Attenuated Health Dictionary

The name applied generally to dead or attenuated living infectious material introduced into the body, with the object of increasing its power to resist or to get rid of a disease. (See also IMMUNITY.)

Healthy people are inoculated with vaccine as a protection against a particular disease; this produces ANTIBODIES which will confer immunity against a subsequent attack of the disease. (See IMMUNISATION for programme of immunisation during childhood.)

Vaccines may be divided into two classes: stock vaccines, prepared from micro-organisms known to cause a particular disease and kept in readiness for use against that disease; and autogenous vaccines, prepared from microorganisms which are already in the patient’s body and to which the disease is due. Vaccines intended to protect against the onset of disease are of the former variety.

Autogenous vaccines are prepared by cultivating bacteria found in SPUTUM, URINE and FAECES, and in areas of in?ammation such as BOILS (FURUNCULOSIS). This type of vaccine was introduced by Wright about 1903.

Anthrax vaccine was introduced in 1882 for the protection of sheep and cattle against this disease. A safe and e?ective vaccine for use in human beings has now been evolved. (See ANTHRAX.)

BCG vaccine is used to provide protection against TUBERCULOSIS. (See also separate entry on BCG VACCINE.)

Cholera vaccine was introduced in India about 1894. Two injections are given at an interval of at least a week; this gives a varying degree of immunity for six months. (See CHOLERA.)

Diphtheria vaccine is available in several forms. It is usually given along with tetanus and pertussis vaccine (see below) in what is known as TRIPLE VACCINE. This is given in three doses: the ?rst at the age of two months; the second at three months; and the third at four months, with a booster dose at the age of ?ve years. (See DIPHTHERIA.)

Hay fever vaccine is a vaccine prepared from the pollen of various grasses. It is used in gradually increasing doses for prevention of HAY FEVER in those susceptible to this condition.

In?uenza vaccine A vaccine is now available for protection against INFLUENZA due to the in?uenza viruses A and B. Its use in Britain is customarily based on advice from the health departments according to the type of in?uenza expected in a particular year.

Measles, mumps and rubella (MMR) vaccines are given in combination early in the second year of life. A booster dose may prove necessary, as there is some interference between this vaccine and the most recent form of pertussis vaccine (see below) o?ered to children. Uptake has declined a little because of media reports suggesting a link with AUTISM – for which no reliable medical evidence (and much to the contrary) has been found by investigating epidemiologists. (See also separate entry for each disease, and for MMR VACCINE.)

Pertussis (whooping-cough) vaccine is prepared from Bordetella pertussis, and is usually given along with diphtheria and tetanus in what is known as triple vaccine. (See also WHOOPING-COUGH.)

Plague vaccine was introduced by Ha?kine, and appears to give useful protection, but the duration of protection is relatively short: from two to 20 months. Two injections are given at an interval of four weeks. A reinforcing dose should be given annually to anyone exposed to PLAGUE.

Poliomyelitis vaccine gives a high degree of protection against the disease. This is given in the form of attenuated Sabin vaccine which is taken by mouth – a few drops on a lump of sugar. Reinforcing doses of polio vaccine are recommended on school entry, on leaving school, and on travel abroad to countries where POLIOMYELITIS is ENDEMIC.

Rabies vaccine was introduced by Pasteur in 1885 for administration, during the long incubation period, to people bitten by a mad dog, in order to prevent the disease from developing. (See RABIES.)

Rubella vaccine, usually given with mumps and measles vaccine in one dose – called MMR VACCINE, see also above – now provides protection against RUBELLA (German measles). It also provides immunity for adolescent girls who have not had the disease in childhood and so ensures that they will not acquire the disease during any subsequent pregnancy – thus reducing the number of congenitally abnormal children whose abnormality is the result of their being infected with rubella via their mothers before they were born.

Smallpox vaccine was the ?rst introduced. As a result of the World Health Organisation’s successful smallpox eradication campaign – it declared the disease eradicated in 1980 – there is now no medical justi?cation for smallpox vaccination. Recently, however, there has been increased interest in the subject because of the potential threat from bioterrorism. (See also VACCINATION.)

Tetanus vaccine is given in two forms: (1) In the so-called triple vaccine, combined with diphtheria and pertussis (whooping-cough) vaccine for the routine immunisation of children (see above). (2) By itself to adults who have not been immunised in childhood and who are particularly exposed to the risk of TETANUS, such as soldiers and agricultural workers.

