Cholera (Vibrio cholerae)

Description/Background Information

Cholera (Vibrio cholera) is a comma-shaped, Gram-negative bacterium that is the causative pathogen of the cholera disease. The bacterium has several serogroups, two of which (serogroups 01 and 0139) have been confirmed to cause cholera outbreaks. The global prevalence of cholera has reduced significantly over the decades, with recent WHO reports indicating that 1.3-1.4 million cholera incidences occur annually, resulting in 21,000 -143,000 annual deaths (Mohapatra et al., 2023). Regions that have been affected mainly by cholera in recent years include conflicting sub-Saharan African countries like Niger, Ethiopia, and DRC, as well as heavily populated Asian countries like India, Pakistan, and Bangladesh, as well as Haiti and the Dominican Republic. Cholera is also associated with historical global pandemics that began in the 1810s in Europe and North America and the 1880s pandemic that originated in India and spread to the rest of the world (Jensen et al., 2021). The current and last cholera surge began in Indonesia in the 1960s and has spread across the globe.

Recent Findings

There have been tremendous developments in cholera research, particularly in genomic sequencing, vaccine development, antimicrobial resistance, community engagement, and behavioral interventions. Advances in vaccine development and new immunization strategies have led to adequate and affordable cholera vaccines (Montero et al., 2023). There have also been progressive developments in genomic sequencing of different cholera bacteria serogroups. These have generated valuable insights into its genetic diversity, antibiotic resistance patterns, virulence, and other aspects contributing to the pathogen’s profile. Research focusing on interventions has also generated progressive outcomes, ranging from new mathematical modeling and AI-guided analytics that have led to a better understanding of outbreak and spread patterns, risk factors, and optimal public health responses (Walton et al., 2023). New research has also increasingly justified the one health approach, a preventive framework that considers health’s human, animal, and environmental aspects. There have also been new findings suggesting new approaches to effective community engagement based on a better understanding of underlying behaviors about hygiene, healthcare seeking, and distancing (Walton et al., 2023). These findings have provided new knowledge guiding preventive and responsive approaches to cholera.

Relationship to Microbiology

Vibrio cholera is relevant to microbiology because it impacts gastrointestinal anatomy and function, fluid and electrolyte balance, and the overall immune response. First, cholera’s impact on the general bodily immune system through adaptive and innate mechanisms has broadened the scope of microbiology. Particularly, cholera’s disruptions on the immune system have refocused microbiological research to investigate the specific immune responses to cholera by exploring its microbial pathogenesis, toxin production and distribution, response to intestinal epithelial cells virulence, and adaptation within the human intestinal environment (Yoon & Waters, 2019). The bacterium serogroups 01 and 0139 secrete toxins that alter the anatomy and functions of the mucosal lining and intestinal microvilli, which play crucial roles in the absorption of food nutrients. The bacterium also alternates the physiological functioning of various intestinal cells, resulting in watery diarrhea, which is an indication of intense dehydration and disruption of electrolyte balance (Yoon & Waters, 2019). Also, one of the foundational symptoms of cholera is that it leads to intense dehydration and electrolyte losses from various body cells. This aspect has facilitated an in-depth exploration of its effect on body fluid dynamics, electrolyte transportation mechanisms, and endogenic influences of essential hormones like antidiuretics and aldosterone.

Causes and Risk Factors

• Infection with Vibrio cholerae serogroups 01 and 0139 produces critical virulence factors for observable symptoms, mainly dehydration (Mohapatra et al., 2023).
• Poor sanitation practices and consumption of contaminated food and water: The transmission of cholera toxins occurs through the fecal-oral route, which is made possible through ingesting food or water pre-exposed to cholera contamination. Consumption of water contaminated with untreated sewage or unhygienic food handling can cause cholera (Mohapatra et al., 2023).
• Crowded and unhygienic living environments- Epidemiologic studies of cholera have demonstrated that overcrowded environments like slums, refugee camps, and communities with limited access to proper healthcare and sanitation facilities have higher cholera prevalence (Mohapatra et al., 2023). Environment-focused studies have also established that environments with higher temperatures, heavier rainfall, and open and stagnant water surfaces enhance the microbial survival of the cholera pathogen. Cold and wet climatic conditions also complicate recovery from dehydration (Mohapatra et al., 2023).
• Weak immunity, malnutrition, and inadequate access to quality healthcare services also increase the risk factors of cholera infection across communities. Cholera is likely to spread more in resource-constrained communities that lack adequate healthcare services, which is connected with lower overall diagnostic tests, poorer treatment methods, and less adequate public health interventions (Mohapatra et al., 2023).

