**Health Seminar Series - Emerging Diseases**

**March 24, 2000**

Session 6 -- "Remote Sensing: Geographical Information System Technology
Applications for Disease Identification "

Mr. Ray Gavert introduced the sixth session in the Health Seminar Series
on Emerging Diseases, the sixth of a series of continuing education
programs sponsored by NASA's Occupational Health Program, Office of
Health Affairs (OHA), in cooperation with the Uniformed Services
University of the Health Sciences (USUHS). Ms. Catherine Angotti
introduced the speakers for this session: Dr. Durland Fish, Associate
Professor of Epidemiology and Public Health at the Yale University
School of Medicine; and Dr. Anwar Huq, Research Associate Professor at
the University of Maryland, Biotechnology Institute Columbus Center.

Dr. Fish discussed the landscape epidemiology of emerging vector-borne
diseases. He referred to the National Academy of Sciences report,
*Emerging Diseases---Global Threats for Human Health*, from a panel
headed by Dr. Joshua Letterberg. That publication listed about 54
diseases that were considered emerging or reemerging. About one-third of
those diseases are zoonotic diseases---diseases that find their origins
in non-human animals. Although the concept of emerging diseases is new,
the process of disease emergence is old. Many human diseases have
zoonotic origins, and these represent a threat to human health. Some of
the emerging viral zoonoses are: Crimean Congo hemorrhagic fever, Dengue
fever, ebola, hanta virus, lassa fever, rabies, Rift Valley fever, Ross
River encephalitis, Venezuelan equine encephalitis, and yellow fever.
Also, West Nile virus has been introduced from the Old World into North
America. Many of the viral zoonoses are transmitted to human by
arthropod vector. In addition, there are a number of emerging non-viral
zoonoses: Lyme disease, cholera, ehrlichiosis, e. coli 0157:H7, malaria,
giradiasis, toxoplasmosis, and babesiosis. About half of these are
vector borne. Although malaria is not a zoonoses disease, it is included
here because it is the most important vector-borne disease. The study of
zoonotic diseases is not new. Work by Dr. Evgeny Pavlovsky was published
in 1931---*Natural Nidality of Transmissible Diseases*. The concept of
natural nidality (nest or home) was new in the 1930's; this concept has
not been well received, but it has a strong basis in ecology. It means
that climate and geology interact to form a distinct and characteristic
vegetation. That vegetation provides resources for vertebrates and
vectors are dependent upon plant resources and vertebrates. Vegetation
can also form a particular microclimate that has influence on what can
survive there and can have a direct effect on pathogens. In vector-borne
disease, the pathogens are transmitted by the vector to the vertebrate
host. The activity of the pathogen is dependent upon all of the
ecological parameters, which can be characterized. We have new
technologies for studying landscape epidemiology that have been
developed in the last decade: remote sensing from satellites (landscape
composition); geographic information systems (provides spatial
relationships); geostatistics (to conduct spatial analysis); and
biotechnology (easier pathogen detection).

These zoonotic diseases are influenced by environmental change, which is
the driving force for the evolution of new and emerging diseases. These
changes can be grouped into two areas: spatial and temporal. Spatial
environmental change can include invasion of an area by vectors or new
pathogens, changes in forestation, and urbanization. Some diseases are
dependent upon temporal change---seasonality, stochastic weather
anomalies (floods, droughts), and cyclic anomalies (El Nino). In terms
of remote sensing, to study those diseases that have spatial dependency
we need sensing instruments that have high spatial resolution and low
temporal resolution. The opposite is needed to study diseases that have
temporal dependency.

