# Presentation: 537364

## AFB-MICROSCOPY FOR TB DIAGNOSIS

**Main values**
**speed**
**extremely high specificity**
** ****Main disadvantage**
**relative insensitivity**
** ****Highly accurate diagnoses**
**made by paramedical personnel**
**using simple and available equipment**

## AFB-MICROSCOPY: SPECIFICITY

**Over 99% for AFB**

## SPECIFICITY OF AFB+ SMEARS FOR TB

_**REFERENCE / COUNTRY         HIV+     AFB PATHOGENS, NOT TB**_
**Long, Haiti, 1991****	****      ****	****26%****	****	****4/199 patients**
**	****	****	****	****	****	****	****	****(2/2 HIV+/-)**
**Githui, Kenya, 1992****	****	****33%****	****	****0/320 patients**
**Warndorff, **
**	****Malawi, 1997****	****     ****	****	****>50%?****	****	****2/904 patients**
**	****	****	****	****	****	****	****	****(1/1 HIV+/-)**
**Van Deun, **
**	****Bangladesh, 2001  ****	**** ****	****<1%****	****	****3/1065 patients**

## AFB-MICROSCOPY: SPECIFICITY

**Over 99% for AFB**
**from re-checking**
**(few percent of smear+ / culture-)**
**two positives needed to confirm a case ?**
**with good quality control: < 1% not confirmed**
**IUATLD/WHO threshold to declare positive **
**1 AFB per 10 fields :  ?**
**comparison with culture**
**	****early studies India, Algeria: 3-4/100**
**	****Kubica: 1/100**
**confirmation by further smears**

## Slide 5

## AFB-MICROSCOPY: SENSITIVITY

**2-3 smears = sensitivity of 1 culture**
**Over 95% of infectious cases**
**priority for treatment**
**control of the disease**
**individual  prognosis**
**big majority in highly endemic countries**
**passive detection **
**late presentation**

## Slide 7

## OVERALL SMEAR/CULTURE POSITIVITY RATE
Reference / country                                                            % smear+ out of cult.+  
Boyd and Marr, USA 1975					22 %
Marraro et al., USA 1975					24 %
Rickmann and Moyer, USA 1980				25 %
Urbanczik, Germany					37 %
Burdash et al., USA 1976					43 %
Pollock and Wieman, USA 1977				50 %
MRC, England/Wales 1992					53 %
Kubica, Africa/Europe 1980			53 % (Ziehl Neelsen)
		  , USA/Asia				63 % (fluorescence)
Petersen, Germany					54 %
Blair et al., USA 1976					62 %
Levy et al., S.Africa 1989				66 % (serial sputum)
							54 % (first sputum)
Joseph et al., Indonesia 1976			68 % (fluorescence)
Alausa et al., Nigeria 1977					77 %
Neher et al., Nepal 1997				80 % (3 smears)				(after Urbanczik 1985)
.

_**Reference / country                                                            % smear+ out of cult.+**_**  **
**Boyd and Marr, USA 1975****	****	****	****	****	****22 %**
**Marraro et al., USA 1975****	****	****	****	****	****24 %**
**Rickmann and Moyer, USA 1980****	****	****	****	****25 %**
**Urbanczik, Germany****	****	****	****	****	****37 %**
**Burdash et al., USA 1976****	****	****	****	****	****43 %**
**Pollock and Wieman, USA 1977****	****	****	****	****50 %**
**MRC, England/Wales 1992****	****	****	****	****	****53 %**
**Kubica, Africa/Europe 1980****	****	****	****53 % (Ziehl Neelsen)**
**	****	****  ****, USA/Asia****	****	****	****	****63 % (fluorescence)**
**Petersen, Germany****	****	****	****	****	****54 %**
**Blair et al., USA 1976****	****	****	****	****	****62 %**
**Levy et al., S.Africa 1989****	****	****	****	****66 % (serial sputum)**
**	****	****	****	****	****	****	****54 % (first sputum)**
**Joseph et al., Indonesia 1976****	****	****	****68 % (fluorescence)**
**Alausa et al., Nigeria 1977****	****	****	****	****	****77 %**
**Neher et al., Nepal 1997****	****	****	****	****80 % (3 smears)****	**_**	**__**	**_**	****(after Urbanczik 1985)**
- .

