1. Misdiagnosed pulmonary Tuberculosis
Zhanna Laushkina, MD, PhD
Novosibirsk TB Research Institute
Novosibirsk, Russia

2. Novosibirsk Tuberculosis Research Institute2

3. Supervision zone of NTRI
2/3 territory of Russia
near 17% population 3

4. Novosibirsk TB Research Institute
Strong governmental mandate for TB Control
Certified to educate in Health Care issues
Official feed-back and monitoring
Ability to initiate changes in official TB Control regulations, based on scientific analysis and results and approval 4

5. NTRI Quality control service Clinical departments
Scientific department
Laboratory service
NCE 2015 for WHO SRLN Network
NTRI-WHO CC RUS-123
Therapeutic department for drug sensitive TB
Scientific and organizing sector
Bacteriological laboratory
Quality control service
Therapeutic department for drug resistance TB
laboratory and experimental sector
Clinical diagnostic laboratory
Surgical department
Clinical studies
Molecular Genetic laboratory
Extra pulmonary TB department
Diagnostic departments

6. Areas of research activity
Epidemiological TB monitoring in Siberian and Far East Federal Districts
Development of new approaches and TB management mechanisms in Siberian and Far East Federal Districts
Diagnostic and treatment methods improvement
Differential diagnosis of pulmonary tuberculosis
Improvement of surgical treatment for patients with pulmonary and extrapulmonary TB

7. The proportion of patients from supervised regions and Novosibirsk region in 2016 (%)

8. Complex anti-TB therapy for patients with TB (1)
Inhalation with anti-TB drugs,
bronchodilators, mucolytics
Physiotherapy

9. Complex anti-TB therapy for patients with TB (2)
Treatment of comorbidities
Early rehabilitation
(anti-stress neurophysiological
correction)

10. Complex anti-TB therapy for patients with TB (3)
Sanatorium treatment

11. TB incidence (per 100 000 of population)

12. Purpose of the study To analyze causes of diagnostic errors
and improve the quality of in-hospital
management for patients supposed
to have pulmonary TB

13. Research object Medical records of 230 most difficult diagnostic cases
Previously
established diagnosis
of pulmonary TB
was rejected
Noncomparative
retrospective study
OR and 95% CI
were presented 13 13

14. Clinical and laboratory
Methods
Clinical and laboratory
analysis
Analysis of
medical
history
Physical
examination
Laboratory
methods
Instrumental
methods of
Endoscopy
X-ray
CBC, urinalysis,
blood chemistry,
Microscopy, Culture,
etc.
Respiratory
function
Biopsy 14 14

15. Structure of clinical cases
Misdiagnosed pulmonary TB
n = 230
Communitн-acquired
pneumonia
Lung
cancer
(24 %)
Sarcoidosis
(15 %)
COPD
(5 %)
(46 %)
Other diseases
(10 %)

16. Comorbidity and bad habits
COPD 13 %
Gastrointestinal diseases – 24 %
Cardiovascular diseases – 14 %
Viral hepatitis B or C – 8 %
Diabetes – 3 %
Other diseases – 19 %
Alcohol addiction – 7 %
Drug addiction – 3 %
Smoking – 60 %

17. Lung cancer (1) Males 65 %, average age 55 ± 14 yrs.
The period between the disease manifestation and correct hospital diagnosis was 106±68 days, between first symptoms and seeking medical care - 25±30 days.
39% of patients were previously treated against assumed pneumonia before to the TB hospital.
All patients admitted to the hospital with wrong diagnosis "pulmonary TB", a principal cause was misinterpretation of chest X-ray results.
48% of patients have been receiving anti-TB treatment before a correct diagnosis was made.

18. Lung cancer (2) Negative association with diagnosis of lung cancer :
acute disease beginning,
fever,
absence of hematological changes,
growth of nonspecific microflora in sputum.
Positive association with diagnosis lung cancer:
age old,
low body weight,
lost of appetite,
dyspnea,
leukocytosis,
ESR acceleration,
lymphopenia,
rounded opacities on chest X-ray,
pleural effusion,
presence of atypical cells in sputum,

19. Clinical case (1) Patient B, 46 years old, unemployed Complaints:
cough, dyspnea, weakness, loss of appetite, chest pain, weight loss
3 weeks of anti-TB treatment before admission
to the NTRI
At admission to NTRI:
In CBC leukocytosis, lymphopenia, accelerated ESR, thrombocytosis anemia
AFB in sputum
not detected
Chest X-ray
widespread, bilateral lesion of lung tissue
Atypical cells in sputum
After endoscopy:
Cancer of stomach

20. Chest X-ray (widespread-metastatic cancer)

21. Community-acquired pneumonia (1)
Males 62%, average age was 47 ± 17 yrs.
Absence of laboratory inflammatory hematological disturbances - 29% of cases.
Absence of auscultative lungs changes - 61% of patients.
Process was localized in I and/or II segments - 77%, in VI segment - 13%.
Destructive cavities on chest X-ray – 19% of cases.
Only from 31% of patients growth of nonspecific microflora in sputum was identified
In 7% of all cases a few acid-fast bacilli were found in sputum by luminescent microscopy (that we suppose as false-positive result).

