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Anti-infective nasal spray for
preventing influenza and colds
Influenza is a particularly serious viral infection of the upper respiratory tract and is one of the major contributors to morbidity and mortality. Approximately 10-20% of the US develops flu each year. In non-pandemic years this can result in 130 000 hospital admissions and up to 20 000 deaths each year. In a pandemic, the numbers can easily increase 10 fold.
Children, having immature immune systems and the elderly, having a less active immune system, are particularly at risk from developing complications. The greatest complication is the progression from upper to lower airway infection leading to either viral pneumonia or secondary bacterial pneumonia due to colonization with Streptococcus pneumoniae, Staphylococcus, or Haemophilus. Some pandemics like the 1917-18 Spanish flu have resulted in the deaths of tens of millions of people throughout the world. Consequently there is a great need to develop protective treatments against influenza.
Vaccination
Vaccination is the traditional strategy to achieve maximum protection. However, vaccines have their limitations and particularly with the influenza virus, which under selective pressure is capable of rapid mutation into antigenically different strains. Selective pressure results in incremental changes in the amino acid sequence of HA and NA and is referred to as antigenic drift. This leads to the re-emergence of previous strains and is responsible for the yearly flu epidemics. The problem is compounded by the sporadic appearance of genetic crossing between viruses from different hosts giving rise to an entirely new HA or NA gene and a completely new subtype. This antigenic shift is responsible for pandemic outbreaks in which there is little or no cross-protection from antibodies to previous infections. This is of particular concern in the case of the H5 viruses, which have not circulated in the human population before and against which there are no protective antibodies and in consequence the entire world population is at risk.
Recently in 1997 an avian H5N1 variant appeared and although bird to human transmission is possible, H5N1 is not efficient at transmission between humans. Nevertheless it is a very potent virus and of the 18 cases reported in Hong Kong, 6 proved fatal and the severity of disease in apparently healthy individuals is of particular concern.
This leaves the population at risk as new strains emerge and in the interval between the identification of new strains and the development of an effective vaccine. The lengthy production schedule means that in the worst-case scenario, the first wave of a pandemic would be over before a vaccine is ready for release and before sufficient doses are distributed.
The lungs are a major portal of entry for pathogenic and non-pathogenic bacteria, viruses and fungal spores. The ability to fight off infections depends on a healthy and robust immune system in the nasal and respiratory mucosal membranes. The early response is vital to stop the microbes becoming established and to prevent them proliferating. This first line defence is referred to as the Innate Immune system. The major effectors of this first line defence are the phagocytic cells - the macrophages, dendritic cells and natural killer cells (NK cells). These not only directly recognise and destroy microbes but also produce the warning signals to galvanise the immune system to respond. The principle cytokines are IL-12 produced by phagocytes when they encounter microbes and IFN( produced by NK cells either directly or when activated by IL-12. These cytokines set in action a series of events that result in the attraction of activated effector cells, including macrophages, dendritic cells, NK cells and neutophils to the sight of infection. Immune enhancers, which are often the by-products of microbes, provide a method of stimulating and activating the defensive response against potential infection. This is of particular importance for those with a weak immune system - the elderly, or those with a chronic disease such as AIDS or cystic fibrosis. There is also a need for strengthening the immune system of children, whose immune system is in the early stages of development.
CMP as prophylactic
The protective immune enhancement provided by CMP is due to the fact that the immune system of the respiratory tract has evolved to counter the threat of fungal infection from air borne spores and that the main component of the fungal spore wall is chitin, which is chemically identical to the chitin extracted from shrimp and used to make CMP.
The implication from the accumulating studies on CMP is that stimulating the macrophages, NK cells and other components of the respiratory mucosa with a nasal spray containing CMP enhances protection against influenza and probably other respiratory infections and CMP would be very suitable for general use, including vulnerable groups such as the elderly and children owing to the excellent safety profile of CMP.
The ease of production and the physical / chemical stability of CMP are of great importance as it would mean that mass production and distribution of CMP based nasal spray bottles would be relatively easy and would not require refrigeration.
CMP nasal spray could be used as a simple immunoprophylactic to enhance resistance to infection by emerging influenza strains including avian flu and that this simple measure could be of great importance as part of a mass health program for combating epidemics and the next potential flu pandemic. In combination with other anti-viral drugs, the CMP nasal spray might be of particular value for the management of viral infection at identified sites of outbreak as part of a co-ordinated effort to contain infections while logistical programmes are put in place. And of course the lag time before the identification of viral strain and development, manufacture and distribution of the appropriate protective vaccine is a major problem where the need for prophylactics is essential.
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Scientific Papers
Prophylactic Effects of Chitin Microparticles on Highly Pathogenic H5N1 Influenza Virus.
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