Twenty Buses a Day: The High Stakes Race to Create a Global Cholera Early Warning System

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A team of researchers are developing a method to provide early warning of cholera outbreaks. If successful, the effort could drastically reduce the number of cholera deaths.

A scanning electron microscope image of Vibrio cholerae bacteria. Image Credit: Dartmouth Electron Microscope Facility.

A scanning electron microscope image of Vibrio cholerae bacteria. Image Credit: Dartmouth Electron Microscope Facility.

On a cold, rainy afternoon in Geneva, Switzerland, Rifat Hossain guides a room full of health researchers and Earth observation specialists attending the Group on Earth Observations‰Ûª (GEO) annual meeting through a simple mental exercise.

‰ÛÏImagine 20 buses filled with children,‰Û directs Hossain, head of the World Health Organization‰Ûªs (WHO) global information management system.

When they have that picture in mind, Hossain instructs the group to imagine the buses smashing into each other at high speed.

‰ÛÏEvery child on every bus is killed,‰Û Hossain says, his calm voice belying the horrific image. ‰ÛÏThat is what happens every day around the globe.‰Û

Global childhood deaths by cause. Data from WHO Global Health Observatory Data Repository, 2011.

Global childhood deaths by cause. Data from WHO Global Health Observatory Data Repository, 2011.

The buses are, of course, a metaphor. It‰Ûªs actually diarrheal diseases that every year kill 645,000 children under the age of five. In fact, more children in this age group die annually from diarrheal diseases than from the better known calamities of malaria, measles, and AIDS. (Among infectious diseases, only pneumonia is deadlier.)

Rifat Hossain, World Health Organization, speaking at the GEO-X plenary, January 2014. Image Credit: Osha Gray Davidson.

Rifat Hossain, World Health Organization, speaking at the GEO-X plenary, January 2014. Image Credit: Osha Gray Davidson.

The water-borne disease, cholera, is one of the largest causes of diarrheal deaths among children in the developing world. Even so, deaths from cholera are vastly under-reported, according to WHO, which estimates that its figures may reflect just 5-10 percent of actual cases. In its most recent cholera report, WHO warned that its count doesn‰Ûªt include ‰ÛÏthe estimated 500,000‰ÛÒ700,000 annual cases labeled ‰Û÷acute watery diarrhoea‰Ûª occurring in south-eastern and central Asia.‰Û

Paradoxically, for all the deaths caused by cholera, the disease is easily preventable. Hossain calls cholera a poor man‰Ûªs disease, explaining that ‰ÛÏpeople in good housing with good sanitation don‰Ûªt get it.‰Û

In that way, cholera differs from his metaphor of highway mayhem.

‰ÛÏA bus crash is an accident,‰Û Hossain insists. ‰ÛÏThese deaths happen because people don‰Ûªt have access to clean water and sanitation.‰Û

The long-term challenge is obvious: Ensure that everyone has a safe water supply and an adequate sewage system. Hossain is part of a team that also is working on a more immediate strategy which could save tens of thousands of lives annually. The Global Initiative for Cholera Early Warning (GICEW), a joint project of WHO, the U.S. National Oceanic and Atmospheric Administration (NOAA), and the German company Fraunhofer, would integrate a vast number of data sets, including public health, infrastructure, and socioeconomic and environmental information. The goal, NOAA‰Ûªs GICEW point-person, Juli Trtanj, tells Earthzine, is to ‰ÛÏweave these assets, and others that exist, combined with additional data and tools as needed by country, into a functional tool to inform decision-makers about potential risks, with sufficient lead time to take actions that reduce risk and save lives.‰Û

Juli Trtanj, NOAA, presenting the Global Initiative for Cholera Early Warning, at GEO-X. Image Credit: U.S. Mission Geneva.

Juli Trtanj, NOAA, presenting the Global Initiative for Cholera Early Warning, at GEO-X. Image Credit: U.S. Mission Geneva.

If that sounds ambitious, it is. But GICEW draws on recent advances in predictive health programs, including EO2HEAVEN, a European Union-funded effort focusing on cholera to develop mobile application tools for collecting and managing health and environmental data in Uganda. And if successful, the initiative could transform how cholera ‰ÛÒ and many other killers ‰ÛÒ are fought.

