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Fertilizer use and the epidemiology and evolution of cholera in Bangladesh

This proposal examines another possible consequence of fertilzer-dependent intensive agriculture, the worsening of infectious disease epidemics by microbes that live in the same aquatic habitats that also harbor algae and other components of this complex ecosystem. One such infectious agent is Vibrio cholerae, the cause of asiatic cholera, a devastating diarrheal illness that occurs as a seasonal epidemic in the Ganges Delta region of Bangladesh. This interdisciplinary team will explore the idea that the over use of chemical fertilizers might exacerbate cholera epidemics through their effects on algal ecology in the rural agrarian district of Bangladesh.

Funding Year: 
2007
Region(s): 
Asia
Research Areas: 
Oceans
Public Health
Principal Investigators: 

By Cassandra Brooks

Cholera affects hundreds of thousands of people worldwide, and the increased use of fertilizer in developing countries may be fueling the problem, according to Stanford University researchers.

"We're trying to link a farming practice with the epidemiology and evolution of a very significant infectious disease," said Gary Schoolnik, professor of medicine and infectious diseases and senior fellow at Stanford's Woods Institute for the Environment.

Cholera is an extremely virulent diarrheal disease that can kill healthy adults within hours. The first recorded global pandemic arose in the 19th century, although the disease has likely existed in the Ganges River region of Bangladesh since antiquity, according to the World Health Organization (WHO).

1961 marked the beginning of a major global pandemic, but by 2001, the number of cholera cases began to drop. However, in 2005, with a growing number of people living in unsanitary conditions worldwide, the disease re-emerged. More than 200,000 cases and 6,000 deaths were recorded in 2006, although the WHO estimates that reported cases only represent about 5 to 10 percent of actual cases worldwide.

In recent years, Schoolnik and a team of Stanford researchers have traveled to the Ganges region of Bangladesh to investigate a hypothesis built on previous studies of cholera ecology: that the use of chemical fertilizers might be exacerbating cholera outbreaks. If the hypothesis turns out to be true, it could lead to changes in how chemical fertilizers are used in south Asia, the researchers said. Their work is supported by a Woods Institute Environmental Venture Projects (EVP) grant.

Environmental fluctuations

The Vibrio cholerae bacterium occurs naturally in the environment but normally in quantities too low to cause harm. "This is an organism that lives in the water as a natural component of the ecosystem but emerges periodically to cause human diseases," Schoolnik said.

A person has to consume roughly 100,000 V. cholerae to become dangerously ill. Once consumed, the bacteria multiply rapidly in the human gut. In a 24-hour period, an infected person can excrete up to 40 pints of fluid containing 20 billion bacteria. Without treatment and access to health care, people can die from the intense diarrhea, which drains them of water, salts, electrolytes and nutrients.

In 2006, Stanford researcher Kendall Madden traveled to Matlab, Bangladesh, a rural agrarian town of 200,000 where cholera is endemic. The annual fluctuation of the disease has been studied in this region for several decades.

In Matlab, communities build their houses around artificial ponds that are essential to their survival. These ponds provide water for adjacent rice fields, livestock and aquaculture, as well as for bathing and washing dishes and clothes.

The pond environment fluctuates dramatically throughout the year. During the summer monsoon season, heavy rains flood the land and fill the ponds with freshwater. But the rains also flush fertilizer from crops, along with human and animal waste that may be contaminated with cholera.

Throughout the monsoon season, the pond water is deep and frequently replenished, preventing cholera populations from reaching levels that infringe on public health. But during the rest of the year when it's hot and dry, the ponds become stagnant. Cholera outbreaks have been recorded during these dry periods, particularly just before the monsoons begin and a few months thereafter. "There are changes in the ecosystem that cause the V. cholerae organism to become abundant and transformed into a human pathogen," Schoolnik explained.

Impact of fertilizer

Chemical fertilizers help crops grow in regions where the soil is nutrient depleted, and the researchers suspect that when the fertilizers run off into ponds, massive algal blooms can grow. The algae provide food for the cholera and for copepods, tiny shrimp-like crustaceans. As copepods grow, they shed their shells frequently, a process called molting. The cholera feast on the shells, and their populations explode.

What's more, when copepods molt or die, they release their DNA into the environment. Cholera has the ability, unique to only a few species of bacteria, to pull in DNA from the surrounding environment and incorporate it into their genome. This process, called horizontal gene transfer, allows the bacteria to evolve rapidly.

"The hypothesis we have is that the more fertilizer a farmer uses, the more algal blooms there are, which lead to more copepods and a larger number of cholera," Schoolnik said. "With more copepods, the cholera can evolve more rapidly, and the greater chance they could take in genes with new virulence."

When cholera takes up extra genes, new highly virulent strands of bacteria may evolve, he added. This happened in 1992 when a new infectious strand of cholera arose, causing an extensive epidemic in Bangladesh.

Assessing the problem

Since 2006, Madden and Schoolnik have made several trips to Matlab, working in collaboration with the International Center for Diarrheal Disease Research (ICDDR)in Dhaka, the capital of Bangladesh. The ICDDR is collecting pond water samples every two weeks to assess nutrients, algae density and the abundance and species of cholera.

The center also is conducting household surveys twice a week to inquire about agricultural activities, as well as hygiene and health status. Through the surveys, the researchers can assess the true prevalence of cholera in a community, since many people with mild cases do not go to the hospital.

"The ultimate goal is to make policy and management suggestions and education programs to use fertilizer more effectively and conservatively," said Madden, a research associate with Stanford's Program on Food Security and the Environment.

She and Schoolnik will be analyzing the data in summer 2009 to determine if there is a correlation among fertilizer, phytoplankton blooms and cholera.

The research team also is developing a numerical model that mathematically simulates how changes in pond ecology (e.g., nutrient levels) might affect the risk of cholera. "It's going to be a very general model that we can apply to any pond, " said EVP collaborator Kevin Arrigo, associate professor of environmental Earth system science at Stanford.

Eventually, the researchers hope to expand the study region beyond Bangladesh and identify local and global predictors of cholera outbreaksfor example, a certain threshold where algae or nutrient levels are high enough to cause excessive bacteria growth. That kind of warning would give people the opportunity to change their water source or begin water filtration before the pathogen has a chance to strike.

"We believe cholera can be contained," Madden said. "It's a disease of primarily poor communities. It's easy to prevent if you have proper sanitation and clean water."

EVP collaboration

In addition to Schoolnik, Arrigo and Madden, the EVP study includes other researchers from Stanford's Program on Food Security and the Environment and the schools of Medicine and Earth Sciences. "It was a really great learning experience working with people who do things that are so different from what I do," Arrigo said. "The EVP really fosters those kinds of collaborations."

Added Schoolnik: "A project that has all these faculty representing all these diverse fields is really the way we have to go. The way we build universities is by departments, and people use the term 'silo.' There is this silo mentality, everyone works in their own paradigm and they don't talk to each other. We can't solve the big problems by doing it that way. We have to break down those barriers."

Cassandra Brooks is a science-writing intern at the Woods Institute for the Environment at Stanford.