## Slide 9

## AFB-MICROSCOPY: SENSITIVITY

**Slightly less in HIV-positives**
**depends on degree of immune-depression**
**also cultures less often positive**
**requires more efforts**
**value of concentration techniques ?**

## RATE OF TB CULTURE+ PATIENTS FOUND SMEAR+
REFERENCE/COUNTRY      TECHNIQUE                    ALL        HIV-        HIV+	
Klein,USA 1989             3-4 sputa, concentr., Kinyoun		81%	45% 
			              	same, first sputum			61%	29%
Long, Haiti 1991	        2-3 morning				79%	66%
Githui, Kenya 1992       3 sputa, fluorescence			89%	89%
Githui, Kenya 1993       ZN staining			65%
			        fluorescence			80%
Elliot, Zambia 1993      3 sputa?, direct, fluor.			76%	57%
Yajko, USA 1994	        1 sputum, concentr., fluor.		55%	55%
Smith, USA 1994	        3 sputa, concentr., fluor.		60%	57%
Allwood, Malawi 1997  1 smear, ZN, direct		43%
Finch, USA 1997	        many sputa, fluor.			71%	70%
			        first sputum				64%	55%
Johnson, Uganda 1998					98%	96%
Karstaedt, S. Africa 1998					79%	68%		

_**REFERENCE/COUNTRY      TECHNIQUE                    ALL        HIV-        HIV+**__**	**_
**Klein,USA 1989             3-4 sputa, concentr., Kinyoun****	****	****81%****	****45% **
**	****	****	****              ****	****same, first sputum****	****	****	****61%****	****29%**
**Long, Haiti 1991****	****        2-3 morning****	****	****	****	****79%****	****66%**
**Githui, Kenya 1992       3 sputa, fluorescence****	****	****	****89%****	****89%**
**Githui, Kenya 1993       ZN staining****	****	****	****65%**
**	****	****	****        ****fluorescence****	****	****	****80%**
**Elliot, Zambia 1993      3 sputa?, direct, fluor.****	****	****	****76%****	****57%**
**Yajko, USA 1994****	****        1 sputum, concentr., fluor.****	****	****55%****	****55%**
**Smith, USA 1994****	****        3 sputa, concentr., fluor.****	****	****60%****	****57%**
**Allwood, Malawi 1997  1 smear, ZN, direct****	****	****43%**
**Finch, USA 1997****	****        many sputa, fluor.****	****	****	****71%****	****70%**
**	****	****	****        ****first sputum****	****	****	****	****64%****	****55%**
**Johnson, Uganda 1998****	****	****	****	****	****98%****	****96%**
**Karstaedt, S. Africa 1998****	****	****	****	****	****79%****	****68%****	**_**	**_

## AFB-MICROSCOPY: SENSITIVITY

**Highly dependent on technical factors**
**quality of smear, staining**
**quality and number of sputa**
**morning sputum 10-100% more positives**
**3 sputa, spot-morning-spot?**

## OPTIMAL SPUTUM SAMPLING STRATEGY

**Spot-morning-spot: compromise proposed in a non-integrated setting ****(Andrews & Radhakrishna)**
**Evidence : third sample is not efficient**
**early studies Bangalore NTI..: third smear 3%**
**NTP reports: China, Tanzania 2.5%, Malawi 4%**
**own study in HIV-free population**
**3 morning sputa:  only 1 % increment with third**