Bad Outcomes

Most residents of the wealthy industrialized world have never seen cholera‰Ûªs harrowing effects on the human body. Dr. David Olson has. As a deputy medical director of the Nobel Peace Prize-winning organization, MÌ©decins Sans Fronti̬res/Doctors Without Borders (MSF), Olson has battled cholera outbreaks in Nigeria, Zimbabwe, Chad, and the Democratic Republic of Congo. Most recently, Olson was in Haiti, where 8,000 people have died from the disease since late 2010 when infected sewage from a United Nation‰Ûªs relief camp was accidentally allowed to flow into a river, following a massive earthquake that leveled large parts of the capitol city, Port-au-Prince.

In a phone interview, Olson described what happens when a child contracts cholera. His medical explanation follows, but be forewarned: It‰Ûªs not for the faint of heart.

‰ÛÏThe first thing to understand,‰Û says Olson, ‰ÛÏis that the dose of vibrio needed to cause the disease is not small.‰Û

A patient exhibiting typical signs of cholera receiving oral rehydration solution. Image Credit: Centers for Disease Control.

A patient exhibiting typical signs of cholera receiving oral rehydration solution. Image Credit: Centers for Disease Control.

In fact, it takes between 10,000 and 100 million of the microscopic bacteria, Vibrio cholerae, to cause an infection. That‰Ûªs partly because vibrios are easily destroyed by stomach acid. A common condition in the tropics, called achlorhydria, however, reduces the strength of stomach acid and allows vibrios to pass through this natural barrier.

The immune system plays an even greater role in determining who contracts the disease. In a healthy body, repeated exposure to low and moderate levels of vibrios builds up an immunity to cholera. The younger the child, the lower his or her resistance to vibrios. Even in adults, sufficient immunity will wane over two to three years in the absence of further exposure. Still, only a fraction of those infected become symptomatic.

Once vibros have evaded these defenses, the bacteria line the small intestine and produce a toxin that alters the normal transport of electrolytes (salts) across the intestinal lining. As an abnormal concentration of these electrolytes builds up, water is drawn from adjacent tissues, flooding the intestines. Very quickly, the colon‰Ûªs ability to reabsorb water is overwhelmed. The result is catastrophic diarrhea.

‰ÛÏIn severe cases,‰Û Olson says, ‰ÛÏa person can lose up to a liter of water an hour.‰Û That‰Ûªs a gallon of water lost in less than four hours. At that rate, a person can quickly go from mild to extreme dehydration.

‰ÛÏThis is the only type of diarrhea that you can die from within hours,‰Û Olson explains.

Stools filled with little more than electrolytes and vibrio bacteria take on a characteristic translucent appearance, referred to as ‰ÛÏrice water,‰Û for its resemblance to the starchy residue from rinsing rice. Enormous quantities of bacteria are contained in this fluid; a single teaspoon holds enough vibrios to infect 5,000 people.

Those who are lucky enough to reach a hospital or health clinic are placed in special beds ‰ÛÓ cots covered in plastic sheeting with a hole cut out in the center and a bucket below. These cholera beds are needed because diarrhea quickly becomes uncontrollable.

The outward signs of dehydration include a white coating on the mouth and tongue and a condition called ‰ÛÏsunken eyes.‰Û Normally, the tissue surrounding our eyes is well-hydrated. As dehydration grows more severe, this watery cushion is depleted and the eyeballs drop into their sockets. The skin loses its elasticity. If pinched and released, healthy skin will flatten in a second or less. As the cholera victim loses water, pinched skin will remain intact and upright for several seconds. With less water is available, the volume of oxygenated blood in the body decreases, giving the skin a bluish tinge.

Other symptoms can include a weak pulse and muscle cramps. Young children in the early stages of dehydration become irritable and cry constantly. Before long, they stop crying ‰ÛÓ but not because the pain is gone. This quiet stage signals that their small bodies no longer have enough water to produce tears. In the advanced stages of cholera, the amount of blood reaching the brain decreases and mental capacities ebb. Lethargy is followed by unconsciousness.

‰ÛÏWithout treatment at this point,‰Û says Olson, ‰ÛÏyou can expect a lot of bad outcomes.‰Û

Asked what constitutes a bad outcome, Olson pauses before answering. ‰ÛÏIt means death.‰Û

The good news is that treating cholera is remarkably simple, effective, and cheap. As cholera expert and former director of the National Science Foundation Rita Colwell explained in a 2012 interview with Earthzine, oral rehydration solution (ORS) can save up to 80 percent of infected patients. An ORS packet, containing mostly glucose (sugar) and salt (sodium chloride), costs only about 8 U.S. cents. Fifty cents worth of medicine can save an adult‰Ûªs life. It costs just half that to save a child. Since 1978, when WHO adopted ORS as its standard treatment, the number of deaths from acute diarrhea has dropped from 5 million a year to its present level of 1.3 million.

