mosquito Transmission
1948 Garnham Liver Stage
5
History
• Most important of all tropical diseases
(WHO)
– Vast morbidity and mortality
– 40% of world population at risk of
infection
– 300-500 million cases >90% in sub-
Saharan Africa
– At least 1 million deaths per year
– Mostly African children (75%)
6
History
• WWI
– Almost 5,000 cases in US Navy and
Marines
– More than 100,000 cases in British
and French soldiers
WWII
– 500,000 cases in US Army
– More than 110,000 cases in US Navy
7
Resurgence of Malaria
• Ecological change
• Breakdown of control activities
• Political events
• Population movement
• Marginal populations
8
Etiology
• Plasmodium protozoa
– P. vivax
– P. ovale
– P. malariae
– P. falciparum
9
Plasmodium life cycle
•Two phases
Extrinsic phase
In Anopheles – sexual – definitive
host
Intrinsic phase
In human –asexual – intermediate
host 10
7-14 days
8-30 days
11
Pathogenesis
Severity dependent upon:
• Species
• Parasitaemia
• Health status
• Immunity
12
Pathogenesis
Fever (Febrile paroxysm)
Many symptoms due
to
– Erythrocyte break-down
products
– parasite proteins
13
Pathogenesis
3 stages (paroxysm)
• Pattern of fever (paroxysm):
– 1- Cold stage (shivers)
– 2- Hot stage (flush, rapid pulse)
severe headache
joint pains, vomiting, diarrhoea
– 3- Sweating stage
profuse sweating decrease in
Temperature exhaustion
14
Pathogenesis
Anaemia
• Haemolytic
• Usually most severe in P. falciparum
Hepatosplenomegaly
• Begins in early acute infection
• Spleen may be very enlarged in chronic
malaria after repeated infections
Jaundice
Usually mild but may be severe in P. falciparum due to liver damage
15
Abiotic and Biotic Factors
influencing malaria
• Abiotic
• Increased temperature
• An increase in greenhouse gases
• Biotic
• An increase in parasites
• An increase in mosquitoes
• Increase in human population
16
Factors influencing malaria
Climate
Changes in Change Population
Land Use Growth
Increased Increased
Precipitation Temperature
Increased
Breeding Movement of
Increase in the
Sites People
Dispersion of
Mosquitoes and parasite
Human / Insect
Increased Chance
Interactions
Spread of of Susceptibility
Malaria
Increase in Increase in
Resistance Mortality
17
Descriptive
epidemiology
and
occurrence 18
1 -Incubation Period
Prepatent period (I.P of parasitemia)
The time from infection to the
appearance of parasites in the
blood (usually 7-10 days)
Incubation period
The time from infection to the
appearance of symptoms (14 days)
19
Incubation Period
– P. falciparum 7-14 days
– P. vivax 8-14 days
– P. ovale 8-14 days
– P. malariae 7-30 days
–By blood transfusion is shorter
20
2- Natural course
• Relapse
– Hypnozoites - dormant phase in P.
vivax and P. ovale
– Relapse - reactivation of the infection
via hypnozoites
• Recrudescence
– Parasitaemia falls below detectable
levels and then later increases to a
patent parasitaemia (P. malariae) 21
Natural course
P. vivax
• If untreated, usually lasts for 2-3
months with diminishing
frequency and intensity of
paroxysms
• 50% experience a relapse in a few
weeks to 5 years after the initial
illness.
22
Natural course
P. ovale
• Similar to P vivax infections
• Are usually less severe
• Often resolves without treatment.
23
Natural course
P. malariae
• Asymptomatic for a much longer
period of time
• Recrudescence is common
• It often is associated with a nephrotic
syndrome
• Possibly resulting from deposition of
antibody-antigen complex upon the
glomeruli. 24
Natural course
P. falciparum
• The most malignant form of malaria
• Not limited to RBCs of a particular age
• The highest level of parasitemia
• Vascular obstruction due to its ability to
adhere to endothelial cell walls
• Cerebral malaria, pulmonary edema,
rapidly developing anemia, and renal
problems.
