Context:Cholera is an intestinal infection caused by Vibrio cholera and transmitted by the fecal-oral route. The source of V. cholerae in nature is human and the most common vehicle of this infection is water and infected food. Here, we reviewed diagnosis, treatment, and prevention routes of cholera.
Evidence Acquisition:Electronic databases (PubMed and EMBASE) were searched from 1980 to 2013 regarding epidemiology, treatment, and prevention routes of cholera. Keywords including cholera, epidemiology, clinical manifestation, and treatment of cholera, and control and prevention routes were searched. In this review article, we focused mainly on the treatment and control of cholera.
Results:Cholera is a rare disease in industrialized countries; but, is still common in other parts of the world, including the Indian subcontinent, Sub-Saharan Africa, and Latin and Central American countries (like Haiti). Symptoms begin with a sudden onset of painless watery diarrhea which can quickly become voluminous. Antibiotics regimen is also recommended in addition to adequate hydration. Health education and education in environmental control are critical for the prevention of cholera.
Conclusions:Safe water supply and adequate sanitation and hygiene are the important routes for the control and prevention of cholera infection.
Cholera, an acute intestinal infection is rare in industrialized countries; however, the disease is still prevalent in other parts of the world, including the Indian subcontinent and sub-Saharan Africa. It is an important health problem in many developing countries including India, Pakistan, Bangladesh, Latin and Central American countries (like Haiti) and African countries (Zimbabwe, South Africa, Mozambique, Botswana and Zambia (1-4). Epidemic infection sometimes occurs in Southeastern of Iran in the border of Pakistan and Afghanistan. Cholera is an ancient disease like tuberculosis. Although the disease may be asymptomatic or mild, severe cholera can cause dehydration, renal failure and death within hours of onset (3).Cholera is caused by the bacterium Vibrio cholerae. Discovery of V. cholerae is credited to Robert Koch a German bacteriologist, who identified the micro-organism in 1883 during an outbreak in Egypt (5). The genus name refers to the fact that the organism appears to vibrate when moving. Since 1816, 7 cholera pandemics have occurred. The seventh pandemic of cholera began in 1961 and continued to 1991. This seventh pandemic caused by the El Tor biotype of V. cholerae O1 and originated from the Celebes Islands and Indonesia. A new strain of infection, V. cholera serogroup O139 (Bengal) observed in the fall of 1992 and caused outbreaks in Bangladesh and India in 1993. Now, this strain is endemic in at least eleven countries. In some endemic countries, cholera outbreaks were occurred in a significant seasonal pattern (6-8). Huq et al. defined a significant correlation of water temperature, water depth, and rainfall with the occurrence of cholera from the data on four rural regions of Bangladesh (7). Hashizume et al. also found that the number of patients with cholera increased with both high and low rainfall in the weeks preceding hospital visits in Dhaka, Bangladesh (8). Lower temperature predicted a lower incidence of cholera in the first 15 weeks of the year, and low rainfall predicted a peak in spring, and high rainfall predicted a peak at the end of the monsoon (9). Due to the sensitivity of V. cholera to climate changing, the world health organization (WHO) has suggested an early warning system for cholera epidemics, using climatic parameters (10).
2. Evidence Acquisition
Electronic databases (PubMed and EMBASE) were searched from 1980 to 2013 regarding epidemiology, treatment, and prevention routes of cholera. Keywords including cholera, epidemiology, clinical manifestation, treatment of cholera, control and prevention routes were searched. We found many papers about the cholera, but we selected mainly those which discussed diagnosis, new treatment, and control of cholera.
3.2. Host Factors
V. cholerae is not acid-resistant therefore, use of antiacid, proton pump inhibitors and histamine receptor blockers can increase the risk of infection and predispose to severe disease (15). Moreover, gastrectomy and chronic gastritis secondary to Helicobacter pylori infection are two the important risk factors for severe clinical disease. Malnutrition increases the chance of infection and then clinical diseases. The incidence of cholera is twice in people with type O blood compared with other blood groups. The reason for increased susceptibility in type O blood is unknown (16). Infection with V. cholerae 01 dose not lead to immunity against V. cholerae 0139. People who had a history of El Tor cholera are not protected against further infection episodes. Nonetheless, those infected with classic biotype of V. cholerae usually produce antibodies that protect them against recurrent infection by either biotype (17). Infection rates of household contacts of cholera infection vary from 20-50%. This rate is lower in areas where infection is endemic and people, especially adults, may have antibodies from previous infection with the organism. For this reason, adults patients are less symptomatic than children, and second infections rarely occur or are mild (17, 18).
