EM image of cholera

3x deadlier than ISIS

In Opinion by Morgan Bye2 Comments

The cholera had broken out at the post, and five or six men were dying daily.Buffalo Bill
We are in the middle of a global pandemic. In one small country, population 10 million, 4000 dead. Another 200,000 infected. All in under 3 months. International efforts have had little effect. 5 years later, 9000  lie dead. Almost three-quarters of a million infected. The sick are highly infectious. Food and water are not safe from infection. This pandemic, by World Health Organisation numbers, is claiming up to 142,000 lives EVERY YEAR.[1]World Health Organisation Bulletin (2011) – article 3 years of civil war in Syria and the rise of ISIS is estimated at 170,000 deaths.[2]BBC (2014) – link

80 % of cases are easily treatable, with nothing more than water, salt and sugar.

The disease itself, easily preventable.

This latest pandemic, has a Harvard professor worried,[3]The Atlantic (2015) – link

…as opposed to burning out after 5 to 20 years as all previous pandemics have done… seems to be picking up speed.Prof. Edward T. Ryan

The disease, cholera.

A global pandemic

Cholera is the infection caused by ingestion of food or water contaminated with the bacterium Vibrio cholerae.

Following the earthquake in Haiti back in September 2010, over 220,000 people were dead and a further 1.3 million were made homeless. Even before this, Haiti ranked as one of the poorest countries in the world – 168th in the United Nations Human-Development Index[4]United Nations (2014) – table – with 70 % of the population living on less than $2/day. Yet, the island nation had no history of cholera for the last 100 years.

As relief workers came to the aid of Haiti in the days after the earthquake, many came directly from other disaster areas. As aid arrived, so did cholera.

World outbreaks of cholera from 2011-2013, Haiti highlighted by the red arrow[5]World Health Organisation (2014) – link

World cholera outbreaks

In October 2010, Cuban medical units working in Haiti first reported a worrying increase in the number of patients with watery diarrhoea and vomiting. 61 cases in the first week. 28 new cases in the second week with 2 deaths.

5 years later, it is the worst outbreak of the disease in modern history.

For context, a British journalist wrote of the 1991 Peruvian cholera outbreak[6]Rose George (2009) – book (via Google)

When Peru had a cholera outbreak in 1991, losses from tourism and agricultural revenue were three times greater than the total money spent on sanitation in the previous decade.Rose George

Hundreds of aid workers, the Haitian government and millions of dollars in international aid have been combating cholera for 5 years, with no success. Cholera is still a massive problem. Why?

The history of cholera

Cholera’s symptoms can be found inscribed on a temple wall in India, dating from the 4th century BC.[7]Brian Williams(1997) – link

1817 saw the first recorded pandemic of cholera, where it laid waste to the Bengal region. This outbreak was shocking, even by the standards of a region that was used to cholera. An area so used to cholera it had its own cholera goddess “Ola Beebee” (translated as “our Lady of the Flux“)

In 1832, British doctors and hospitals were attacked by the public after the “Asiatic cholera” of Bengal had reached England. The lower classes at the time rioted across the nation, convinced that cholera was a plot by the wealthy to do away with them.[8]Mosaic (2015) – link

[9]CDC (2003) – link

The German scientist, Robert Koch in 1884, made the first observations of cholera sending samples back from Calcutta to the German Ministry of the Interior noting that it was “a little bent, like a comma“.

The 19th century, with an increase in global trade, allowed cholera to spread across the world – far from its origins in the Ganges delta. Six subsequent pandemics have killed millions of people across all continents. The current (seventh) pandemic started in South Asia in 1961, reaching Africa in 1971 and the Americas in 1991. Cholera is now endemic in many countries.

Decades past it was a paradox. Cholera is one of the most understood bacterial pathogens from a biological point of view, yet rates of cholera weren’t declining.Professor John Clemens, International Centre for Diarrhoeal Disease Research, Bangladesh

Why is cholera so deadly?