Dr. Fish discussed lyme disease in the context of spatial aspects.
Forests provide a habitat for deer; adult stage ticks are parasites that
are solely dependent upon deer, and the pathogen that causes lyme
disease occurs only in specific kinds of ticks. When the pathogen gets
into humans, it causes disease. Disease in humans is directly related to
presence of forests. Dr. Fish showed the national lyme disease risk map,
which depicted the focality of lyme disease. There have been over
100,000 cases of lyme disease reported to the CDC since 1982. Ninety
percent of the cases occur in high-risk areas (100 counties in the
U.S.). The reforestation of the Northeastern U.S. was one of the
greatest ecological events of the century. Agriculture was abandoned in
the northeast and the forests have regenerated. Also, in the early part
of the century, deer were reintroduced and have increase dramatically.
This has resulted in many non-urban residents being exposed to ticks and
deer. Epidemiological studies have shown that the risk for lyme disease
is primarily a domestic risk (acquired around the home). Dr. Fisk
illustrated the biting activity of the deer tick that transmits lyme
disease. Nymphs appear in the summer. The onset of illness for lyme
disease coincides with the biting activity of nymphs and is confined to
a two-month period during the summer months. Because of the nymph's
size, most people acquiring lyme disease never remember having been
bitten by a tick. The rash associated with lyme disease can be a benign
event and is frequently missed. Untreated, the disease can disseminate
and cause more serious conditions. Remote sensing can provide us with
information on lyme disease risk that we can't otherwise accumulate. Dr.
Fisk showed a satellite image of Westchester County, NY, from the
Landsat Thematic Mapper. The image was classified into several landscape
classes. The class of "residential/dense vegetation" was of particular
interest because ticks have high survival in this type of landscape.
Also, the broadleaf forest class (very extensive in Westchester County)
was of interest because it is the habitat of deer and mice. The process
was to go through the Landsat image and measure the frequency of
adjacency between these two classes (shown as red pixels and green
pixels) in each of the 23 municipalities in the county to give a measure
of lyme disease risk. To measure the activity of the lyme disease
spirochete, the results of a serology of dogs was used. When the two
data sets (prevalence of antibodies in dogs and total area of adjacent
red and green pixels) were compared, there was a good correlation
between remotely sensed landscape features and the activity of a
pathogen. The study went further to determine who was at risk, and a
model was developed for determining individual properties. There was
data from a CDC study on about 350 residences in central Westchester
County. During the project, the abundance of ticks on these properties
was measured. The data on tick abundance was combined with Landsat data
and was transformed to provide continuous variables (greenness and
wetness). Both the greenness index and the wetness index were higher on
those properties that had a high abundance of ticks. The intent was to
differentiate between two types of properties: low risk (open, only a
few shade trees) and high risk (more shade trees and bushes, greater
humidity). This model was tested through random sample of 1000
households (bite history). The overall accuracy of the exercise was 77%.

Dr. Fish discussed how these results could be applied. The county health
department could direct its public health education toward those
municipalities that were at high risk. This information could also be
used for selecting high-risk populations for studies on clinical trials
of vaccines, vaccine marketing, pest control marketing, intervention
planning, and epidemiological research. It is also applicable to other
emerging zoonoses, particularly tick-borne diseases such as
ehrlichiosis, babesiosis, and tick-borne viruses, as well as la crosse
encephalitis (a tree-hole mosquito vector) and hanta virus (woodland
mouse vector). Dr. Fish thanked the organizations that have supported
research in landscape epidemiology using remote sensing: NASA ARC, NIH
NIAID, CDC NCID, \*USDA Agricultural Research Service, and the Mathers
Foundation.\*

Questions:

HQ: Of the different zoonotic diseases, are there any others besides
lyme disease or rabies that would be transmitted through domestic
animals?

Dr. Fish: Dogs are not involved in the cycle of lyme disease, but they
can bring the ticks into the house and increase the risk of exposure;
however, you don't get the contact directly from that animal. One
disease that could be transmitted from cats is toxoplasmosis.

HQ: In your chart that shows the larva nymphs and the adults and the
occurrence of symptoms from lyme disease that happens in June or July,
has the research actually done a cause and effect, or is it because
people are out in their yards at that time?

Dr. Fish: Yes, it has been narrowed to the nymphs as the prime vector.
There is a 24-hour grace period between the time the tick bites and the
time the spirochete is transmitted. Most people don't notice the nymphs
because they are so small; people would notice the adult ticks---they
feed for up to seven days and get to the size of a jellybean. People
usually find the adult ticks before the grace period is over and remove
them. We see very few cases of lyme disease during the adult period.

Moscow: What about West Nile fever in New York this year?

Dr. Fish: So far, they have been able to find the virus in overwintering
mosquitoes. Just two weeks ago, the virus was isolated from a red-tailed
hawk in Westchester County. It appears that the virus still persists and
we can expect to see West Nile activity next summer.

HQ: Because it was isolated from a hawk, does that increase the
potential for spread because of the wide area that a hawk would cover?

