Cholera is increasingly being reported, and more countries are now experiencing outbreaks 
, some lasting for several months. In 2001, the World Health Organization (WHO) recommended the use of oral cholera vaccines (OCV) in populations at risk in endemic areas but not reactively once an outbreak has begun 
. While this recommendation has been updated in March 2010, to include reactive use of these vaccines 
, OCVs have only been used for reactive cholera control in 2000, when a live attenuated OCV (CVD-103HgR) was used in an outbreak in Micronesia 
. The CVD-103HgR was assessed to be effective in this outbreak, although this was an observational study. In contrast, CVD-103HgR conferred no protection in the only randomized controlled efficacy trial of this vaccine 
, and this vaccine is no longer manufactured. There is one internationally licensed killed oral cholera vaccine, the recombinant B subunit killed OCV (rBS-WC, Dukoral, Crucell/SBL), but it has not been routinely adopted for public health use due to its high cost, limited duration of protection and logistic issues with vaccine administration. A variant of this oral vaccine, containing only killed whole cells (Vibrio cholerae
O1 and O139) is manufactured in Vietnam following technology transfer from Swedish scientists. Vietnam is the only country in the world to use an OCV in its public health system for cholera control. Since 1997, this killed OCV (ORC-Vax) has been licensed and produced locally by the Company for Vaccine and Biological Production (VaBiotech) in Hanoi. The vaccine was found to confer 66% protection against an El Tor cholera outbreak occurring eight months following vaccination among all individuals aged 1 year and older 
and 50% protection, three to five years after vaccination 
. It is safe, inexpensive, and easy to administer 
. Packaged in five-dose vials, each 1.5 ml liquid vaccine dose is drawn and squirted into the mouth by a syringe without a needle. Each dose contained: 5.0×1010
formalin-killed V. cholerae
Inaba, El Tor strain Phil 6973; 2.5×1010
heat-killed V. cholerae
Ogawa, classical strain Cairo 50; 2.5×1010
formalin-killed V. cholerae
Inaba, classical strain 569B; and 5.0×1010
formalin-killed V. cholerae
O139 strain 4260B. After oral administration, individuals are asked to drink water, but no oral buffer is required. Given in two doses, one to four weeks apart, it may be given to individuals aged one year and older.
Since the seventh pandemic reached Vietnam in 1964, cholera has been reported annually. A review of reported cases to the National Institute of Hygiene and Epidemiology (NIHE) from 1991 to 2001 showed that cholera is endemic in the central and southern provinces 
. Compared with shigellosis and typhoid fever, cholera cases have decreased dramatically in 1997 to 2001. This decrease in cholera cases has been partly attributed to the extensive use of the killed OCV in Vietnam 
From 1997 to 2005, 9.2 million doses of the killed OCV have been used in the Expanded Programme of Immunization (EPI) of 20 cholera endemic provinces and metropolitan areas in Vietnam, mostly located in the central and southern areas (). Vaccines are routinely provided in the endemic areas through regular monthly immunization sessions. In the routine EPI setting, depending on the commune, eligible children, aged 2–5 years are gathered for immunization on the same days for cholera vaccination. OCVs are provided 2 to 4 weeks apart. The killed OCV is also used preemptively in mass campaigns whenever an increase in the number of culture-confirmed cases are reported. National diarrheal disease surveillance is performed routinely and culture confirmation of organisms is available at the 61 provincial Centers for Preventive Medicine and in the national and four regional Institutes of Hygiene and Epidemiology. When cholera cases are detected in known endemic areas, mass vaccinations are arranged in designated locations such as schools, commune and district health facilities or government offices in the affected areas.
Map of Vietnam indicating cholera endemic areas in the Central coastal regions and in the South where cholera vaccines were used from 1997 to 2005.
In October 2007, an increase in acute watery diarrhea cases was reported in Hanoi, caused by genetically altered Vibrio cholerae
O1 Ogawa biotype El Tor producing classical biotype cholera toxin. Prior to this outbreak, the strain had never been isolated in Vietnam 
. From 24 October to 4 December 2007, nearly 2,000 diarrhea cases were reported from Hanoi and neighboring provinces, of which 295 were laboratory confirmed. In response the Ministry of Health of Vietnam mandated the provision of free medical treatment for anyone suffering from acute diarrheal illness.
New cholera cases were identified on 24 December 2007 from Hanoi, thus, in the first week of January 2008, just prior to the Vietnamese Tet New Year, a decision was made to immunize two particularly hard hit districts of Hanoi – Hoang Mai and Thanh Xuan (combined population of ~462,570). These districts are located close to waterways into which sewage drains. The Vietnam National Institute of Hygiene and Epidemiology (NIHE) together with the Ministry of Health launched the mass vaccination campaign on 16–28 January 2008, providing two doses of the killed oral cholera vaccine, spaced one week apart. Because of the absence of cases detected during the outbreak among children less than 10 years of age, vaccines were only provided to residents aged 10 years and older. Pregnant residents were also not eligible for vaccination. The campaign was announced in newspapers and radio and eligible residents were invited to proceed to commune health centers. Vaccination cards were provided to vaccinees and logbooks containing the names of vaccine recipients were maintained. It was estimated that ~80% of the estimated 370,000 age-eligible individuals received one or more doses of the killed OCV. In addition, educational health campaigns were also conducted to inform the public of the signs of illness and to improve sanitary practices.
From 24 December 2007 to 6 February 2008, 59 diarrhea cases (33 culture confirmed V. cholerae O1) were identified, all cases coming from Hanoi. No cases were detected until 5 March 2008, when the number of diarrhea cases increased and V. cholerae O1 Ogawa was again identified as the causative agent. The NIHE requested the International Vaccine Institute (IVI) to assist in the outbreak investigation, specifically looking into the role of vaccines for control. This provided a unique opportunity to assess the effectiveness of reactive oral cholera vaccination in a cholera outbreak, as there has been little experience in the use of OCVs in cholera epidemics. shows the clinical cholera cases in Hanoi from 24 October 2007 to 15 July 2008.
Clinical cholera cases in Hanoi, 2007 to 2008.