Symptoms

• Profuse diarrhea and vomiting- Cholera toxins result in profuse, painless, watery diarrhea with a characteristic milky (rice-water-like) appearance. Further, cholera is also associated with varying episodes of vomiting (Learoyd & Gaut, 2019). The vomit may sometimes have stomach content in the initial instances of infection but is often transparent and watery as the disease progresses.
• Intensive dehydration, symptomatic vomiting, and diarrhea associated with cholera can cause excessive and detrimental dehydration if left unchecked. Some of the observable indications of dehydration among cholera patients include excessive thirst, sudden sunken eyes, dry skin, mouth and throat, tachycardia (speedy heartbeat rate) and hypotension (high blood pressure), general fatigue, dizziness, joint pain, muscle pull, and confusion (Hwang et al., 2021).
• Electrolyte balance disruptions- The pathogenesis of the cholera bacterium has brought about notable imbalances in potassium, chloride, and sodium ions. The observable symptoms include arrhythmias, muscle weakness, numbness, hypokalemia, and hypernatremia (Learoyd & Gaut, 2019).
• Metabolic Acidosis- Extended and unchecked dehydration can trigger metabolic acidosis, ushering the body to unusually acidic pH levels. Acidosis is revealed through rapid and un-rhythmic breathing, general weakness, and confusion (Learoyd & Gaut, 2019). In children and infants, acidosis may manifest through sunken fontanels, reduced tearing, less salivation, and general irritability.

Diagnosis

Clinical evaluation and laboratory assessment-Prompt and accurate diagnosis of cholera is crucial to inform treatment. The first step, clinical assessment, involves a thorough assessment of observable symptoms like vomiting, diarrhea, and indications of dehydration, as well as the evaluation of medical history and epidemiological information to trace and identify potential risk factors (Chowdhury et al., 2022). The necessary lab tests include stool-sample analysis (to culture and isolate the pathogen etic bacterium), serum antibody testing (done to detect the presence of pathogen antigens in the blood), PCR testing (to trace Vibrio cholerae DNA from stool sample), and cholera toxin detection conducted through either the Enzyme-linked immunosorbent assay (ELISA) or the rapid diagnostic tests (RDTs) methods (Falconer et al., 2022). Differential diagnosis may also be conducted to discern the absence of other pathogens like Salmonella and Shigella, which have symptoms that overlap with those of cholera.

Treatment

• Rehydration therapy and nutritional support- Rehydration therapies vary with the patient’s dehydration levels. Oral Rehydration Solutions (ORS) are salts with sodium, potassium, or chloride ions that restore electrolyte balance for patients with mild to moderate dehydration. For severe dehydration, intravenous fluids like Ringer’s lactate or normal saline are provided to restore electrolyte balance (Sousa et al., 2020). Rehydration is also complemented with dietary support, including supplemental zinc and low-fat transitional meals to reduce gastrointestinal discomfort that may aggravate dehydration through diarrhea.
• Antibiotic therapy- The provision of antibiotics like tetracycline, erythromycin, or Trimethoprim-sulfamethoxazole (TMP-SMX) cuts down diarrhea intensity and duration, decreases pathogenic shedding and mitigates infection. In large outbreak settings, single-dose antibiotic regimens like ciprofloxacin and azithromycin are provided to curb widespread infections (Sousa et al., 2020). There also needs to be close post-treatment monitoring and follow-up to ensure adequate medication, trace potential sources of complications, and address potential lingering symptoms.

Prognosis

• Prompt and thorough diagnosis followed up with appropriate treatment using rehydration and antibiotics and adequate follow-up and close monitoring. However, severe and unchecked dehydration may lead to life-threatening situations. Adequate response to treatment also improves prognosis (Walton et al., 2023).
• Patients with mild to moderate symptoms have a higher prognosis compared to those with severe dehydration or underlying conditions. Elderly patients have higher risks of developing dehydration-related complications that cause electrolyte imbalance, organ failure, or acidosis and may have a lower prognosis (Yoon & Waters, 2019).
• Healthcare access and public health intervention measures- Communities with better and well-equipped healthcare facilities, well-trained clinical professionals, and adequate diagnosis and essential medication have better cholera prognosis. Similarly, well-implemented preventive and counter-infection public health measures improve cholera prognosis and alleviate cholera burden across communities (Montero et al., 2023).