Dr. Fish: It was unusual to find the virus in the hawk in the middle of
winter. It obviously was not recently infected from a mosquito. It seems
to persist in birds from some period of time. Having found the virus in
overwintering mosquitoes is a concern because infected mosquitoes will
come out again in the spring.

HQ: How effective is the vaccination for lyme disease?

Dr. Fish: The clinical studies showed about 80% effectivity for the
current vaccine. In order to achieve that level of protection, three
shots are required over a period of a year. There will be new vaccines
coming out. People in high-risk occupations might benefit from the
vaccine.

ARC: How do you account for the distribution on the map? There are large
empty areas---how do you explain this somewhat patchy distribution of
lyme disease?

Dr. Fish: There is the "hole in a donut" phenomenon. In Ohio and states
south there are very few, if any, records of the tick species being
present in those areas. We do not know enough about the ecological
dependence of this particular tick to explain why it is not present in
that area. In the western desert and mountain areas, it is too dry. On
the Pacific coast, there is a different tick species, which has
different adaptation and ecology.

Dr. Huq discussed the development of a predictive model based upon the
data attained via satellite remote sensing, with the ultimate goal of
cholera intervention. In 1832, the first attack of cholera in Paris
killed about 18,000 people in a very short period of time. It is a
devastating disease. The patient is dehydrated, the skin and eyes are
sunken. Doctors try to give intravenous fluid first, then fluids orally.
Oral rehydration therapy has been a great success. Cholera is a
water-borne disease. In 1884, Dr. Koch stated that the ways in which
cholera can spread in a place are extremely diverse. We are working on
this principle today. Dr. Huq described the spectrum of illness in
persons infected with Vibrio cholerae 01. Severe illness is associated
with high dose exposure, low gastric acidity, and blood group O. There
were a number of countries reporting cholera 1992---South America,
Central America, Africa, India, Asia, etc. About 3000 people in South
America died in 1992-1993. There are still a large number of cases in
Africa. Vibrio cholerae organisms are almost everywhere, but are not
necessarily infectious because of the low number. Many times the
organisms go undetected. Dr. Huq described the viable but non-culturable
cycle of Vibrio cholerae. If the right tools or methods are not used,
the organisms may be undetected although they are present and capable of
producing disease. This was proven through accumulation of fluid in the
rabbit's ileal loop, diarrhea in healthy human volunteers, and the
cytopathic effect on tissue cell line culture. The impact of viable but
non-culturable organism can lead to underestimation of the total number
of bacteria, inaccurate reports, misguidance of health workers, and an
outbreak without prior detection (this happened in Russia). The
important thing is to find these organisms. A cholera DFA test was
developed. It is a monoclonal antibody base direct fluerescent antibody
test for direct detection. It detects all organisms whether they are
viable or non-culturable, and it has proven to be a handy and accurate
test so far.

About twenty years ago, we started looking at where these organisms are
coming from. The University of Maryland found that the copepods have a
very close association with Vibrio cholerae and the Vibrio cells survive
over 14 days; without copepods, they die within 5-6 days. During a
three-year study (1987-1990) in Bangladesh, V. cholera was found
throughout the year; however, there are two peaks---spring and fall.
Based on this work, a model was developed for the transmission of V.
cholerae from the environment to humans. When people interact with water
having a large number of organisms, transmission is facilitated. Dr. Huq
showed the global spread of cholera from 1961 to 1991. Most of the
epidemics started in the coastal regions where organisms are found.
Later, they moved to the interior of the country or continent. A new
epidemic of 0139 started in Bangladesh in 1992. In a recent study in
Matlab, there was a correlation in cholera cases and river water
temperatures over time. Whenever water temperature was higher, there was
a higher incidence of cases. Because cholera cases are tied to seasonal
blooms of plankton, ocean parameters can be monitored with remote
sensing data, which can measure chlorophyll concentration, turbidity,
sea surface temperature, and sea surface height. V. cholerae attaches to
plankton, especially zooplankton. Sufficient nutrients and proper ocean
temperatures lead to increased phytoplankton. Remote sensing is useful
in tracking phytoplankton and zooplankton feeds on phytoplankton. Remote
sensing can be used to monitor and predict these interactions. The
University of Maryland is developing the model for cholera prediction,
using data collection and ground survey. Dr. Huq showed the correlation
between Bangladesh cholera and sea surface temperature in 1991-1994, and
the correlation between cholera cases in Lima, Peru and sea surface
temperature in 1991. Remote sensing showed that the sea surface
temperature and, in some years, the cholera outbreak cycle was similar.
Sea surface height indicates ocean intrusion onto land, suggesting
greater plankton-human contact. Part of this work is published in a
Proceeding of the National Academy of Science, February 15, 2000. Dr.
Huq showed the correlation among sea surface temperature, sea surface
height, and cholera in Bangladesh from 1992 to 1995 and from 1997-1998.

