Clinical Significance of Erythrocyte Sedimentation Rate in Tuberculosis

 

Sonti Sulochana, Gayathri, Jalvadi Rahul Siddartha, Jennifer fathima

1Professor of Pathology, Saveetha Medical College, Thandalam, Chennai , Tamilnadu.

2,4AHS MLT, Saveetha Medical College, Thandalam, Chennai , Tamilnadu.

3Stanley Medical College, Chennai, Tamilnadu.

*Corresponding Author E-mail: sulochanamaster@gmail.com, gayathrijo1999@gmail.com, rahul.siddhu03@gmail.com, jfatima538@gmail.com

 

ABSTRACT:

Background: Tuberculosis is a chronic infectious disease caused by Mycobacterium tuberculosis and still it is a common disease in developing countries. A variety of hematological parameters are studied in tuberculous patients such as decreased Hb(anemia), increased WBC count, increased ESR, and thrombocytopenia. Nowadays TB is a curable and preventable disease. The present study was undertaken to study the ESR values in TB patients and compare their values with ZiehlNelson staining. Method: The present study was carried out on 328 patients who had sputum smear-positive for AFB. based on the recommendation of the RNTCP grading system of AFB in Sputum ZiehlNelson staining, the cases of PTB group were further categorized into four subgroups AFB– 3+, AFB – 2+, AFB –1+ and scanty. The ESR was performed by a rapidly modified Westergren method on EDTA whole blood sample. Results: out of the 324 cases of tuberculosis collected from our hospital, male 252, female 72 from 14-80 years of age. ESR was elevated in patients with an increased grading of sputum positive (3+). The distribution of the mean value of, ESR in different grades of ZN staining of sputum in AFB positive patients was scanty(35.5), 1+(27.5), 2+(30.2),3+(42.4). respectively. Conclusion: Our study concluded that active TB is associated mostly with very high ESR values (≥ 100 mm/h) and with markedly raised values in all the grades of sputum AFB positive patients.

 

KEYWORDS: Tuberculosis, erythrocyte sedimentation rate, Westergreens Method, AFB positive, ZN staining.

 

 


INTRODUCTION:

Tuberculosis (TB) is a common infectious disease caused by Mycobacterium tuberculosis, and despite developments in its diagnosis and treatment, it remains an important public health problem1. It is still a common communicable disease in developing countries2. It affects millions of people each year and is ranked the second leading cause of death from an infectious disease worldwide, after the Human Immunodeficiency Virus (HIV). HIV and malnutrition are some of the major reasons for the prevalence of TB; the reason may be abnormal depression of the immune system3.

 

A variety of hematological changes have been described in patients with tuberculosis such as anemia, increased ESR, low serum albumin level, and leucocytosis 4. The ESR is a blood test measuring the rate of fall of red blood cells in a column of anticoagulated blood in 1 hour, with the units expressed in millimeters per hour(mm/hr). ESR is an inexpensive, easily available investigation particularly in resource-poor countries, where tuberculosis is common. In clinical practice, the ESR test is done as a non-specific test in many pathological conditions such as acute or chronic infections, systemic inflammatory conditions, and neoplastic conditions. collagen diseases, metastatic malignant tumors, and renal disease are to be the leading causes of elevated values >=100mm/hr. During the initial diagnostic workup for TB, which is a chronic bacterial infection, the ESR is commonly done as a non-specific test. A few studies have documented ESR values associated with TB infection5,6,7. The use of the ESR’s in the diagnosis of pulmonary TB is still widely used in clinical laboratories. It is a simple, fast, and inexpensive procedure. Determination of ESR in pulmonary diagnosis shows that in pulmonary tuberculosis infection there is an inflammatory process, there is an increase in levels of fibrinogen and plasma globulin associated with acute phase reactions causing ESRs values to rise. ESR values also increase in various other conditions of infection or inflammation, so that ESRs are not specific to TB. However, ESR value is useful for monitoring the disease's response if the patient was on Anti-Tuberculosis therapy8. Tuberculosis remains a serious public health problem worldwide. Zheil-Neelsen stained smear and culture on Lowenstein Jensen(LJ)media are conventional methods used for the diagnosis of Mycobacterium tuberculosis in most developing countries. But nowadays PCR and GeneXpert studies are used, which is a rapid and sensitive method for the early diagnosis of pulmonary and extra pulmonary tuberculosis and also MDR TB 9, 10. Nowadays Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis are generally thought to have high mortality rates and it is due to. Inappropriate and extensive use of antibiotic drugs is a major factor that contributes to the emergence of antibiotic resistance. The major mechanism of antibiotic resistance includes enzymatic transformation, modification of molecular targets, sequestration of the drug, active efflux from the cell interior, and prevention of entry of the compound into the cell. To overcome the resistance development of new antibiotics is required11.