The bacterium Vibrio cholerae lives in water and is easily ingested by the consumption of dirty water, infected food or simply through inadequate hand-washing.

The cholera bacteria quickly sets up camp in the small intestine by attaching to the walls of the gut and multiplying. The bacteria secrete a toxin that causes certain channels in the gut wall to stay open. This is great for the bacteria because it means they get valuable nutrients. It also means that the gut is flooded with chloride ions – an important electrolyte. Wherever chloride goes in the body, sodium ions and water follow.

A healthy person can catch cholera at daybreak and be dead before sundown.

A huge surge of chloride, sodium and water in the gut causes huge volumes of fluid to be evacuated from the body.

This is great for cholera. It means that newly replicated bacteria are free to infect new hosts.

A cholera victim can lose several litres of fluid in just a few hours.

A healthy person can catch cholera at daybreak and be dead before sundown.

Cholera is not a difficult organism for your body’s immune system to fight, the problem is that patients typically dehydrate so fast that they often die before any immune response has time to kick-in.

Cholera treatments

Médecins Sans Frontieres (MSF) (commonly known as “Doctors without Borders” in English) treat up to 80 % of cholera cases with a simple oral rehydration solution. Salt, sugar, water.

Most cholera treatment centres are simple affairs, with clinic workers maintain that

Chlorine is our best friend

Wards do not smell. The fact is what comes out of patients is little more than salty water.  In Haiti it is called dlodiri from de l’eau de riz or, “rice-water“. The wards themselves contain only special beds with a hole cut out of the canvas with a bucket underneath for easier cleaning. Serious cases way warrant more than oral rehydration and additionally receive an IV drip.

Cholera Clinic in Dhaka [10]Mark Knobil via Wikipedia (2005) – link

Haiti has many cholera treatment centres, and whilst almost all are understaffed and ill-equipped the biggest problem remains society. The local community are well educated as to hand-washing and the importance of clean water. However, being able to enact such basic measures in a country so lacking of infrastructure is not easy.

Social stigma is also working against the relief effort. Those that receive soap, water sterilising tablets or even a bucket are considered by their neighbours as dirty.

The fear of this social stigma is so great that many suffers in Haiti would rather travel hours on motorbikes to get to a clinic far away from their neighbours. Sadly, the truth is that many die en route, just so that the neighbours do not find out.

Cholera in Haiti

Cholera, it is often said, is a symptom of poverty. Cholera loves chaos. Haiti, home to both chaos and poverty, is a place where cholera thrives. Between corrupt governments, coups, earthquakes and hurricanes the people of Haiti suffer.

Under international pressure, the Haitian cholera was genetically tested. We now know that the Haitian cholera outbreak is a particular strain that had previously been confined to Asia and parts of Africa. It is also known that a cholera outbreak had been reported in Kathmandu, Nepal just a few days before UN peacekeepers from Nepal arrived in Haiti. The investigation also strongly suggested that the cholera outbreak had been a result of sewage being discharged directly into local rivers.

Haiti was in a state of terror. Nobody dared shake hands or touch, never mind eat the fish.

By the end of December 2010, there had been 185,351 cases and 4,101 deaths. Haiti was in a state of terror. Nobody dared shake hands or touch, never mind eat the fish. There were so many corpses that sometimes people transported their dead relatives on a motorbike, propped up between two passengers.

In their desperation, fear allowed superstition. People turned to voodoo priests, but when things only continued to get worse the priests were blamed and the panic only got worse.

Following the earthquake, there was also a huge effort from the Haitian government, international aid, non-government organisations and the UN in treatment and prevention of cholera. Cholera treatment centres were established. A widespread public safety campaign was launched focussing on personal hygiene, reminding everyone to wash their hands before eating and after defecating.