The Next Advance

Map showing cholera outbreaks clustered along rivers in Mali, which serve as transmission pathways for the disease. Image Credit: Rifat Hossain.

Map showing cholera outbreaks clustered along rivers in Mali, which serve as transmission pathways for the disease. Image Credit: Rifat Hossain.

The Global Initiative for Cholera Early Warning could represent another advance in the fight against cholera. If outbreaks were predictable, countries and international organizations could get ORS, clean water, and other resources exactly where they‰Ûªre needed ahead of time.

‰ÛÏThen we could change the outcome,‰Û says NOAA‰Ûªs Juli Trtanj. ‰ÛÏAnd that‰Ûªs really the end game.‰Û

Trtanj and Rita Colwell have worked closely together for years. In 2006, Colwell was a distinguished scholar at NOAA‰Ûªs Oceans and Human Health Initiative (OHHI), a program run by Trtanj. In 2008, Colwell co-authored a seminal study showing that cholera outbreaks in Matlab, Bangladesh, followed elevated sea-surface temperatures, increased sea-surface height, and intense rainfall events.

‰ÛÏWhen the ecology of V. cholerae is considered in predictive models,‰Û the study concluded, ‰ÛÏa robust early warning system for cholera in endemic regions of the world can be developed for public health planning and decision-making.‰Û

Exactly how environmental factors fit into patterns of cholera outbreaks is complicated, but here‰Ûªs the simplified version. In the 1960s, Colwell discovered that V. Cholerae existed naturally in rivers, estuaries and coastal waters. Previously, scientists believed that the bacteria were transmitted exclusively among humans. Colwell‰Ûªs research, which was highly controversial at that time, established that vibros flourished in the gut and on the surfaces of microscopic aquatic organisms called copepods. High concentrations of vibros occur when environmental conditions are favorable for copepods.

When elevated sea-surface temperatures are combined with increased plankton populations in the water, vibrio-laden tidal waters move inland, bringing more people in contact with high concentrations of the bacteria. Heavy rainfall on land can carry nutrients into rivers, feeding phytoplankton blooms followed by the copepod populations carrying the cholera bacteria, and bringing the cholera bacteria into the water supplies.

Colwell stresses the importance of Earth observation to her work, predicting that ‰ÛÏremote sensing will prove to be a valuable public health tool as it allows monitoring globally and specifically cholera endemic sites.‰Û

Thanks in large part to advances in remote sensing and data sharing, she said, ‰ÛÏWe have reached a point of being able to do early prediction based on climate events.‰Û

The GICEW team is now preparing pilot systems to use in four countries, an effort that could lead to an operational program in 3 -5 years. But, according to NOAA‰Ûªs Trtanj, a number of critical hurdles still have to be cleared before a global early warning system becomes a reality.

These include the availability of environmental and health surveillance data, country-level technical and institutional capacity, and, of course, funding that‰Ûªs adequate to these tasks.

‰ÛÏTo help with the environmental data hurdle,‰Û Trtanj says, ‰ÛÏwe are working through GEO. We also have a challenge in collecting useful health, water sanitation, and social and behavioral data at the appropriate scale.‰Û

Currently, WHO‰Ûªs cholera data is based on what countries choose to report. The fear that reporting a high incidence of the disease could reduce tourist and export revenues can lead to under-reporting the true number of cholera cases. ‰ÛÏSome countries that have cholera,‰Û Trtanj observes, wryly, ‰ÛÏdon‰Ûªt officially have cholera.‰Û The challenge in some countries is to find the people who have the correct data ‰ÛÒ and are willing to share it. That‰Ûªs no small task.

But Trtanj and Hossain are confident that all of these challenges can be met and overcome. After all, this is how smallpox, a disease that once ravaged the globe, was eradicated — by determined teams working together across disciplines and national boundaries.

Besides, says Hossain, the stakes are too high to simply give up. As he puts it in a rhetorical question posed as the session in Geneva winds down, ‰ÛÏWe‰Ûªre here to save lives, right?‰Û