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Clinicoepidemiologic considerations in the diagnosis of tuberculous lymphadenitis: evidence from a high burden country

  • Author Footnotes
    # These authors contributed equally to this work.
    Wubshet Assefa
    Correspondence
    Corresponding author: Wubshet Assefa, Debre Markos University, Tel: +251921872183.
    Footnotes
    # These authors contributed equally to this work.
    Affiliations
    Department of Pathology, School of medicine, Debre Markos University, Debre Markos, Ethiopia
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  • Author Footnotes
    # These authors contributed equally to this work.
    Tewodros Eshete
    Footnotes
    # These authors contributed equally to this work.
    Affiliations
    Department of Health informatics, College of Health Sciences, Debre Markos University, Debre Markos, Ethiopia
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  • Author Footnotes
    # These authors contributed equally to this work.
    Yoseph Solomon
    Footnotes
    # These authors contributed equally to this work.
    Affiliations
    Department of Surgery, School of medicine, Debre Markos University, Debre Markos, Ethiopia
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    # These authors contributed equally to this work.
    Bersabeh Kassaye
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    # These authors contributed equally to this work.
    Affiliations
    Armauer Hansen Research Inistitute (AHAI), Addis Ababa, Ethiopia
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  • Author Footnotes
    # These authors contributed equally to this work.
Open AccessPublished:September 24, 2022DOI:https://doi.org/10.1016/j.ijid.2022.09.030

      Highlights

      • Tuberculous lymphadenitis (TBL) often presents as a fluctuant neck mass with raised erythrocyte sedimentation rate.
      • Most TBL patients have no constitutional symptoms or cough.
      • HIV infection and chronic medical illness are infrequent in TBL patients.

      Abstract

      Objectives

      Tuberculosis is the biggest health issue worldwide, with tuberculous lymphadenitis (TBL) being its most common extrapulmonary manifestation. Clinical diagnoses of TBL often pose challenges; thus, this study aimed to analyze the clinical, epidemiologic, and laboratory aspects of TBL in Debre Markos Specialized Comprehensive Hospital, northwest Ethiopia.

      Methods

      The study was conducted at Debre Markos Specialized Comprehensive Hospital from October 2019 to March 2021. Patients with lymphadenitis displaying cytomorphologic features of tuberculosis were enrolled. A checklist was used to collect clinicodemographic data.

      Results

      Among a total of 294 patients with TBL, 237 (80.61%) were adults aged 15-45 years. A fluctuant consistency (177; 60.20%; n = 294) with predominant involvement of cervical lymph nodes (229; 77.8%) was the most frequent presentation. Most patients did not have either HIV infection (235; 94.37%; n = 261) or known chronic medical illnesses (250; 95.8%). Constitutional symptoms (113; 41.85%; n = 270) and chronic cough (56; 20.74%; n = 270) were infrequent. The erythrocyte sedimentation rate (ESR) was increased in the majority of patients (133; 80%; n = 165), of whom extreme elevation (≥100 mm/hour) seen in 63 (38.18 %) patients and the mean ESR for our participants was 78.64 mm/hour.

      Conclusion

      TBL typically presents as a fluctuant neck mass, predominantly in young adults. The majority of patients have no constitutional symptoms or cough. HIV infection or chronic medical illnesses are uncommon. The raised erythrocyte sedimentation rate is a fairly consistent finding.

