Use of CBC in the early differentiation of childhood TB from community-acquired pneumonia
Editors:
- Dr. Praful B. Godkar (Ph.D)
Eminent Author, Medical Biochemist and Scientist, Technical Education consultant. AGD Biomedicals (Pvt) LTD. - Dr. Gauri Kulkarni MD (Pathology)
Vice President, AGD Biomedicals (Pvt) LTD. - Dr. Arsala Mulla DNB, DCP (Path)
Consultant Pathologist / DNB Teacher BDBA Municipal General Hospital, Mumbai
Two very important and common respiratory infections with high rates of hospitalization and complications in childhood are tuberculosis (TB) and Community acquired pneumonia (CAP)(2,5). Due to the overlapping symptoms and inconclusive laboratory test results, differential diagnosis between TB and CAP is difficult in children (1,2). An early and accurate diagnosis of these two childhood diseases is necessary for effective treatment, as well as for the identification of index cases, to prevent spread of TB and CAP(1). For the early differentiation of childhood TB from CAP, complete blood count (CBC) report parameters performed on fifth generation, cutting edge AGD Hematology analyzers are suggested as inexpensive and quick diagnostic markers, with additional prescribed tests(1,11).
NOTE(1,2)
(A) The diagnosis of TB in children is generally based on the following points:
(1) Clinical features
(2) Complete contact history,
(3) tuberculin skin test report,
(4) complete blood count,
(5) Microbiological culture and
(6) Radiology reports.
During the initial stage, pulmonary TB can be misdiagnosed as community-acquired pneumonia (CAP), due to similar symptoms and related radiology reports.
(B) A delay in the diagnosis of TB can lead to increase in the transmission of infection and further suffering of the patient.
Q1. What are the common overlapping symptoms of childhood TB and CAP?
ANS: Common symptoms of tuberculosis (TB) and CAP in children include, fever, headache, a persistent cough, shortness of breath, chest pain, weight loss, weakness, and fatigue.
Q2. What are the various types of microorganisms that may lead to lower respiratory tract and lung infections? Give examples.
ANS: Bacteria, viruses and fungi are responsible for lower respiratory tract and lung infections.
NOTE(11)
(A) Examples of bacteria that cause lower respiratory tract and lung infections include common Gram positive bacteria such as Streptococcus pneumoniae, Staphylococcus aureus, Streptococcus pyogenes and Haemophilus influenzae, as well as Gram-negative bacteria such as Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter species.
(B) Viruses that cause lower respiratory tract and lung infections include SARS-CoV-2 (which causes COVID-19), influenza viruses, parainfluenza viruses, rhinoviruses, adenoviruses, respiratory syncytial virus (RSV), etc. Other viruses that cause lung and lower respiratory infections in immunocompromised individuals include, varicella zoster virus (VZV), measles virus and cytomegalovirus (CMV)
(C) The following are various types of fungi that cause lower respiratory tract and lung infections, mainly in immunocompromised persons: Candida, Aspergillus, Histoplasma, Coccidioides, Cryptococcus, and Blastomyces.
Q3. What are the latest fifth generation CBC parameters that can differentiate early childhood TB and CAP infections?
ANS: CBC parameters with neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet to-lymphocyte ratio (PLR), neutrophil -to-monocyte-plus-lymphocyte ratio (NMLR)
NOTE(1,2)
(A) The following two representative Case histories (CASE 1 and CASE 2) are listed from a group of 210 cases of Children suffering from TB and CAP from rural areas. All TB patients were diagnosed as pulmonary TB. Patients with extra pulmonary TB were not included in this study.
(B) All the TB patients were suffering from primary TB. Patients with chronic inflammatory conditions or a history of use of antibiotics for more than 24 hours at the time of enrollment were excluded from the study. Patients with the diagnosis of pulmonary TB and patients with CAP who did not have previous antibiotic treatment were considered for the study.
(C) The diagnosis of TB was made through clinical, chest X-ray findings and laboratory test results. In the absence of microbiologic confirmation, patients were considered to have probable TB; if they had (1) signs or symptoms of TB, (2) Positive Immunology laboratory tests of M. tuberculosis with positive Tuberculin Skin Test (TST) findings, and (3) A complete diagnostic evaluation, with anti-TB drug combinations.
