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Letters |
1 Advanced Biologicals, 111 Sabe Lane, Htanbingon, Sawbwagyigone, Insein,
Yangon 11013, Myanmar
2 Eaton Lodge, 10 Station Road, East Leake, Loughborough, Leicestershire
LE12 6LQ
SIR, - Haemorrhagic septicaemia is a common disease in many countries in Asia and sub-Saharan Africa. It is the infectious disease causing the most fatalities in cattle and buffaloes in some of these countries. Governments in many countries attempt control by vaccination. Inactivated vaccines include oil-adjuvanted preparations providing protection for nine to 12 months, and alum-precipitated vaccines (APVs), which provide protection for up to six months (Bain and others 1982). A live vaccine that protects for at least one year (Myint and others 2005) has also been developed. Vaccines are usually produced locally in government laboratories.
APV is established as the most widely used vaccine partly because it is simple to produce. During preparation, a hot solution of potash alum is added to a diluted suspension of formalin-killed Pasteurella multocida cells to make 1 per cent alum in the final product. It is necessary to then add sodium hydroxide solution to raise the pH to 6·5 to obtain a very fine suspension of vaccine (Bain and others 1982).
The duration of protective immunity provided by APVs appears to have dwindled from six months (Bain and others 1982) to three to four months (De Alwis 1999). Postvaccination shock, reported by Bain and others (1982) to occur at rates varying from 0·1 per cent to 10 per cent, is still recognised as a disadvantage of this vaccine (De Alwis 1999). It has been found that some haemorrhagic septicaemia vaccine laboratories do not check the pH of their APVs, contrary to the recommendation of Bain and others (1982). APVs produced in Myanmar before 1977 were not pH adjusted, and adrenaline injections were frequently required to treat postvaccination shock. Reports of these adverse reactions ceased following the introduction of pH-adjusted vaccines (A. Myint, unpublished data). The efficacy of the vaccine is possibly also improved as evidenced by extension of the duration of immunity beyond six months (Myint and others 1987).
The procedure for the preparation of APVs in the manual of the World Organisation for Animal Health (OIE) requires modification because it instructs dilution of the bacterial suspension, adjustment of the pH to 6·5, and then addition of a hot 20 per cent solution of potash alum to give a final concentration of 1 per cent alum (OIE 2004). In fact, the pH should be adjusted after adding the hot potash alum (Bain and others 1982). The pH of the mixture drops rapidly following addition of hot potash alum solution, causing a granular flocculation that settles to produce packed sediment. After pH adjustment, by addition of sodium hydroxide solution, the volume of the precipitate increases and the stored vaccine rapidly returns to a fine suspension after a few shakes. A pH of 6·5 could be optimal for the binding of aluminium ions to antigens and best expression of the adjuvant action of alum. Anaphylactic reactions to vaccination could also be much reduced because only a minimum amount of free antigen is present in the pH-adjusted vaccine.
APV constitutes 80 per cent of haemorrhagic septicaemia vaccine production in south-east and south Asian countries where haemorrhagic septicaemia is enzootic, and is still the most widely used haemorrhagic septicaemia vaccine in Asia and Africa (De Alwis 1999). If the simple step of adjusting the pH of the vaccine were to be widely adopted, the safety and efficacy of APV would be substantially improved, resulting in better control of haemorrhagic septicaemia on these continents.
This recommendation concerning pH adjustment may apply to other vaccines being produced by a similar procedure.
DE ALWIS, M. C. L. (1999) Haemorrhagic Septicaemia. ACIAR Monograph 57. Canberra, Australian Centre for International Agricultural Research
MYINT, A., CARTER, G. R. & JONES, T. O. (1987) Prevention of experimental haemorrhagic septicaemia with a live vaccine. Veterinary Record 120,500 -501[Abstract]
MYINT, A., JONES, T. O. & NYUNT, H. H. (2005) Safety, efficacy and cross-protectivity of a live intranasal aerosol haemorrhagic septicaemia vaccine. Veterinary Record 156, 41-45[Abstract]
OIE (2004) Haemorrhagic septicaemia. In Manual of Diagnostic Tests and Vaccines for Terrestrial Animals. Version adopted May 2005. Paris, World Organisation for Animal Health. www.oie.int/eng/normes/mmanual/A_00063.htm. Accessed December 6, 2006
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