Typhoid vaccine was introduced by Wright and Semple for the protection of troops in the South African War and in India. TAB vaccine, containing Salmonella typhi (the causative organism of typhoid fever – see ENTERIC FEVER) and Salmonella paratyphi A and B (the organisms of paratyphoid fever – see ENTERIC FEVER) has now been replaced by typhoid monovalent vaccine, containing only S. typhi. The change has been made because the monovalent vaccine is less likely to produce painful arms and general malaise, and there is no evidence that the TAB vaccine gave any protection against paratyphoid fever. Two doses are given at an interval of 4–6 weeks, and give protection for 1–3 years.... vaccine

(Bacillus Calmette-Guêrin) A live attenuated vaccine used in tuberculosis.... bcg

been recognised from earliest times. Evidence of the condition has been found in Egyptian mummies; in the fourth century BC Hippocrates, the Greek physician, called it phthisis because of the lung involvement; and in 1882 Koch announced the discovery of the causative organism, the tubercle bacillus or Mycobacterium tuberculosis.

The symptoms depend upon the site of the infection. General symptoms such as fever, weight loss and night sweats are common. In the most common form of pulmonary tuberculosis, cough and blood-stained sputum (haemoptysis) are common symptoms.

The route of infection is most often by inhalation, although it can be by ingestion of products such as infected milk. The results of contact depend upon the extent of the exposure and the susceptibility of the individual. Around 30 per cent of those closely exposed to the organism will be infected, but most will contain the infection with no signi?cant clinical illness and only a minority will go on to develop clinical disease. Around 5 per cent of those infected will develop post-primary disease over the next two or three years. The rest are at risk of reactivation of the disease later, particularly if their resistance is reduced by associated disease, poor nutrition or immunosuppression. In developed countries around 5 per cent of those infected will reactivate their healed tuberculosis into a clinical problem.

Immunosuppressed patients such as those infected with HIV are at much greater risk of developing clinical tuberculosis on primary contact or from reactivation. This is a particular problem in many developing countries, where there is a high incidence of both HIV and tuberculosis.

Diagnosis This depends upon identi?cation of mycobacteria on direct staining of sputum or other secretions or tissue, and upon culture of the organism. Culture takes 4–6 weeks but is necessary for di?erentiation from other non-tuberculous mycobacteria and for drug-sensitivity testing. Newer techniques involving DNA ampli?cation by polymerase chain reaction (PCR) can detect small numbers of organisms and help with earlier diagnosis.

Treatment This can be preventative or curative. Important elements of prevention are adequate nutrition and social conditions, BCG vaccination (see IMMUNISATION), an adequate public-health programme for contact tracing, and chemoprophylaxis. Radiological screening with mass miniature radiography is no longer used.

Vaccination with an attenuated organism (BCG – Bacillus Calmette Guerin) is used in the United Kingdom and some other countries at 12–13 years, or earlier in high-risk groups. Some studies show 80 per cent protection against tuberculosis for ten years after vaccination.

Cases of open tuberculosis need to be identi?ed; their close contacts should be reviewed for evidence of disease. Adequate antibiotic chemotherapy removes the infective risk after around two weeks of treatment. Chemoprophylaxis – the use of antituberculous therapy in those without clinical disease – may be used in contacts who develop a strong reaction on tuberculin skin testing or those at high risk because of associated disease.

The major principles of antibiotic chemotherapy for tuberculosis are that a combination of drugs needs to be used, and that treatment needs to be continued for a prolonged period – usually six months. Use of single agents or interrupted courses leads to the development of drug resistance. Serious outbreaks of multiply resistant Mycobacterium tuberculosis have been seen mainly in AIDS units, where patients have greater susceptibility to the disease, but also in developing countries where maintenance of appropriate antibacterial therapy for six months or more can be di?cult.

