# Presentation: 138341

## DIAGNOSTIC MICROBIOLOGY LAB METHODS FOR TB

**Still mainly the old proven methods**
**even in rich countries**
**many newer techniques**
**serious shortcomings**
**or not well evaluated**
**choice depends not only on costs**
**speed**
**sensitivity, specificity**
**appropriateness**

## Slide 2

## INFLUENCE OF PREVALENCE ON TEST PERFORMANCE

**50%**

**0.01%**

**Spec.:**

**99%**

**Spec.:**

**99%**

**Sens.:**

**70%**

**Sens.:**

**70%**

**+**

**-**

**Total**

**+**

**-**

**Total**

**+**

- 3500

- 50

- 3550

**+**

- 1

- 100

- 101

**-**

- 1500

- 4950

- 6450

**-**

- 0

- 9899

- 9899

**Total**

- 5000

- 5000

- 10000

**Total**

- 1

- 9999

- 10000

**NPV**

**76.7%**

**NPV**

**100.0%**

**PPV**

**98.6%**

**PPV**

**0.7%**

**Elisa **

**result**

**Elisa **

**result**

**HIV+**

**HIV+**

**Example: HIV-Elisa**

**East African TB patients: **

**Prevalence of positives=**

**Blood donors in Europe: **

**Prevalence of positives=**

## DIAGNOSTIC METHODS FOR PTB RELATED TO NUMBERS OF 

**DIAGNOSTIC METHODS FOR PTB RELATED TO NUMBERS OF **

**BACILLI PRESENT**

**0**

**1**

**10**

**100**

**1000**

**10,000**

**100,000**

**1,000,000**

**AFB per ml of sputum**

**Frequency**

**X-Ray and clinical (15%)**

**Poor microscopy (30%)**

**Excellent microscopy (65%)**

**Culture, PCR (85%)**

## Review of main techniques

**Culture**
**more sensitive, but relative**
**low income countries : only 25% gain over smear ?**
**and in these settings less specific ?**
**main problem: DELAYS**
**on classical media (Lowenstein-Jensen....)**
**newer commercial media (BACTEC..)**
**	****	****faster (about 10 days)**
**	****	****but expensive++, technical demands**
**mostly self-healing cases**
**not useful for control in high prevalence**
**first step for susceptibility testing**

## Slide 6

## Slide 7

## Review of main techniques (2)

**Genetic tests, type PCR**
**main advantages: speed + sensitivity**
**sensitivity : **
**in principle able to pick up 1 TB bacillus**
**in practice : less sensitive than culture**
**specificity problem : precautions ++**
**infrastructure lab**
**meticulous technique; commercial systems**
**expensive +++**

## Slide 9

## PCR utility in practice

**Barcelona, 5 years routine experience**
**IJTLD 2003; 7: 886-91.**
**MTDT Genprobe (best commercial test)**
**specificity almost 100% (gold standard: culture + clinical/history)**
**PTB**
**total 260 cu+ against 238 MTDT+**
**sensitivity in sm+/cu+ :****	****	****99%**
**sensitivity in sm-/cu+ : ****	****	****69%**
**EP**
**total 73 cu+ against 56 MTDT+**
**sensitivity in sm+/cu+ : ****	****	****94%**
**sensitivity in sm-/cu+ : ****	****	****52%**

## Review of main techniques (3)

**Chromatography**
**gas-liquid (GLC), high-performance liquid (HPLC)**
**for tuberculostearic acid, mycolic acids **
**sensitive, specific, rapid**
**very expensive equipment, not available**

## Review of main techniques (4)

**Serology on antigens, antibodies...**
**rapid, simple, cheap**
**many tests described since the time of Koch**
**new technology, still no perfect Ag / Ab**
**the perfect antigen??**
**variable antibody response**

## Slide 13

## Review of main techniques (5)

**Serology on antigens, antibodies...**
**ELISA best, but equipment not always there**
**high sens.+spec. only with special techniques**
**too complicated for routine**
**best results: in smear-positives!**
**sm-, EPTB, children: none of proved value**
**often too much aspecific**
**e.g. at 95% specificity > 50% false pos.!!**
**avoid, mistrust publicity**
**at this moment not approved for sm- / EPTB**

## Slide 15

## Slide 16

## OTHER DIAGNOSTIC METHODS

**All less reliable and/or useful**
**Clinical examination**
**no specific signs**
**useful to exclude complications**
**ESR, WBC (total, differential count)**
**ESR highly aspecific**
**WBC : variable ++**

## OTHER DIAGNOSTIC METHODS (2)

**Tuberculin test (Mantoux)**
**demonstrates allergy**
**interpretation in high-prevalence ??**
**immune-competent adults: exclude diagnosis**
**EP, children : can be positive diagnostic element**
**false positive, false negative reactions**

## OTHER DIAGNOSTIC METHODS (2)

**Chest X-Ray**
**easy, rapid, clean**
**preferred by physicians **
**	****	****	****THEIR tool**
**sensitivity about 50% more than smear, but**
**not all cases (HIV !!); not all sm+ !!**
**non-priority cases**
**technical requirements : quality pictures ??**
**expertise requirements : quality readers ??**

## OTHER DIAGNOSTIC METHODS (3)

**Chest X-Ray continued**
**no typical image of TB exists : aspecific ++**
**in practice 50% over-diagnosis ?**
**especially old, cured TB : relapse diagnosis on X-Ray ??**
**useless for follow-up**

## PLACE OF DST IN TB CONTROL

**Epidemiological & NTP monitoring**
**random surveys**
**H, R, E, S**
**baseline levels, later evolution**
**requirements for reliable surveillance !!**
**Individual patient management: rarely needed**
**well chosen standard regimens +/- 100% effective**
**rarely amplification of resistance with safe regimens**
**clinical, smear evolution**

## PLACE OF DST IN TB CONTROL (2)

**Individual management: potentially dangerous**
**mistakes: technical errors**
**significance of resistance, i.e. to E, T, low H ??**
**results too late, may be no longer valid**
**MDR-treatment in low-income countries: **
**	****	****standardised indications and regimen**