| Home | E-Submission | Sitemap | Contact Us
Korean J Intern Med > Volume 32(6); 2017 > Article
Bozdemir, Altıntop, Uytun, Aslaner, and Torun: Diagnostic role of mean platelet volume and neutrophil to lymphocyte ratio in childhood brucellosis

Abstract

Background/Aims

Brucellosis patients present various non-specific clinical symptoms, such as fever, fatigue, sweating, joint pain, arthritis, myalgia, and headache. Based on the nonspecifity of its clinical signs and symtoms, we decided to evaluate whether mean platelet volume (MPV) , neutrophil to lymphocyte ratio (NLR), and platelet to lymphocyte ratio (PLR) will contribute to the diagnosis.

Methods

In this retrospective study, we reviewed hospital-records of 60 children with a confirmed diagnosis of brucellosis in Kayseri between January 2013 and January 2016, and compared the hematological parameters; white blood cell (WBC) count, hemoglobin (Hb), neutrophil count, lymphocyte count, platelet count, MPV, NLR, and PLR with 55 healthy age and gender matched children. Also, the well known inf lammation markers; erytrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were compared between the patient and control group.

Results

We found significant difference among the Hb, platelet count, MPV and NLR values between the patient and control group (p < 0.05). There was no difference between WBC, neutrophil count, lymphocyte count and PLR between the patient and control group (p > 0.05). When the patients were divided into groups as arthritis positive and arthritis negative and compared to the control group; we found that the NLR is more significant in between the arthritis positive and control group (p = 0.013). Also, we found significant difference among the ESR and CRP values between the patient and control group (p < 0.001).

Conclusions

The results of this study indicates that MPV and NLR values can be used as markers of inflammation in childhood brucellosis. Also, NLR is more valuable in children with brucella arthritis.

INTRODUCTION

Brucellosis is a bacterial zoonotic disease transmitted directly or indirectly by contact with infected animals or contaminated dairy products. It is a common disease in middle, east, and southeast region of Turkey, and affects the children as well as adults [1,2]. Different from the adults, almost all of the pediatric cases are due to unpasteurized milk or milk products consumption [3-6]. Following the initial infection, the bacteria proliferates in the regional lymph nodes, passes into blood and causes systemic infection involving tissues and several organs, primarily the reticuloendothelial system. Brucellosis patients present non-specific clinical symptoms; such as fever, fatigue, sweating, joint pain, arthritis, myalgia, and headache [1,5-8]. Although the gold standart test for the diagnosis of brucellosis is culture method, standart tube agglutination test with a titre of 1/160 is used most commonly [9]. Laboratory findings such as leukocytosis/leukopenia, relative lymphocytopenia, anemia, thrombocytopenia, high C-reactive protein (CRP), and high erytrocyte sedimentation rate (ESR) can be found in patients, but does not help directly to the diagnosis [10]. While searching for other markers contributing to the diagnosis of childhood brucellosis, we decided to evaluate the mean platelet volume (MPV), neutrophil to lymphocyte ratio (NLR), and platelet to lymphocyte ratio (PLR) in our patient group. There are many studies investigating the hematological parameters MPV, NLR, and PLR as markers of inflammation in several rheumatologic, cancer, and/or infectious diseases [11-15]. In this study, we compared the MPV, NLR, and PLR values of our brucellosis patients with healthy children to determine their usability in the diagnosis of childhood brucellosis on admission.