 

The present study was designed to study the ESR value among TB patients to contribute to the clinical knowledge on the levels of ESR elevation in active TB disease and also to compare the ESR values with the grading of the ZiehlNelson staining of sputum.

 

MATERIALS AND METHODS:

The study subjects included 324 patients of sputum positive tuberculosis and their ESR values included from Jan2017 – Dec2019 (3 years) in the department of microbiology and hematology, Saveetha Medical College and Hospital. The inclusion criteria were patients' first-time diagnosis, no current or previous anti-tuberculous drug treatment, and not to be suffering from any other chronic disease. The study got approval from the Institutional Ethical Committee.

 

Sputum collection and slide preparation:

Smear was prepared from the yellow purulent or blood-tinged portion of the sputum specimen using a stick in the pre-marked area over the new glass slide. All the smears were stained by the Ziehl-Nelson technique using a standard protocol12. The smear could air dry for 15-30 min. The smear was fixed by passing the slide over the flame 3-4 times. Carbol Fuschia is poured over the smear and heated gently till fumes appear; keeping precaution to avoid overheating. Carbol Fuschia could act for 5 minutes and then washed off with tap water. Acid-alcohol decolorizer was poured and kept for one minute. This step was repeated until the slide appeared light pink. In the end, the slide was washed with tap water. Counterstain i.e. Methylene blue was poured and kept for two minutes and washed with tap water. The slide was air-dried; examined under the oil immersion objective to observe for Acid-fast bacilli (bright red) against the background of is blue, yellow, or green depending on the counterstain used. A positive report can be given only if two or more typical bacilli have been seen. A negative report should not be given until at least 300 fields have been examined. Smears are graded based on RNTCP recommendations in India.

 

ESR:

About 2-3 ml peripheral venous blood was drawn aseptically with the help of sterile syringes. Transferred into a tube containing 0.2 ml of 4% Ethylene Diamine Tetra Acetic Acid (EDTA) anticoagulant. ESR values are estimated here by the modified Westergren method. Normal values for males : 0-10 mm/hr and For females : 0-15 mm/hr

 

OBSERVATION AND RESULTS:

A total of 324 sputum smear-positive patients from Saveetha Medical College, Thandalam were collected to evaluate different values of ESR of patients with tuberculosis and their correlation with the grading of the ZN staining.

 

Out of 324 patients, the males were 252(77.8%) and the female was 72(22.2%). The age and sex-wise analysis of the patients with mean ESR values showed. The mean age of the patients is 46.05 years and patients with a minimum of 14 years and a maximum of 93 years were recorded. Most patients came in between 41-50 and 51-60 in study groups. Both groups have more than 46% of patients (Table 1)

 

Elevated ESR to a different level is one of the indicators of the severity of disease and a prognostic tool, which was evident in our study. It elevates on those patients with an increase in sputum positivity, especially in higher sputum grades, the Erythrocyte Sedimentation Rate(ESR) values were significantly higher(Table 2, Fig-1).

 

In our study showed that the maximum patients are seen in grade III (46.2%) followed by grade II (23.4%), Grade I (20.3) and 10.1% scanty according to RNTCP grading system of ZN staining of sputum for acid-fast bacilli and the mean ESR values are 42.4,30.2, 27.5 and 25.5 respectively (Table 2, Fig-2).