25
Natural course
Classic paroxysm :
• Begins with shivering and chills
• Lasts 1-2 hours
• Followed by a high fever
Finally,
• The patient experiences excessive
diaphoresis
• Body temperature drops to normal or
below normal.
26
Natural course
Classic paroxysm :
• Many patients may have
several small fever spikes a day
• Maintain a high index of suspicion for
malaria in any patient exhibiting any
malarial symptoms and having a
history of travel to endemic areas
27
Natural course
Classic paroxysm :
Less common symptoms
include the following:
• Anorexia and lethargy
• Nausea and vomiting
• Diarrhea
• Headache
28
Natural course
Physical:
•Tachycardia
• Fever
• Hypotension
• Signs of anemia
• Splenomegaly
29
Natural course
Laboratory finding
• Normochromic, normocytic
anemia
• WBC count is normal but in
severe malaria may be raised
• ESR and CRP are high
• the platelet count is reduced
30
Patients with malaria admitted
in Sina hospital Kermanshah
60 55.5 WBC count
50
40.6
40
30
20
10 3.9
0 31
1001-4500 4501-10500 10501-30000
Patients with malaria admitted
in Sina hospital Kermanshah
HEMOGLOBINE
4/7-11/9
38%
12-HI
62%
32
Patients with malaria admitted
in Sina hospital Kermanshah
100 99.5 99
90 symptoms
80
70 63
60 55.8
50 47
40
30 28.4
24 24
20 14.4 12.5
10 10 8.7
2.4 1.9
0
myalgia
nosea
diarrhea
epistaxia
arthralgia
chest pain
constipation
fever
headache
black urine
vomiting
sweating
chills
pain
ab
.
33
Patients with malaria admitted
in Sina hospital Kermanshah
90 82.6
80 signs
70
60 57.2
50
40 37.2
30 26 25 21.5
20
10 7.2 4.3
0.5
0
tachypnea
hepatomegalia
tachycardia
splenomegalia
fever
jundice
paleness
herpes l
edema
. .
p
o
.
34
Complications
• Coma (cerebral malaria)
• Seizures
• Renal failure
• Hemoglobinuria (blackwater fever)
• Noncardiogenic pulmonary edema
• Profound hypoglycemia
• Lactic acidosis
• Hemolysis
• Bleeding (coagulopathy)
35
Complications / Coma
• Altered mental status, or multiple seizures with
P falciparum
• Cerebral malaria is the most common cause of
death in malaria patients
• If untreated, is lethal
• Even with treatment, 15% of children and 20%
of adults who develop cerebral malaria die
• The symptoms of cerebral malaria are
similar to those of toxic encephalopathy
36
Complications of P. falciparum
Organ Symptoms Misdiagnosis
Stomach & Vomiting & Gastric flu, cholera
intestines diarrhoea
Brain Deliria, coma, Encephalitis,
convulsions meningitis
Kidneys Renal failure Nephritis
haemoglobinuria
Liver Jaundice & fever Hepatitis
Lungs Pulmonary
oedema
37
Host immune
response
• In high transmission areas 5-6yr
child immune to lethal disease, Adults
usually mild flu-like episodes
• IgG limits parasitaemia
• But suppressed by pregnancy,
severe illness, immunosuppressive
drugs
38
Host immune
response
• Both humoral immunity and
cellular immunity are necessary
for protection
• The mechanism of each are
incompletely understood
• Premunition ??
39
Host immune response
Non-immune protection
• Sickle cell
– Glutamic acid replaced by valise in
haemoglobin (Hb)
– Change in Hb conformation/reduced
oxygen carrying
– Heterozygotes - 80-90% protection
against severe malaria
– Homozygotes – usually die before 30yrs
40
Host immune
response
Non-immune protection
• Thalassemia
– Defective synthesis of Hb chains
• Duffy blood group antigens
– Fy/Fy (Duffy negative)
– Erythrocyte plasma membrane
receptor not expressed
– P. vivax cannot enter erythrocytes
– Resistance to lethal P. falciparum
41
3 - Geographical distribution
• Malaria occurs in over 103 countries
and territories
• Central and South America,
Hispania (Haiti and Dominican
Republic), Africa, the Indian
subcontinent, Southeast Asia, and
the Middle East.
