“Knowing the enemy by sight”: how to avoid cholera

Cholera - symptoms and treatment

Cholera is an acute infectious diarrheal disease that poses a particular danger to people. It is caused by the bacteria Vibrio cholerae. Penetrating through the mouth, bacteria affect the intestinal mucosa, disrupting the functioning of the digestive tract. In the absence of adequate treatment, the disease can quickly lead to dehydration, seizures and death [8].

Etiology

Taxonomy of the causative agent of cholera:

• domain - bacteria;
• type - proteobacteria;
• class - gamma bacteria;
• order - Vibrionales;
• family - Vibrionaceae;
• genus - Vibrio (vibrios);
• species - Vibrio cholerae (Vibrio cholerae).

There are many varieties of Vibrio cholerae, but only two serogroups - O1 and O139 - are capable of causing cholera outbreaks. Each of them has its own biotypes:

• Vibrio cholera O1 classica - classic biotype;
• Vibrio cholera O1 El Tor - predominates at present;
• Vibrio cholera O139 Bengal - known since 1992, has caused a major cholera epidemic in Bangladesh, India and other neighboring countries.

The causative agents of cholera are short, curved gram-negative bacteria. In their shape they resemble commas. Their size reaches 0.4-0.6 microns in width and 1.5-3 microns in length.

The bacteria are mobile and do not form spores or capsules. When sowing material, their bluish colonies resemble a school of fish. They are facultative anaerobes, as they are able to obtain energy both in conditions of oxygen and without it. They grow well in alkaline nutrient media.

Vibrios cholerae have a species-specific antigen A and a type-specific antigen O. They contain the genetic information of bacteria and cause an immune response in the body.

The pathogenicity factors of Vibrio cholerae include:

• flagella - make bacteria motile;
• mucinase enzyme - thins the intestinal mucous barrier, facilitating access to the surface of its epithelium;
• neuraminidase enzyme - promotes the production of toxins.

The causative agent of cholera produces two types of toxins :

• endotoxin lipopolysaccharide - does not play a significant role in the development of cholera disease, but can potentially provoke an immune response;
• Cholerogen exotoxin - has a toxic effect only on the intestinal mucosa, causing a massive release of electrolytes and fluid from its cells, leading to diarrhea and dehydration.

Bacteria are very sensitive to acids and alcohol. In feces with sufficient humidity and lack of sunlight they live up to 150 days, in cesspools - over 100 days, in soil - up to 60 days, on fruits and butter - up to 30 days. They survive quite well in low temperatures and freezing conditions. When boiled they die instantly, at a temperature of 56 °C - in 30 minutes. Most antibiotics (mainly tetracyclines and fluoroquinolones) contribute to their destruction [1][2][5][6].

Epidemiology

The source of infection is only humans (patient and carrier). It is most contagious in the first week of illness.

The main foci of cholera are in Africa, Southeast Asia and Haiti, but small outbreaks and isolated cases of the disease are reported throughout the world. The average annual number of cases of the disease is about 5 million people, deaths are about 130 thousand [11].

The transmission mechanism is fecal-oral (water, food and household contact). The main mode of transmission is water. The second most important route is the food route: through meat, seafood, milk, vegetables and fruits that have not undergone adequate heat treatment.

A person, being in the same room with other people, cannot directly infect them. Only the patient’s secretions (feces and vomit) are dangerous if they enter the mouth of a healthy person.

The group at increased risk of developing the disease includes people with blood group O, chronic diseases of the gastrointestinal tract and other organs, the absence or reduced amount of hydrochloric acid in the stomach (achlorhydria or hypochlorhydria).

Cholera spreads much more easily than other acute intestinal infections: it sooner leads to massive release of the cholera pathogen in feces and vomit, which do not have an unpleasant odor or color.

Once in bodies of water (including coastal waters), cholera vibrios can persist for a long time and even multiply. This is facilitated by warm, stagnant, slightly brackish water. Also, reproduction and concentration of the pathogen is possible in zooplankton. In general, cholera is a problem in regions where there is no adequate disinfection and purification of drinking water and hygiene rules are not observed.

Susceptibility to the disease is high. Seasonality is usually summer-autumn. In cities, the incidence is higher than in rural areas. Men get sick more often.

The immunity is strong, but it does not protect the body from infection with other types of Vibrio cholerae. Mortality in the modern world is 1-3% [1][3][5][8].

When to see a doctor?

The risk of a cholera outbreak in industrialized countries is low. Even in regions where it exists, the likelihood of infection is minimal if food safety recommendations are followed. However, cases of cholera occur throughout the world.

Therefore, if a person develops severe diarrhea after visiting an area with recent cases of cholera, it is time to seek immediate medical attention².