No end in sight

By 2014, it was working. Thanks to a combined domestic and international effort, the dreadful death seen in 2010 through 2012 was falling – disease spread and fatality were being cut by nearly half each year.

In 2011, over 350,000 recorded cases resulted in almost 3000 deaths. By 2014, there were only 30,000 new cases and 295 deaths. Sadly, Haiti’s new cases equal the rest of the world combined. But hope was still there. The UNICEF emergency manager said of Haiti,[11]Mosaic (2015) – link

In 2014 we were close to eliminating cholera. We were really closeGregory Bulit

Back in 2013, the government launched a ten-year National Plan for the Elimination of Cholera in Haiti. 10 years sounds like a long time for something that is killing people now, but the hard reality is that this is a poor country with little to no infrastructure.

The plan includes such ambitious targets as making all public water systems chlorinated and monitored by 2017. By 2022, Haiti wants water and sanitation “to at least the average level of the countries of Latin America and the Caribbean

The problem is always the same, money.

When you talk of international issues that require attention, there are only 3 answers. Ebola, Syria, Ukraine.

The fact is, there was an earthquake and the world gave generously in support to one of the world’s poorest nations. But then, we went back to our own lives knowing that Haiti could take care of itself now. But despite everything, it did not.

This is an island nation with a border. It is possible to contain it. Cholera is so crazy and so easy to treat.Oliver Schulz, MSF

Vibrio cholerae itself is a daunting adversary. Around 75 % of infected carriers show no symptoms but remain contagious for up to two weeks. Cholera can also survive outside of a human in aquatic environments, making it incredibly difficult to eradicate.

A medical solution?

In the 19th century the Russian scientist, Ilya Metchnikov, deliberately swallowed Vibrio cholerae to research why some people got sick with cholera and why some did not. Be believed that the intestinal flora, the bacteria we have within our bodies, might have something to do with it.

When Metchnikov suffered no effects but watched a fellow member of the lab nearly die from swallowing the same sample, he grew curious. He took samples from their guts and looked at the microbes under a microscope and found that some bacteria within the gut slowed cholera whilst others made it flourish.

The first injectable vaccinations against cholera were available from the late 1800s. Whilst oral vaccination has been available since the 1990s.[12]Cochrane Database of Systematic Reviews (2011) – article

It is important to remember that Vibrio cholerae at this point has several subspecies, each with a unique feature here-and-there as a result of the relative isolation where it developed. However, the main problem is not the bacteria evolving or growing antibiotic resistance, but a lack of basic healthcare systems.

The World Health Organisation actually has 2 different vaccines stockpiled for the most common of choleras. Their costs range from $0.10 to $4.00 per dose.

EM of cholera [13]Robert Koch Institut (2014) – link

In Vietnam, an oral cholera vaccine is administered to children in schools and has so far successfully administered 9 million doses.

The problem has been that the vaccine is only a temporary measure. Typically the vaccination is 85 % effective during the first six months and 50–60% effective during the first year. The effectiveness decreases to less than 50 % after 2 years.

Whilst for travellers the cholera vaccine might be very effective, for communities it needs to be combined with clean water and proper sanitation. With time, a combined vaccination and societal effort creates a herd immunity, whereby even those with no immunity have a significantly reduced chance of catching the disease.

The vaccine works.

The problem is that there is currently only one manufacturer in the world – and they cannot keep up with demand. Economics tells us, that when supply is short, the price rises and as a result rich travellers will always have access to a cholera vaccine over the people of Haiti.

What about the rice?

A team out of the University of Tokyo to much fanfare have bioengineered a rice with a cholera vaccine built in.[14]The New York Times (2014) – link On paper this sounds like a win-win. Most of the areas with cholera problems are extremely poor and often wet. This is both ideal conditions for rice paddies and cholera outbreaks.