Future Directions

• Enhance vaccine research, development, and deployment to high-risk regions to improve vaccination and foster routine immunization programs (Chowdhury et al., 2022).
• Sanitation governance-Broadening investment in water purification technologies and sanitation across high-risk populations and communities to reduce transmission risks.
• Surveillance and early warning enhancement through accurate epidemiological data, GIS–aided environmental warning, and AI-guided targeted interventions (Chowdhury et al., 2022).
• We are broadening community engagement and behavioral intervention through targeted awareness creation on appropriate hygiene practices, food safety, and mobilization combinations (Chowdhury et al., 2022).

Summary

Cholera-related morbidity and mortality have reduced tremendously since the 20th Century thanks to extensive research that has generated valuable prevention, infection mitigation, treatment, and management mechanisms. However, the cholera outbreak remains a threat in conflicted regions like Africa’s Sahel, the Middle East, and Haiti, where population densities are high in refugee camps, and sanitation has become secondary. While progressive research has informed tremendous improvements in various aspects of the disease, governments and healthcare policymakers across the world, but particularly in high-risk regions and countries, must take proactive actions towards enhancing vaccine production, distribution, and accessibility, improving sanitation governance, broadening awareness creation mechanisms to combat predisposal to high-risk conditions, and improving exploiting data technologies to improve surveillance and early warning. These strategies can help nations address the disease through prevention and mitigation.

References

Chowdhury, F., Ross, A. G., Islam, T., McMillan, N. A., & Qadri, F. (2022). Diagnosis, Management, and Future Control of Cholera. Clinical Microbiology Reviews, 35(3), e00211-21.

Falconer, J., Diaconu, K., O’May, F., Gummaraju, A., Victor-Uadiale, I., Matragrano, J., et al. (2022). Cholera diagnosis in human stool and detection in water: A systematic review and meta-analysis. PLoS One, 17(7), e0270860-63.

Hwang, S., Kim, Y., Jung, H., Chang, H.-H., Kim, S.-J., Park, H.-K., et al. (2021). A Fatal Case of Bacteremia Caused by Vibrio cholerae Non-O1/O139. Infection & Chemotherapy, 53(2), 384-390.

Jensen, P. K., Grant, S. L., Perner, M. L., Hossain, Z. Z., Ferdous, J., Sultana, R., et al. (2021). Historical and contemporary views on cholera transmission: are we repeating past discussions? Can lessons learned from cholera be applied to COVID‐19? APMIS, 129(7), 421–430.

Learoyd, T. P., & Gaut, R. M. (2019). Cholera: underdiagnosis and differentiation from other diarrhoeal diseases. Journal of Travel Medicine, 25(Supp 1), S46–S51.

Mohapatra, R. K., Kutikuppala, L. V., Kandi, V., Mishra, S., Tuglo, L. S., & Dhama, K. (2023). The recent surge in cholera outbreaks globally during the COVID-19 pandemic era is a potential threat to the African continent and salient counteracting strategies. International Journal of Surgery, 109(3), 631–633.

Montero, D. A., Vidal, R. M., Velasco, J., George, S., Lucero, Y., Gómez, L. A., et al. (2023). Vibrio cholerae, classification, pathogenesis, immune response, and trends in vaccine development. Frontiers in Medicine, 10(1), 1-9.

Sousa, F. B., Nolêto, I. R., Chaves, L. S., Pacheco, G., Oliveira, A. P., Fonseca, M. M., et al. (2020). A comprehensive review of therapeutic approaches available for the treatment of cholera. Journal of Pharmacy and Pharmacology, 72(12), 1715-1731.

Walton, M. G., Cubillejo, I., Nag, D., & Withey, J. H. (2023). Advances in cholera research: from molecular biology to public health initiatives. Frontiers in Microbiology, 14(1178538), 1-12.

Yoon, S. H., & Waters, C. M. (2019). Vibrio cholerae. Trends in Microbiology, 27(9), 806–807.