Sunday, April 17, 2011

Cholera in Haiti and Association to South Asia and Scientific Study to Reduce Recurrence

In the fall of last year, unprecedented outbreak and epidemics of cholera in Haiti agitated locals, news media, health workers. There has been a long debate about this epidemics. The situation has been highlighted by famous science journals, and come to my attention.

Although the cholera outbreak had been diminishing, and the overall fatality rate was down to 2 % from earlier 9%, and 4,550 deaths and 231,070 cases were reported, still there were few cases, as United Nations, Geneva said at the beginning of February. The serotype of the causative agent, Vibrio cholerae, has been identified that resembles with South Asian strain. The mortality rates of untreated cholera is 50-60% (one of the highest mortality rate).

Transmission
Vibrio cholerae is transmitted to humans as fecal oral route via water or food. The reservoir of the organism is suspected as the aquatic environment. In its extreme manifestation, cholera is one of the most rapidly fatal illnesses known.

Clinical Symptoms
Cholera begins with sudden onset of massive diarrhoea, excretion of protein-free fluid and associated electrolytes, bicarbonates and ions within a day or two. This loss of fluid leads to dehydration, anuria, acidosis and shock. The watery diarrhoea is speckled with flakes of mucus and epithelial cells ("rice-water stool") and contains enormous numbers of vibrios. The loss of potassium ions may result in cardiac complications and circulatory failure.

(Technical Terms Starts)  
"Vibrio cholerae, Morphology and Culture
It is a Gram-negative non-sporing, non-capsulated, curved rod, motile, monotrichous (single polar flagellum), oxidase-positive (distinguished from enteric), glucose fermenter, non-lactose fermenter bacterium. Widely used enrichment medium for this bacterium are; alkaline peptone water (APW), Cary-Blair transport medium, etc. And the common selective media for the isolation are; alkaline bile salt agar (BSA) medium (colonies are very similar to those on nutrient agar), Monsur's gelatin tauro cholate trypticase tellurite agar (GTTA) medium (small translucent colonies with a grayish black center), Thiosulpbate citrate bile salt (TCBS) agar medium (yellow nucleated colonies), polymyxin-mannose-tellurite (PMT) agar medium (differentiate between V. cholerae O1 from V. cholerae non-O1 based on mannose-fermentation), etc.

Disease Mechanism
V. cholerae start to produce the toxic proteins (cholera toxin, CTX / CT) only after reaching the intestine. It is an oligomeric complex made up of six subunits: one (A subunit), and five (B subunit). The B subunits binds to GM1 gangliosides on the intestinal epithelium cells. So the protein enter the cell via receptor-mediated endocytosis. Then the A1 subunit becomes free and bind with ADP-ribosylation factor 6 (Arf6), which permanently ribosylate the Gs alpha subunit of the heterotrimeric G protein. This results in constitutive cAMP production and pump out Cl−, HCO3−, etc., into the lumen of the small intestine which prevents sodium ions from entering the cell, and these ions create a salt-water environment, which through osmosis can pull up to 6 L  of water per day through the intestinal cells, creating the massive amounts of diarrhoea, and rapid dehydration. 

Virulent strains of V. cholerae is due to temperate bacteriophage called CTXf or CTXφ. V. cholerae is well adapted and can, economically, produce different proteins in different environment e.g., in intestine, TcpP/TcpH proteins, which, together with the ToxR/ToxS proteins, activate the expression of the ToxT regulatory protein. ToxT then directly activates expression of cholera toxins, and allowing the bacteria to colonize the intestine." (Technical Terms Finished)

Risk Factors
For cholera, anybody can be at risk, i.e., there is no correlation between vulnerability of infection and age, gender, malnutrition status, etc. It is one of the dangerous infectious disease that can kill healthy people quickly. After the onset of symptoms, victim may die within 4 hours to few days if no treatment is provided. However, people whose stomach is making less amounts of gastric acid than normal or recently had stomach surgery or taking drugs that inhibit the gastric acid production or person of blood type O, are at higher risk. In Peru, virtually all indigenous people have blood type O, and were at higher risk.

