Monday, January 7, 2013

Tuberculosis


Tuberculosis (TB)

       Historically has been one of the world’s worst killer diseases. Traces of TB have been found in skeletons of the late Stone Age. (P01) show the death rate from tuberculosis in England and wales from 1838 to 1970. It was one of the world’s great killer diseases in the nineteenth century and was the largest signal cause of death in England and wales during that time, accounting for one fifth of all death. By 1990, the number of children dying from the disease has been reduced to less than 1 in 1 million in developed countries, nut at least 30million people worldwide still sufficed symptoms, 95% of whom were living in developing countries. Up to 3 million a year are currently dying from TB, and up to one-third of the world’s population carry the bacteria with no ill effects.
   In the early 1990s the WHO declared the disease a global emergency as case in the developed world, including Britain, began to increase against and resistance to drugs began to grow. In 1992 there were 5802 new cases in England. Worldwide, 8 million new cases are reported every year. In 1993, Dr Kochi, manager of the WHO’s TB programme, said ‘TB is out of control in many part of the world. The disease, which is preventable and treatable, has been grossly neglected and no county is immune to it.’
 The disease is caused by a fungus like bacterium called Mycobacterium tuberculosis, first discovered by Robert Koch in 1882. It is some time referred to as the tubercle bacillus, bacilli being rod shaped bacteria. The most common from in the UK is pulmonary TB which infects the lungs, although other organs may be affected. Tow strains 0f the bacterium may cause the disease, the human and bovine forms. The latter can be present in cattle and can enter the milk of cow. It is very resistant and can remain alive for long period in milk products. It is a very serious disease of cattle and has also been responsible for a great deal of illness and death in human in the past, particularly in children. Today, however, all milk in the UK is produced from cow that have been ‘tuberculin tested’, that is certified free of Mycobacterium. The milk also undergoes treatment at bottling plants where it is subjected to pasteurization, sterilization or ultra high temperature. These processes destroy at least 99% of all bacteria, including all pathogens. Thus bovine tuberculosis is no longer of significance in humans.

                 Transmission, signs and symptoms

Transmission of pulmonary TB is by inhaling the bacteria into the lungs (droplet infection). It is much less infectious than the common cold, and requires prolonged contact between people. This account for the fact that it is associated with overcrowded living condition, particularly where there is poor ventilation. The bacterium can also resist drying out and can survive in the air and in house dust for long periods. It is associated with poverty and bad housing where people sleep several to a room. Refugee camps, dormitories for the homeless, and prisoner of war camps are other situation in which it commonly spreads. In such conditions, malnutrition and other infections resulting in a weakened immune system can reduce resistance to the disease.
   Tuberculosis can affect almost any tissue or organ in the body, but disease of the lungs is by far the most frequent. It was commonly known as ‘consumption’ in the past because it consumed the body, causing it to waste away. The outcome of infection by tubercle bacilli depends on a variety of factors. These include the age of the patient, the state of nutrition (which is usually related to social class) and the presence or absence of immunity. Immunity can be acquired by an individual as a result of a previous mild infect or by vaccination.
              The disease frequently shows itself by vague symptoms such as loss of weight and excessive sweating. There are often no symptoms in early tuberculosis and the disease may only be accidentally discovered through a routing X-ray of the lungs. The diseases start as an inflammation in one lung, which develops into a cavity. Then further cavities develop, spreading into both lungs. As progressive destruction of the lungs occurs the symptoms become more dramatic with coughing, appearance of blood in the sputum, cheats pains, shortness of breath, fever and sweating, poor appetite and weight loss.
                   Treatment and prevention