      Keywords

      Introduction

      Tuberculosis (TB) is a communicable disease, placed as one of the top 10 causes of mortality worldwide and the leading cause of death caused by a single infectious agent (ranked ahead of HIV/AIDS). In 2019, an estimated 10 million individuals worldwide contracted TB, from which 5.6 million males, 3.2 million women, and 1.2 million children comprise the population (
      • Chakaya J
      • Khan M
      • Ntoumi F
      • Aklillu E
      • Fatima R
      • Mwaba P
      • et al.
      Global tuberculosis Report 2020 - Reflections on the Global TB burden, treatment and prevention efforts.
      ). According to
      World Health Organization
      Global Tuberculosis Report.
      report, Ethiopia is among the 30 high TB burden countries in the world. Despite efforts made by the international community, targeting to end the worldwide TB epidemic by 2030, the TB burden still remains high (
      • Lönnroth K
      • Raviglione M.
      The WHO's new End TB Strategy in the post-2015 era of the Sustainable Development Goals.
      ).
      TuberculousB lymphadenitis (TBL) is a chronic specific granulomatous inflammation that causes necrosis in a lymph node (LN) (
      • Brizi MG
      • Celi G
      • Scaldazza AV
      • Barbaro B.
      Diagnostic imaging of abdominal tuberculosis: gastrointestinal tract, peritoneum, lymph nodes.
      ). It is the most common clinical presentation of extrapulmonary TB (EPTB), which most frequently involve the cervical LNs, followed by mediastinal, axillary, and mesenteric LNs (
      • Nayak S
      • Mani R
      • Kavatkar AN
      • Puranik SC
      • Holla VV.
      Fine-needle aspiration cytology in lymphadenopathy of HIV-positive patients.
      ).
      The World Health Organization estimates that the proportion of EPTB among the total number of new TB cases is about 36.6%. Ethiopia ranks third in the number of EPTB cases worldwide, most of which are TBL (
      World Health Organization
      Global Tuberculosis Report.
      ).
      In Ethiopia, EPTB accounted for 34.8% of TB cases, with TBL being the most common type (80%) (
      • Biadglegne F
      • Tesfaye W
      • Sack U
      • Rodloff AC.
      Tuberculous lymphadenitis in Northern Ethiopia: in a public health and microbiological perspectives.
      ). This is in contrast to the proportion of EPTB in other high TB burden Asian nations, such as India (14.9%), China (4%), and Indonesia (2.5%), as well as African countries like Nigeria (4.3%) (
      World Health Organization
      Global Tuberculosis Report.
      ).
      Fine-needle aspiration cytology (FNAC) technique remains a cheap and effective method for the diagnosis of TBL because it provides reliable cytomorphological features with clearly defined sufficient criteria (
      • Saboorian MH
      • Ashfaq R.
      The use of fine needle aspiration biopsy in the evaluation of lymphadenopathy.
      ;
      • Sulaiman A
      • Afshan S
      • Tazeen M
      • Talat M
      • Akbar A.
      Rafiq k. A comparison of fine needle aspiration cytology with Ziehl Neelsen staining in diagnosis of tuberculosis lymphadenitis.
      ).
      The clinical diagnosis of TBL in suspected cases may be difficult due to atypical and diverse presentations, and a definitive diagnosis needs microbiological, cytopathological, histopathological, and molecular methods, all of which may be costly and associated with diagnostic delay (
      • Ahasan HN
      • Bala CS.
      Hurdles in management of extra pulmonary tuberculosis.
      ;
      • Golden MP
      • Vikram HR.
      Extrapulmonary tuberculosis: an overview.
      ;
      • Zeka AN
      • Tasbakan S
      • Cavusoglu C.
      Evaluation of the GeneXpert MTB/RIF assay for rapid diagnosis of tuberculosis and detection of rifampin resistance in pulmonary and extrapulmonary specimens.
      ). For timely and appropriate diagnoses of TBL, clinicians in resource-scarce areas strongly rely on the supporting clinical and laboratory findings. Hence, this study aimed to investigate the epidemiologic, clinical, and laboratory aspects of TBL in one of the high TB burden regions of Ethiopia.

      Material and methods

      Study area and period

      The study was conducted in Debre Markos Specialized Comprehensive Hospital (DMSCH), which is found in Debre Markos town, Amhara regional state, in the northwestern part of Ethiopia. DMSCH is a teaching university hospital serving an estimated 3.5 million patients.
      The pathology department is one of the major units in DMSCH that has an estimated annual flow of 7000 cases. It is the unit where this research was carried out from October 2019 to March 2021.

      Populations

      Source population: all patients with lymphadenitis who presented to the cytopathology department.
      Study population: patients with lymphadenitis who displayed cytomorphologic evidence of TB during the study period.

      Sample size and sample technique

      All the patients who came within the study period and fulfilled the inclusion criteria were included in this study.

      Inclusion and exclusion criteria

      Inclusion criteria: all patients with lymphadenitis who presented to the cytopathology department during the study period, showing cytomorphologic features of TB.
      Exclusion criteria: patients on anti-TB treatment at the time of the LN aspiration were excluded from the study.
      Study design: a cross-sectional study design with prospective data collection was used.

      Data collection instrument

      Recruitment of study participants and data collection: clients with suspected TBL were subjected to FNAC, from which only those cases which showed the cytomorphologic features of TB were recruited, and a structured questionnaire was used to assess the sociodemographic and clinical information. Moreover, a medical record review was made to collect relevant laboratory and radiologic results.
      FNAC sample collection and processing: at the DMSCH Pathology Department, after receiving written informed consent, the FNAC of LN was performed as follows (
      • Kocjan G.
      Fine needle aspiration cytology: diagnostic principles and dilemmas.
      ): first, the FNAC was done on enlarged peripheral LN using a sterile 21-gauge needle. The overlying area was cleaned with 70% alcohol. Then, the target LN was immobilized with one hand, and the needle was carefully introduced into the lesion by developing a negative pressure in the syringe. At least six in and out passes were made by the needle without exiting the node. After removing the needle, two drops of aspirate were placed on three clean slides for cytomorphologic evaluation. The FNAC smears were prepared on clean slides on the spot. The slides were air dried and flooded with freshly filtered Weltered Wright stain and buffered with clean tap water. The buffered slides were then continuously stained with Wright stain for 10 minutes and with tap water, and air dried.
      Finally, the slides were examined by pathologists to evaluate for the presence of the following cytomorphologic features of TBL: epithelioid cell aggregate with or without Langerhans giant cells and necrosis, epithelioid cell aggregate without necrosis, necrosis without epithelioid cell aggregate, or polymorphocytes with necrosis.
      Data collector: a pathologist and three technical assistants participated in the data collection and preparation process.

