Wüstenschiff

Cholera: Die Impfung mit dem Reiskorn
25.06.2007

Japanische Forscher haben einen essbaren Impfstoff zur Prävention der Cholera entwickelt. Die Vakzine lässt sich in Reispflanzen kultivieren und übersteht auch längere Lagerzeiten ungekühlt.

Die bei Cholera auftretenden starken Durchfälle werden durch das Bakterium Vibrio cholerae ausgelöst. Sein Exotoxin verursacht massive Verluste von Flüssigkeit und Mineralien im Darm, was unbehandelt tödlich enden kann. Wissenschaftler der Universität in Tokio modifizierten das Erbgut von Reispflanzen nun dahingehend, dass sie Fragmente des Bakteriengiftes in ihren Körnern produzieren. Der entstandene Impfstoff zeichnet sich durch seine ungewöhnliche Robustheit aus: Weder eine ungekühlte Lagerung noch die unterschiedlichen pH-Werte des Verdauungstraktes vermindern die Qualität der Vakzine.

Anhand eines Tierexperimentes ließen sich sowohl im Blut als auch auf Schleimhäuten entsprechende Immunreaktionen nachweisen. Das macht den Impfstoff besonders effektiv, so die Forscher, da in der Regel als erstes Schleimhäute mit dem Erreger in Kontakt kommen. Seine kostengünstige Herstellung ohne aufwändige Reinigungsverfahren, die Haltbarkeit bei Temperaturen über 8 Grad Celsius und eine injektionsfreie Applikation erleichtern den Einsatz des Impfmittels auch unter schwierigen Bedingungen. Vor allem Entwicklungsländer, in denen Cholera aufgrund mangelnder Hygiene häufiger auftritt, könnten von der neuen Reis-Vakzinen Kombination profitieren.

Quelle: Nochi, T. et al.: PNAS, Online-Vorabveröffentlichung, DOI: 10.1073/pnas.0703766104

Cholera
Revised September 2007

Cholera is an acute diarrhoeal infection caused by ingestion of the bacterium Vibrio cholerae. Transmission occurs through direct faecal-oral contamination or through ingestion of contaminated water and food. The disease is characterized in its most severe form by a sudden onset of acute watery diarrhoea that can lead to death by severe dehydration and kidney failure. The extremely short incubation period - two hours to five days - enhances the potentially explosive pattern of outbreaks, as the number of cases can rise very quickly. About 75% of people infected with cholera do not develop any symptoms. However, the pathogens stay in their faeces for 7 to 14 days and are shed back into the environment, potentially infecting other individuals. Cholera is an extremely virulent disease that affects both children and adults. Unlike other diarrhoeal diseases, it can kill healthy adults within hours. Individuals with lower immunity, such as malnourished children or people living with HIV, are at greater risk of death if infected by cholera.

Background
During the 19th century, cholera spread repeatedly from its original reservoir or source in the Ganges delta in India to the rest of the world, before receding to South Asia. Six pandemics were recorded that killed millions of people across Europe, Africa and the Americas. The seventh pandemic, which is still ongoing, started in 1961 in South Asia, reached Africa in 1971 and the Americas in 1991. The disease is now considered to be endemic in many countries and the pathogen causing cholera cannot currently be eliminated from the environment.

Two serogroups of V. cholerae - O1 and O139 - can cause outbreaks. The main reservoirs are human beings and aquatic sources such as brackish water and estuaries, often associated with algal blooms (plankton). Recent studies indicate that global warming might create a favourable environment for V. cholerae and increase the incidence of the disease in vulnerable areas. V. cholerae O1 causes the majority of outbreaks worldwide. The serogroup O139, first identified in Bangladesh in 1992, possesses the same virulence factors as O1, and creates a similar clinical picture. Currently, the presence of O139 has been detected only in South-East and East Asia, but it is still unclear whether V. cholerae O139 will extend to other regions. Careful epidemiological monitoring of the situation is recommended and should be reinforced. Other strains of V. cholerae apart from O1 and O139 can cause mild diarrhoea but do not develop into epidemics.

Risk factors and vulnerable populations
Cholera is mainly transmitted through contaminated water and food and is closely linked to inadequate environmental management. The absence or shortage of safe water and sufficient sanitation combined with a generally poor environmental status are the main causes of spread of the disease. Typical at-risk areas include peri-urban slums, where basic infrastructure is not available, as well as camps for internally displaced people or refugees, where minimum requirements of clean water and sanitation are not met. However, it is important to stress that the belief that cholera epidemics are caused by dead bodies after disasters, whether natural or man-made, is false. Nonetheless, rumours and panic are often rife in the aftermath of a disaster. On the other hand, the consequences of a disaster -- such as disruption of water and sanitation systems or massive displacement of population to inadequate and overcrowded camps -- can increase the risk of transmission, should the pathogen be present or introduced.