42
Geographical distribution
p. V
p. v p. f
p. v p. m
p. f
p. o
p. V p. V
p. f p. f
43
Geographical distribution
14000000
12260130
12000000
10000000
8000000
6000000 5288916
4000000
2000000
105223 112329
0
Africa Asia Americas Oceanis 44
Endemicity
Parasitemia rate or palpable spleen
rates in children 2-9 years of age :
• Hypoendemic 75%
45
Malaria in Iran
• Sistan-Baluchestan,
• Fars,
• Boshehr,
• Khuzestan,
• Ilam,
• Lorestan,
• Charmahal, and Bakhtiari;
• Kerman;
• Hormozgan.
46
Malaria in Iran
• Strong malaria control program
• There has been a decreasing trend in recent years
• 16% out of the total population live in non-
malarious areas
• 66% lived in areas freed from malaria
• 12% in areas with sporadic transmission Mostly
P.vivax,
• 6% in areas of continuous transmission with a
high proportion of P.falciparum.
47
Malaria in Iran
• During 1997, 38,766 were found to
be positive
• 22% were due to P. falciparum
• 22 fatalities were reported.
48
Malaria in Iran / Regions
1.Regions to the north of the Zagros range
• Annual Parasite Incidence (API)
in this area was 0.14 per 1,000 in
1997
• About 77% of the malaria cases
were imported from abroad or the
south eastern part of the country
49
Malaria in Iran / Regions
2.Regions to the south of the Zagros range
• API was reported to be 0.18 per
1,000
• 48% were classified as imported.
50
Malaria in Iran / Regions
3.The south eastern corner of Iran
• Consists of Sistan and Buluchistan
Province, Hormozgan Province and the
tropical part of Kerman Province
• A combined population of approximately
3 million is considered to be a refractory
malaria region
• API was reported to be 8.74 per 1,000
population
51
Malaria in Iran / Regions
3.The south eastern corner of Iran (2)
• It is more difficult to control than
elsewhere in Iran
• Drug resistance of P.falciparum
• Vector resistance to insecticides
• Importation of malaria, mostly
P.falciparum, from Afghanistan
and, to a lesser extent, Pakistan.
52
4 - Timeline trend
• Pandemics
• Epidemics
• Outbreaks
• Seasonality
53
Seasonality
•Summer,
•Autumn,
•Spring
54
seasonal distribution of malaria,
Kermanshah 1988-99
winter Spring
Automn
2% 20%
21%
Summer
57% 55
5 – Age,
Gender,
Occupation,
Social conditions
56
• Age:
• All ages are affected by malaria
• Mortality is very high in children
younger than 5 years
• Sex:
• Males and females are affected
equally.
