Vaccines for Cholera Control: Does Herd Immunity Play a Role?

Shenvi N (2007) Controlling endemic cholera with oral vaccines. PLoS Med 4(11): e336. doi:10.1371/journal. pmed.0040336 Using data from Bangladesh Vaccines for Cholera Control: Does Herd Immunity Play a Role? Lorenz von Seidlein 0 Disease Burden 0 0 Lorenz von Seidlein is a Senior Lecturer at London School of Hygiene and Tropical Medicine , London , United Kingdom and a Senior Lecturer at Mahidol- Oxford Tropical Medicine Research Unit , Bangkok , Thailand - Cholera is a diarrhoeal disease caused by Vibrio cholerae O1 and O139, transmitted through the faeco-oral route. The disease occurs in outbreaks but can establish itself permanently. The full impact of the disease is difficult to assess. The currently preferred measure of disease burden, disability-adjusted life years, fails to capture the enormous impact of a cholera outbreak, which spares no age group and paralyses the economy in severely affected areas. The seventh cholera pandemic began in Indonesia in 1961 and spread quickly to other Asian countries, which became the epicentre of cholera outbreaks. With the economic emergence of Asia the number of cholera cases reported from that region has decreased. There are several possible reasons to explain this decline. First, massive investment has been made in providing a safe water supply and in sanitation. Second, reporting of cholera has become less reliable, because global trade especially trade in seafoodand tourism are negatively affected by cholera outbreak reports. In 1970 Vibrio cholerae O1 El Tor invaded sub-Saharan Africa, which had not experienced cholera for more than 100 years. In 2006, Africa reported 234,349 cases of cholera to the World Health Organization (WHO), accounting for 99% of the officially notified global cholera [1]. Between 1995 and 2005, 66% of cholera outbreak reports to ProMedmail (a global electronic reporting system for outbreaks of emerging infectious diseases and toxins, run by the International Society for Infectious Diseases, at http://www.promedmail. The Perspectives section is for experts to discuss the clinical practice or public health implications of a published article that is freely available online. org/) came from sub-Saharan Africa [2]. There is growing evidence of the large and increasing burden of cholera in Africa. Most recently the US-led invasion of Iraq has been accompanied by a reemergence of cholera in that country. As of September 2007, nearly 7,000 cholera cases from the Sulaymaniyah and Kirkuk Governates have been reported to WHO [3]. Cholera Control and Vaccines Cholera was eliminated from the industrialized world through safer water supplies, better sanitation, and improved food hygiene. These have been the accepted control mechanisms for the disease, but as the emergence of cholera in Iraq illustrates, the provision of safe water and sanitation breaks down during wars and complex humanitarian emergencies. In addition to these crisis situations, cholera also thrives in the ever-increasing slums of some megacities such as Kolkata (formerly Calcutta), India, which are not quickly accessible to improvements in infrastructure. In 2002, WHO mentioned for the first time the potential use of oral cholera vaccines in endemic and epidemic situations [4]. Up to that point cholera vaccines were recommended for individual travellers to endemic countries but not for public health use in endemic countries. Far from embracing vaccinations for cholera control, WHO experts recommended gaining more experience through demonstration projects. Since then, mass oral cholera vaccinations have been conducted in Beira, Mozambique, in Darfour, Sudan, and in Aceh, Indonesia. These projects demonstrated the feasibility and effectiveness of vaccination under actual public health conditions [5]. A WHO meeting at the end of 2005 suggested that the use of oral cholera vaccines in certain endemic situations should be recommended [6]. The slow acceptance of vaccines for cholera control is probably related to the poor performance of earlier generations of cholera vaccines made from phenol-killed whole-cell preparations of V. cholerae O1 organisms and administered by injection as two doses, two weeks apart. The vaccine offered about 50% protection for a short duration, was associated with painful local inflammatory reactions, Competing interests: The author has in the past received funding from International Vaccine Institute and from World Health Organization. Copyright: 2007 Lorenz von Seidlein. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abbreviations: WHO, World Health Organization and is no longer recommended for use [7]. Currently two cholera vaccines are internationally licensed: (1) Dukoral, consisting of inactivated whole cells of V. cholerae O1 combined with the B-subunit (BS-WC) of the cholera toxin, and (2) the live attenuated vaccine CVD 103HgR (Orochol or Mutacol). Both vaccines have an excellent safety profile and afford high rates of protection over several years. The companies producing each vaccine have been acquired in the last two years by the publicly listed Dutch company Crucell. Only Dukoral is currently produced, and for this reason was used in the abovementioned vaccination campaigns in Mozambique, Sudan, and Indonesia. Dukoral costs travellers more than US$10 per dose, and two doses two weeks apart are recommended for immunisation. Most tourists can afford this vaccine, and well-supported foundations can purchase this vaccine for interventions in larger populations. Yet Dukoral is likely to remain too expensive for governments of choleraendemic regions to vaccinate at-risk populations. The technology on which Dukoral is based has previously been transferred to manufacturers in Vietnam, and has been more recently transferred to an Indian vaccine producer with certification to produce internationally licensed vaccines. There is therefore a justified hope that this vaccine candidate will become available internationally at an affordable price. The ideal cholera vaccine is safe and affords extended if not lifelong protection after a single dose. It can be stored for extended periods at room temperature and is in the same price range as vaccines included in the WHO Expanded Program on Immunization. Promising candidates approaching this ideal are under development. Peru15, for example, is a live, attenuated vaccine candidate that has been found to be safe and immunogenic in infants and children in Bangladesh [8,9]. Because cold storage presents a challenge for the use of this vaccine in tropical cholera endemic regions, a thermostable vaccine is under development. A promising live, attenuated cholera vaccine candidate is being developed by the Cuban Finley Institute (Camaguey, Cuba); this candidate is currently under e (...truncated)