(D) For the diagnosis of community-acquired pneumonia, the definition determined by the World Health Organization (WHO) was used. The significant observations of these studies were as follows:
(E) The following Case histories: CASE 1: Child diagnosed with TB and CASE 2: Child diagnosed with CAP, have similar symptoms. Their respective CBC reports are examples of CBC parameters that can be useful to differentiate childhood tuberculosis (TB) and Community acquired pneumonia (CAP).
CASE STUDY 1
A 6-year-old male child was presented with a history of low-grade fever for past two weeks, chronic cough, shortness of breath, chest pain, weight loss, weakness, and fatigue. His complete hemogram report values were as follows:
COMPLETE BLOOD COUNT
| PARAMETER | RESULT | REFERENCE RANGE |
| Haemoglobin | 11.6 g/dl | 13–18 g/dl |
| Total erythrocyte count | 4.45 X 1012 /l | 5.0 ± 0.5 X 1012 /l |
| Total leukocyte count | 7.8 X 109/l | 7.0 ± 3.0 X 109/l |
| Differential leukocyte count | ||
| Neutrophils | 44% | 40–75% |
| Lymphocytes | 50% | 20–45 % |
| Eosinophils | 2% | 1–4 % |
| Monocytes | 4% | 2–8 % |
| PCV | 37% | 36–48% |
| MCV | 85 fL | 82–92 fL |
| MCH | 29 pg | 27–32 pg |
| MCHC | 33% | 32–36 % |
| RDW-CV | 14 | 12–14 |
| Platelet count | 270 X 109/l | 150–400 X 109/l |
| MPV | 8.6 | 7.5-12.0 |
| PDW | 15.8 | 15-17 |
| Absolute Neutrophil count | 3,432 | 2,500-7,500 |
| Absolute Lymphocyte count | 3,900 | 1,000-4,000 |
| Absolute Monocyte count | 312 | 200-800 |
| Neutrophil-to-lymphocyte ratio (NLR) | 0.88 | 0.78-3.53 |
| Monocyte-to-lymphocyte ratio (MLR) | 0.08 | 0.1-0.4 |
| Platelet to-lymphocyte ratio (PLR) | 69.2 | 97-194 |
| Mentzer Index (MI) | 19.10 | |
PERIPHERAL BLOOD SMEAR EXAMINATION FINDINGS:
RBC: Mild Anisocytosis, normocytic few microcytes hypochromia
WBC:(DLC): P45 L48 E01 M 06 (relative lymphocytosis)
Platelet: Adequate on smear
CASE STUDY 2
A 9-year-old male boy was presented with a history of fever for past one week (100-1030 F), headache, a persistent cough, shortness of breath, chest pain, weight loss, weakness, and fatigue. His complete hemogram report values were as follows:
COMPLETE BLOOD COUNT
| PARAMETER | RESULT | REFERENCE RANGE |
| Haemoglobin | 12.6 g/dl | 13–18 g/dl |
| Total erythrocyte count | 5.45 X 1012 /l | 5.0 ± 0.5 X 1012 /l |
| Total leukocyte count | 16.3 X 109/l | 7.0 ± 3.0 X 109/l |
| Differential leukocyte count | ||
| Neutrophils | 76% | 40–75% |
| Lymphocytes | 20% | 20–45 % |
| Eosinophils | 1% | 1–4 % |
| Monocytes | 3% | 2–8 % |
| PCV | 40% | 36–48% |
| MCV | 90 fL | 82–92 fL |
| MCH | 30 pg | 27–32 pg |
| MCHC | 32% | 32–36 % |
| RDW-CV | 16 | 12–14 |
| Platelet count | 144 X 109/l | 150–400 X 109/l |
| MPV | 14 | 7.5-12.0 |
| PDW | 18.6 | 15-17 |
| Absolute Neutrophil count | 12,338 | 2,500-7,500 |
| Absolute Lymphocyte count | 3,260 | 1,000-4,000 |
| Absolute Monocyte count | 489 | 200-800 |
| Neutrophil-to-lymphocyte ratio (NLR) | 3.8 | 0.78-3.53 |
| Monocyte-to-lymphocyte ratio (MLR) | 0.15 | 0.1-0.4 |
| Platelet to-lymphocyte ratio (PLR) | 44.17 | 97-194 |
| Mentzer Index (MI) | 16.5 | |
PERIPHERAL BLOOD SMEAR EXAMINATION FINDINGS:
RBC: Predominant Normocytes, few microcytes, hypochromic RBCs
WBC :(DLC) P74 L22 E01 M03 ;Toxic granules noted in the neutrophils
Platelet: Lower limit of normal
NOTE
- In Case 2 ( Pneumonia) The CBC parameters: TLC( Total leukocyte count),ANC( Absolute Neutrophil Count), MPV( Mean platelet volume), NLR( neutrophil lymphocyte ratio), MLR ( Monocyte lymphocyte ratio), are significantly higher compared to Case1 (Tuberculosis patient).