57
Sex distribution of malaria,
Kermanshah 1988-99
74.9
80
60
40 25.1
20
0
Female Male
58
6- Predisposing factors /
Pregnancy
• Especially primigravid women
• 10 times more likely to contract
Severe malaria
• Pregnant women with P. vivax &
falciparum are at high risk for
severe malaria
59
Predisposing factors / Pediatrics
• Has a shorter course, often rapidly
progressing to severe malaria
• Hypoglycemia, seizures, severe anemia,
and sudden death
• Much less likely to develop renal failure,
pulmonary edema, or jaundice
• Commonly recover from malaria, even
severe malaria, much faster than adults
60
7 – Susceptibility and Resistance
• Tolerance in highly endemic
• Duffy negatives
• Sickle cell trait
61
8 – Secondary attack rate
Period of communicability
• Untreated patients may be a source
of mosquito infection for :
• More the 3 years in malariae
• 1-2 years in vivax
• 1 year in falciparum
• The mosquito remains infective for
life
62
9 - Transmission
Transmission requires complex
interaction between:
Humans,
Mosquitoes,
Parasites, and
Local environment
63
Transmission
• All 4 species are transmitted
through the bite of an infected
female Anopheles
• Via a blood transfusion, needle
stick injury, sharing of needles by
infected drug addicts organ
transplantation
• Congenitally between mother and
fetus 64
Transmission
• The mosquito must survive for
> 7 days
• At temperature <16-18°C
sporogony is not completed and
transmission does not occur
65
Anopheles in Iran
• A. superpictus
• A. sacharovi
• A. stephensi
• A. d’thali
• A. fluviatilis
• A. maculipenis
66
Prevention
and
Control 67
Prevention and Control
• Primary Prevention:
Prevention of disease in “well”
individuals
• Secondary Prevention:
Identification and intervention in
early stages of disease
Tertiary Prevention:
Prevention of further deterioration,
reduction in complications
68
1 - Primary prevention
1) Personal protection
2) Chemoprophylaxis
3) Vaccination
4) Vector control
69
Primary prevention
Personal protection
• Avoidance of exposure to
mosquitoes at their peak
feeding times
• Use of insect repellents
(DEET 10-35%)
• Use of bed nets
70
Anti malarial drugs
Drug Usage
Mefloquine Used in areas where
chloroquine resistant
malaria has been reported
Atovaquone-proguanil As alternative to
mefloquine or doxycycline
As alternative to
Doxycycline mefloquine or ato.-prog.
Chloroquine Used in areas where
chloroquine resistant
malaria has not been
71
reported
Primary prevention
Chemoprophylaxis (1)
• Depends on knowledge of local
patterns of:
• Drug sensitivity & Resistance
• Likelihood of acquiring
malarial infection
72
Chemoprophylaxis (2)
• When there is uncertainty, drugs
effective against resistant
p. falciparum should be used
• Mefloquie
• Atovaquone-proguanil
• Doxycycline
• Primaquine
• Chemoprophylaxis is never
entirely reliable
73
Chemoprophylaxis (3)
Pregnant women
• If travelling to malarious areas
should be warned
• In endemic areas they should
receive prophylaxis :
• Chloroquine 300 mg weekly alone or with proguanil
200 mg daily) or . . .
74
Chemoprophylaxis (4)
Children
• Children borne to non immune
mothers in endemic areas
• Intermittent prophylaxis
75
Chemoprophylaxis (5)
Travelers
• Should start taking anti malarial drugs
at least 1 week before departure
• Should continue for 4 weeks after has
left the endemic area
• If atovaquone-proguanil or primaquine
has been taken, only for 1 week after
departure
76
Chemoprophylaxis (6)
Mefloquine
• 250 mg weekly in adults
• Is choice for much of the tropics
• Effective against MDR f. malaria
• Well tolerated
• Mild nausea, dizziness, . . .
• During pregnancy is uncertain
77
Chemoprophylaxis (7)
Atovaquone-proguanil
• 250/100 mg once daily
• Very well tolerated
• Fewer adverse effects
• Effective against all types of malaria
• May be discontinued 1 week after
departure
• Insufficient data on safety in pregnancy
78
Chemoprophylaxis (8)
Doxycycline
• 100 mg daily
• Effective alternative to mefloquine
• Well tolerated
• May cause vulvovaginal thrush,
diarrhoea, photosensitivity
• Can not be used by children < 8 years
• Can not be used by pregnant women
79
Chemoprophylaxis (9)
Chloroquine
• Drug of choice for drug-sensitive p. f.
