ZIEHL-NEELSEN STAINING
This method is a modification of Ehrlich’s (1882) original method for the differential staining of tubercle bacilli and other acid-fast bacilli with aniline gentian violet followed by strong nitric acid. It incorporates improvements suggested successively by Ziehl and Neelsen.
Principle:
The ordinary aniline dye solutions do not readily penetrate the substance of the tubercle bacilli and therefore unsuitable for staining it. However by the use of a powerful staining solution that contains phenol, and the application of heat, which act as a mordant and the dye can be made to penetrate the bacillus. Once stained the tubercle bacillus will withstand the action of powerful decolorizing agents for a considerable time and thus still retains the stain when everything else in the microscopic preparation has been decolorized.
Method:
- Make a smear on clean slide, dry and fix by flaming.
- Cover the slide with filtered basic carbol fuchsin.
- Heat the slide until steam rises, but without boiling. Allow the preparation to stain for 5 minutes, applying the heat at intervals to keep the stain hot. Do not allow the stain to dry on the slide, if necessary pour on more carbol fuchsin to cover it.
- Wash both sides of the slide with water from the tap.
- Cover the slide with 25 % sulphuric acid. The red color of preparation is changed to yellow brown. After 3 minute, wash the slide with water, and pour on fresh acid. Repeat this procedure for total 3 times. Decolorization generally requires contact with sulphuric acid for a total time of at least 10 minutes. When it is complete, the film, after washing is only very faintly pink.
- Wash the slide well with water to remove all traces of acid.
- Counterstain with Loeffler’s methylene blue for 15-20 seconds.
- Wash, blot with clean paper, dry and mount.
Result:

Acid-fast bacilli are stained bright red, while other organisms, tissue cells and debris are stained blue.
Acid Fastness:
- Acid fast bacteria are rich in lipids, fatty acids & higher alcohol. Acid fastness is mainly due to the presence of unsaponifiable wax of the nature of hydroxyl acid known as mycolic acid.
- Acid fastness is also depends on the structural integrity of the cell because when the cell is ruptured by mechanical means or autolysis, its acid fastness is lost.
- Acid fastness is lost due to exposure to INH-drug.
Variations:

- ZN staining for M. leprae: M. leprae is less acid-fast than M. tuberculosis. In this modification for M. leprae procedure is same except 5% sulphuric acid is used as a decolorizer instead of 25 % used in Z-N stain for M. tuberculosis.
- Kinyoun stain(cold staining): This modification of Z-N stain is used for staining of parasitic cysts from stool specimens e.g. Cryptosporidium and Cylclospora. Here heat is not applied while 0.5 – 1% sulphuric acid is used.
Examples:
Acid-fast Organisms:
- Mycobacterium tuberculosis
- Mycobacterium leprae
- Atypical mycobacteria
- Nocardia
- Spores of certain parasites. Like:
- Cryptosporidium,
- Cyclospora,
- Isospora
Sputum Grading: (RNTCP)
Bacilli | Result | Grading | No. of fields examined |
> 10 AFB / OIF | Positive | 3+ | 20 |
1-10 AFB / OIF | Positive | 2+ | 50 |
10-99 AFB / OIF | Positive | 1+ | 100 |
1-9 AFB / OIF | Scanty | Record actual number | 100 |
No AFB / OIF | Negative | 0 | 100 |
OIF = Oil Immersion Field