Infectious Disease epidemiology BMTRY 713 Department of...
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Infectious Disease epidemiology BMTRY 713 (Lecture 20) Epidemiology of Malaria
April 4, 2017Department of Public Health Sciences
Selassie AW (DPHS) 1
Infectious Disease EpidemiologyBMTRY 713 (A. Selassie, DrPH)
Learning Objectives1. Overview of malaria—Global perspectives
2. Identify clinical manifestations
3. Factors increasing transmission
4. Discuss Prevention strategies
April 4, 2017Lecture 20
Vector-Borne Disease (Part I)Epidemiology of Malaria
• Hippocrates described the manifestation of the disease to time of the year and to where the patients live, perhaps influencing the nomenclature of the disease (Latin word (mal) bad + (aria) air)).
• In 1879, Alphonse Laveran, a French Physician in Algeria explained the role of the particles of black pigment found in the blood of people suffering from malaria. Won the Nobel Prize in 1907.
• In 1898, Plasmodium was discovered as etiologic agent of malaria by a team of Italian researchers.
• Discovery of the Anopheles mosquito as the biological vector of malaria was made in 1897 by Ronald Ross. He won the Nobel prize in 1902.
History of Malaria
• Malaria is a remittent and intermittent fever caused
by a protozoan parasite that invades the red blood.
• The parasite is developed in and transmitted by
mosquitoes in tropical and subtropical regions.
• People with malaria often experience high fever,
chills, and flu-like illness. Left untreated, they may
develop severe complications and die
Malaria
Infectious Disease epidemiology BMTRY 713 (Lecture 20) Epidemiology of Malaria
April 4, 2017Department of Public Health Sciences
Selassie AW (DPHS) 2
Population at Risk
3.4 billion people live in areas at risk of malaria transmission
106 countries have risk of malaria
214 million clinical episodes and 438,000 deaths in 2015
In the US, 1,500–2,000 cases of malaria every year, almost all in recent travelers; Endemic 1947-1957 and sporadic since.
91% of the deaths are in Africa
Malaria Worldwide
Africa
South East Asia
Central and South America
Europe
United States
94 million cases
5-10 million
1-2 million
500,000
1200
Infectious Disease epidemiology BMTRY 713 (Lecture 20) Epidemiology of Malaria
April 4, 2017Department of Public Health Sciences
Selassie AW (DPHS) 3
Agent of the disease
Protozoan parasites of the genus Plasmodium
5 phases of the life cycle involving the mosquito vector and human host
Affinity for erythrocytes varies with species
P. falciparum is associated with most virulence and highest mortality in endemic African countries
The female Anopheles mosquito feeding on a human arm
Anopheles gambiae
Schizont
Trophozoites
Lifecycle of malarial parasite
Infectious Disease epidemiology BMTRY 713 (Lecture 20) Epidemiology of Malaria
April 4, 2017Department of Public Health Sciences
Selassie AW (DPHS) 4
Hemoparasite ‒ P. falciparum
Hemoparasite ‒ P. falciparumTrophozoite stage
Infectious Disease epidemiology BMTRY 713 (Lecture 20) Epidemiology of Malaria
April 4, 2017Department of Public Health Sciences
Selassie AW (DPHS) 5
Hemoparasite ‒ P. vivax
Hemoparasite ‒ P. ovale
Hemoparasite ‒ P. malariae
Infectious Disease epidemiology BMTRY 713 (Lecture 20) Epidemiology of Malaria
April 4, 2017Department of Public Health Sciences
Selassie AW (DPHS) 6
Asexual Cycle of Plasmodium
Mosquito injects saliva first in to the host, which serves as anticoagulant
Saliva has sporozoites; mature in the liver and attach to RBC receptor sites
Lysis of the RBC releases mature sporozoites
Clinical signs and symptoms are a result of this release of pyrogens
Asexual division takes 48-72 hours
Sexual Life Cycle of Plasmodium
Gametocytes released as blood meal in RBC are digested in the mosquito
Gametocytes form zygotes which
mature into sporozoites
Migration of sporozoites to salivary
glands of mosquito
Life Cycle of Plasmodium
Extrinsic (sporogonic phase) takes 7-12 days
Dependent on species and ambient
temperature
As temperature increases, length of
developmental cycle decreases
Infectious Disease epidemiology BMTRY 713 (Lecture 20) Epidemiology of Malaria
April 4, 2017Department of Public Health Sciences
Selassie AW (DPHS) 7
Anopheles Mosquito and Plasmodium Protozoan
(Immature RBC) (Immature RBC)
Mosquito Life Cycle
Mate, store sperm, lay eggs 3-12 batches/life time
Each batch requires blood meal from vertebrate
Larvae hatch and feed at water’s surface 5-15 days
Pupal stage is 2-4 days
Female adult must survive 7-12 days for the extrinsic cycle in order to transmit infection
Transmission occurs with each blood meal
Lifecycle of Mosquito
Infectious Disease epidemiology BMTRY 713 (Lecture 20) Epidemiology of Malaria
April 4, 2017Department of Public Health Sciences
Selassie AW (DPHS) 8
Vector Variables
Host feeding preferences
Digestion rates
Frequency of blood meals
Biting and resting habits
Favored habitats for egg laying
Predators/enemies
Density of vectors related to humans
Survival probability of vector during extrinsic incubation
At Risk Host
Infection: Depends on parasite transmission and availability of prophylaxis for susceptible
