Cholera Case StudyCholera’s past seven pandemics in the past two-hundred years have killed millions across the globe, with the seventh one still occurring.Causative PathogenThe causative pathogen of Cholera is Vibrio cholerae bacteria of serogroups O1 and O139. V.cholerae O1 has caused all recent outbreaks where as V.cholerae O139 caused outbreaks in the past but now only has been identified in sporadic cases. Vibrio CholeraeMode of Transmission of PathogenInfection of cholera happens by ingestion of water or food, contaminated indirectly or directly by faeces or vomit from infected individuals. For example; eating fish or shellfish from contaminated waters or drinking contaminated water. Cholera affects only humans as there is not an insect vector or animal reservoir host.Adaptations of entry and transmission to hostWhen V.cholerae is transmitted into the host, it enters the stomach and must respond to extreme physiological stresses. For example; exposure to acid. Adaption to these stresses is vital for progression to the small intestine, where the bacteria induces virulence.Shape adaption is important for V.Cholerae to enter the host. CrvA Protein allows the bacterium V.cholerae to morph into a cylinder shape which further assists the pathogen to escape the protective mucus lining the inside of the gut. CrvA is activated through the process of quorum sensing, in which bacteria communicate with one another to coordinate infection.Adaption to low pH is also crucial as after ingestion, V.cholerae cells suffer through extreme acidity as the bacteria passes through the stomach, where the pH is 1-3. V.cholerae grow best at a neutral pH and has a low tolerance for acidic conditions. However the bacteria still manages to survive prolonged acid exposure in the stomach – where it on average stays for around 20-60 minutes. This is because growth in biofilm enhances the pathogen’s acid tolerance and provides it physical protection against acid shock. Therefore Ingestion of biofilm is hypothesised to increase the survival rate of V.cholerae in the host.Lastly Adaptation to reaction nitrogen species (RNS) is important for V.cholerae as it must cope with DNA damage generated by RNS. Nitrate from food sources and saliva deposited in the stomach, where the low pH generates acidified nitrite that can be reduced to RNS, causes DNA damage to V.cholerae. V.cholerae deals with RNS by expression hmpA, which encodes an enzyme responsible for destroying nitric oxide (NO).These three adaptions are vital for the entry and transmission of V.cholerae to the host.   Signs and symptoms of diseaseMany people exposed to Vibrio Cholerae don’t become ill and never know they are infected. However there is still a major risk the infected can affect others because the infected shed the cholerae bacteria in their body from seven to fourteen days.The incubation periods range from six hours to five days, making the onset of cholera immediate.The signs and symptoms, ranging from mild to severe include:Severe, watery diarrhoeaNausea and vomitingMuscle cramps, which occur because of the loss of salts (ie-chloride, sodium and potassium)Dehydration (shrivelled skin, lethargy, infrequent urination)Hypovolemic shock (most serious sign) – caused from a low blood volume which results from a drop in blood pressure. This causes a reduction of the amount of oxygen reaching the tissues.Response in the human body to the diseaseCholera begins, with the ingestion of the bacteria; V.cholerae. Once the pathogen passes through the stomach to the large intestine, the bacteria multiply rapidly. Soon after a toxin from the bacteria penetrate the cell walls of the intestine. The toxin prevents the intestine from absorbing water, from food and results in dehydration and diarrhoea. The pathogenic effects of cholera bacteria on the human gut.The body responds to the primary exposure of Vibrio Cholerae, with the innate response and the adaptive response. The innate respond starts with the creation of cytokines (ie. Interleukin). Then neutrophils migrate into the gut lining and antibacterial peptides are produced which destroy the bacteria directly. The adaptive response begins with IgA being secreted by the gut lining to protect it from bacterial colonisation. A week later, there is a sudden increase in circulating B lymphocytes specific to V.cholera antigens. Serum antibody peaks at one to three weeks after initial infection and decreases after about a year. The creation of B memory cells provide a stronger response to the secondary exposure of V.cholerae to the host.The natural microorganisms of the gut, (microbiome), play an important role in regulating the immune response against V.cholerae. For example; they provide colonisation resistance against bacteria.This occurs through Quorum sensing, which is the bacterial communication between cell to cell that can occur between the pathogen and microbiota.    