##  YIELD OF THREE SPUTUM SMEARS: % SM+

**REFERENCE/** **	****	****	****	****% POSITIVE ****	****INCREMENT ON**
**COUNTRY ****	****	****TECHNIQUE ****	****   ON FIRST ****	****SECOND    THIRD**
**______________________________________________________________________**
** ****Andrews, India 1959****	****spot-morning-spot****	****79%****	****    18% ****	****         3%**
** ****Blair, USA 1973****	****	****	****	****	****81%****	****    10%****	****         9%**
** ****Nelson, USA 1998****	****fluorescence, conc.****	****77%****	****    15%****	****         8%**
** ****Urbanczik 1985****	****	****	****	****            80-82%****	****  10-14%       5-8% **
** ****Ipuge, Tanzania 1996****	****3 morning****	****	****88%****	****     9%****	****         3%**
** ****Harries, Malawi 1996****	****spot-morning-spot****	****83%****	****    13%****	****         4%**
** ****Finch, USA 1997****	****fluorescence, HIV-****	****89%****	****    10%****	****         1%**
** ****	****	****	****fluorescence, HIV+****	****79%****	****    21%****	****           -**
** ****Salim, Bangladesh 1998 ****	****spot-morning-spot****	****85%****	****    14%****	****         1%**
** ****Van Deun, Bdesh 2002 ****	****morning- morning ****	****95%****	****     4%****	****         1%****	****	****	****- morning ______________________________________________________________________**

## AFB-MICROSCOPY: SENSITIVITY

**Highly dependent on technical factors**
**quality of microscopic reading**
**instrument, light**
**effort: ****	****number of fields examined**

## Slide 16

## AFB-MICROSCOPY FOR FOLLOW-UP OF TREATMENT

**Technically more difficult**
**low numbers**
**more difficult to stain**

## POSITIVITY RATES IN AFB FOLLOW-UP 

**POSITIVITY RATES IN AFB FOLLOW-UP **

**EXAMINATIONS, KINSHASA 2000**

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**% POSITIVE FOLLOW-UP SPUTUM SMEARS**

**NUMBER OF CENTRES**

**POOR MICROSCOPES**

**POOR QUALITY CONTROL**

## POSITIVITY RATES IN AFB FOLLOW-UP 

**POSITIVITY RATES IN AFB FOLLOW-UP **

**EXAMINATIONS, DF BANGLADESH 1999**

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**% POSITIVE FOLLOW-UP SPUTUM SMEARS**

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**REGULAR EFFICIENT QUALITY ASSURANCE**

## AFB-MICROSCOPY FOR FOLLOW-UP OF TREATMENT(2) 

**End of first phase smear & prolongation**
**evidence ? **
**same cut-off ?**
**influence of type of standard treatment regimen ?**

## PROLONGATION STUDY USING 2EHRZ/6HT

**All differences highly significant**
**	****	****	****	****	****Failed (%)****	****Recurr. 12M(%)**
**	****2M smear-neg.****	****	****126 (0.9%)****	****    247 (1.8%)**
**	****	****(n=13,747)**
**	****2M sm+ prolonged****	****  25 (2.0%)****	****      10 (0.8%)**
**	****	****(n=1252)**
**	****2M****	****non-prolonged****	****  50 (4.4%)****	****      34 (3.0%)**
**	****	****(n=1125)**
** ****Damien Foundation Bangladesh****, ****unpublished data**

## Slide 22

## Slide 23

## AFB-MICROSCOPY FOR FOLLOW-UP OF TREATMENT(2) 

**End of first phase smear & prolongation**
**extent of the disease at start !**

## Slide 25

## AFB-MICROSCOPY FOR FOLLOW-UP OF TREATMENT(2) 

**End of first phase smear & prolongation**
**drug resistance ?**

## Slide 27

## Slide 28

## AFB-MICROSCOPY FOR FOLLOW-UP OF TREATMENT (3)

**Declaration of failure**
**over-diagnosis of failure ?**
**aspecificity of smear for viable AFB**
**differential conversion smear vs. culture**

## Slide 30