Medicine for Africa - Medical Information Service

HOLERA

Definition:

Cholera is an acute, intestinal infection that can develop into a serious and life-threatening disease within just a few hours after infection.

The bacterium that causes cholera is called Vibrio (V.) cholerae – a bacterium that is usually transmitted through water and/or food products, contaminated by human or animal/aquatic feces.  Recently performed studies also connect global warming to a more favorable environment for the progression of V. cholerae, and an associated increase of disease outbreaks.

The bacterium V. cholerae is a non-invasive (epithelial) bacterium that produces a so-called enterotoxin (a protein-based toxin, released by local bacteria), causing a characteristic more or less severe diarrhea reaction, instigated by an infection-related reaction by the surface epithelium of the small intestine.  The bacterial influence on the intestinal epithelium (mucosa) results in severe changes of the permeability characteristics of the intestinal wall, thus leading to considerable loss of interstitial fluid, water and life-sustaining electrolytes.

It is this massive loss of body fluids and electrolytes that results in the disease’s fatal outcome – death within hours, unless a life-sustaining therapy has been instigated within the early (two to six) hours of the time that obvious infectious symptoms occur.

Although the infection is usually – and most of the time – a mild, self-limited and sub-clinical disease process, if cholera occurs in the context of a local epidemic ‘catastrophe’ (such as violent rainfalls with resulting, uncontrollable flooding over large areas), it can easily develop into an uncontrollable deadly epidemic, demanding an extraordinary amount of innocent victims in its path.

Historic review puts cholera’s early appearances on the Indian subcontinent, although there are reports of cholera-like epidemics dating back as far as Hippocrates, around 400 BC.  It was only in 1883, that Robert Koch was able to successfully isolate the V. cholerae bacterium from the intestinal discharge of patients, thus proving that the bacterium was indeed the agent of this disease process.

Since the early 1960s, cholera has spread from Indonesia throughout Asia, extending into Europe and Africa. While most of the developed world has been able to limit the outbreak occurrence of cholera, it has become an epidemic disease in many of the less developed countries of the world, especially throughout the African continent, from where, at this point in time, 95% of cases worldwide, are reported.

While the Vibrio organisms are the most common organisms in surface waters throughout the world, V. cholerae and V. parahaemolyticus are pathogenic (disease causing) organisms for humans.  Both species produce more or less severe diarrhea – while the former is a non-invasive organism, affecting primarily the colon (large intestine), the latter is a non-invasive organism that expresses its effects on the small intestine by way of the secretion of its enterotoxins.

If the vibrio bacterium is able to survive the acid gastric secretions, it will be well adapted to survive within the small intestine; thus, V. cholerae will be able to produce its devastating toxin through its effects on activating an enzyme (adenylate cyclase) within the cells of the intestinal mucosa, which cause increased secretion (loss) of water, sodium and potassium, as well as other life-sustaining electrolytes, such as chloride and bicarbonate into the lumen of the small intestine.  It is this toxic effect of short-term loss of life-sustaining electrolytes that causes the most severe and at times deadly effects of the disease.

The main track of contamination of cholera is by way of contaminated water and food products.  Contamination progresses via a fecal-oral pathway, meaning that water/food products that have been infected by fecal derived cholera organisms will enter the future patient orally by ingesting the contaminated food/water resources.  Thus, the less efficient a community’s sewage and waste removal system, the more likely an outbreak of cholera may occur.  The other major cause of a cholera outbreak is associated with natural catastrophes, such as extensive rainfall associated with extensive flooding and insufficient availabilities of water and sewage drainage in over-exposed areas.   

Also, in urban slum areas without basic infrastructure such as clean water and proper sewage system, the chances of a cholera outbreak are always present.

Cholera remains a global threat to public health and is one of the key indicators of a country’s social development.  The World Health Organization (WHO) reported that in 2006 cholera outbreaks showed a dramatic increase, reaching the level of the late 1990s.  In 52 mostly less developed countries, a total of over 230,000 cases of cholera infections were reported, including over 6,300 deaths. In addition, WHO estimates that only about 10% of actual cases have been reported, thus the actual burden of the disease is grossly underestimated.

Although today the disease is not an issue anymore in developed countries, many famous people died of cholera over the last few centuries.  Thus, cholera has been said to be the cause of death of the Russian composer Pyotr Ilyich Tchaikovsky, as well as James K. Polk, the 11th president of the USA. King Charles X of France died of cholera, as did well known writers in Germany (Hegel), Poland (Mickiewicz) and Ireland (John Dillon), among many other victims.

Symptoms:

Cholera typically presents itself with a sudden onset of massive watery diarrhea, the so-called ‘rice-water stools’ – watery diarrhea, speckled with mucus flakes, epithelial cells and V. cholerae bacteria. It is also often accompanied by vomiting.

The bacterial enterotoxin causes the extraction of water and electrolytes from blood and tissues, pumping it into the intestine, and finally excreting it as watery diarrhea. It is this massive loss of fluids and essential electrolytes over just a few hours that lead to dehydration (loss of water), anuria (no urine output), acidosis (‘acid blood’), and shock.

Signs and symptoms include tachycardia (increased heart beat) and hypotension (low blood pressure), dry mucous membranes and thirst, loss of skin turgor (elasticity), and muscle cramps. 

