DIPHTHERIA

DIPHTHERIA-

• it is caused by gram (+)ve corynebacterium diphtheria. Naturally, it is pathogenic only to humans. It colonizes the nasopharyngel  tract and lives in the superficial layers of respiratory mucosa.
• it is spread between humans by respiratory droplets.
• There is little tissue damage and mild inflammatory reactions due to growth of the organism. It's virulence is mainly due to it's exotoxin.
• The toxin causes destruction of the underlying tissue and this results in the formation of a tough fibrous membrane  comprised of WBC, fibrin and dead epithelial cells of the respiratory  system.
• This membrane is very suffocating.

Besides,exotoxin is also responsible for systemic manifestations like ;
1)myocardial damage which results in congestive heart failure; and
2)neurologic damage resulting in muscle weakness or paralysis.

The exotoxin is encoded by Tox gene of phage B; so only those strains that carry the lysogenic phage beta are able to produce toxin.

The toxin consists of :
1)A binding chain
2)A toxin chain

• The binding chain helps the bacteria to bind to the ganglioside receptors present on the host cell and thus in internalization of exotoxin.
• Toxicity results from inhibitory effect of the toxin chain on protein synthesis.
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• The diptheria toxin is very potent as only it's single molecule can kill the cell.

Diptheria toxoid:

• The diptheria toxoid is prepared by treating the toxin with formaldehyde. This binding leads to irreversible loss in the toxicity of toxin but it's antigenicity is retained.
• The toxoid is administered as DPT vaccine to 6-8 weeks old kids. Immunizations with toxoid results in the production of anti-toxin.
• Because, anti-toxin levels decline slowly overtime. So,booster doses are given every 10 years to maintain antitoxin level within protective range.

TUBERCULOSIS :

• Although many mycobacterium species can cause tuberculosis ;but Mycobacterium Tuberculosis is the principal causative agent.
• It is spread thtough respiratory secretions.
• The inhaled bacteria gets in to alveoli of lungs; and are ingested by alveolar macrophages ;  in the macrophage,  they are able to survive and multiply intracellularly by inhibiting the formation of phagolysosome.
• When the infected macrophage lyse; then large number of  bacilli are released. This leads to activation of CD4+ cells and a large number of macrophages are infiltrated to the site of infection.
• The activated macrophages wall off the organism inside a granulomatous lesion called tubercle.

Role of cytokines :

• CD4+ T cells produce cytokines such as IL-12 and IFN-gamma. IL-12 stimulate the production of T-helper  (1) cells and also induces the production of chemokines to attract macrophages to the site of infection.  When IL-12 is blocked by anti-IL12; then granuloma formation is blocked. Similarly,  mice vaccinated with BCG vacvine dies when IFN-gamma was not present and survived in it's presence.

Treatment :

• Tuberculosis is treated using several drugs in combination like rifampin,streptomysin,iisoniazid etc.
• The combination therapy of rifampin and isoniazid has been very effective. But, the intracellular growth of the bacteria make it difficult for the drug to reach them. And so, drug therapy must be continued for atleast 9 months to eliminate the bacteria.
• DOT ensures compliance with the lengthy drug regimen.
• Only vacvine for tuberculosis is an attenuated strain of M.bovis called BCG (bacilli calmette guerin). The vaccine has proved effective agaun8chtonic pulmonary tuberculosis;  but has been consistent against pulmonary tuberculosis.
• In different studies ,BCG has been gound to be 0 to 80% effective in the vaccinated individuals. In many cases, it has even increased the risk of infection.