Infectious Disease epidemiology BMTRY 713 Department of ...people.musc.edu/~selassie/BMTRY713_IDEpi/Lec20_04... · 4/4/2017 · • The parasite is developed in and transmitted by

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




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




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




Hemoparasite ‒ P. falciparum

Hemoparasite ‒ P. falciparumTrophozoite stage




Hemoparasite ‒ P. vivax

Hemoparasite ‒ P. ovale

Hemoparasite ‒ P. malariae




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




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




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




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




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




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




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




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




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

Documents

Infectious Disease epidemiology BMTRY 713 Department of ...people.musc.edu/~selassie/BMTRY713_IDEpi/Lec20_04... · 4/4/2017 · • The parasite is developed in and transmitted by