Effective medical treatment only began in 1947 with the introduction of the antibiotic streptomycin. Mass vaccination did not begin in the Britain unit 1954. The decline up to this point must have been due mainly to improving social conditions, particularly improved housing. Vaccination accelerated the decline and by 1970 the annual death rate in Britain had fallen to 1526.
                   Vaccination,    
  The development of an effective vaccine against the disease resulted from the work of two French scientists, Alber Calmette and Camille Guerin hence the names of the vaccine bacilli calmette-Guerin (BCG). As far back as 1921 they developed attenuated (less virulent) strains which were found to be effective for vaccination. Before treating any individual it is important to check if they are already suffering from TB or have recovered from it. The test is to puncture the skin with a special instrument which has a ring of six short needles (the Heaf test). This introduces a protein called tuberculin, purified from dead tubercle bacilli. In the absence of past or present TB the skin show no reaction, but if an individual has the disease or recovered, then the skin swells and reddens at the injection site. This indicates a substantial immunity and no vaccine is offered.
         A detailed study of50000 healthy children, reported on in 1963, showed that the incidence of the TB per 1000 children was 1.91 if unvaccinated, and 0.4 if vaccinated. The benefit of vaccination therefore lasts for a long period of time because the children still had immunity after more than ten years. Today children are vaccinated at age twelve to fourteen years. Tuberculin tests indicate that about 10% of children are positive at this age. These children are given a routine X-ray to ensure that no active pulmonary tuberculosis is present, and very few children have the disease.
Antibiotics,
A cure for people already affected by TB did not come until 1943 when the antibiotic streptomycin was discovered. The number of cases started to fall more rapidly after this and continued to decline up to the mid 1980s, aided by the introduction of further antibiotics such as rifampicin, isoniazid and others.
At that time in western countries more than 80% of all active TB cases were of people over sixty years of age.

                   Resurgence of the disease
After1980, the demographics of the disease shifted in that more and more young people between the age of the twenty five and thirty were developing that disease. Between 1980 and 1986 five different surveys in the USA showed a relationship between the rise of homelessness and surges of TB young adult populations. It became clear by 1985 that new mutant strain of drug-resistant TB were also present in the population. In 1986 patient with strains of Mycobacterium resistant to both isoniazid and rifampicin numbered 0.5% of cases, by 1991 this had resent to 3% and to 6.9% in 1994. The main contributing factors were courses of treatment lasts 6-8 month and require consumption of at least three or four antibiotics to reduce the chance of a strain multiplying which is resistant to one of the antibiotics. The problem is made worse by the fact that the patients starts to feel well again after a few weeks. Supervision by health workers is difficult not only in developing countries, but also in large cities such as new York where many sufferers are homeless, and where TB has become a new epidemic.
    From the beginning of the AIDS epidemic it was noted that HIV positive member of the community developed a high rate of tuberculosis. Many developing countries took steps to heed a WHO warning regarding this relationship between HIV and TB. Doctors in the USA and most of Western Europe, however, took little notice of these facts for they tended to view the TB risk for HIV patent as the third world problem. In Africa TB began to spread rapidly and HIV patent did not respond well to the two cheapest antituberculosis drug, thiacetazone and streptomycin. By 1990 health experts in some Africa countries were predicting defeat in their efforts to control tuberculosis.
   The new strain of drug resistant bacteria spread rapidly and there were clear interconnections between this new strains and HIV. Patients with AIDS, with its immunodeficiency, were very susceptible to infection, and death rates rose to 90-100% fatality. The percentage increases in TB for different European countries are sown in table (02). These are directly related to the increase in drug resistant strains and HIV infection.
  A reported in 1996 on TB in Edinburgh during the period 1998-1992 showed the followings.
4.1% increase in TB cases recorded among people over 65 years
12.6% increase in TB cases recorded in younger patent.
In the elderly, most cases were the result of reactivation of TB caught in childhood or youth. The rise in both age groups was entirely due to the increased resistance to antibiotics of the tubercle bacilli.
    Immigration is also associated with an increase in TB. For example areas in Britain with large immigrant population have shown increase 25% higher than in the indigenous resident.
    The world health organization has started to achieve a more successful treatment of TB with its DOTS campaign (directly observed treatment under the supervision). The patient is given pills under supervision and watched each time to check the pills are swallowed. This is done 0ver a period of 6 to 8 month and results in a cure of over 85% of cases.   







                                           po1





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                                                    P2



 
               Chest X-ray TB sufferer.








Friday, January 4, 2013

Vaccination programmers.


Vaccination programmers


                                      Children in the UK can be given a series of vaccine to protect them against a range of disease (P1). In some countries vaccination is a legal requirement. Vaccination programmers have been particularly successful in virtually eliminating polio (poliomyelitis) and diphtheria in develop countries. Polio my soon become extinct worldwide. Diphtheria is vary rate in the UK, reduced to only 13 cases and no death between 1986 and 1991.
By 1984 the world health organization’s programme of vaccination, which is targeted against six major diseases (measles, pertussis,[whooping, cough], tetanus, polio, tuberculosis, diphtheria) had immunized some 50% of the children in the world and this has risen to 80% by the mid 1990. It has been estimated that this programme prevented more than one million deaths annually between 1974 and 1984. However, despite great progress, by 1990 about 3 million were still dying each year from these diseases and about 4.6 million were still fully vaccinated. Measles was killing 1.4 million annually (one every 20 seconds). Another 490,000 died of pertussis annually and 450,000 of TB. The manual cost, one-third of which is given in aid, is about US$1.5 thousand million.
       The world health organization expanded programme of  Immunization (EPI) aims to immunize more than 90% of the world’s new born against  a number of viral and bacterial diseases by the year 2000. Hepatitis B is now also being targeted and it is hoped to eradicate polio by the year 2000.
             There is still a need for new vaccines, for example against malaria, dengue fever, sleeping sickness, warm infection, HIV, leprosy and others. Not only are new vaccines required, also more effective and safer vaccines than those in used at the present time are needed. For example the vaccine for cholera is only effective in 50% of patents and the duration of immunity is relatively short. The flu vaccine also needs improvement to make it more effective.



