Cholera: A disease with unending epidemics
According to WHO, Vibrio cholerae causes 1.3 to 4 million infections and 21,000 to 143,000 deaths worldwide each year. The disease incidence and severity disproportionately affect children aged younger than 5 years. Cholera is spread by water or food contaminated with human feces from a person with active cholera or from a person who is convalescing from cholera or has had asymptomatic or mildly symptomatic cholera. Following cholera infection, excretion of the organism can last for at least 2 weeks. Estimates of the ratio of asymptomatic to symptomatic people range from 3:1 to more than 100:1. The bacterium can also survive in the environment in brackish rivers and coastal waters for long periods.
Cholera is endemic in Africa, South Asia and Southeast Asia. It is a disease that affects only humans. In modern times, there have been periodic flares of epidemics in these and other areas. Most recently, there have been large epidemics in Haiti, where in 2010 the organism was introduced following an earthquake, and now in Yemen, where there is an ongoing war. Epidemics are precipitated and enhanced by circumstances that interfere with sanitation and the state’s ability to supply safe water. These circumstances include earthquakes, war and flooding.
Over the past 2 centuries, there have been seven cholera pandemics that have killed many millions of people (Table). Children and the elderly are disproportionately affected in terms of disease and its case-fatality rate. In between each pandemic, cholera almost disappeared. The pandemics spread from people moving along trade routes, emigrating, going on religious pilgrimages, fighting in wars or traveling for other reasons. The years assigned to the pandemics have varied in different historical accounts. In the 19th century, about 250,000 Americans died from cholera. Zachary Taylor, the 12th president of the United States, purportedly died while in office from cholera.
The first six pandemics were caused by known or presumed classical serotype V. cholerae O1. The seventh pandemic was caused by a biotype of V. cholerae O1 called El Tor. A new serotype, V. cholera O139, was discovered in Bangladesh and India in 1992 and has been detected in several Asian countries since then. It has caused outbreaks in the past but not recently.
Cholera is endemic in many countries in the world, and in 2017, there have been outbreaks in Asia (including Pakistan, Afghanistan, India and the Philippines), many African countries, and Haiti and the Dominican Republic in the Americas. The two large epidemics in recent times occured in Haiti and Yemen.
In January 2010, there was a major earthquake in Haiti, which further disrupted water supplies and sewage disposal systems that were already inadequate. In October 2010, cholera was introduced, apparently by United Nations peacekeepers from Nepal, to a population that had never experienced cholera and was immunologically naive. Over the next year, more than 450,000 cases and 6,000 deaths were recorded. The outbreak affected approximately 5% of the population, with some spread to the Dominican Republic and Cuba. The epidemic in Haiti has continued with upticks during the rainy and hurricane seasons. To date there have been over 800,000 cases and more than 9,000 deaths (case-fatality rate about 1.1%).
The cholera epidemic in Yemen started in October 2016. One year later, as of Oct. 17, there have been over 840,000 cases of cholera and more than 2,150 deaths, with a case-fatality rate of about 0.3%. The epidemic had tapered off with only several hundred cases and seemed to be under control when in April 2017, the sewer system in Sana — a city with a population of 1.7 million — failed because of the war. There was a surge in cases starting in mid-May that has continued to today, and the epidemic has spread to involve most of the country. It is reported that there have been about 5,000 new cases a day. It is doubtful that adequate water supplies and sanitation can be restored until the fighting ends. The number of cases within 1 year of onset far exceeds the rate of new cases in the Haiti epidemic in its first year.
Although the great majority of cholera infections are asymptomatic or relatively mild, about 5% to 10% of those with clinical cholera develop very severe disease with vomiting and voluminous watery diarrhea. In these patients, the loss of fluids and electrolytes can be so profound that death can occur within hours. The case-fatality rate in these patients has been as high as 80% without adequate treatment.
The mechanism for the diarrhea is secretion of fluid and electrolytes in response to cholera toxin without damage to the small intestinal epithelium. The primary approach to therapy of cholera is fluid and electrolyte replacement. If possible, oral replacement is used with fluids containing electrolytes, glucose (which helps rapid absorption of salt and water), and micronutrients. Zinc has been found to be of particular importance. If oral replacement is not possible, IV replacement must be used, but this is often not feasible in underdeveloped countries. Antibiotic therapy with a tetracycline (usually doxycycline) and azithromycin in children reduces fluid requirements and shortens the illness.
Oral replacement therapy (ORT), developed in the late 1960s and 1970s and used by ORT centers during cholera epidemics, has been called “potentially the most important medical advance” of the 20th century. The low case-fatality rates in the Haiti and Yemen epidemics are evidence that the ORT centers have had a major effect in reducing mortality. Mortality rates during the 19th century were reported to be as high as 50%. Before ORT, even with IV therapy (when it was available), case-fatality rates were reported to be as high as 15%.
There are several older oral vaccines — Shanchol (Shantha Biotechnics); Euvichol (EuBiologics); Dukoral (Valneva); and mORC-Vax (VaBiotech), which is available only in Vietnam — that consist of killed whole bacterial cells with or without inactivated cholera toxin. They are all about 65% effective in endemic areas but require two doses for this level of protection. Protection lasts for 2 to 5 years depending on the vaccine. The newest and only vaccine available in the United States is the recently approved live-attenuated, single-dose oral vaccine, Vaxchora (PaxVax), indicated for adults aged 18 to 64 years who are traveling. It is 90% effective 10 days after immunization and 80% effective 3 months after immunization. It cannot be used if antibiotics are being administered. Its effectiveness in developing countries has not been established.
Although there have been major advances in the treatment of cholera and in vaccine development, the most important approach to the eradication of cholera is the provision of safe drinking water and proper sewage disposal. This is often difficult in developing countries and always difficult in the presence of war and national disasters.
Recently, the Global Task Force on Cholera Control (GTFCC), comprising more than 50 international organizations including the United Nations and WHO, launched an effort to reduce cholera-related deaths by 90% in 13 years. The GTFCC is targeting hotspots in 47 African, Asian and Caribbean countries to improve access to safe water, sanitation, hygiene and oral cholera vaccines.
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- Stop Cholera. Oral Cholera Vaccine (OCV): What You Need to Know. https://www.stopcholera.org/sites/cholera/files/oral_cholera_vaccine_what_you_need_to_know.pdf. Accessed on October 19, 2017.
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- For more information:
- Donald Kaye, MD, MACP, is a professor of medicine at Drexel University College of Medicine, associate editor of the International Society for Infectious Diseases’ ProMED-mail, section editor of news for Clinical Infectious Diseases and an Infectious Disease News Editorial Board member.
Disclosure: Kaye reports no relevant financial disclosures.