Immune: Depends on number of infected
Susceptible: Depends on number of immune
Human Population
Immunes
Susceptibles Infected
Immunity and Endemicity
Climatic conditions that favor vector and parasite development contribute to a sustained infection rate among the population
Seasonal climates allow loss of collective immunity
Infectious Disease epidemiology BMTRY 713 (Lecture 20) Epidemiology of Malaria
April 4, 2017Department of Public Health Sciences
Selassie AW (DPHS) 9
Host Response
Intense and widespread immunological and
cellular response
Clinical response includes classic shaking
chills, fever, sweats
Childhood picture of P. falciparum include
coma and convulsions, along with
nonspecific stomach cramps, headache,
cough, muscle aches
Host Immunological Response
Humoral
Cellular
Immunoglobulinemia
Antibody dependent cellular inhibition
Cytokine cascade defense
Reticulocytosis
Phagocytosis
Host Factors
Nutritional deficiencies are aggravating– PABA, Mg., Pyridoxine, Riboflavin,
Vit. C & E (Vitamin A supplementation helps combat disease)
– Protein Energy Malnutrition
– Iron deficiency anemia (value of treatment is greater than risk of intensifying disease)
Sickle Cell Trait is protective
Infectious Disease epidemiology BMTRY 713 (Lecture 20) Epidemiology of Malaria
April 4, 2017Department of Public Health Sciences
Selassie AW (DPHS) 10
Diagnosis
ELISA/RIA– Presence of antibodies lack clinical
relevance in endemic areas
PCR– promising in drug trials
Giemsa Stain– Dependent on life cycle at parasite stage
– False positive in endemic areas
– Skilled eye and good microscopy
Treatment/Prophylaxis
Drugs– Chloroquine (increasing resistance)
– Amodiaquine
– Chloproguanil and Dapsone (antifolates)
– Fansidar (Sulafanilamide and Pyrimethamine)
Antimalarials protect against disease, not infection
Experimental Treatment
Artesunate suppositories– for treatment en route to hospital when
patient is too sick take med by mouth and IV access is not available
Malaria vaccines– Anti-sporozoite vaccines prevent infection
– Anti-sexual blood stage vaccines reduce severity
– Transmission-blocking vaccines reduce transmission
Infectious Disease epidemiology BMTRY 713 (Lecture 20) Epidemiology of Malaria
April 4, 2017Department of Public Health Sciences
Selassie AW (DPHS) 11
Environmental Influences
Climate variables are distant in the web of
causation but critical
Risk assessments are difficult to predict
Temperature and Rainfall were the only
factors considered in this analysis
Research
Climate Change
Research
Climate Change
Temperature Influences
Mosquito longevity
Frequency of blood meals
Incubation period of the parasite
Infectious Disease epidemiology BMTRY 713 (Lecture 20) Epidemiology of Malaria
April 4, 2017Department of Public Health Sciences
Selassie AW (DPHS) 12
Mosquito Longevity and Survival Probability
Optimal is 20º-25º (C)
Threshold is 16º (C)
Minimum is assumed to be 9º (C)
Maximum tolerated
0.90 at 25º (C)(77ºF ♀=6-8 wks; ♂=10 days)
0.82 at 16º (C) (61 ºF)
<0.01 at 9º (C)(48 ºF)
0.04 at 40º (C)(104 ºF)
Frequency of Blood Meals (Human Blood Index)
Product of frequency and proportion of such meals from humans
Depends on rate of digestion
Digestion increases with ambient
temperature
Ideal altitude <2,000 ft
Basic Reproduction Rate (Ro)
Average number of secondary infections produced when one infected individual is introduced into a host population where everyone is susceptible
Measure of an individual parasite’s reproductive potential
Infectious Disease epidemiology BMTRY 713 (Lecture 20) Epidemiology of Malaria
April 4, 2017Department of Public Health Sciences
Selassie AW (DPHS) 13
Basic Reproduction Rate (Ro)
Ro <1: Disease will die out
Ro >1: Disease will spread indefinitely
Allows calculation of critical density threshold of hosts necessary for parasite transmission
Malaria Transmission
Entomologic Inoculation Rate (EIR)– Human host parameter
• based on landing rate and sporozoite rate
Vectorial Capacity (VC)– Vector parameter
• based on vector density, blood meals taken, survival probability, and extrinsic incubation
Epidemic potential – is reciprocal of vectors population’s critical
density
Rainfall Influences
Aquatic stage of mosquito
Longevity of adult mosquito
Infectious Disease epidemiology BMTRY 713 (Lecture 20) Epidemiology of Malaria
April 4, 2017Department of Public Health Sciences
Selassie AW (DPHS) 14
Rainfall Criterion
> 80 mm per month
Minimum of 1.5 mm/day
50-60% relative humidity needed to
survive
relationship is poorly defined
Critical Density of Hosts for Malaria Transmission
22
1
( )n
N L og pK
N a p
2
1
NN = Number of malaria mosquitoes per human (Critical Density)
p = survival probability of mosquito a = frequency of taking human blood n = incubation period in vector K = constant incorporating variables independent of temp. Epidemic Potential is the reciprocal of the critical density
1
2
1
N
N
Other Influences
Rising populations
Deforestation
Health care access
Drug resistant parasites
Wars resulting in mass migration
Agriculture, commerce causing migration of non-immune into endemic areas
Water development projects