Streptomycin was the ?rst useful agent identi?ed in 1944. The four drugs used most often now are RIFAMPICIN, ISONIAZID, PYRAZINAMIDE and ETHAMBUTOL. Three to four agents are used for the ?rst two months; then, when sensitivities are known and clinical response observed, two drugs, most often rifampicin and isoniazid, are continued for the rest of the course. Treatment is taken daily, although thrice-weekly, directly observed therapy is used when there is doubt about the patient’s compliance. All the antituberculous agents have a range of adverse effects that need to be monitored during treatment. Provided that the treatment is prescribed and taken appropriately, response to treatment is very good with cure of disease and very low relapse rates.... nature of the disease tuberculosis has

Introduced in 1962, the attenuated live oral vaccine (Sabin) against POLIOMYELITIS replaced the previous inactivated vaccine introduced in 1956 (see SALK VACCINE).... sabin vaccine

n. reduction of the disease-producing ability (virulence) of a bacterium or virus by chemical treatment, heating, drying, by growing under adverse conditions, or by passing through another organism. Treated (attenuated) bacteria or viruses are used for many *immunizations.... attenuation

(in Britain), a vaccine currently offered to all 2- and 3-year-olds in the form of a spray into each nostril. It contains live forms of the influenza virus that have been attenuated (weakened). The vaccine stimulates the immune system but does not cause disease in healthy people.... nasal flu vaccine

an oral vaccine against (E954) poliomyelitis, prepared by culture of the virus under special conditions so that it loses its virulence (i.e. it becomes attenuated) but retains its ability to stimulate antibody production. [A. B. Sabin (1906–93), US bacteriologist]...  sabin vaccine

Strychnos nux-vomica

Loganiaceae

San: Karaskara;

Hin: Kajra, Kuchila;

Mal: Kanjiram; ;

Tam: Itti, Kagodi, Kanjirai Mar:Jharkhatchura;

Kan: Hemmushti, Ittangi;

Tel: Mushti, Mushidi; Ori: Kora, Kachila

Importance: It is a large deciduous tree, with simple leaves and white fragrant flowers.

Strychnos is highly toxic to man and animals producing stiffness of muscles and convulsions, ultimately leading to death. However, in small doses it can also serve as efficacious cure forms of paralysis and other nervous disorders. The seeds are used as a remedy in intermittent fever, dyspepsia, chronic dysentery, paralytic and neuralgic affections, worms, epilepsy, chronic rheumatism, insomnia and colic. It is also useful in impotence, neuralgia of face, heart disease, spermatorrhoea, skin diseases, toxins, wounds, emaciation, cough and cholera. Leaves are applied as poultice in the treatment of chronic wounds and ulcers and the leaf decoction is useful in paralytic complaints. Root and root bark used in fever and dysentery (Nadkarni, 1982; Kurup et al, 1979).

Distribution: The plant is distributed throughout India in deciduous forests up to 1200m. It is also found in Sri Lanka, Siam, Indochina and Malaysia.

Botany: Strychnos nux-vomica Linn. is a large tree belonging to the family Loganiaceae. Leaves are simple, opposite, orbicular to ovate, 6-11.5x6-9.5cm, coriaceous, glabrous, 5 nerved, apex obtuse, acute or apiculate, transverse nerves irregular and inconspicuous. Inflorescence is many flowered terminal cymes, 2.5-5cm across. Bracts (5mm) and bracteoles (1.5mm) small. Flowers are white or greenish white and fragrant. Calyx 5 lobed, pubescent and small (2mm). Corolla salver shaped, tube cylindrical slightly hairy near the base within and greenish white, tube much elongate than the lobes. Tube 7mm and lobes 2.5mm long. Lobes 5 and valvate. Stamens 5, filaments short, 0.1mm long. Anthers 1.5mm subexerted, linear oblong. Ovary 1.5 mm, pubescent, 2 celled, ovules one to many. Style 9mm, stigma capitate. Fruit is a berry, 5-6cm diameter, globose, indehiscent, thick shelled, orange red when ripe with fleshy pulp enclosing the seeds. Seeds 1-many, discoid, compressed, coin like, concave on one side and convex on the other, covered with fine grey silky hairs.

The leaf fall is during December (do not shed all the leaves at a time) and new foliage appears in February. Flowering is during March - April and fruiting during May - December. Fruits take about 8-9 months to mature.

Properties and activity: Strychnine and brucine are the most important and toxic alkaloids present in the plant. They occur not only in the seeds but also in roots, wood, bark, fruit pulp and hard fruit shells. The minor alkaloids present in the plant are vomicine, -colubrine, -colubrine, pseudostrychnine and N-methyl-sec-pseudobrucine (novacine). Loganin a glycoside is also present (Warnat, 1932; Martin et al, 1953; Guggisberg et al, 1966; Bisset and Chaudhary, 1974). Chatterji and Basa (1967) reported vomicine as the major constituent alkaloid along with unidentified alkaloid in leaves and identified another alkaloid kajine (N-methyl pseudostrychnine) from the leaves of very young plants.