Type of vaccine
         The different types of vaccine are described in section type of vaccination. There has been much debate about the relative merits of live and killed vaccines. Generally speaking, live vaccines are more effective although in the past they have been more risky. Other factor such has cost, safely, politics and social acceptance can determine whether there is high uptake of a particular vaccine and whether successful.
        There are many approaches to making and using a vaccine. For example in the UK three different vaccines have been licensed for typhoid vaccination.
     1. A killed whole cell vaccine (no longer available),
     2. A polysaccharide extract from the capsule of the typhoid bacterium.
     3. A live attenuated string of the typhoid bacterium, salmonella typhi.
               The second one is the most recent, having been introducing in 1992. It requires the least number of does and is the most preferred.
   The most important issue for developed countries is the safety of the vaccine, whereas in a developing country the question of cost and how to deliver the vaccines are probably of greater importance.
    A relatively recent development in the production of vaccine is that of using genetic engineering techniques. Many pathogens cannot be cultured outside their natural host. Thus the conventional approaches to vaccination cannot be used. For example, the microbe causing human syphilis (treponema pallidum) and the bacterium that causes leprosy (mycobacterium leprae) have never been grown in vitro (outside the body). Thus is not possible to generate live attenuated or inactivated vaccine by culturing techniques. In these examples recombinant DNA technology offer an alternative approach, allowing genes for antigens to be transferred from these organisms to more useful hosts such as E. coil, yeast or mammalian cells. These can then be used to produce bulk quantities of antigens for vaccines. For example, the surface antigen gene of hepatitis is simple to identify, clone and express. However, not all protective antigens are as simple to develop.  
    
Safety and effectiveness of vaccines
       There is sometimes public controversy regarding the effectiveness of vaccines. Up to 1986,160 million doses of measles vaccine (a live attenuated virus) had been administered in the UK, with an excellent record of protection. Of the children given vaccination, 5-15% developed fever on the fifth day, lasting several days. One recipient of vaccine in one million developed a disorder of the central nervous system know as encephalitis. This can cause extreme concern in parents when these facts appear in newspaper just as vaccination campaigns begin. The chances of this complication from measles vaccination are, in fact, less than the incidence of encephalitis from an unknown origin. Whooping cough (pertussis) vaccine, which contains dead bacteria, sometimes has a rare neurological adverse reaction resulting in convulsions and brain damage. This occurs once in about 100000 doses and the possibility of permanent brain damage occurs once in 300000 doses. Both measles and diphtheria vaccines can have local reactions of inflammation and laryngitis. However, deaths from these diseases still occur amongst unvaccinated children and parents must weigh up the information and take the responsibility of deciding whether or not to have their children vaccinated.     


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                                                       P 01
    

Thursday, January 3, 2013

Types of immunity


Types of immunity
Immunity may be described as active or passive. Both types may be acquired naturally or artificially. Providing immunity artificially is called Immunization. 

Natural active immunity
   This is the kind of immunity which is obtained as a result of an infection. The body manufactures its own antibodies when exposed to an infectious agent. Because memory cells, produced on exposure to the first infection, are able to stimulate the production of massive quantities of antibody when exposed to the same antigen again, this type of immunity is most effective and generally persists for long time, sometimes even for life.