22. Community-acquired pneumonia (2)
Negative association with diagnosis pneumonia
Positive association with diagnosis pneumonia
Absence of symptoms (OR 0.31, 95% CI ),
Absence of auscultative lungs changes (0.53, 95% CI ),
Low body weight (OR 0.54, 95% CI ),
Destructive cavities on chest X-ray (OR 0.38, 95% CI 0.22— 0.66),
Detection of AFB (OR 0.22, 95% CI ).
Male sex (OR 1.63, 95% CI )
Alcoholism (OR 2.63, 95% CI )
Acute disease beginning (OR 4.46, 95% CI )
Fever (OR 2.84, 95% CI )
Cough (OR 1.74, 95% CI )
Limited changes on chest X- ray (OR 2.17, 95% CI )
Growth of nonspecific microflora in sputum (OR 3.24, 95% CI )

23. Sarcoidosis (1) Males 37 %, average age was 44.6 ± 11.8 yrs.
The period between the disease manifestation and correct final diagnosis was 167.7± (mean±SD) days.
26 % of patients were previously treated against assumed pneumonia before admittion to the TB hospital.
54 % of patients have been receiving anti-TB treatment before a correct diagnosis was made (120.7±99.4 days).
All patients have been hospitalized with wrong diagnosis “pulmonary TB”.
In 6 % of all cases a few acid-fast bacilli were found in sputum by luminescent microscopy.

24. Sarcoidosis (2) Urban residents (OR 2.58, 95% CI 1.04-6.38),
Positive association with diagnosis sarcoidosis:
Urban residents (OR 2.58, 95% CI ),
Office workers (OR 4.24, 95% CI ),
No complaints (OR 3.42, 95% CI ),
Normal parameters of CBC (OR 2.29, 95% CI ),
Dissemination on chest X-ray (OR 77.63, 95% CI ),
Enlarged intrathoracic lymph nodes (OR 18.6, 95% CI ).
нОмал

25. Sarcoidosis (3) Negative association with diagnosis sarcoidosis:
male sex (OR 0.32, 95% CI ),
poorness (OR 0.18, 95% CI ),
acute disease beginning (OR 0.24, 95% CI ),
low body weight (OR 0.10, 95% CI ),
fever (OR 0.23, 95% CI ),
weakness (OR 0.43, 95% CI ),
productive cough (OR 0.34, 95% CI ),
infiltrative changes on chest X-ray (OR 0.02, 95% CI ),
destructive cavities on chest X-ray (OR 0.05, 95% CI ),
detection of AFB (OR 0.22, 95% CI ).

26. Clinical case (2) Patient D, 30 years old, cook
Complaints: did not have
Patient D, 30 years old, cook
MTB +
(by fluorescence microscopy)
before admission
to the NTRI
2 months
anti-TB treatment before admission
to the NTRI
On admission to NTRI:
In CBC:
normal levels
AFB in sputum
not detected
CT scan:
Widespread bilateral lesion in lung tissue, cavities, enlarged lymph nodes of the bifurcation group
for 3 months received anti-TB treatment
VATS biopsy: sarcoidosis
Without effect

27. CT scan on admission

28. Biopsy result
Sarcoid type granulomas surrounded by mature fibrosis in the lung tissue
Sarcoid granulomas and mature fibrosis in the lymph node

29. COPD Negative association with diagnosis COPD:
Males 83.3 %, average age was 54,1 ± 10,8 yrs.
Negative association with diagnosis COPD:
Age less than 30 years (OR 0.13, 95% CI )
Villagers (OR 0.11, 95% CI )
Positive association with diagnosis COPD:
Age over 45 years old (OR 5.78, 95% CI )
Smoking (OR 1.74, 95% CI )
Cough (OR 16.9, 95% CI )
Dyspnea (OR 4.98, 95% CI )
Growth of nonspecific microflora in sputum (OR 3.24, 95% CI )
Wheezing with auscultation (OR 10.4, 95% CI )
Pneumosclerosis on chest X-ray (OR 8.78, 95% CI )
Normal X-ray (OR 25.79, 95% CI )

30. On admission to NTRI:
Liquid culture (Вастес 960) - M. fortuitum; GeneXpert + R resistance.
In CBC: normal levels.
Spirography- the vital capacity of the lungs is significantly reduced, marked by a sharp violation of bronchial patency. The ventilation capacity of the lungs is sharply reduced.
Clinical case (3)
Patient B, 39 years old,
Unemployed. In 2013 COPD was diagnosed.
Pulmonary tuberculosis was diagnosed in 2013 in prison. Antituberculous treatment until 2015.
In September 2016 AFB were found in sputum by luminescent microscopy. In culture was growth of M. fortuitum.
Patient was sent to NTRI.
The patient had a combination of pulmonary tuberculosis, mycobacteriosis and COPD.

31. CT scan on admission

32. CT scan after 2 months

33. M. fortuitum in the smear, by Ziehl-Nielsen mycroscopy

34. Growth of M. fortuitum colonies on the Levenstein-Jensen medium

35. Predictors misdiagnosis of tuberculosis
Socio-demographic predictors
Predictors misdiagnosis of tuberculosis
Clinical predictors
Laboratory predictors
Radiological predictors

36. Factors found to be associated with false-positive TB diagnosis in all patients
detection of AFB in sputum (OR 55.7, 95% CI )
destructive cavities on chest X-ray (OR 0.38, 95% CI 0.22—0.66)
nonspecific inflammatory findings detected by flexible bronchoscopy (OR 2.7, 95% CI ),
low body weight (OR 9.4, 95% CI )
age more than 40 years (OR 1.8, 95% CI ( )).

37. Conclusion
Several reasons for misdiagnosis of tuberculosis were found, but the main reason was misinterpretation of chest X-ray.
It is important to consider low sensitivity of chest X-ray.
Other important reasons for misdiagnosis: non-typical symptoms, false-positive detection of AFB in sputum, comorbidity, similarity of clinical and radiological symptoms for some of lung diseases.
Often diagnosis requires histological confirmation.
Due to high incidence of tuberculosis in our country there is a tendency to over diagnose of tuberculosis.
The results would allow to optimize the diagnostic approaches to such patients.

38. Thank you!