Table-1. Age, gender, and mean ESR

Age

No of patients

Male

Female

ESR(mean)

14-30

68

39

29

35.1

31-40

55

43

12

34.4

41-50

71

56

15

39.0

51-60

77

67

10

37.4

61-70

42

37

5

39.6

71-80

8

7

1

69.3

>80

3

3

0

60.3

 

Table-2.  Sputum grading, frequency and percentage of TB bacilli comparative with ESR

Sputum grading

Frequency

Percentage

ESR(mean)

ESR(average)

scanty

32

10.1

25.5

70.2

1+

66

20.3

27.4

72.4

2+

76

23.4

30.2

85.0

3+

150

46.2

42.4

86.1

 

Fig-1 Number of TB cases and ESR

 

Fig-2; sputum grading of TB bacilli: A-Scanty, B-1+,C- 2+,  D-3+

 

DISCUSSION:

The male to female ratio was approximate 3:1 and the present study was similar to Pravat Kumar Thatoi et al13 and BR Hungund et al14. The results obtained by previous studies reported TB was more common among men than women. According to Zaman et al, Vijayakumar et, al, Amany SH et al15, 16,17found that men are more commonly affected by pulmonary tuberculosis than women. Thus, PTB case notification rates in most of the countries are higher in male patients than female patients, which are also consistent in our study. This study showed the gender distribution where male patients 78% and females are 22%in number.

 

Another study from South Africa18 considered that the ESR in patients with active TB (88% of cases had pulmonary TB with HIV positive in 83% of patients).

 

The cases of PTB group were further categorized based on the recommendation of the RNTCP grading system of AFB in Sputum ZN staining into four subgroups AFB – 3+, AFB – 2+, AFB –1+ and scanty.

 

Our study shows that maximum patients have an increased level of ESR. It also shows higher grading of sputum positive patients had higher ESR levels, which indicates the likelihood to detect tuberculosis since a higher ESR rate may be due to this infectious disease. Thus ESR could be used as a diagnostic marker for the diagnosis of tuberculosis by correlating the higher ESR value to this infectious disease. The increased ESR might be due to acute and chronic infection and systemic inflammation in pulmonary tuberculosis. The highest mean ESR value of the study was found to be 48.1 mm/hr obtained in AFB3+ and the level of ESR value was found to be gradually decreasing with the grades of AFB positive patients with the lowest of 15.7 mm/hr in the scanty group. Mohammed Shameem et al (2012) also reported the maximum number of patients with AFB – 3+19. Our study also showed increased ESR in grade AFB+3. The ESR value was found to be directly proportional to the severity of the disease. our data suggested that ESR increased with the increased severity of the disease. Sarkar K et at (2004) and Kanfer and Nicol et al (1997) also reported that increase of ESR from moderate to extremely elevated levels in moderate to acute phases of tubercular patients 20.

 

In earlier studies the elevated ESR is also reported by different scientists in tuberculosis patients. These findings are in agreement with previous studies by Chakraborti et al and Janssens et al 21, 22. In another study, conducted in India, the authors concluded that it probably holds that a lower ESR value in a TB case might be associated with HIV infection in a developing country such as India and that the higher the ESR value, the lower the chance of an associated HIV infection20.

Tuberculosis is a destructive disease as well as a chronic disease and therefore, fibrinogen and gamma globulin levels increase, which will increase the rouleaux formation and thereby greater the level higher is the ESR and which may help to find out the gravity of the disease process. Determination of ESR after treatment with antitubercular drugs helps determine the effectiveness of the drugs used and thereby the prognosis if good or bad. For the control of tuberculosis, early diagnosis of active cases and their treatment under supervision is important. Adequate educational training should be provided to future doctors regarding complete knowledge of tuberculosis, its impact in society in the form of economic burden, prevention, and proper management of tuberculosis23,24,25. A personal experience with Tuberculosis by Prabha Grace said that the girls suffering with Tb are more prone to problems due to stigma about tuberculosis. So advancement of knowledge and elimination of stigmatization are good measures to control TB and also to prevent the transmission of disease in young adult26. WHO goals for default and treatment failure, so it is important to identify and mobilize those patients to take complete treatment. So the country can continue to reduce the burden of TB on its community. An effort to improve the tuberculosis patient’s observance is a suitable preventive strategy to reduce the economic burden Acid-fast staining of sputum is the best method if performed by experienced microbiologists, as it is reliable and economical. Its diagnostic yield can be increased by liquefaction and centrifugation of sputum and by examining more than one sample.