Dr. Huq talked about one of the lower-tech methods for intervention. One
method is a simple filtration method---sari-filtration. A four-fold sari
can remove 99% of the bacteria attached to the copepods. A field trial
on this method was funded by the National Institute of Nursing Research.
Dr Huq provided a list of the people on the team and the collaborators.

Questions:

HQ: Under what circumstances does the organism change its shape? Is this
part of the normal life cycle or are there particular conditions? Is
there any difference in pathogenicity between one stage and the other?

Dr. Huq: When the organisms are culturable, they are more pathogenic;
when they are non-culturable, larger doses are required to cause
disease. It is still unclear whether this is a part of the life cycle or
whether it is due to nutritional deficiency or temperature effect. In
the laboratory, lower temperatures force these organisms to enter into
the non-culturable state. The inocular dose given in the presentation
was for the culturable organism.

KSC: It seems that by watching the temperature in the ocean, you not
only can see the spread but perhaps forecast whether it will be a bad
year for increased cases. Has any predictive capability been tried?

Dr. Huq: This is exactly what we are working on right now with the help
of NASA and other institutes. We are first trying to develop a model for
Bangladesh; if it works, that model will be applied for global
prediction.

KSC: Do you see any remote sensing being helpful in terms of urban areas
for other organisms?

Dr. Huq: Right now, we are focusing on indirect detection (the
chlorophyll measurement, sea surface temperature). We are trying to
speciate the phytoplankton and zooplankton. If this is successful, it
will be used in the predictive model.

HQ: What exactly do you take in your personal medical bag when you
travel to Bangladesh?

Dr. Huq: Acid is the biggest enemy of V. cholorae. If you do not drink
water that is not safe, do not eat fresh vegetables and fruits, and
drink any kind of soda before eating, that is the best protection.

HQ: What about the vaccine for cholera?

Dr. Huq: There were vaccines that WHO recommended a long time ago, but
WHO does not recommend them anymore because they are not really
effective. There is no really good vaccine in the market.

Dr. Fish: To avoid tick-borne diseases in the northeast, I took up
sailing.

Can remote sensing be used to detect or forecast plague in India?

Dr. Huq: I don't know.

Dr. Fish: What was the rehydration therapy?

Dr. Huq: The original rehydration therapy was electrolyte balance, but
the new rehydration therapy is cereal-based, which not only provides
electrolyte balance but also provides nutrients. This is now being used
all over the world. The local staple is used in the mix. There is an
attempt by the WHO to teach rural populations how to make a rehydration
formula at home. This is quite effective.

Dr. Huq: V cholerae is not a problem in the U.S., but 150 years ago,
many people died of cholera. Global climate changes can affect the
number of organisms and may lead to a greater risk.

Dr. Fish: Plague endemic areas have unique characteristics, but they are
not endemic throughout the world. The CDC has been doing some work with
endemic plague in Colorado and New Mexico and is making progress in
characterizing plague habitats and wild rodents. It is not a simple
model. The outbreak of that plague in India was preceded by a flood, but
how frequently plagues are associated with floods remains a question to
be answered.

HQ: What are saris made from? Is the weave count important?

Dr. Huq: We found that the cheapest kind of sari made from cotton is the
best, and the old saris are better than the newer ones. When it is used
over a period of time, the mesh size becomes smaller. When you put
multiple layers together, the size becomes smaller and smaller. In new
saris, the thread is very tight, and the size does not become smaller.
This technique is ideal for poor people. In our field trial, we are
using nylon filters.

HQ: How far into rivers does the organism progress? Is there a water
environment that you can determine from remote sensing?

Dr. Huq: The organisms have an absolute requirement of sodium to express
the toxin gene. In fresh water, there is minimal amount of sodium, but
the organism can survive with this minimum amount. Zooplankton are
present everywhere. Temperature is also an important factor to make the
infectious dose. The multi-varient risk factor approach is important.