Since 2005, the re-emergence of cholera has been noted in parallel with the ever-increasing size of vulnerable populations living in unsanitary conditions. Cholera remains a global threat to public health and one of the key indicators of social development. While the disease is no longer an issue in countries where minimum hygiene standards are met, it remains a threat in almost every developing country. The number of cholera cases reported to WHO during 2006 rose dramatically, reaching the level of the late 1990s. A total of 236 896 cases were notified from 52 countries, including 6311 deaths, an overall increase of 79% compared with the number of cases reported in 2005. This increased number of cases is the result of several major outbreaks that occurred in countries where cases have not been reported for several years. It is estimated that only a small proportion of cases - less than 10% - are reported to WHO. The true burden of disease is therefore grossly underestimated.

Prevention and control of Cholera outbreaks
Among people developing symptoms, 80% of episodes are of mild or moderate severity. Among the remaining cases, 10%-20% develop severe watery diarrhoea with signs of dehydration. If untreated, as many as one in two people may die. With proper treatment, the fatality rate should stay below 1%.

Measures for the prevention of cholera have not changed much in recent decades, and mostly consist of providing clean water and proper sanitation to populations potentially affected. Health education and good food hygiene are equally important. In particular, systematic hand washing should be taught. Once an outbreak is detected, the usual intervention strategy is to reduce mortality by ensuring prompt access to treatment and controlling the spread of the disease.

The majority of patients - up to 80% - can be treated adequately through the administration of oral rehydration salts (WHO/UNICEF ORS standard sachet). Very severely dehydrated patients are treated through the administration of intravenous fluids, preferably Ringer lactate. Appropriate antibiotics can be given to severe cases to diminish the duration of diarrhoea, reduce the volume of rehydration fluids needed and shorten the duration of vibrio excretion. Routine treatment of a community with antibiotics, or "mass chemoprophylaxis", has no effect on the spread of cholera and can have adverse effects by increasing antimicrobial resistance. In order to ensure timely access to treatment, cholera treatment centres should be set up among the affected populations whenever feasible.

The provision of safe water and sanitation is a formidable challenge but remains the critical factor in reducing the impact of cholera outbreaks. Recommended control methods, including standardized case management, have proven effective in reducing the case-fatality rate. Comprehensive surveillance data are of paramount importance to guide the interventions and adapt them to each specific situation. In addition, cholera prevention and control is not an issue to be dealt by the health sector alone. Water, sanitation, education and communication are among the other sectors usually involved. A comprehensive multidisciplinary approach should be adopted for dealing with a potential cholera outbreak.

Oral cholera vaccines
The use of the parenteral cholera vaccine has never been recommended by WHO due to its low protective efficacy and the high occurrence of severe adverse reactions. An internationally licensed oral cholera vaccine (OCV) is currently available on the market and is suitable for travellers. This vaccine was proven safe and effective (85–90% after six months in all age groups, declining to 62% at one year among adults) and is available for individuals aged two years and above. It is administered in two doses 10-15 days apart and given in 150 ml of safe water. Its public health use in mass vaccination campaigns is relatively recent. Within the past few years several immunization campaigns were carried out with WHO support. In 2006, WHO published official recommendations for OCV use in complex emergencies.

Travel and trade
Today, no country requires proof of cholera vaccination as a condition for entry and the International Certificate of Vaccination no longer provides a specific space for recording cholera vaccinations.

Past experience clearly showed that quarantine measures and embargoes on movements of people and goods - especially food products - are unnecessary. At present, WHO has no information that food commercially imported from affected countries has been implicated in outbreaks of cholera in importing countries. The isolated cases of cholera that have been related to imported food have been associated with food which had been in the possession of individual travellers. Therefore, it may be concluded that food produced under good manufacturing practices poses only a negligible risk for cholera transmission. Consequently, WHO believes that food import restrictions, based on the sole fact that cholera is epidemic or endemic in a country, are not justified.

Rita Colwell [...] die inzwischen 84-jährige Mikrobiologin [...] entdeckte bereits in den 1960er Jahren, dass die Ausbrüche der Krankheit mit dem Plankton im Meer zusammenhingen: Traten vor der Küste besonders viele dieser kleinen Krebse auf, kam es an Land zu Krankheitsfällen. Das Bakterium lebt unter anderem auf den Panzern der Kleinstlebewesen und ernährt sich dort vom Chitin. In den folgenden Jahrzehnten fand sie immer mehr Indizien dafür, dass Cholera-Epidemien vom Wetter beeinflusst werden. »Es geht um Niederschlag, um Wassertemperaturen und auch um den Salzgehalt des Wassers – alles, was das Wachstum des Planktons und damit auch des Cholera-Bakteriums beeinflusst. Deswegen wissen wir heutzutage sehr gut, welche Bedingungen wir beobachten müssen, wenn wir Ausbrüche untersuchen oder prognostizieren wollen«, erläutert Colwell. Mit ihrem Team begann sie, diese Faktoren in ein Computermodell zu speisen, das künftige Hotspots identifizieren sollte.