METHODS

This retrospective study was performed in the Pediatric Clinic of Kayseri Training and Research Hospital. The medical records of patients who were diagnosed and treated for brucellosis in the pediatric clinic between January 2013 and January 2016 were evaluated. A total of 60 children with brucellosis and 55 age- and gender-matched healthy controls were enrolled in the study. Healthy children were selected through children who applied to hospital for routine check-up, or vaccination status screening or for preoperative evaluation of minor elective surgery (for example, hernia repair). Children with any sign of infection or systemic illness were excluded from the control group. The diagnosis of brucellosis was established according to the presence of isolation of Brucella species from blood culture and/or, positive brucella serology test equal or higher than the titre of 1:160, using standard agglutination test (SAT) for patients presenting symptoms suggestive of brucellosis. Other demographic, clinical and laboratory data, and treatment modalities and outcomes were obtained from patients’ follow-up folders and hospital records.
Patients with an underlying pathology (like rheumatic disease, autoimmune disease), or evidence of other bacterial infection (culture positivity for another bacteria), or who were over 18 years old and whose file records were unreachable were excluded from the study.
Hematological parameters including white blood cell (WBC) count, hemoglobin (Hb), neutrophil count, lymphocyte count, platelet count, and MPV were recorded for both groups. NLR and PLR were calculated as the ratio of neutrophils to lymphocytes and platelets to lymphocytes, respectively. CRP of all patients and controls and ESR of patients and controls whose existing were recorded. Comparison between the patients and the control subjects was performed with regards to WBC, neutrophil count, lymphocyte count, platelet count, MPV, NLR, and PLR. White blood cell, Hb, neutrophil count, lymphocyte count, platelet count, and MPV, NLR and PLR values, CRP, and ESR were compared between the patients and control groups. Also, patients were divided into two groups as arthritis positive and artritis negative groups and WBC, neutrophil count, lymphocyte count, platelet count, MPV, NLR, and PLR values compared to the controls one by one. All kinds of blood cell counts were made in Sysmex XN-350 (Sysmex, Kobe, Japan) and CRP measures were held on BN Prospec (Dade Behring, Siemens, Deerfield, IL, USA) Nephelometer.
The Non-Interventional Clinical Ethics Committee of Erciyes University Medical Faculty approved the study protocol.

Statistical analysis

The normality of data distribution was determined using the Kolmogorov-Smirnov test. Normally distributed numerical variables were expressed in mean ± standard deviation. Normally distributed numerical variables were compared using the Student t test or One-way analysis of variance test. Tukey test was used for post hoc tests. Data corresponding to an abnormal distribution were expressed in median (minimum–maximum). Abnormally distrubuted numerical data were compared using the non-parametric Mann-Whitney U test or Kruskal-Wallis test. The chi-square test was used to compare categorical variables between the groups. p values of less than 0.05 were considered statistically significant. The data were analyzed using SPSS version 22.0 (IBM Co., Armonk, NY, USA).

RESULTS

The median age of the patients was 130 months (range, 1 to 204) and 81.7% (n = 49) of the patients were male. The median age of the control group was 104 months (range, 1 to 204) and 70.9% (n = 39) were male. There were no significant differences in the median ages (p = 0.249) and gender distribution (p = 0.174) between the patient and the control group. The most common symptoms at admission were fever (100%), arthralgia (93.3%), and weakness (90%). Seven patients had hepatosplenomegaly (11.6%), one patient had only splenomegaly (1.7%). The frequency of arthritis was 28.3% (17/60) and the most commonly affected joint was knee (47%, 8/17). The presence of brucella arthritis was not related to serum aglutination titer (p = 0.507) and blood culture positivity (p = 0.646). The most frequent SAT was 1/160 in 50% of all patients. One case of congenital infection had a SAT of 1/20. The culture positivity rate was 31.2%. Most of the patients (36.7%, 22/60) were treated with a combination of rifampicin plus doxycycline. Frequency of SAT and treatment modalities are listed in Table 1. The ESR was studied in 46 patients (76.70%) and in 18 controls (32.7%), and the median values were 9.5 mm/hr (range, 2 to 56) and 2.5 mm/hr (range, 2 to 10), respectively. There was a significant difference between the patient and control group (p < 0.001). The median CRP value was 8.93 mg/L (range, 3.17 to 252.0) in patient group, 3.28 mg/L (range, 3.17 to 5.04) in control group and there was a significant difference between the patient and control group (p < 0.001) (Table 1). Median WBC was 6,870/mm3 (range, 1,220 to 18,370), Hb was 12.6 ± 2.0 mg/dL, platelet count was 272,366 ± 91,913/mm3, MPV value was 8.9 ± 1.14 fL, NLR was 0.99 (range, 0.31 to 10.2) and PLR was 95.2 (range, 22.2 to 370) in the patient group. Median WBC was 6,500/mm3 (range, 3,590 to 10,770), Hb was 13.4 ± 1.4 mg/dL, platelet count was 309,963 ± 73,000 mm3, MPV value was 9.3 ± 0.76 fL, NLR was 0.89 (range, 0.17 to 1.39) and PLR was 93.05 (range, 1.4 to 172) in the control group. There was statistically significant difference in Hb, platelet count, MPV, and NLR values between the two groups (p < 0.05). There was no statistically significant difference between the WBC, neutrophil count, lymphocyte count and PLR values between the two groups (p > 0.05) (Table 2). When the patient group was divided into two groups as arthritis positive and negative group, the comparison of NLR resulted more significant between the arthritis positive and control group (p = 0.002). Also, the difference of MPV between arthritis negative and control group was found more significant (p = 0.034) (Table 3).