In Nepal, May-July is the main season of cholera outbreaks.

Treatment of Cholera
Treatment involves the rapid intravenous replacement of the lost fluid and ions. Following this replacement, administration of isotonic maintenance solution should continue until the diarrhoea ceases. By this simple treatment, the mortality rate of cholera can be reduced by ten-fold. A few antibiotics (e.g. tetracyclines) may shorten the duration of diarrhoea and reduce fluid loss.

Few years ago, I got chance to study on  V. cholerae, 01, El Tor, Ogawa biotype, while I was in NAST (former RONAST), the strain was kindly provided by Mr. Nabaraj Dahal, Patan Hospital. It was not so dangerous in terms of antibiotics resistance as compared to other strains, I investigated, such as Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, etc., which were almost all commonly used antibiotics resistant. Diarrhoea due to enteropathogenic E. coli is more complicated than cholera, in therapy.

The problem with the management of cholera is the consumption of unhygienic food and contaminated water. Contamination problem is mainly during both dry and rainy seasons. This is significantly enhanced due to drinking water pipe, which remains together with sewage pipe, and in some places, drinking water pipe remains inside sewage Hume pipe.

In Haiti, cholera had proliferated due to flood. Certainly, flood not only contaminate drinking water, but also destroy human's habitat and obstacle the disease treatment strategy. There are many places in Nepal where people rely on river, stream for drinking water, so they are always in risk of these kind of diarrhoeal diseases. Two years ago, death of more than 200 people due to the epidemics of diarrhea (one of the simple/neglected disease), in rural area of Nepal indicates inaccessibility of modern medicine, and in fact they still have to rely on medicinal plants and rituals.
water purifier
Make pure water
water purifier in bicycle
Water purifier operated by bicycle
Recently, Singapore water company, Glowtec has discovered a water purifying filter system, which can filter Decaliters of pure water within a minute (800 liter/hr). This can be operated by chain and the paddle of bicycle, and it can be transported anywhere as it is simple and light. It has been found very effective and significantly reduced the incident of waterborne diseases in flood affected area of Pakistan, Myanmar, Yemen, Taiwan, Philippines, and Vietnam. Vaccination is good option to avoid cholera epidemics. Nepal, and probably all developing countries can't afford the cost and also, V. cholerae has the high mutation rate, and new vaccination antigen and strategy needed within short period of time for full coverage. People should keep re-hydration solution like Jeevanjal, standby and should be immediately available in each home.

Acknowledgment: I thank to Dr. Joachim Schindler for reviewing and some suggestions.
Picture : Quantum geoservices

References:
  1. Martin Enserink, Science, 330, 5 November 2010, p. 738-739, Haiti’s Outbreak is Latest in Cholera’s New Global Assault
  2. Martin Enserink, Science, 331, 28 January 2011, p. 388-389, Despite Sensitivities, Scientists Seek to Solve Haiti’s Cholera Riddle
  3. Declan Butler, Nature, 468, p. 483-484 (2010), Cholera tightens grip on Haiti
  4. David Cyranoski, Nature, 469, p. 273-274 (2011), Cholera vaccine plan splits experts
  5. Kalpit P., Asianews, 2009 July 23, Epidemic hits western Nepal, More than 200 dead.
  6. Katherine Harmon, ScientificAmerican, 25 October 2010, Why Is Cholera Spreading in Haiti Now?  
  7. Debora MacKenzie, NewScientist, 15 November 2010, Haiti faces years of cholera
  8. Debora MacKenzie, NewScientist, 07 December 2010, Haiti: Epidemics of denial must end
  9. Debora MacKenzie, NewScientist, 10 December 2010, Haitian cholera strain could dominate the Americas

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