Unfortunately, the rice only provides partial immunity. The cholera toxin consists of 6 protein subunits: 1 A subunit and 5 copies of the B subunit. The engineered rice, MucoRice, only contains the B subunit. This is a great start for the immune system, as it will now be able to recognise the part of the cholera toxin, but it does provide any assistance to the body in actually recognising or fighting the bacteria.

Meanwhile, other researchers are using rice for other purposes. Researchers at Switzerland’s Lausanne’s Swiss Federal Institute of Technology (EPFL) are investigating rice powder in oral rehydration therapy. The body actually cannot absorb pure water, it needs ions and electrolytes in it to actually be able to absorb the water. This is why IV drips use saline (salt water) and not pure water. An important part to fast absorption is the inclusion of sugar, specifically glucose (the body’s sugar of choice). The Swiss team found that the sugar normally found in oral rehydration therapy actually helps the cholera to divide faster. However, when they replaced the glucose with starch (a more complex sugar) from rice powder or potatoes it did not help the cholera and reduced its toxicity by 75 %.[15]PLoS Neglected Tropical Diseases (2014) – article

The silver lining

Not everyone has given up on researching a third-world disease. A team in Bangladesh, with funding from the Bill and Melinda Gates Foundation, this month published a large study of over 250,000 people in a dense, urban population with inherent cholera over 2 years.

The study found that the Shanchol vaccine ($1.85/dose) administered as a two-dose vaccination, 2 weeks apart reduced the incidence of cholera in the population was reduced by 45 %, with their hospitalisation rate more than halved.[16]The Lancet (2015) – article

The article’s lead author commented

Ultimately, the key to controlling cholera is clean water and adequate sanitation, which half the developing world (around 2.5 billion people) lack, but this remains a rather difficult reality for the world’s poorest nations as well as those affected by climate change, war and natural disaster.Dr. Firduausi Qadri, the International Centre for Diarrhea Disease Research, Bangladesh

Conclusion

Cholera exacts a tremendous toll on public health globally. 91,000 deaths and 2.8 million cases of cholera are reported every year. Estimates put 1 billion people at risk.

Of all these deaths, approximately half are in children under 5 years of age.

The burden of cholera is greatest in the developing countries of Africa and South Asia where a large number of people live in unsanitary conditions without access to clean water, factors which are critical to the spread of cholera.

[17]CDC (2005) – link

The history books remember the great English physician John Snow. With careful tracking of outbreaks (now called epidemiology) in London he traced the source to infected water. In 1854, clean water public pumps were instigated, whilst cesspits were moved away from water sources.

A problem, solved in London 160 years ago, still lingers in the developing world.

Part of the solution must be a cultural shift. People need to understand the importance of hygiene. However, in the developing world – especially after disasters – the knowledge and risk does not outweigh the necessity.

Otherwise, thousands of people will continue to die every year from a disease that is easily preventable, easily immunised against and is easily treatable.

About the Author

Morgan Bye

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Morgan Bye is a British science writer, out of Vancouver, Canada, dedicated to helping scientists better communicate their science. He has a Masters in Biochemistry, a PhD in Biophysical Chemistry and even spent time as a scientist at an Israeli research institute.

Feature image is adapted from [18]Hans R. Gelderblom (2014) – link

References   [ + ]

1. World Health Organisation Bulletin (2011) – article
2. BBC (2014) – link
3. The Atlantic (2015) – link
4. United Nations (2014) – table
5. World Health Organisation (2014) – link
6. Rose George (2009) – book (via Google)
7. Brian Williams(1997) – link
8. Mosaic (2015) – link
9. CDC (2003) – link
10. Mark Knobil via Wikipedia (2005) – link
11. Mosaic (2015) – link
12. Cochrane Database of Systematic Reviews (2011) – article
13. Robert Koch Institut (2014) – link
14. The New York Times (2014) – link
15. PLoS Neglected Tropical Diseases (2014) – article
16. The Lancet (2015) – article
17. CDC (2005) – link
18. Hans R. Gelderblom (2014) – link