Features of cholera in children

At the age of under 3 years, the dehydration characteristic of cholera is much more severe. Because of this, children quickly develop signs of dysfunction of the nervous system in the form of severe general lethargy, convulsions and even loss of consciousness. Moreover, unlike adults, the body temperature of children with cholera often rises to 37.5-38.0°C.

Prognosis and prevention

With mild and moderate forms of the disease, the prognosis is relatively favorable. However, even in such cases, without timely assistance, complications can develop that lead to death. After an illness, a person has a strong immune system.

Although cholera is rare in Europe, the risk of infection still exists. You should also take additional precautions when visiting countries with active cholera outbreaks among the population. For this purpose, specific and nonspecific prevention is used.

The main measures for nonspecific prevention of cholera include:

• Compliance with personal hygiene rules. You should wash your hands frequently with soap and water, especially after using the toilet and before handling food. If soap and water are not available, an alcohol-based hand sanitizer should be used.
• Drink only high-quality water. It is important to drink only safe water, including bottled, boiled or disinfected water. It can even be used to brush your teeth. Hot drinks, drinks in cans or bottles are generally safe, but the outside of the package must be disinfected before opening. Also, you should not add ice to drinks unless you are sure that it is made from clean water.
• Eating only proven food. You should give preference to home-cooked and hot food, and if possible avoid food from street vendors. It is recommended to avoid sushi, as well as any raw or improperly prepared fish and seafood. It is important to eat fruits and vegetables that you can peel yourself, such as bananas, oranges and avocados.

Vaccination against cholera

Specific prevention of cholera is represented by a vaccine that is taken orally. Currently, three drugs have been developed and approved for use⁴:

• WC/rBS. The composition includes killed whole cells of Vibrio cholerae.
• CVD 103-Hg-R. Developed from live, attenuated, genetically modified Vibrio cholerae.
• Vaxchora is an attenuated live vaccine. Currently not registered in Russia.

Vaccination against cholera is given to people living in endemic regions and at high risk of infection. It is also recommended for people planning to travel to countries where cholera outbreaks have recently been reported. In this case, immunization is carried out at least 10 days before travel.

The complete vaccination program depends on the drug and the age of the person and may include 2-3 doses, administered at intervals of 1-2 weeks. A full course of vaccination provides protection against cholera for three years, while a single dose provides short-term protection.

No cholera vaccine provides 100% protection, and vaccination does not replace standard prevention and control measures, including food and water precautions⁴.

Complications

Without proper treatment, cholera can quickly become fatal. In the most severe cases, loss of large amounts of fluid and electrolytes can cause death within hours. In other cases, people who do not receive the necessary care may die from dehydration and dehydration shock 1-2 days after the first symptoms of cholera² appear.

Although severe dehydration is considered the most dangerous complication of cholera, other problems can occur with this pathology:

• Low blood sugar (hypoglycemia). Low levels of sugar (glucose) in the blood - the main source of energy for the body - are characteristic of severe forms of cholera. Hypoglycemia can be accompanied by convulsions, loss of consciousness and lead to death. Children are most susceptible to low glucose levels due to cholera.
• Low potassium levels (hypokalemia). Patients with cholera, due to diarrhea, lose a large amount of electrolytes, including potassium, as a result of which the functioning of the heart and nervous system is disrupted, which poses a threat to the patient’s life.
• Kidney failure. When the kidneys lose their filtering ability, excess fluid, some electrolytes and metabolic products accumulate in the body, which is also life-threatening.
• Secondary infection. Against the background of cholera, the body becomes more susceptible to other bacteria. This can lead to complications such as pneumonia, abscesses, and sepsis.

Classification

Several classifications of cholera are used in clinical practice. This is due to differences in the symptoms of the disease and treatment approaches in different cases. Also, some forms of the disease may have a course uncharacteristic of classical cholera.

Depending on the developing symptoms, cholera is divided into the following forms:

• Typical or gastrointestinal. The classic form of cholera, accompanied by gastrointestinal disorders.
• Atypical. It includes several subspecies that differ significantly from the typical variant of the disease. Atypical forms of cholera include:

1. Lightning fast. It is characterized by extremely rapid development with pronounced vomiting and diarrhea, due to which severe dehydration quickly develops, and dehydration shock occurs within 3-4 hours.
2. Dry. It is characterized by a sharp deterioration in the general condition of a person. Even before the onset of diarrhea, a coma may develop.
3. Erased. It has relatively mild symptoms: the frequency of bowel movements per day ranges from 1 to 3 times, and the stool is not modified. The general condition is often satisfactory; the diagnosis is established only at the stage of laboratory tests.
4. Asymptomatic. A variant of infection that occurs without any clinical manifestations. It is detected only after laboratory diagnostics.

