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Cholera in Bangaldesh introduction, Ana Weil, Internal Medicine MGH 2






           The International Centre for Diarrheal Disease Research, Bangladesh (icddr, b) where I am working in cholera is a research center and hospital in Dhaka, unique because of the commitment of those who work there to savings lives through both clinical care and research. Known in Dhaka as the �cholera hospital� or �diarrhea hospital�, admission to the hospital requires diarrhea (except in HIV patients). During cholera season two times a year, up to a thousand patients per day can present at the hospital for treatment; during these times, tents for makeshift cholera wards are assembled in the parking lots. Cholera cots, or wooden cots lined with plastic sheeting with holes in the middle for stool collection and measurement of fluid losses, appear in every corner of the hospital.
           
            The staff at the icddr, b knows that if a patient arrives to the hospital breathing, death can be avoided. Even if a pulse is absent, an IV is placed and rehydration is initiated. The speed at which this treatment begins is incredible; I have seen large-bore IVs placed in an unconscious patient still in the doorway in the arms of a family member. The nurses and IV teams at the hospital know how important speed is; they are empowered to save lives and go to great extents to do so. They are the world�s experts in treating cholera. Medical staff from the icddr, b has traveled to every major cholera outbreak in the world in the last decade to train local staff. Because the amount of rehydration required in cholera is much more than used in other diarrheal diseases, inexperienced staff can inadvertently under resuscitate patients and death can result. Research studies have documented the decrease in case-fatality rate that occurs after an icddr, b team arrives at the site of a cholera outbreak.

            Oral rehydration solution was first used in Bangladesh during a cholera outbreak in the 1970s. This simple mixture of clean water, sugar and salt is one of the most important medical discoveries of the 21st century, and has saved millions of lives. For several decades, the icddr, b and other sites in Bangladesh have been leaders in research and clinical care of patients with diarrheal disease.


            More recently, the icddr, b has changed HIV care in Bangladesh. HIV is thought to be rare in Bangladesh, and the prevalence of disease is not known. The icddr, b is the only hospital in the country with an HIV ward with care specifically for HIV patients and their families. During my month in Dhaka I was able to join in on rounds during my time out of the lab, and also took part in teaching medical residents working in the HIV ward.
           
            For more than a decade the icddr, b and MGH have collaborated to study the immune responses to cholera with an aim to improve cholera vaccines. After cholera, patients are protected from severe disease for at least several years through immune mechanisms that are not well understood. We believe that anamnestic memory responses in the gut confer protection, and T cells may have a role in the creation or maintenance of this response. When a person is diagnosed with cholera at the icddr,b, a large field team in Dhaka enrolls patients and their household contacts in the immunology studies at the time of hospitalization for cholera. In the lab, we receive blood from the patient on day 2 of their hospitalization (usually also the day of discharge) after their stool culture grew Vibrio cholerae overnight. With fresh blood, PBMCs are extracted for B cell studies and whole blood is prepared for flow cytometry examination. During the next year, this same patient and their household contacts with have blood drawn several times, and field workers will visit their homes to ask them about any symptoms they have and send them back to the icddr, b for severe illness. My immunology work is focused on T cell responses to acute cholera infection, and utilizes unique techniques in preparation of whole blood for flow cytometry.
            During medical school I worked at the icddr,b for one year, and made lifelong friendships with my colleages in the lab at the iccdr,b. Together we stayed late in the lab, came in on weekends, and spent hours troubleshooting the flow cytometer. It was wonderful to return to the lab and continue this work, see old friends, and spend time in this colorful city. The relationship between the icddr, b and the community allow work in cholera immunology to enter a second decade, and I hope to continue to be part of this work because of both the importance of the science and the wonderful people I have had the privilege of working with.  

Cholera in Bangaldesh introduction, Ana Weil, Internal Medicine MGH



           I am a 2nd year medicine resident from MGH spending one month in Dhaka, Bangladesh to work in an immunology lab studying responses to cholera. I received a Center for Global Health Travel grant to pursue this work, and in these blogs will introduce the topic of cholera with a few details about the research I am doing and the institution where this research is conducted. 

            In Bangladesh, the most densely populated country in the world, the capitol city of Dhaka contains at least 15 million residents, many of whom live in urban slums. Dhaka is a colorful and chaotic city, and every day thousands of people come to Dhaka from the countryside of Bangladesh in search of a better life. Nearly all cholera patients come from the urban slums, particularly one called Mirpur. This slum contains around 3 million people living in shacks and makeshift residences, and the water supply is heavily manipulated by people tapping in water lines illegally. This manipulation leads to sewage lines mixing with the water supply. Most people do not boil or treat their water prior to using it, since fuel for a fire and water treatment supplies cost money. In Dhaka, diarrhea is a common and somewhat normalized fact of life for both visitors and the Bengali people, especially children. The usual causes are E coli spp as well as rotavirus, shigella, typhoid and other bacterial, fungal and viral causes, in addition to cholera.

            Cholera occurs in areas of the world where the 20th century innovations of clean water and latrine use are not yet realized. There are 3-5 million cases of cholera each year and most cases are in southeast Asia. Children are disproportionately affected. The organism that causes cholera, Vibrio cholerae, lives in the environment in the Ganges Delta, which is the largest river delta in the world. This flat, easily flooded plain includes much of Bengal in northeastern India, as well as Bangladesh. This area has supported large populations for thousands of years, and for centuries cholera has caused disease both year round and in epidemic spikes during the two rainy seasons each year. V. cholerae is spread by fecal-oral transmission and causes a range of disease from asymptomatic or subclinical infection to severe dehydrating diarrhea that can cause death within 6-12 hours if untreated. In this short time, patients can lose more than 10% of their body weight in fluid losses, and adults can loose 20 liters or more. The primary treatment is rehydration, and in most patients oral rehydration is sufficient. In cases accompanied by severe vomiting, or dehydration that progresses to depressed consciousness, intravenous rehydration is required. Antibiotic treatment decreases the severity of disease and shortens the duration of symptoms. In Dhaka, tens of thousands of cases of cholera occur each year.
            There are several vaccines for cholera, and these have improved significantly in the last several years. They provide partial protection for several years, but are not very effective in children. My work in immunology is focused on understanding the immune response to natural cholera infection, in an effort to understand what creates the longer-lasting immunity we see after natural infection versus the partial, shorter-lasting protection observed after vaccination.

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