DISCUSSION

Changes in hematological parameters are commonly seen in brucellosis patients, but they do not have diagnostic value and turn to normal values rapidly with the treatment of brucellosis. Aypak et al. [16] reported that the most frequent hematological abnormality in a total of 69 children with brucellosis was thrombocytopenia with 15.9% (11/69). The other abnormalities were thrombocytosis with 7.3%, leukopenia with 5.8%, anemia 4.3%, and bicytopenia 4.3%. Tanir et al. [17] reported the hematological abnormalities in a total of 90 children with brucellosis as anemia with 26.7%, leukopenia 10%, thrombocytosis 5.6%, thrombocytopenia 3.3%, and leukocytosis 1.1%. Karakukcu et al. [18] reported the frequency of pancytopenia as 14.8% among a total of 54 patients. In our study, hematological abnormalities were anemia 10%, bicytopenia 5%, and pancytopenia 3.3%, respectively. These results show that the hematological parameters in brucellosis patients vary from patient to patient. However, the most frequent abnormalities are announced as mild anemia, leukocytosis/leukopenia, and thrombocytopenia in literature [3,16,19].
The physiological immune responses of circulating leukocytes to various stressful events are characterized by an increased neutrophil count and decreased lymphocyte count. An increase in total leukocyte and neutrophils is an inflammatory reaction, particularly when caused by a bacterial infection. Brucella lipoproteins possess proinflammatory properties that could contribute to the localize tissue injury and inflammation by direct activation of neutrophils [20,21]. Lymphocytopenia has also been described as a diagnostic marker of bacterial infection [22,23]. In the lightning of these data, NLR is becoming a more valuable inflammation marker than neutrophilia or lymphocytopenia alone for predicting bacterial infection. As a result of changes caused by the inflammation in neutrophils, platelets, and lymphocytes, NLR and PLR have turned into inflammatory markers. Also, NLR and PLR can easily be calculated from a routine total blood count with no additional cost. Recently, NLR and PLR are used to predict the disease activity, prognosis, and survival rates in some systemic inflammatory diseases such as juvenile idiopatic artrit, Crohn disease; in cancer patients with hepatocellular, breast and other cancers; and in bacterial infections like tuberculosis and bloodstream infections.
In literature search, we found only two studies investigating NLR and PLR in brucellosis. In the study by Olt et al. [10], Hb and NLR were found to be significantly associated with brucellosis in adult patients. In the study by Aktar et al. [24], NLR and PLR were found as indirect markers of inflammation in children with brucella arthritis. There was no other study investigating the NLR and PLR values in children with brucellosis. In our study, we found that Hb and NLR are significantly different in children with brucellosis from healthy control children (p < 0.05). Also, we evaluated the, NLR and PLR in our patients by dividing the group as arthritis positive and arthritis negative. Similar to the study of Aktar et al. [24], we found that NLR is significantly different in arthritis positive group compared to the control group (p = 0.002). However, different from the previous studies, we found no significant difference in PLR either between patients and control group, or arthritis positive/arthritis negative and control group (p > 0.05).
As another hematological parameter, MPV was investigated in many systemic inflammatory diseases, also in brucellosis. Previous studies reported that interferon-γ, tumor necrosis factor α, interleukin 1 (IL-1), and IL-12 secreted in brucellosis. Over releasing of these proinflammatory cytokines might influence the maturation of platelets and result in a reduction in size of platelets during brucellosis infection [25,26]. In literature search, we found four studies investigating MPV in brucellosis patients. In the study by Okan et al. [27] there was statistically significant difference in MPV (p < 0.001) and platelet count (p < 0.05) between a total of 96 adult brucellosis patient and control group. In the study by Kucukbayrak et al. [28] platelet count and MPV were found significantly meaningfull markers of inflammation in a total of 40 brucellosis patients. However, in the study by Togan et al. [29] MPV was found to be insignificant (p = 0.897) in a total of 250 patients with brucellosis. In our study, we found the MPV significantly different in children with brucellosis from healthy control children (p = 0.049). However, different from NLR value, the difference for MPV was more significant between the arthritis negative and control group (p = 0.034).
The limitations of our study are its resrospective nature and the relatively small sample size of patients; especially with brucella arthritis.
In conclusion, MPV and NLR can be used as inflammatory markers of brucellosis, and NLR can be used especially in patients with arthritis on admission. Further prospective studies are needed to compare our results and make decision.

