1. Tuberculosis Case Study Presenter Xoliswa Poswa TB Laboratory, NHLS/CMID

2. Case History 47 year old man Presents to the clinic with a 4 weeks history of cough He noticed a tinge of blood in his sputum He has lost weight and is also sweating a lot at night The nurse suspected tuberculosis and asked him to spit into a specimen bottle A diagnosis of TB is confirmed by the laboratory using smear microscopy

3. Microbiological Characteristics Microscopic examination of a smear of sputum stained by Ziehl-Neelsen’s method or by auramine shows – acid fast bacilli – may be straight or slightly curved Acid fast – unique characteristic of mycobacteria cell wall due to cell wall constituents –lipid content is very high –hydrophobic –impermeable to basic aneline bacteriological stains –major determinant of virulance

4. Microbiological Characteristics Lipid fraction of M. tuberculosis cell wall has 3 major components Mycolic acid, a unique lipid found in cell wall of MTB –strong hydrophobic molecules forming lipid shell around the cell thus affecting permeability –significant determinant of virulance for MTB i.e prevent attack of mycobacteria by components of immune system (cationic proteins, lysozymes and oxygen radicals in the phagocytic granules

5. Microbiological Characteristics Cord factor –responsible for serpentine cording –it is toxic to human cells, prevents migration of certain immune cells i.e polymorphonuclear cells –produced abundantly in virulent strains Wax-D –cell wall envelope

6. Microbiological Characteristics In summary the high concentration of lipids is associated with the following properties of bacterium: –Impermeability to stains and dyes –Resistance to many antibiotics –Resistance to killing by acidic or alkaline compounds –Resistance to osmotic lysis by complement component of immune system –Resistance to lethal oxidation and survival within macrophages

7. Case cont: The patient was questioned further: –He shared accommodation with his late nephew who had been coughing for the past few months –He now looks after his nephew’s 4 year old daughter who came to stay with them 2 weeks ago

8. Pathogenesis of disease

9. Condition for developing infection: Exposure –Frequency –Duration –Concentration of bacilli –Virulence Host immunity –Extremes of age i.e very young/old –Malnutrition –Alcoholism –HIV/AIDS –Drugs that depress immunity e.g corticosteroids

10. Management Diagnosis –Microscopy of sputum smear –Cultivation of sputum (for growth of mycobacteria) Drug treatment –The patient was given treatment, a combination of 4 drugs which he had to take under supervision for 6 months –Rationale for combination therapy: The various drugs target different forms of bacilli i.e. rapidly growing and dormant forms Prevent development of resistance Prevent development of relapse of disease due to dormant bacilli

11. Management Prevention: –he was told to bring the child to clinic to screen for tuberculosis –screening included intradermal injection with a mixture of proteins derived from MTB (skin test) Induration at injection site occurs within 48-72 hours in a sensitized person (exposed to MTB) –his wife was also educated on the signs and symptoms of TB and to report to clinic should she develop any one of them

12. Management –the skin test was negative and the child was otherwise well with no signs suggestive of active disease/she had BCG vaccination at birth –nurse elected to give prophylactic treatment with one anti-TB drug for 6 months

13. Management –Rationale for screening: Children under 5 years of age who are exposed to MTB are more likely to progress to disease following infection –Rationale for prophylaxis: prevent development of disease after exposure in a young child at risk single drug can be used as there are potentially very few bacilli in the absence of active disease and development of resistance unlikely

14. Management Summary: Treatment –4 drug combination for 6 months under supervision Immune prophylaxis –vaccination with BCG (bacille Calmette-Guerin) vaccine at birth –this does not prevent infection but allows body to react quickly to limit replication of mycobacteria Chemoprophylaxis –with a single anti-TB drug (isoniazid)