 

In conclusion, the findings of our study tend to suggest that active TB is associated mostly with very high ESR values (>=100mm/hr). In patients with suggestive features of TB but without any other underlying disease affecting the ESR, the baseline ESR may be a valuable diagnostic test to suspect TB in resource-poor countries.

 

CONCLUSION:

Out of 324 sputum positive tuberculosis patients, the study shows a male (252) was more infected than female (72) with the age group of 30-60 years common There was an elevated level of ESR in all the patients with tuberculosis were noticed in this study. Especially, in higher sputum grades (3+) the ESR range was significantly high, indicates an increase in bacteria load makes elevation in erythrocyte sedimentation rate and showed the significance of activity level and disease extent. So ESR can be considered as a prognostic factor in TB patients. We support that PCR and GeneXpert study is more useful in clinically suspected cases where the sputum is negative for TB bacilli. We suggest giving effective awareness programs should be launched in rular areas to minimize the chances of the spread of disease. Adequate educational training should be provided to future doctors regarding complete knowledge of tuberculosis, its impact on society in the form of economic burden, prevention, and proper management. So finally an effort is made to reduce the economic burden in the family, society, and country.

 

REFERENCES:

1.      Banerjee M, Chaudhary BL, Shukla S. Hematological profile among pulmonary tuberculosis patients in tertiary care Hospital. International Journal of Bioassays.2015;4(05):3900-2.

2.      Yaranal PJ, Umashankar T, Harish SG. Hematological profile in pulmonary tuberculosis. Int J Helth Rehbil Sci.2013;2(1):50-5.

3.      Uma Sankarviriti, Swarna Latha Surakala, Arun Satyadev Sidhanadam, Neelima Peela. Influence of HIV, Malnutrition and Patient Non-Compliance on the Prevalence and Prognosis of Tuberculosis: A Fatal Infectious Disease. Research J. Pharm. and Tech. 8(10): Oct., 2015; Page 1365-1368.

4.      Olaniyi JA, Aken ‘Ova YA.Haematological profile of patients with pulmonary tuberculosis in Ibadan, Nigeria. Afr J Med Sci 2003; 32:239-42.

5.      Levay PF, Retief JF.Causes of high erythrocyte sedimentation rates in an in patient population.SAfr Med J 2005;95(1):45-46.

6.      AL-Marri MR, Kirkpatrick MB.Erythrocyte sedimentation rate in childhood tuberculosis is it still worthwhile? Int J Tuberc Lung Dis 2000;4:237-239.

7.      Blumberg HM, Burman WJ, Chaisson RE. American Throacic Society/ Centers for Disease Control and Prevention/ Infectious Diseases Society of America: treatment for TB.Am J Resp Criti Care Med. 2003;167(4):603-662.

8.      Mirsacidi SM, Tabarsi P, Amiri MV. Clinical and radiological presentation of adult tuberculous spondylitis. Tanaffos 2003;2:59-65.

9.      Lama Doya, Danial Dalloul, Mohammad Alkhayer, Haissam Yazigi. The importance of diagnosing Mycobacterium tuberculosis by real time PCR Compared with the approved diagnostic methods in the Clinical Laboratory. Research J. Pharm. and Tech 2018; 11(4): 1513-1515.

10.   Oleg A. Zemlyansky., Elena B. Tyurina., Andrey A. Bashkirev., Elena V. Kalyuzhnaya., Ludmila O. Zemlyanskaya. Experience and Efficiency of Laboratory Diagnosis of Tuberculosis with PCR Detector System GeneXpert in Belgorod Region. Research J. Pharm. and Tech. 2017; 10(3): 743-746.

