Epidemiology of hepatitis E

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Epidemiology Control of Infectious
diseases Malaria Shahid Beheshti University of
medical sciences, 2004 By Hatami H. MD. MPH
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Definition History Etiology
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Definition of Malaria

• Disease caused by a unicellular protozoan
  Plasmodium
• The most important of the parasitic diseases of
  humans
• Affecting gt 1 billion people
• Transmission in 103 countries
• Causing 1-3 million deaths each year

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World's Deadliest Scourges
Infectious disease Annual deaths

• Acute Respiratory Infections
• Diarrheal Diseases
  
• Tuberculosis
  
• Hepatitis B
  
• Malaria
  
• Measles
• Neonatal Tetanus
  
• AIDS

• 4,300,000
• 3,200,000
• 3,000,000
• 1-2,000,000
• 1,000,000
• 880,000
• 600,000
• 550,000

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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
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History

• Most important of all tropical diseases (WHO)
• Vast morbidity and mortality
• 40 of world population at risk of infection
• 300-500 million cases gt90 in sub-Saharan Africa
• At least 1 million deaths per year
• Mostly African children (75)

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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

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Resurgence of Malaria

• Ecological change
• Breakdown of control activities
• Political events
• Population movement
• Marginal populations

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Etiology

• Plasmodium protozoa
• P. vivax
• P. ovale
• P. malariae
• P. falciparum

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Plasmodium life cycle

• Two phases
• Extrinsic phase
• In Anopheles sexual definitive host
• Intrinsic phase
• In human asexual intermediate host

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7-14 days
8-30 days
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Pathogenesis

• Severity dependent upon
• Species
• Parasitaemia
• Health status
• Immunity

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Pathogenesis
Fever (Febrile paroxysm)

• Many symptoms due to
• Erythrocyte break-down products
• parasite proteins

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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

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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

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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

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Factors influencing malaria
Climate Change
Population Growth
Changes in Land Use
Increased Temperature
Increased Precipitation
Increased Breeding Sites
Movement of People
Increase in the Dispersion of Mosquitoes and
parasite
Human / Insect Interactions
Increased Chance of Susceptibility
Spread of Malaria
Increase in Resistance
Increase in Mortality
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Descriptive epidemiology and occurrence
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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)

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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

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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)

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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.

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Natural course

• P. ovale
• Similar to P vivax infections
• Are usually less severe
• Often resolves without treatment.

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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.

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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.

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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.

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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

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Natural course Classic paroxysm

• Less common symptoms include the following
• Anorexia and lethargy
• Nausea and vomiting
• Diarrhea
• Headache

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Natural course Physical

• Tachycardia
• Fever
• Hypotension
• Signs of anemia
• Splenomegaly

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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

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Patients with malaria admitted in Sina hospital
Kermanshah
WBC count
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Patients with malaria admitted in Sina hospital
Kermanshah
HEMOGLOBINE
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Patients with malaria admitted in Sina hospital
Kermanshah
symptoms
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Patients with malaria admitted in Sina hospital
Kermanshah
signs
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Complications

• Coma (cerebral malaria)
• Seizures
• Renal failure
• Hemoglobinuria (blackwater fever)
• Noncardiogenic pulmonary edema
• Profound hypoglycemia
• Lactic acidosis
• Hemolysis
• Bleeding (coagulopathy)

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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

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Complications of P. falciparum
Organ Symptoms Misdiagnosis
Stomach intestines Vomiting diarrhoea Gastric flu, cholera
Brain Deliria, coma, convulsions Encephalitis, meningitis
Kidneys Renal failure haemoglobinuria Nephritis
Liver Jaundice fever Hepatitis
Lungs Pulmonary oedema
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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

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Host immune response

• Both humoral immunity and cellular immunity are
  necessary for protection
• The mechanism of each are incompletely understood
• Premunition ??

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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

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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

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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.

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Geographical distribution
p. V p. f
p. v
p. v
p. m
p. f
p. o
p. V p. f
p. V p. f
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Geographical distribution
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Endemicity

• Parasitemia rate or palpable spleen rates in
  children 2-9 years of age
• Hypoendemic lt 10
• Mesoendemic 11-50
• Hyperendemic 51-75
• Holoendemic gt 75

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Malaria in Iran

• Sistan-Baluchestan,
• Fars,
• Boshehr,
• Khuzestan,
• Ilam,
• Lorestan,
• Charmahal, and Bakhtiari
• Kerman
• Hormozgan.

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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.