It is customary to distinguish vibration carriers separately. This is a condition in which an infected person releases Vibrio cholerae into the environment, but does not show signs of illness. He may have the following options:

• Convalescent. It is observed in people who are recovering from cholera.
• Transitional. Characteristic for people who are in the center of a cholera outbreak. They become infected, but their body successfully fights off the infection. As a rule, it lasts no more than 3 months.
• Chronic. A condition in which cholera vibrios remain active in the body and a person continues to release them into the environment for more than 3 months.

Depending on the patient’s condition, the severity of damage to the gastrointestinal tract and the degree of dehydration, the following degrees of severity of cholera are distinguished:

1. Easy. It is characterized by the accumulation of Vibrio cholerae toxins in the body. Defecation is repeated 3-5 times a day, general health remains satisfactory. There are minor feelings of weakness, thirst, dry mouth. The illness lasts 1-2 days.
2. Average. Intoxication of the body is moderate. In this case, diarrhea is accompanied by vomiting, which is not accompanied by nausea. There is intense thirst and other signs of dehydration. Stool up to 15 times a day, copious. Single muscle cramps may be observed. The duration of the disease is 4–5 days.
3. Heavy. Pronounced consequences of severe intoxication of the body. There are pronounced signs of dehydration due to copious (up to 1–1.5 liters per bowel movement) stool with a frequency of up to 35 times a day. Repeated vomiting in a fountain. Painful muscle cramps in the limbs and abdomen. The skin of the hands and feet becomes wrinkled (“washerwoman’s hand”). The face takes on a characteristic appearance: sharpened features, sunken eyes, cyanosis of the lips, ears, earlobes, nose.

“Washerwoman’s hands” is a characteristic symptom of cholera. Photo: PHIL CDC

Diagnostics

Diagnosis is made based on a combination of medical history, clinical manifestations and laboratory results. When collecting an anamnesis, possible routes of cholera infection are clarified (consumption of potentially contaminated water or seafood) and risk factors - for example, a business trip to disadvantaged countries, regions, areas several days before the onset of symptoms.

The following tests are used in the laboratory diagnosis of cholera:

• Complete blood count (CBC). It shows a moderate increase in the level of red and white blood cells, including neutrophils. The saturation of red blood cells with hemoglobin and the erythrocyte sedimentation rate (ESR) also increase. At the same time, the level of monocytes may drop.
• General urinalysis (UCA). In addition to a general decrease in the volume of urine excreted, as dehydration increases, there may be an increase in the level of pathological casts and protein.
• Bacteriological culture. If cholera is suspected, in order to identify the pathogen, a sample of vomit or feces is sown on a nutrient medium. After 1-2 days, colonies grow. If cholera is suspected, the test is repeated twice more.
• Rapid tests with monoclonal antibodies. Allows you to confirm within 5 minutes the fact of human infection with cholera vibrios.
• Indirect blood hemagglutination reaction (IRHA). Makes it possible to detect the presence of specific antibodies in the blood. Their diagnostic titer of 1:160 is considered a positive result. The test is informative only from the 5th day of the disease.
• Polymerase chain reaction (PCR). Allows you to identify the genetic material (in this case, DNA) of the pathogen. In addition to the patient's secretions, water or food, which are a potential source of infection, can also be used for research.

Culture for cholera is one of the diagnostic methods.
Photo: Nathan Reading / Flickr (CC BY-NC-ND 2.0) Differential diagnosis of cholera is carried out with other diseases, which in the early stages may be accompanied by similar symptoms. These include:

• Acute intestinal infections: salmonellosis, typhoid fever, escherichiosis (dysentery), rotavirus infection. They are also accompanied by diarrhea and vomiting. However, unlike cholera, they cause fever, abdominal pain, and often mild or no dehydration.
• Poisoning. Symptoms of chemical intoxication directly depend on the specific reagent. However, in most cases they also present with vomiting, diarrhea and signs of central nervous system dysfunction. In this case, dehydration, as a rule, does not occur.
• Botulism. An acute infection that also leads to disruption of the central nervous system. In addition to skeletal muscle cramps, vision and breathing suffer. Unlike cholera, constipation often occurs. The cause of infection is most often the consumption of spoiled canned food or smoked meats.

Risk factors

Everyone is susceptible to cholera, with the exception of infants who have received immunity from nursing mothers who have previously had cholera. However, certain factors can make a person more vulnerable to the disease or cause the infection to become more severe. These include:

• Poor sanitary conditions. Unsanitary living conditions are common in refugee camps, poor countries, and areas affected by famine, war, or natural disasters.
• Decreased or absent stomach acid. Cholera bacteria cannot survive in an acidic environment, and regular stomach acid often serves as a defense against infection. But people with low stomach acid levels (such as children, the elderly, and people taking medications to reduce stomach acid secretion) do not have this protection.
• I (0) blood group. The reasons are not yet fully understood, but the likelihood of developing cholera in people with the first blood group is twice as high as in others².