Root bark of S. nux-vomica yeilded 4-hydroxy-3-methoxy strychnine, 4 hydroxy strychine, nor-macusine, a new alkaloid 12 , 13 dihydro-12 -hydroxy isostrychnine named protostrychnine (Baser et al, 1979) methoxy strychnine, and mavacurine (Guggisberg et al, 1966). Leaves and root bark also yeilded 11 new alkaloids. 10-hydroxy strychnine, 3-12-dihydroxystrychnine, 12-hydroxy–11- methoxy strychnine, 3-12-dihydroxy- 11-methoxy strychnine,12-hydroxy strychnine-N- oxide 12-hydroxy-11-methoxy strychnine- N-oxide-19,20–dihydro isostrychnine, 16 , 17 dihydro-17 -hydroxy isostrychnine, O- methyl-macusine B, 16-epi-o-methyl–macusine B and normelinone B (Baser and Bisset, 1982).

De and Datta (1988) isolated 5 tertiary indole alkaloids viz. strychnine, brucine, vomicine, icajine and novacine from S.nux-vomica flowers. Bisset et al (1989) isolated and identified two phenolic glycosides salidroside and cuchiloside – a compound consisting of salidroside and an attached xylose unit, from the fruit of S.nux-vomica.

Rodriguez et al (1979) isolated an indole alkaloid from the seeds of S. nux- vomica and identified as a 3-methoxy icajine. A new alkaloid 15-hydroxy strychnine has been isolated from the seeds and the structure of the alkaloid established by spectroscopic data (Galeffi et al, 1979). Cai et al (1990a) isolated 4 new alkaloids isobrucine, isobrucine N-oxide, isostrychnine N-oxide and 2 hydroxy–3-methoxy strychnine from the heat treated seeds of S. nuxvomica and the structure of the alkaloids were determined by 13 CNMR (Cai et al, 1994). Cai et al (1990 b) studied the changes in the alkaloid composition of the seeds during drug processing. Saily et al (1994) determined the mineral elements in Strychnos nux-vomica. Corsaro et al (1995) reported polysaccharides from the seeds of Strychnos species.

Seeger and Neumann (1986) reviewed the physico-chemical characteristics, occurrence, identification, utilisation, poisoning, toxicity, kinetics, differential diagnosis and therapeutic uses of strychnine and brucine. Aspergillus niger, A. flavus and Pencillium citrinum showed regular association with Strychnos seeds and effectively deteriorated the alkaloid content of the seeds (Dutta, 1988; Dutta and Roy, 1992). Nicholson (1993) described the history, structure and synthesis of strychnine which occur in the seeds of S. nux-vomica. Rawal and Michoud (1991) developed a general solution for the synthesis of 2- azabicyclo (3.3.1) nonane substructure of Strychnos alkaloids.

Villar et al (1984) and Hayakawa et al (1984) developed HPLC method for the analysis of strychnine and brucine. Graf and Wittliner (1985), Kostennikova (1986) and Gaitonde and Joshi (1986) suggested different methods for the assay of strychnine and brucine. Biala et al, (1996) developed new method for the assay of alkaloids in S. nux- vomica.

The seeds are bitter, acrid, alexeteric, aphrodisiac, appetiser, antiperiodic, anthelmintic, digestive, febrifuge, emmenagogue, purgative, spinal, respiratory and cardiac stimulant and stomachic. The bark is bitter, and tonic and febrifuge (Nadkarni, 1954; Kurup et al, 1979; Warrier et al, 1996).

The quarternery alkaloid from the root bark of the Sri Lankan plant exhibited muscle-relaxant activity (Baser and Bisset, 1982). Antimicrobial activity of indole alkaloid isolated from the Strychnos nux-vomica was studied by Verpoorte et al, 1983. Shukla et al (1985) evaluated the efficacy of Rasnadigugglu compound consisting of S. nux-vomica, on rheumatoid arthritis and found to be effective in reducing inflammatory oedoma and rheumatoid arthritis. It also exhibited analgesic activity. A compound Unani formulation containing S. nux-vomica significantly attenuated withdrawal intensity in morphine dependent rats (Zatar et al, 1991). Shahana et al (1994) studied the effect of Unani drug combination (UDC) having Strychnos nux-vomica on the abstinence syndrome in moderately and severely morphine dependent rats. The UDC strikingly suppressed the abstinence syndrome was seen to possess central depressant and analgesic action.