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Malaria in Iran

• During 1997, 38,766 were found to be positive
• 22 were due to P. falciparum
• 22 fatalities were reported.

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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

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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.

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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

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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.

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4 - Timeline trend

• Pandemics
• Epidemics
• Outbreaks
• Seasonality

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Seasonality

• Summer,
• Autumn,
• Spring

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seasonal distribution of malaria, Kermanshah
1988-99
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5 Age, Gender, Occupation, Social conditions
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• Age
• All ages are affected by malaria
• Mortality is very high in children younger than 5
  years
• Sex
• Males and females are affected equally.

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Sex distribution of malaria, Kermanshah 1988-99
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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

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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

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7 Susceptibility and Resistance

• Tolerance in highly endemic
• Duffy negatives
• Sickle cell trait

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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

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9 - Transmission
Transmission requires complex interaction
between Humans, Mosquitoes, Parasites, and
Local environment
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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

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Transmission

• The mosquito must survive for gt 7 days
• At temperature lt16-18C sporogony is not
  completed and transmission does not occur

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Anopheles in Iran

• A. superpictus
• A. sacharovi
• A. stephensi
• A. dthali
• A. fluviatilis
• A. maculipenis

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Prevention and Control
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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

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1 - Primary prevention

1. Personal protection
2. Chemoprophylaxis
3. Vaccination
4. Vector control

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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

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Anti malarial drugs
Drug Usage
Mefloquine Atovaquone-proguanil Doxycycline Chloroquine Used in areas where chloroquine resistant malaria has been reported As alternative to mefloquine or doxycycline As alternative to mefloquine or ato.-prog. Used in areas where chloroquine resistant malaria has not been reported
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Primary prevention Chemoprophylaxis (1)

• Depends on knowledge of local patterns of
• Drug sensitivity Resistance
• Likelihood of acquiring malarial infection

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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

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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 . . .

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Chemoprophylaxis (4) Children

• Children borne to non immune mothers in endemic
  areas
• Intermittent prophylaxis

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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

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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

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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

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Chemoprophylaxis (8) Doxycycline

• 100 mg daily
• Effective alternative to mefloquine
• Well tolerated
• May cause vulvovaginal thrush, diarrhoea,
  photosensitivity
• Can not be used by children lt 8 years
• Can not be used by pregnant women

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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

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Chemoprophylaxis (10) Chloroquine

• Safe in pregnancy
• Retinopathy if for more than 5 years
• Amodiaquine is associated with a high risk of
  agranulocytosis

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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

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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

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2 - Secondary Prevention
Identification And intervention in early
stages of disease
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Diagnosis

• Blood smears
• Most common method
• Giemsa stain

• Serodiagnosis
• Immune response for years after disappearance of
  the parasite
• Used mostly for returning western travellers.

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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

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Specific treatment
Chloroquine-resistant P. falciparum  Drugs of
choice Quinine sulfate 650 mg every 8 hr 37
dplusDoxycycline 100 mg bid 7 dorQuinine
followed by Fancidar, 3 tablets on the last day
of quinine treatment
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Specific treatment
Chloroquine-resistant P. falciparum
Alternatives Quinine followed by clindamycin 900
mg tid 5 days orMefloquine 1250 single
doseorHalofantrine 500 mg every 6 hr 3 doses,
repeat 1 wk laterorAtovaquone 1000 mg daily 3
d plus proguanil 400 mg daily 3 d
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Specific treatment
Chloroquine-resistant P. falciparum
Alternatives orAtovaquone 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)
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Specific treatment

• Parenteral regimens
• Quinidine gluconate 10 mg /kg loading dose (max
  600 mg) in normal saline infused slowly over 12
  hr, followed by
• Continuous infusion of 0.02 mg/kg/min until
  patient is able to begin oral treatment

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Specific treatment
Or Quinine dihydrochloride 20 mg salt/kg
loading dose in 5 dextrose over 4 hr, followed
by 10 mg salt/kg over 24 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
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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
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Drug resistance

• Particular to P. falciparum but spreading to
  other species
• Resistance to chloroquine most widespread but
  also newer drugs

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Chloroquine-resistant P. falciparum, 1995
Chloroquine-resistant P. falciparum
CDC
Chloroquine-sensitive malaria
200 million clinical cases annually
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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.

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3 - Tertiary Prevention

• Treatment of complications

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Sources

• Control of communicable diseases, 2000
• Nicholas J. White, Joel G. Breman, Malaria and
  Babesiosis in Harrisons 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