KEY MESSAGE

1. Brucellosis can cause anemia, thrombocytopenia, and neutrophilia in children.
2. Changes of mean platelet volume and neutrophill to lymphocyte ratio (NLR) can be used as inflammatory markers in childhood brucellosis.
3. NLR is a sensitive marker of inf lammation in children with brucella arthritis.

Conflict of interest

No potential conflict of interest relevant to this article was reported.

Table 1.
Demographic and clinical characteristics of the 60 patients
Characteristic Value
Age, mon 30 (1–204)
Male sex 49 (81.7)
Symptoms and clinical signs
 Fever 60 (100)
 Arthralgia 56 (93.3)
 Weakness 54 (90.0)
 Myalgia 50 (83.3)
 Anorexia 34 (56.7)
 Sweating 27 (45.0)
 Arthritis 17 (28.3)
 Peripheral lymphadenopathy 10 (16.7)
 Abdominal pain 8 (13.3)
 Hepatosplenomegaly 7 (11.7)
 Splenomegaly 1 (1.7)
Serum agglutination test results
 1/20a 1 (1.7)
 1/160 30 (50.0)
 1/320 14 (23.4)
 1/640 8 (13.3)
 1/1,280 7 (11.7)
Erythrocyte sedimentation rate, mm/hr 9.5 (2–56)
C-reactive protein, mg/dL 8.9 (3.17–252)
Treatment
 Rifampicin + doxycycline 22 (36.7)
 Rifampicin + doxycycline + gentamicin 15 (25.0)
 Rifampicin + TMP-SMT 13 (21.7)
 Rifampicin + TMP-SMT + gentamicin 8 (13.3)
 Rifampicin + TMP-SMT + cefotaxime/ceftriaxoneb 2 (3.3)

Values are presented as median (range) or number (%).

TMP-SXT, trimethoprim-sulfamethoxazole.

a Case with congenital infection.

b One case with relapsing disease and one case with congenital infection.

Table 2.
Comparison of the laboratory findings of patient and control groups
Variable Patient (n = 60) Control (n = 55) p value
WBC, /mm3 6,870 (1,220–18,370) 6,500 (3,590–10,770) 0.186
Neutrophil, /mm3 2,820 (620–15,690) 2,790 (890–4,850) 0.103
Lymphocyte, /mm3 3,020 (270–6,930) 3,100 (1,520–5,840) 0.223
NLR 0.99 (0.31–10.2) 0.89 (0.17–1.39) 0.032
PLR 95.2 (22.2–370) 93.1 (1.4–172) 0.853
Hemoglobin, g/dL 12.6 ± 2.0 13.4 ± 1.4 0.017
Platelet, /mm3 272,366 ± 91,913 309,963 ± 73,000 0.017
MPV, fL 8.9 ± 1.14 9.3 ± 0.76 0.049
ESR, mm/hr 9.5 (2–56) 2.5 (2–10) < 0.001
CRP, mg/dL 8.93 (3.17–252) 3.28 (3.17–5.04) < 0.001

Values are presented as median (range) or mean ± SD.

WBC, white blood cell; NLR, neutrophil to lymphocyte ratio; PLR, platelet to lymphocyte ratio; MPV, mean platelet volume; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein.