Treatment of CholeraCholera is an easily treatable disease, however prompt access to treatment is essential.Oral rehydration and treatment centres -able to provide intravenous fluids and 24 hour care – are required to be accessible in communities affected by Cholera.Many infected patients can be treated successfully through administration of oral rehydration solution (ORS). The ORS sachet, made up of sugar and salts, is dissolved in clean water.Severely dehydrated patients require immediate administration of Intravenous Fluids (IV fluids) as they are at risk of shock. As well as this, the patients are given appropriate antibiotics to reduce the diarrhoea and the volume of rehydration fluids needed. Mass administration of antibiotics is not recommended by WHO (World Health Organisation) as it has no proven effect on the spread of cholera and contributes to increasing antimicrobial resistance.For children Zinc is an important adjunctive therapy, as it diminishes the duration of diarrhoea and can prevent future cases of acute diarrhoea. Breastfeeding should also be promoted.Incidence and Prevalence of Cholera.Immediate and accurate treatment will keep the fatality rate below 1%.However with untreated cholera, the mortality rate can rise to 50-60%. Researches from WHO estimate that every year there are 1.3 million to 4.0 million cases of cholera and 21 000 to 143 000 deaths worldwide due to cholera. The most concerning aspect of cholera is that the infection rate can spread by a factor of 10, each 10 days. For example; 2000 infected people can quickly result in 20,000 total cholera infections within 10 days.In 2018, so far there have been nine outbreak cases of Cholera, all in the African Region. A study in Uganda recently found that persons living near water such as; fishing villages, are at an increased risk of cholera outbreaks due to poor access to safe water, sanitation and hygiene. They also found that the African region is most heavily affected because of illiteracy, ignorance regarding cholera transmission, poverty and constant population migration. With, consideration to the graph below, it can be seen that children are more susceptible to cholera due to their weaker immune system. Global Cholera Mortality Rate.Effect of the disease on society and the economyAs well as the human hardship and distress caused by cholera, outbreaks of cholera also create panic and havoc, which disrupt the social and economic structure of affected communities. This can stop the communities from developing. Panicked reactions by the international community include travel and import restrictions from countries, where a cholera outbreak is occurring. This has a major impact on the country’s economy.For example; In 1991, Peru suffered a cholera outbreak and it ultimately cost the country US $770 million, as a result from the food trade embargoes and on the reduced tourism. Current methods to prevent and control spread of CholeraExclude infected patients from childcare, preschool, school and work until there has been no symptoms (such as; diarrhoea) for 24 hours. If the patient works as a food handler, the exclusion period should be until there has been no diarrhoea or vomiting for 48 hours.Anyone with cholera infection must not swim until there has been no diarrhoea for 24 hoursSeverely ill patients are expected to be isolated in hospitalLatest Research to treat or prevent the spread of the disease in the futureHygiene promotion and social mobilisation is just one program being implemented across the globe to prevent the spread of Cholera in the future. Health education campaigns, adapted to local culture and beliefs, promote the adoption of appropriate hygiene practises such as hand-washing with soap, safe preparation and storage of food and safe disposal of the faeces of children. Funeral rituals for individuals who die from cholera must also be adapted to prevent infection among attendees.Furthermore, awareness campaigns are planned to be organised during outbreaks and information will be given to communities. It will make them aware of the potential risks and symptoms of cholera, precautions to take to avoid cholera, and to seek immediate treatment when symptoms appear. The location of appropriate treatment will also be shared. This new approach recognises that community engagement and awareness is key to long term changes in behaviour and to the control of cholera.It was recently found that V.cholera protects itself by joining tiny amino acids to large molecules, called endotoxins, on its external surface. The tiny amino acids cause the bacterial membranes electric charge to change from negative to neutral. CAMPs are the positively charged molecules created to destroy bacteria. CAMPs bind to the negative bacterial membrane and kill them. But a neutrally charged membrane mean CAMPs cannot bind. V.cholerae are then able to enter the gut wall and cause cholera symptoms. The adaptive response which occurs, after does not provide defences rapidly enough to allow the infected host (person) to recover before the die from the severe cholera symptoms. This research reveals by creating a drug to disable the amino acids, CAMPs could do their role and reduce the invasiveness of the bacteria, allowing the body’s immune system to be successful. BibliographyCBC. (2018). Cholera’s seven pandemics | CBC News. [online] Available at: https://www.cbc.ca/news/technology/cholera-s-seven-pandemics-1.758504 https://www.cbc.ca/news/technology/cholera-s-seven-pandemics-1.758504 [Accessed 9 Nov. 2018].CBC. (2018). Cholera’s seven pandemics | CBC News. [online] Available at: https://www.cbc.ca/news/technology/cholera-s-seven-pandemics-1.758504 [Accessed 11 Nov. 2018].Gamapserver.who.int. (2018). [online] Available at: http://gamapserver.who.int/mapLibrary/Files/Maps/Global_Cholera(WER)_2016.png [Accessed 14 Nov. 2018].Hayhurst, C. 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