A summary of Cholera

 1. Introduction:

Cholera, a severe diarrheal disease, has plagued humanity for centuries, causing widespread outbreaks and posing significant public health challenges. This assignment delves into the various aspects of cholera, ranging from its historical context to epidemiology, etiology, clinical manifestations, pathogenesis, lab diagnosis, statistics, preventive measures, and a comprehensive conclusion.

Fig: Cholera awareness poster

2. Definition:

Cholera is an acute bacterial infection of the small intestine, primarily caused by the bacterium Vibrio cholerae. The disease is characterized by profuse watery diarrhea, vomiting, and dehydration, and if left untreated, it can lead to rapid and severe electrolyte imbalance, shock, and death.

 

3. History/Background of the Disease:

     For centuries, cholera remained one of the most horrific diseases. It was first described by Hippocrates in the fifth century BC. Traditionally, the Ganges Delta region in Asia is considered the home of cholera. It is believed that cholera spread throughout the world from this region. Several epidemics occurred in Asia during the fifteenth and eighteenth centuries. Seven major pandemics of cholera have occurred since 1817.

Historians believe that the impact of cholera epidemics on the cultural evolution of Western Europe, was far reaching and it altered the social matrix of European culture. During the nineteenth century cholera was not only considered a terrifying disease, but was also a challenge to national identity and national economy.

John Snow performed pioneer work on cholera in London in the 1800s. He established an association between cholera transmission and contaminated water . He discovered the method of prevention and control of cholera by tracing its source back to drinking water. Due to his work on the Soho cholera outbreak in 1854, John Snow has become a legend in epidemiology. Later, in 1883, Robert Koch described the causative agent for cholera as a curved bacillus, V. cholerae.

In 1892, a major cholera outbreak occurred in Germany, killing 10,000 people. It was found to be caused by a defect in the design in the German waste removal system. Seven cholera pandemics occurred during the nineteenth and twentieth centuries. The seventh pandemic began in Indonesia in 1961, reached West Africa in 1970 and the Americas in 1991.

In the United States of America, the risk of cholera is very low. However, in 2005, the floods caused by Hurricane Katrina, created the fear of a cholera epidemic for the first time in a century. The US Centers for Disease Control and Surveillance had 11 confirmed cases of people becoming ill from Vibrio sp. infection. However, only one of those cases had V. cholerae, which was not from the two epidemic-causing serogroups, i.e., O1 and O139.

Fig: The cholera epidemic of 1832

4. Epidemiology:

     Cholera is prevalent in regions with poor sanitation, contaminated water sources, and overcrowded living conditions. It is endemic in parts of Africa, Asia, and Haiti, with sporadic outbreaks reported globally. The disease is often associated with natural disasters and humanitarian crises, where access to clean water and proper sanitation is compromised.

 

5. Etiology/Cause:

Fig: Vibrio cholerae transmitted through water. 

Vibrio cholerae, the causative agent of cholera, is a Gram-negative bacterium with several serogroups, but only two – O1 and O139 – are responsible for epidemic cholera. Transmission occurs through the ingestion of contaminated water or food, with the bacterium colonizing the small intestine, producing cholera toxin, and causing the characteristic symptoms.

Fig: Vibrio cholerae

6. Signs and Symptoms:

     Cholera manifests primarily as watery diarrhea and vomiting, leading to rapid dehydration. Other symptoms include muscle cramps, rapid heart rate, and a characteristic rice-water stool appearance. In severe cases, electrolyte imbalances can result in shock and organ failure.

 

Fig: Two men in suits prepare to inoculate a child, surrounded by a crowd of parents and children. Photograph, 1880/1900.

Cholera is an acute diarrheal illness caused by infection of the intestine with Vibrio cholerae bacteria. People can get sick when they swallow food or water contaminated with cholera bacteria. The infection is often mild or without symptoms, but can sometimes be severe and life-threatening.

Fig: A physician checking a patient for dehydration

 

About 1 in 10 people with cholera will experience severe symptoms, which, in the early stages, include:

• §  profuse watery diarrhea, sometimes described as “rice-water stools”
• §  vomiting
• §  thirst
• §  leg cramps
• §  restlessness or irritability

Health care providers should look for signs of dehydration when examining a patient with profuse watery diarrhea. These include:

• §  rapid heart rate
• §  loss of skin elasticity
• §  dry mucous membranes
• §  low blood pressure

People with severe cholera can develop severe dehydration, which can lead to kidney failure. If left untreated, severe dehydration can lead to shock, coma, and death within hours.