Usually, the disease progresses from first liquid stools to the development of shock within four to 12 hours, and can cause death within 18 hours to several days.  However, life-threatening hypotension can develop within just one hour of the onset of symptoms and cause death within less than three hours, if no treatment is available.

                  

Diagnosis:

The best source for a specimen consists of stool and swab samples, collected during the acute stage of the disease, and prior to administering antibiotics for treatment.  These specimens are then used for the cultivation of cholera vibrios by using special culture media.  The most widely used medium is called TCBS medium, containing thiosulphate (T), citrate (C), bile salts (B) and sucrose (S – sugar); other media that are used, include GTTA (Monsur’s Taurochocolate trypticase Tellurite Agar) and BSA (Bile Salt Agar).

The gram-negative rod-shaped bacteria can also be confirmed by way of blood cultures; while the microscopic detection of the vibrios’ characteristic motility can only be appreciated after enrichment, and followed by inhibition with an appropriate antiserum.

Agglutination with specific sera can also be used to serotype the bacteria. The so-called O antigen distinguishes V. cholerae into 139 known serotypes, almost all of them being non-virulent.  Until the recent emergence of a non-O1 strain (the Bengal strain), a single serotype, designated ‘O1’ has been responsible for epidemic cholera outbreaks.  The O1 antigen has been further classified into three biotypes, named Ogawa, Inaba and Hikojima.  The above mentioned Bengal strain, labeled O139, is a new strain, expressing a unique O-antigen, which, contrary to the other strains, does not provide residual immunity following an infection.

 
Treatment:

Cholera is an easily treatable disease!

The most important cornerstone of an effective cholera therapy consists of intravenously administered fluids and electrolytes, including glucose, given to the patient as soon as possible!

However, especially in developing countries, where cholera is also most prevalent, it may often be impossible to get to a hospital or health care facility in time. In addition, i.v. fluids are expensive and often not available. Thus, oral rehydration has to be performed, which can be equally successful, if started in a timely manner and prepared appropriately.

The 'African' rule of thumb for preparing an adequate solution for oral rehydration treatment consists of:

• One half liter of safe, clean (bottled or preboiled) water;
• One pinch of salt;
• One fistful of sugar - all mixed together, and given in small quantities until the patient recovers. Although the sugar may at first worsen the diarrhea, it is needed to provide sufficient nutrients;
• As soon as possible, eat bananas or drink green coconut water.

The World Health Organisation (WHO) also issued a home-made recipe for oral rehydration therapy, that is a bit more specific in its amounts of ingredients - thus, add to one liter of safe water:

• Salt - 3.5 grams, or 1/2 small spoon;
• Sugar - 40 grams, or 4 big spoons;
• Compensate loss of potassium with bananas or green coconut water
  

Orally given salts, as well as intravenously administered fluids and electrolytes in a timely manner and adequate volumes can reduce the fatality rates to well below 1%.  This kind of treatment can easily be provided, and is a highly effective, safe and inexpensive way to manage the disease.

Additionally, antibiotics as an adjunct therapy may reduce the requirements of fluids that need to be given, and may shorten the duration of the illness.  Tetracycline has been the antibiotic of first choice, although there have already been reports showing the development of resistance against this drug by certain V. cholerae strains.  Other antibiotics that have proven to be effective in cholera include chloramphenicol, cotrimoxazole, doxycycline and erythromycin, among others.

................... Immunity:

Following a cholera infection by V. cholerae, antibodies in the patient’s blood circulation can be detected as early as eight to ten days after the onset of the illness.  Although these ‘vibriocidal’ (potential to kill the vibrio bacteria) antibodies return to baseline within about seven months, infected patients also develop toxin-neutralizing antibodies and local immune defenses on the surface of the intestinal mucosa, mediated by antibodies.

Thus, people who survived a cholera infection have developed a certain amount of immunity that will protect them from another infection, or lessen the impact of a new outbreak.  Children, who are being nursed by a mother who underwent a cholera infection previously, also enjoy a certain degree of protection, afforded by secretory antibodies derived from their mother’s milk.


 
Prevention:

There is a simple rule for travelers, especially to cholera-affected areas:

‘Boil it, cook it, peel it – or forget it!’

High risk food products include fish and shellfish, uncooked or undercooked vegetables, and water that has not been boiled or chlorinated – thus, beware of ice cubes in a drink, coffee and tea if not prepared with chlorinated water, tap-water rinsed green salads and fruits such as grapes, unpeeled apples, pears, peaches, etc.  And never neglect to wash your hands – the more often, the safer.
 
.................... Vaccines:

The fact that a patient who recovered from an infection confers effective and long-lasting immunity against cholera, has led to efforts to develop an effective protection providing vaccine.  Worldwide, there are two vaccines available (neither in the USA), one in Vietnam only, the other one elsewhere.  Both vaccines provide some level of immunity, yet, they are not recommended by the US CDC (Center of Disease Control).  On the other hand, the World Health Organization (WHO) issued official recommendations for the usage of the internationally licensed oral cholera vaccine (OCV), to be used in complex emergencies.  This vaccine has proven to be safe and effective (about 80-90% after six months); it is administered in two doses, about two weeks apart.  

However, the vaccines are not recommended for residents of regions where cholera may be entrenched, because their use may lead to complacency and thus, increased susceptibility to the disease, and long-term use would also lead to unacceptable severe side effects.

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