Artificial active immunity  (vaccination)
This is achieved by injection (or less commonly administering orally) small amounts of antigen, called the vaccine, into the body of an individual. The process is called vaccination. If they whole organism is used as the vaccine, it is first made safe by being killed or attenuated (see below). The antigen stimulates the body to manufacture antibodies against the antigen. Often a second, booster injection is given and this stimulates a much quicker production of antibody which is longer lasting and which protects the individual from the disease for a considerable time. Several types of vaccine are currently in use.                                                                                     
·        Toxoide.  Toxins (poison) produced by tetanus and diphtheria bacteria are detoxified with formaldehyde, yet their antigen properties remain therefore vaccination with the toxoid will stimulate antibody prediction without producing symptoms of the disease.
·        Killed organisms.  Some dead viruses and bacteria are able to provoke normal antibody responses. An example is the flu vaccine which contains dead flu viruses.
·        Live vaccines (attenuated organisms).  An attenuated organism is one which has been ‘crippled’ in some way so that it cannot cause disease. Often it can only grow and multiply slowly. Attenuation may be achieved by culturing the organisms at higher temperatures than normal, or by adding specific chemicals to the culture medium for long period of time. Alternatively, The attenuated organism may be a mutant variety with the same antigens but lacking the ability to cause disease. Attenuated vaccine for the bacterial disease tuberculosis and for measles, mumps, rubella, and polio are in general use.
·        With small pox,  which is now extinct, a live virus vaccine was used. However, the virus in the vaccine was not an attenuated virus but a closely related and harmless form.
·        New vaccine.  Vaccine development and made little progress for many years, but new approaches to vaccine design are now possible using modern techniques of molecular biology and genetics engineering. Antigens are very often proteins and proteins are code for by genes. If the genes for and antigen is transferred into a bacterium, using standard techniques describe in chapter 12, the bacterium can be use as a ‘factory’ for producing large quantities of the antigen for use in vaccines. Cholera, typhoid and hepatitis B vaccines have been prepared in this way. Some vaccine can be made safer in this way. For example the whooping coughs vaccine. An alternative approach is to synthesise antigens artificially froe amino acid once their amino acid sequences are known. 
Vaccination is a common experience in develop countries and is one of the weapons which have help to reduce the incidence of infectious disease so dramatically in those countries. Other weapons have been social and environmental improvement such has treatment to clean water for drinking, better nutrition and sewage treatment.
  An example of the use of vaccination is the recommendation that all children in the UK should have the MMR vaccine at 2 year of age. This protect against measles, mumps and rubella. Also three dose of another trip vaccine, DTP (diphtheria, tetanus, and pertussis (whooping cough)) are recommended at virus age. In some countries vaccination is a legal requirement. Smallpox has been made extinct by vaccination and some childhood diseases such as diphtheria, polio and measles have become extremely rare. Polio may become extinct in the near future. The world health organization, with support from virus organization like UNICEF and the World Bank, has targetted six major diseases in the developing world in its EPI programme (expanded programme on immunization). The diseases are diphtheria, whooping cough, tetanus, polio, measles and TB. Although not feared so much anymore in develop countries, these are still killer disease worldwide. Over 80% of children in develop countries now receive vaccination against these disease. Hepatitis B is also being targeted.
    Improvements to some vaccines, such as the flu vaccine, are still needed and there is still no vaccine against some disease, notable cancers, leprosy, malaria and AIDS, despite intensive research.
                              Passive immunity
In passive immunity antibodies from one individual are passed into another individual. They give immediate protection, unlike active immunity which takes a few days or weeks to build up. However, it only provides protection against infection for a few week, for the antibodies are broken down by the body’s natural processes, so their numbers slowly fall and protection is lost.
                            Natural passive immunity
Passive immunity may be gained naturally. For example, antibodies from a mother can cross the placenta and enter her fetus. In this way they provide protection for the baby until its own immune system is fully functional. Passive immunity may also be provided by colostrum, the first secretion of the mammary glands. The baby absorbs the antibodies through its gut.
                    Artificial passive immunity
Here antibodies which have been formed in one individual are extracted and then injected into the blood of another individual which may or may not be of the same species. They can be use for immediate protection if a person has been or is likely to be, exposed to a particular disease. For example, specific antibodies used for combating tetanus and diphtheria used to be culture in horse and injected into humans. Only antibodies of human origin are now used for humans. Antibodies against rabies and some snake venoms are also available. Antibodies against the human rhesus blood group antigen are used for some rhesus negative mothers when carrying rhesus positive babies.
                 A summary of the different types of immunity is given in table 01.

                                              Active                                             Passive
                                           Antigens received                          antibodies received
Natural                             Natural active                                  natural passive
                                           e.g fighting infection,                     from mother via
                                            Rejecting transplant                       milk of placenta

Artificial                             Artificial active                                artificial passive   
                                            Vaccination (injection                    injection of antibodies
                                            of antigen)

       
                                    

 
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