Table 3.
Comparison of the laboratory findings of artritis positive, arthritis negative patients, and control group
Variable Arthritis (+) Arthritis (–) Control p value
WBC, /mm3 6,850 (3,590–13,710) 6,890 (1,220–18,370) 6,500 (3,590–10,770) 0.310
Neutrophil, /mm3 3,540 (950–10,570)a 2,780 (620–15,690)b 2,790 (890–4,850)b 0.007
Lymphocyte, /mm3 2,710 (1,450–5,650) 3,050 (270–6,930) 3,100 (1,520–5,840) 0.405
NLR 1.38 (0.37–5.9)a 0.95 (0.31–10.2)b 0.90 (0.17–1.3)b 0.002
PLR 92.4 (22.2–214) 99.1 (46.5–370) 93.0 (1.4–172) 0.944
Hemoglobin, g/dL 12.8 ± 1.7 12.6 ± 2.1 13.4 ± 1.43 0.059
Platelet, /mm3 251,823 ± 72,550a 280,488 ± 98,102b 309,963 ± 73,003b 0.035
MPV, fL 9.3 ± 1.08b 8.8 ± 1.14a 9.3 ± 0.76b 0.034

Values are presented as median (range) or mean ± SD.

WBC, white blood cell; NLR, neutrophil to lymphocyte ratio; PLR, platelet to lymphocyte ratio; MPV, mean platelet volume.

a Indicates the difference.

b Indicates the similarity.

REFERENCES

1. Ulug M, Yaman Y, Yapici F, Can-Ulug N. Clinical and laboratory features, complications and treatment outcome of brucellosis in childhood and review of the literature. Turk J Pediatr 2011;53:413–424.
pmid
2. Shaalan MA, Memish ZA, Mahmoud SA, et al. Brucellosis in children: clinical observations in 115 cases. Int J Infect Dis 2002;6:182–186.
crossref pmid
3. Schutze GE, Jacobs RF. Brucella. In: Kliegman RM, Nelson WE, eds. Nelson Textbook of Pediatrics. 19th ed. Philadelphia: Elsevier Saunders, 2011;980–982.