11.   Sandip Zine, Shweta A. Patankar, Sushmita S. Raopati. Rise of Antibiotic Resistance in Tuberculosis. Research J. Pharm. and Tech 2018; 11(7): 3201-3204.

12.   Bala J, Bagdi R, BediS,KumarA.Tuberculosis As A cause of change in Hematological Parameters In A Teritiary Care Hospital.Natl J Integr Res Med 2015;6(4):31-35.

13.   Thatoi PK, Khadanga S.Pulmonary Tuberculosis and its haematological correlates. Thatoi PK/ Transworld Medical Journal. 2013; 1(1):1113.

14.   Hungund BR, Sangolli SS, Bannur HB. Blood and bone marrow findings in tuberculosis in adults-A cross sectional study. Al Ameen J Med Sci.2012;5(4):362-6.

15.   Zaman K. Tuberculosis a global health problem J of health, Population and Nutrition. 2010;1:111-3.

16.   Vijaya Kumar S, Nookala L, Prakash S, Vivean PR. Ziehl-Neelsen (ZN) Stained Method: Presence and Absence of Acid Fast Bacilli (AFB) of Pulmonary and Non Pulmonary Tuberculosis Patients Under Went Anti-Tuberculosis Treatment. Research J. Pharm. and Tech. 8(5): May, 2015; Page 529-532.

17.   Amany SH. Jabe, Kadhimmohan Manhi, Imanhadi Alfayyadh, Saad S. Hamim. Prevalence of Tuberculosis from 2010-2015 in Nasiriyah City/Iraq. Research J. Pharm. and Tech. 2019; 12(5):2275-2278.

18.   Ukpe IS, Southern L. Erythrocyte sedimentation rate values in active tuberculosis with and without HIV co-infection.SAfr Med J 2006;96:427-428.

19.   Muhammad Yousuf, Salih Bin Salih, Sameera Al-Johani, Adel Alothman. “Erythrocyte sedimentation rate at diagnosis in culturepositive cases of active tuberculosis” Pak J Med Sci January – March 2012 Vol. 28 No. 1 87-90.

20.   Sarkar K, Baraily S, Dasgupta S. Erythrocyte sedimentation rate maybe an indicator for screening of tuberculosis patients for underlyingHIV infection, particularly in resource-poor settings: An experiencefrom India. J Health Popul Nutr 2004; 22:220-221.

21.   Chakraborti AK, Dutta AK, Dasgupta B. Hematological changes in disseminates tuberculosis. Ind J Tuber.1995;42:165-8.

22.   Janssens A, Rodeghiero F, Anderson D, Chong BH, Boda Z, Pabinger I, et al. Changes in bone marrow morphology in adults receiving romiplostim for the treatment of thrombocytopenia associated with primary immune thrombocytopenia. Annals of Hematology. 2016;95(7):1077-87.

23.   Roy RK, Roy DK, Rupak KC, Patel I, Poudel K, Shah P, Bhuyan S, Bhuyan SK,Bhuyan R. Knowledge regarding Tuberculosis among undergraduate medical students at Nepalgunj Medical College - Banke, Nepal. Research J. Pharm. and Tech 2020; 13(6): 2833-2837.

24.   P. Mangala Gowri, G. Bhuvaneswari, C. Manoj, R. Varatharajan, Subhashini, Jomcy, Epsimal. Assess the knowledge and associated factors of DOTS defaulter among Tuberculosis clients. Research J. Pharm. and Tech 2018; 11(6):2313-2316. 

25.   Susi Ari Kristina, Tri Murti Andayani, Galih Putri Wulandari. A Systematic Review of the Direct and Indirect Costs among Tuberculosis Patients. Research J. Pharm. and Tech. 2020; 13(1): 456-460.

26.   Sr. Prabha Grace. A Personal Experience with a Tuberculosis patient: A Case Report. Int.J of Advances in Nur. Management. 2018; 6(4): 290-292.

 

 

 

Received on 22.08.2020            Modified on 31.01.2021

Accepted on 28.06.2021           © RJPT All right reserved

Research J. Pharm. and Tech 2022; 15(1):245-249.

DOI: 10.52711/0974-360X.2022.00040