and the other human species
• Resistant p. vivax in :
• Eastern Asia
• Oceania
• Central and South America
Resistant p. falciparum in :
• Many parts of the world 80
Chemoprophylaxis (10)
Chloroquine
• Safe in pregnancy
• Retinopathy if for more than 5 years
• Amodiaquine is associated with a
high risk of agranulocytosis
81
Chemoprophylaxis (11)
Primaquine
• 30 mg daily
• Effective in prevention of DR malaria
• Abdominal pain
• Oxidant hemolysis
• Should not give to G6PDD persons
• Should not give to pregnant & neonate
82
Current programmes
• Roll Back Malaria global partnership (WHO)
• Mosquito breeding sites: Draining,
insecticide against larvae
• House spraying: Newer insecticides
• Insecticide-treated bed nets: Anopheles
bite at night
• Chemotherapy: Artemisinin-based
combination therapies (ACTs)
• Vaccines: Poor results to date
83
2 - Secondary Prevention:
Identification
And
intervention
in early stages of
disease 84
Diagnosis
• Blood smears
– Most common method
– Giemsa stain
Serodiagnosis
Immune response for years after
disappearance of the parasite
Used mostly for returning western
travellers.
85
Specific treatment
P. vivax, P. ovale, P. malariae and
chloroquine-susceptible P.
falciparum :
• 600 mg base chloroquine PO initially,
• followed by an additional 300 mg base
6 hr later, and again
• On days 2 and 3
86
Specific treatment
Chloroquine-resistant P. falciparum
Drugs of choice
Quinine sulfate 650 mg every 8 hr × 3–7 d
plus
Doxycycline 100 mg bid × 7 d
or
Quinine followed by Fancidar, 3 tablets on
the last day of quinine treatment
87
Specific treatment
Chloroquine-resistant P. falciparum
Alternatives
Quinine followed by clindamycin 900 mg tid × 5 days
or
Mefloquine 1250 single dose
or
Halofantrine 500 mg every 6 hr × 3 doses, repeat 1
wk later
or
Atovaquone 1000 mg daily × 3 d plus proguanil
400 mg daily × 3 d
88
Specific treatment
Chloroquine-resistant P. falciparum
Alternatives
or
Atovaquone 1000 mg daily × 3 d plus doxycycline
100 mg bid × 3 days
or
Artesunate 4 mg/kg daily × 3 d plus mefloquine
1250 single dose (750 mg followed 12 hr later by
500 mg)
89
Specific treatment
Parenteral regimens
• Quinidine gluconate 10 mg /kg loading
dose (max 600 mg) in normal saline
infused slowly over 1–2 hr, followed by
• Continuous infusion of 0.02 mg/kg/min
until patient is able to begin oral
treatment
90
Specific treatment
Or
Quinine dihydrochloride 20 mg salt/kg
loading dose in 5% dextrose over 4 hr,
followed by 10 mg salt/kg over 2–4 hr
every 8 hr (max 1800 mg/d) until
patient is able to begin oral treatment
Artemether 3.2 mg/kg intramuscularly,
then 1.6 mg/kg daily × 3 d
91
Specific treatment
Prevention of Relapse Due to
P. Vivax or P. Ovale
Primaquine phosphate 15.3 mg
base per day PO for 14 days
or
45 mg base per week × 8 wk
92
Drug resistance
• Particular to P. falciparum
but spreading to other
species
• Resistance to chloroquine
most widespread but also
newer drugs
93
Chloroquine-resistant P. falciparum, 1995
Chloroquine-resistant P. falciparum
CDC Chloroquine-sensitive malaria
200 million clinical cases annually
94
Artemisinin or Qinghaosu ("ching-how-soo")
• Active principal of Chinese medicinal
herb Artemisia annua. - used to treat
fevers in China for more than 1000
years.
– Terpinoid active anti-malarial
constituents isolated in 1971.
- artesunate artemether and arteether
– Activated by parasite-digested haem –
free radical formed that kills Plasmodium.
– Short half-life.
– Used in combination with other drugs. 95
3 - Tertiary Prevention:
• Treatment of complications
96
Sources :
• Control of communicable diseases, 2000
• Nicholas J. White, Joel G. Breman, Malaria and
Babesiosis in Harrison’s principles of internal
medicine, 16th ed. 2005
• Mandell 2000
• BSL 2014, Parasites and Pathogens of Man, Dr
Ron Stanley
• Nicole T. McCadie, The Impact of Global
Change on the Spread of Malaria
97