The profuse diarrhea produced by cholera patients contains large amounts of the infectious Vibrio cholerae germ that can infect others if swallowed. This can happen when the bacteria get on food or into water.

To prevent the bacteria from spreading, all feces (human waste) from sick persons should be thrown away carefully to ensure it does not contaminate anything nearby.

People caring for cholera patients must wash their hands thoroughly after touching anything that might be contaminated with patients’ feces (poop).

When cholera patients are treated quickly, they usually recover without long-term consequences. Cholera patients do not typically become carriers of the cholera bacteria after they recover, but they get sick if exposed again.

7. Pathogenesis:

    V. cholerae infects the small intestine, where it produces cholera toxin. This toxin stimulates the secretion of chloride and water into the intestinal lumen, leading to the massive watery diarrhea characteristic of cholera. The rapid loss of fluids and electrolytes contributes to the dehydration and potentially life-threatening complications associated with the disease.

V. cholerae lacks the acid resistance genes found in many other intestinal pathogens and therefore has a high infectious dose. One must ingest over one million microbes in order to contract cholera because many of the bacteria will die in the stomach due to its highly acidic environment. The incubation period is dependent upon how many organisms successfully passed through the stomach into the small intestine where V. cholerae can colonize. Therefore, the incubation period before showing symptoms ranges from a few hours to five days, typically taking two days before causing symptoms. Once in the small intestine, studies show that some of the bacteria use their flagella to swim towards the epithelial cells and adhere in the crypts of the intestine using a toxin-coregulated pilus to keep from being flushed out

Fig: Pathogenicity and virulence regulation of Vibrio cholerae at the interface of host-gut microbiome interactions

 

8. Lab Diagnosis:

     Laboratory diagnosis involves isolating V. cholerae from stool samples, rectal swabs, or vomitus. Culture methods, serological tests, and molecular techniques such as PCR play crucial roles in confirming the diagnosis. Rapid diagnostic tests are also available for field use during outbreaks.

The confirmatory test for cholera is done by culture of a stool specimen or rectal swab. For transport of specimen, Cary Blair media is the most appropriate, and for isolation and identification of the organism, the selective thiosulfate–citrate–bile salts agar (TCBS) is the medium of choice. Commercially available rapid test kits should not be used for routine diagnosis as they cannot determine the subtypes and are not able to isolate the antimicrobial susceptibility. However, they are useful during epidemics.

9. Statistics (Local/Global):

9.1: Global statistics:

Cholera is an acute diarrheal infection characterized, in its severe form, by extreme watery diarrhea and potentially fatal dehydration. It is caused by the ingestion of food or water contaminated with the bacterium Vibrio cholerae. It has a short incubation period, ranging between two hours and five days. Most people will develop no or only mild symptoms; less than 20% of ill persons develop acute watery diarrhoea with moderate or severe dehydration and are at risk for rapid loss of body fluids, dehydration, and death. Despite being easily treatable with rehydration solution, cholera remains a global threat due to its high morbidity and mortality in vulnerable populations with a lack of access to adequate health care.

Seven distinct pandemics of cholera have been recorded during the past two centuries. The seventh pandemic, which is still ongoing today, is considered to have occurred principally between 1961 to 1974. During this period, following (re)introduction, many countries transitioned to becoming cholera-endemic. While global incidence greatly decreased in the late 1990s, cholera remained prevalent in parts of Africa and Asia.

The global burden of cholera is largely unknown because the majority of cases are not reported, however, previous studies estimate 2.9 million cases, and 95,000 deaths occur annually.

Fig:  Cholera cases reported to WHO by year and continent, global CFR, 1989-2021. 

Global cholera statistics fluctuate, but the World Health Organization (WHO) estimates millions of cases and over 100,000 deaths annually. Local statistics vary widely, with developing regions facing the highest burden due to inadequate sanitation and healthcare infrastructure.

Fig: Incidence of cholera cases per 100,000 population reported to WHO from 1 January to 30 November 2022.

 

9.2: Local statistics:

Between 2000 and 2021, there was a total of 10350 V. cholerae positive cases, with 8221 (79%) cases from the urban Dhaka Hospital and 2129 (20.6%) from the rural Matlab Hospital. Female patients made up 43% of the urban site and 51% of the rural site. In both urban and rural areas, the majority of patients were between the age of 15–60 years (59% and 47%, respectively) and more than 50% belonged to the poor and lower middle class (54.3%). 30% of households in the urban site did not treat their drinking water, specifically boiling, and 9% of families disposed of waste in their courtyard; but in the rural site 1.37% of the household treat drinking water and more than 99% households disposed their waste outside the courtyard. Dehydration levels were predominantly in the “some/severe” range at both sites, and most patients required both ORS and IV fluid 77.7% and 61.3% in urban and rural areas respectively (Supplementary table 1).