Melone et al (1992) reported brucine-lethality in mice. Panda and Panda (1993) and Satyanarayanan et al (1994) reported antigastric ulcer activity of nux vomica in Shay rats. Banerjee and Pal (1994) reported the medicinal plants used by the tribals of plain land in India for hair and scalp preparation and S. nux-vomica being used to cure alopecia (baldness) by the tribals. Tripathi and Chaurasia (1996) studied the effect of S. nux-vomica alcohol extract on lipid peroxidation in rat liver.... strychnine tree

An acute arbovirus (see ARBOVIRUSES) infection caused by a ?avivirus of the togavirus family, transmitted from animals to humans by various species of forest mosquito (jungle/sylvan yellow fever), and from human to human by Aëdes aegypti (urban yellow fever). Mosquito transmission was shown by Walter Reed and his colleagues in 1900. It is ENDEMIC in much of tropical Africa and Central and South America but does not occur in Asia. In the urban cycle, humans constitute the reservoir of infection, and in the jungle/sylvan variety, mammals – especially subhuman primates – are involved in transmission. Historically, yellow fever was enormously important, causing devastating epidemics (see EPIDEMIC); it also carried a high mortality rate in travellers and explorers. Differentiation from other infections associated with JAUNDICE was often impossible.

Clinically, yellow fever is characterised by jaundice, fever, chills, headache, gastrointestinal haemorrhage(s), and ALBUMINURIA. The incubation period is 3–6 (up to 10) days. Differentiation from viral hepatitides, other viral haemorrhagic fevers, severe Plasmodium falciparum malaria, and several other infections is often impossible without sophisticated investigative techniques. Infection carries a high mortality rate. Liver histology (biopsy is contraindicated due to the haemorrhagic diathesis) shows characteristic changes; a fulminating hepatic infection is often present. Acute in?ammation of the kidneys and an in?amed, congested gastric mucosa, often accompanied by haemorrhage, are also demonstrable; myocardial involvement often occurs. Diagnosis is primarily based on virological techniques; serological tests are also of value. Yellow fever should be suspected in any travellers from an endemic area.

Management consists of instituting techniques for acute hepatocellular (liver-cell) failure. The affected individual should be kept in an isolation unit, away from mosquitoes which could transmit the disease to a healthy individual. Formerly, laboratory infections were occasionally acquired from infected blood samples. Prophylactically, a satisfactory attenuated VACCINE (17D) has been available for around 60 years; this is given subcutaneously and provides an individual with excellent protection for ten years; international certi?cates are valid for this length of time. Every traveller to an endemic area should be immunised; this is mandatory for entry to countries where the infection is endemic.... yellow fever

chick embryos injected with the living, attenuated strain (17D) of pantropic virus. Only one injection is required, and immunity persists for many years. Re-inoculation, however, is desirable every ten years. (See YELLOW FEVER.)

Haemophilus vaccine (HiB) This vaccine was introduced in the UK in 1994 to deal with the annual incidence of about 1,500 cases and 100 deaths from haemophilus MENINGITIS, SEPTICAEMIA and EPIGLOTTITIS, mostly in pre-school children. It has been remarkably successful when given as part of the primary vaccination programme at two, three and four months of age – reducing the incidence by over 95 per cent. A few cases still occur, either due to other subgroups of the organism for which the vaccine is not designed, or because of inadequate response by the child, possibly related to interference from the newer forms of pertussis vaccine (see above) given at the same time.

Meningococcal C vaccine Used in the UK from 1998, this has dramatically reduced the incidence of meningitis and septicaemia due to this organism. Used as part of the primary programme in early infancy, it does not protect against other types of meningococci.

Varicella vaccine This vaccine, used to protect against varicella (CHICKENPOX) is used in a number of countries including the United States and Japan. It has not been introduced into the UK, largely because of concerns that use in infancy would result in an upsurge in cases in adult life, when the disease may be more severe.

Pneumococcal vaccine The pneumococcus is responsible for severe and sometimes fatal childhood diseases including meningitis and septicaemia, as well as PNEUMONIA and other respiratory infections. Vaccines are available but do not protect against all strains and are reserved for special situations – such as for patients without a SPLEEN or those who are immunode?cient.... yellow fever vaccine is prepared from