4. Bosilkovski M, Krteva L, Caparoska S, Labacevski N, Petrovski M. Childhood brucellosis: review of 317 cases. Asian Pac J Trop Med 2015;8:1027–1032.
crossref pmid
5. Buzgan T, Karahocagil MK, Irmak H, et al. Clinical manifestations and complications in 1028 cases of brucellosis: a retrospective evaluation and review of the literature. Int J Infect Dis 2010;14:e469–e478.
crossref pmid
6. Caylak SD, Sozen H, Gonen I, Sahin C. A brucellosis case presenting with vesicular and maculopapular rash and febrile neutropenia. J Microbiol Infect Dis 2014;4:39–41.
crossref
7. Minas M, Minas A, Gourgulianis K, Stournara A. Epidemiological and clinical aspects of human brucellosis in Central Greece. Jpn J Infect Dis 2007;60:362–366.
pmid
8. Fanni F, Shahbaznejad L, Pourakbari B, Mahmoudi S, Mamishi S. Clinical manifestations, laboratory findings, and therapeutic regimen in hospitalized children with brucellosis in an Iranian Referral Children Medical Centre. J Health Popul Nutr 2013;31:218–222.
crossref pmid pmc
9. Cirakli S, Karli A, Sensoy G, Belet N, Yanik K, Cirakli A. Evaluation of childhood brucellosis in the central Black Sea region. Turk J Pediatr 2015;57:123–128.
pmid
10. Olt S, Ergenc H, Acikgoz SB. Predictive contribution of neutrophil/lymphocyte ratio in diagnosis of brucellosis. Biomed Res Int 2015;2015:210502.
pmid pmc
11. Demir F, Karadeniz C, Ozdemir R, et al. Usefulness of neutrophil to lymphocyte ratio in prediction of coronary artery lesions in patients with Kawasaki disease. Balkan Med J 2015;32:371–376.
crossref pmid pmc pdf
12. Uygur F, Tanriverdi H, Aktop Z, et al. The neutrophil-to-lymphocyte ratio in patients with obstructive sleep apnoea syndrome and its relationship with cardiovascular disease. Heart Lung 2016;45:121–125.
crossref pmid
13. Kucuk A, Erol MF, Senel S, et al. The role of neutrophil lymphocyte ratio to leverage the differential diagnosis of familial Mediterranean fever attack and acute appendicitis. Korean J Intern Med 2016;31:386–391.
crossref pmid pmc pdf
14. Atan D, Ikinciogullari A, Koseoglu S, et al. New predictive parameters of Bell’s palsy: neutrophil to lymphocyte ratio and platelet to lymphocyte ratio. Balkan Med J 2015;32:167–170.
crossref pmid pmc pdf
15. Yin X, Xiao Y, Li F, Qi S, Yin Z, Gao J. Prognostic role of neutrophil-to-lymphocyte ratio in prostate cancer: a systematic review and meta-analysis. Medicine (Baltimore) 2016;95:e2544.
crossref pmid pmc
16. Aypak A, Aypak C, Bayram Y. Hematological findings in children with brucellosis. Pediatr Int 2015;57:1108–1111.
crossref pmid
17. Tanir G, Tufekci SB, Tuygun N. Presentation, complications, and treatment outcome of brucellosis in Turkish children. Pediatr Int 2009;51:114–119.
crossref pmid
18. Karakukcu M, Patiroglu T, Ozdemir MA, Gunes T, Gumus H, Karakukcu C. Pancytopenia, a rare hematologic manifestation of brucellosis in children. J Pediatr Hematol Oncol 2004;26:803–806.
pmid
19. Araj GF. Update on laboratory diagnosis of human brucellosis. Int J Antimicrob Agents 2010;36 Suppl 1:S12–S17.
crossref pmid
20. Zwerdling A, Delpino MV, Pasquevich KA, et al. Brucella abortus activates human neutrophils. Microbes Infect 2009;11:689–697.
crossref pmid
21. Skendros P, Boura P. Immunity to brucellosis. Rev Sci Tech 2013;32:137–147.
crossref pmid
22. Wyllie DH, Bowler IC, Peto TE. Relation between lymphopenia and bacteraemia in UK adults with medical emergencies. J Clin Pathol 2004;57:950–955.
crossref pmid pmc
23. Yoon NB, Son C, Um SJ. Role of the neutrophil-lymphocyte count ratio in the differential diagnosis between pulmonary tuberculosis and bacterial community-acquired pneumonia. Ann Lab Med 2013;33:105–110.
crossref pmid pmc
24. Aktar F, Tekin R, Bektas MS, et al. Diagnostic role of inflammatory markers in pediatric Brucella arthritis. Ital J Pediatr 2016;42:3.
crossref pmid pmc
25. Gasparyan AY, Ayvazyan L, Mikhailidis DP, Kitas GD. Mean platelet volume: a link between thrombosis and inflammation? Curr Pharm Des 2011;17:47–58.
crossref pmid
26. Caron E, Gross A, Liautard JP, Dornand J. Brucella species release a specific, protease-sensitive, inhibitor of TNF-alpha expression, active on human macrophage-like cells. J Immunol 1996;156:2885–2893.
pmid
27. Okan DH, Gokmen Z, Seyit B, Yuksel K, Cevdet Z, Deniz A. Mean platelet volume in brucellosis: correlation between brucella standard serum agglutination test results, platelet count, and C-reactive protein. Afr Health Sci 2014;14:797–801.
crossref pmid pmc
28. Kucukbayrak A, Tas T, Tosun M, et al. Could thrombocyte parameters be an inflammatory marker in the brucellosis? Med Glas (Zenica) 2013;10:35–39.
pmid
29. Togan T, Narci H, Turan H, Ciftci O, Kursun E, Arslan H. The impact of acute brucellosis on mean platelet volume and red blood cell distribution. Jundishapur J Microbiol 2015;8:e20039.
crossref pmid pmc
TOOLS
PDF Links  PDF Links
PubReader  PubReader
ePub Link  ePub Link
Full text via DOI  Full text via DOI
Download Citation  Download Citation
CrossRef TDM  CrossRef TDM
  E-Mail
  Print
Share:      
METRICS
0
Crossref
0
Scopus
1,486
View
147
Download
Related article
Editorial Office
101-2501, Lotte Castle President, 109 Mapo-daero, Mapo-gu, Seoul 04146, Korea
Tel: +82-2-2271-6792   Fax: +82-2-790-0993    E-mail: kaim@kams.or.kr
Copyright © 2017 The Korean Association of Internal Medicine. All rights reserved.
About |  Browse Articles |  Current Issue |  For Authors and Reviewers
powerd by m2community