3.4. Metabolic Manifestations
After dehydration is occurred, hypoglycemia is the most common lethal complication of cholera especially in children (17, 18). Hypoglycemia is a result of diminished food intake during the acute illness and defective neoglucogenesis secondary to insufficient storage. Hypokalemia results from potassium loss in stool. Hypokalemia develops only after correction of acidosis and intracellular hydrogen ions are exchanged for extracellular potassium. Hypokalemia is most severe in children with preexisting malnutrition status who have diminished body stores of potassium, which may be presented as paralytic ileus (17-20). Bicarbonate loss in the stool is another complication. Rehydration therapy with bicarbonate-containing fluids can also produce hypocalcemia by decreasing the proportion of ionized serum calcium. Accumulation of lactate due to decreased perfusion of peripheral tissues occurs and hyperphosphatemia is common (19). Patients are faced with accidemia, when respiratory system is not able to sustain a normal blood pH. Cholera sicca is an old term describing a rare, severe form of cholera, which manifests as ileus and abdominal distention from massive outpouring of fluid and electrolytes into dilated intestinal loops. Mortality rate is high, and failure of diagnosis is common which is because of the unusual clinical presentation (15-17).
Oral or intravenous hydration is the most important aspect in the treatment of cholera. In conjunction with suitable hydration, treatment with antibiotics is also recommended (15, 23-25). Antibiotics should be prescribed for patients severely or moderately dehydrated and those who lost a large volume of stool during the rehydration therapy. Antibiotic therapy is also recommended for all hospitalized patients. Antibiotics should be selected using local antibiotic susceptibility patterns. In most countries, doxycycline is recommended as the first-line treatment for adults (23, 25), and azithromycin as the first-line treatment for pregnant women and children (15, 24). Other antibiotics effective against V. cholera are trimethoprim-sulfamethoxazole (TMP-SMX), erythromycin, and ciprofloxacin. Azithromycin is more effective than erythromycin and ciprofloxacin (23-25). There are no guidelines to recommend antibiotics as prophylaxis for cholera prevention. All guidelines recommended that antibiotics should be administered along with aggressive hydration. Treatment with a single 300 mg dose of doxycycline has shown to be equivalent to tetracycline treatment for 3 days. Resistance to tetracycline and other antimicrobial agents among V. cholerae has been reported in endemic and epidemic cholera settings. Resistance can be acquired through selected mutations over the time, or due to widespread use of antibiotics for prophylaxis in asymptomatic individuals (15, 23-28). Antibiotic resistance has been observed in previous epidemics in the context of prophylaxis for household contacts of patients with cholera. It is suggested that antibiotic using can reduce secondary transmission of cholera (26).
For prevention of cholera, more attention to strategies to integrate all services in the general health system is very important. Health education is recommended for high-risk groups. Considering children and pregnant women and immune-compromised patients as high-risk groups is very important (29-33). WHO recommends safe water supply and adequate sanitation and hygiene (WASH) as the main steps to prevent cholera (28). Official recommendations also include the use of oral cholera vaccines (OCVs) for control of cholera outbreaks (26, 29, 30, 33). Two cholera vaccines are available and recommended by WHO (30).
Oral cholera vaccines are safe, effective and currently licensed by WHO as follows: 1-Dukoral (Crucell, Leiden, Netherlands), and 2-Shanchol (Shantha Biotechnics Ltd., Basheerbagh, Hyderabad, India). Both vaccines are given as a two-dose regimen. Vaccines are safe and provide sustained protection for several years. In 2010, they were added to WHO recommendations to control cholera outbreak (29, 30). However, doubts about feasibility, timeliness, and acceptability by the people at risk, and the fear of discouraging to use other preventative routes have discouraged their use during epidemics. Although, the Shanchol vaccine showed 66% efficacy over a three year period (29). In conclusion; Education in environmental control, safe water, adequate sanitation, and hygiene are important and critical for the prevention of cholera.
Cholera can be acquired by ingestion of water and food contaminated with pathogenic microorganism. Infection can also occur through person-to-person transmission, especially among members of the same household or in the crowded places, such as nursing homes and day care centers. Successful prevention of infection in the community depends mainly on adequate control measures such as rapid and accurate microbiological diagnosis, prompt treatment, patient isolation and preventative education, and adequate follow-up strategies to monitor fecal shedding after treatment in at risk groups.
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