Table 1 shows the characteristics of V. cholerae-positive diarrhea patients admitted in urban and rural sites from 2000 to 2021, while 2000–2005 was compared with 2006–2010,2011–2015, and 2016–2021 admission years after adjusting for patient's age, sex, status of breastfeeding (under 3 children), use of antibiotic before hospitalization, number of family members, parental education, drinking water, toilet facility, water treatment method, garbage disposal method, asset index, and urban and rural sites. In all admission years, patients aged 15–60 years and above 60 years had a significantly higher likelihood of cholera and less than 3 days of diarrhea duration compared to the patients from the year 2000–2005. We found that the risk was significantly rising year by year. Compared to 2000–2005, the hazards were roughly two times as high in the years 2006–2010, three times as high in the years 2011–2015, and 3.5 times as high in the years 2016–2021. Boiling water was found to be protective, while waste disposal in their courtyard was associated with significantly increased cholera risk. When compared to the reference admission year, moderate to upper-class households were found to have a significantly higher risk of cholera. In contrast, patients were shown to have a lower likelihood of experiencing some dehydration from 2011 to 2021.

Fig: Age-specific distribution of V. cholerae positive patients admitted in the urban and rural sites during 2000–2021.

10. Preventive Measures:

        Preventing cholera involves improving sanitation, ensuring access to clean water, and promoting hygiene practices. Vaccination, particularly with oral cholera vaccines, is an essential tool in controlling outbreaks. Additionally, prompt and appropriate treatment of cases can prevent the progression to severe disease.

10.1. Cholera control

Cholera-endemic areas should prioritize cholera control measures [23]. Countries facing complex emergencies and displacement of internally displaced people (IDP) on a large scale or refugees to places where the provision of safe water and proper sanitation is compromised, and they are vulnerable to cholera outbreaks. In such situations, it is critical to depend on surveillance data to watch for an outbreak and to implement appropriate intervention measures. Thus, strengthening of surveillance system and early warning system is vital in places at high risk of cholera outbreak.

The main strategies for cholera control include appropriate and prompt management of cholera cases; strengthening laboratories; training and capacity building of health-care workers; and availability of adequate medical supplies for management. In addition, access to safe water, proper sanitation, appropriate waste management; personal hygiene and food hygiene practices; improved communication and public information are needed for the control of cholera outbreaks.

 

10.2 Cholera vaccines

Oral Cholera Vaccine should always be used as an additional public health tool in complex emergencies and should not replace usually recommended control measures such as improved water supplies, adequate sanitation, and health education. Once a cholera outbreak has started, the vaccine is not recommended as it takes time to provide protection and is also not cost-effective [33]. Reyburn et al (2011) estimated that an organized mass vaccination campaign could prevent 34,900 (40%) cholera cases and 1695 deaths (40%) in Zimbabwe. However, the cost of the vaccines was an important barrier along with other logistic issues .

A well-organized, multisectoral approach is required to control cholera outbreaks. The effectiveness of public health interventions depends on an efficient surveillance system. There must be frequent and timely information-sharing at local as well as global level. The administration of cholera vaccines may be considered for high risk population in high risk areas. Funds and resources should be provided to the deserving countries to improve cholera prevention and preparedness activities.

 

10.3 International travel and trade:

Currently, there is no obligation of cholera vaccination for international travel. It is learned with experience that quarantine and restrictions on travel and trade are not very effective in controlling the spread of cholera. However, the travelers should be provided information regarding signs, symptoms, and prevention of cholera. The neighboring countries of cholera-affected areas should be advised to enhance their surveillance system for early detection and prompt response if any outbreak occurs.

Fig: Photograph showing Waldemar Mordecai Wolffe Haffkine (1860-1930), Bacteriologist with the Government of India, inoculating a community against cholera in Calcutta, March 1894

11. Conclusion:

Cholera remains a formidable public health challenge, particularly in resource-limited settings. The disease's history, epidemiology, etiology, clinical manifestations, pathogenesis, and diagnostic methods all contribute to the complex landscape of cholera. Preventive measures, including vaccination and improvements in sanitation, are crucial in reducing the global burden of this devastating disease.

12. References:

https://www.who.int/news-room/fact-sheets/detail/cholera

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2822%2900330-0/fulltext

https://www.intechopen.com/chapters/50256