- Whereas in Case 1 (tuberculosis ) CBC parameters : ALC (Absolute lymphocyte count, PLR (platelet lymphocyte ratio) were significantly higher than in case 2 (Pneumonia)
- The comparative results of this study suggest that, the Complete Blood Count (CBC) parameters with additional features offered by 5th-generation hematology analyzer, such as TLC, ANC,MPV, PDW, NLR,MLR etc., can be cost-effective and extremely useful markers, mainly during the initial stage, in differentiating pulmonary childhood tuberculosis from community-acquired pneumonia with no additional efforts and tests .
ACKNOWLEGEMENT
We acknowledge with great appreciation; the evaluation of this Newsletter with additional appropriate changes suggested by Dr. Arsala Mulla MD: DNB Teacher and Consultant Pathologist: Shatabdi Hospital, Kandiwali West, Mumbai.
References
(1) Can Complete Blood Count Parameters and Serum Electrolyte Levels Have a Predictive Role in Differential Diagnosis of Tuberculosis from Community-acquired Pneumonia in Children? Deniz Aygün1 , Pınar Önal2 , Ayşe Ayzıt Kılınç3 , Fatih Aygün4, Rengin Şiraneci1, Haluk Çokuğraş2 DOI: 10.5152/TurkArchPediatr.2024.24015.
(2) Liam CK, Pang YK, Poosparajah S. Pulmonary tuberculosis presenting as community-acquired pneumonia. Respirology. 2006; 11(6):786-792.
(3) Aygün D, Yıldırım T, Öner ÖB, Şiraneci R. Evaluation of clinical and laboratory characteristics of childhood tuberculosis. Turk Pediatr Ars. 2020;55(3):236-243.
(4) Togun TO, MacLean E, Kampmann B, Pai M. Biomarkers for diagnosis of childhood tuberculosis: a systematic review. PLoS One. 2018;13(9):e0204029.
(5) Rudan I, Boschi-Pinto C, Biloglav Z, Mulholland K, Campbell H. Epidemiology and etiology of childhood pneumonia. Bull World Health Organ. 2008;86(5):408-416.
(6) Iliaz S, Iliaz R, Ortakoylu G, Bahadir A, Bagci BA, Caglar E. Value of neutrophil/lymphocyte ratio in the differential diagnosis of sarcoidosis and tuberculosis. Ann Thorac Med. 2014;9(4):232-235.
(7) de Jager CP, van Wijk PT, Mathoera RB, de Jongh-Leuvenink J, van der Poll T, Wever PC. Lymphocytopenia and neutrophil-lymphocyte count ratio predict bacteremia better than conventional infection markers in an emergency care unit. Crit Care. 2010;14(5):R192.
(8) Kang YA, Kwon SY, Yoon HI, Lee JH, Lee CT. Role of C-reactive protein and procalcitonin in differentiation of tuberculosis from bacterial community acquired pneumonia. Korean J Intern Med. 2009;24(4):337-342.
(9) Bozdemİr ŞE. Role of NLR and MLR in differentiating childhood tuberculosis from community acquired pneumonia. J Contemp Med. 2021;11(4):500-505.
(10) Karadag-Oncel E, Ozsurekci Y, Kara A, Karahan S, Cengiz AB, Ceyhan M. The value of mean platelet volume in the determination of community acquired pneumonia in children. Ital J Pediatr. 2013;39:16.
(11) Godkar PB, Godkar DP. Textbook of Medical laboratory technology (4th edition, 2024), Bhalani Publishers, Mumbai. India.