      Statistical analysis

      After the data collection was completed, data were coded, edited, and entered into Epidata version 3.1. The statistical analysis was conducted using statistical software (STATA 14.1). Description of results was done using frequency, percentage, tables, and graphs. The chi-square test was conducted to look into the relationship of various independent variables with dependent variables.

      Data quality control

      The data collection was conducted by a well-trained and experienced senior pathologist, medical laboratory technicians, and technical assistants. On-the-spot supervision was done by the principal investigator, using a checklist and monitoring sheet to ensure the completeness of the information. Laboratory investigation was conducted as per the standard operating procedure manual, and the data collection instrument was pretested and checked for its validity.

      Results

      A total of 294 patients with cytomorphologic diagnoses of TBL using the FNAC method were enrolled in this study. Most of the participants (237; 80.61%) were under the age of 45 years. A vast majority (241; 82.25%) were from rural areas, and the female-to-male ratio in our study participants was 1.25: 1.
      The most common sites of LN involvement by TB were found to be the cervical LNs (229; 77.89%), followed by axillary LNs (35; 11.90%), and generalized LN involvements were identified in about 11 (3.74%) cases. Over half (177; 60.2%) of the LNs were fluctuant in consistency, and approximately one-fourth of the participants (72; 24.49%) had sinus tract formation. Although more than half (161; 54.76%) of the patients took antibiotics within 2 weeks before their hospital visit, only 16 (5.44%) had a history of anti-TB medications.
      Among our study participants, most (221; 75.17%) had no contact history with known patients with TB, and only a few (11; 3.74%) were found to have a chronic medical illness. Of the 249 subjects tested for HIV, 14 (5.6%) were found to be HIV-positive. In this study, we have found that most of the patients (157; 53.4%) and 214 (72.79%) had no constitutional symptoms and cough, respectively.
      The mean erythrocyte sedimentation rate (ESR) for all our participants was 78.64 mm/hour. Raised ESR was seen in 133 (80.6%) patients. Although 29 (17.6%) patients had mild ESR elevation (ranging from 20-49 mm/hour for females and 15-49 mm/h for males), 42 (25.5%) and 63 (38.2%) patients had moderate (50-99 mm/hour) and extreme (>100 mm/hour) elevation of ESR, respectively. To assess factors associated with ESR, chi-square testingwas done, and no statistically significant difference in mean ESR values was seen between age groups, distribution pattern, HIV status, and presence of constitutional symptoms.
      The chest X-ray finding was suggestive of pulmonary TB (PTB) in around 10 (10.75 %) patients (Table 1).
      Table 1Characteristics of patients presented with TBL at Debre Markos Specialized Comprehensive Hospital (2021) (n = 294).
      Sociodemographic characteristicsFrequencyPercent
      Age<15237.82
      15-3014047.62
      31-457425.17
      46-604314.63
      SexMale13144.56
      Female16355.44
      ResidenceUrban5217.75
      Rural24182.25
      Clinical characteristics of TBL
      Distribution pattern of TBLGeneralized113.74
      Cervical22977.89
      Axillary3511.90
      Inguinal62.04
      Others134.42
      Consistency of affected lymph nodeFirm11739.80
      Fluctuant17760.20
      Presence of sinus tractYes7224.49
      No22275.51
      Constitutional symptomsPresent11338.44
      Absent15753.40
      Unknown248.16
      CoughPresent5619.05
      Absent21472.79
      Unknown248.16
      Medical history
      History of antibiotic treatmentPresent16154.76
      Absent6020.41
      Unknown7324.83
      History of anti-TB treatmentPresent165.44
      Absent22275.51
      Unknown5619.05
      Contact with TB patientPresent186.12
      Absent22175.17
      Unknown5518.71
      Chronic medical illnessPresent113.74
      Absent25085.03
      Unknown3311.22
      Investigation findings
      Chest X-ray finding (n=93)Suggests Pulmonary TB1010.75
      Not pulmonary TB8389.25
      HIV Test (n=249)Positive145.62
      Negative23594.38
      Erythrocyte sedimentation rate (n=165)Normal3219.39
      Raised13380.61
      TB, Tuberculosis; TBL, Tuberculous lymphadenitis.
      After the chi-square tests were conducted, age was the only variable that was found to be significantly related to the distribution of TBL (Table 2).
      Table 2Chi-square test of respondent's characteristics with consistency and distribution of TB lymphadenitis (n=294).
      Sociodemographic characteristicsConsistencyDistribution
      (firm or fluctuant)(cervical or noncervical)
      AgeChi2 = 1.3332Chi2 = 9.9077
      P-value = 0.856P-value = 0.042
      SexChi2 = 1.5139Chi2 = 1.3033
      P-value = 0.219P-value = 0.254
      ResidenceChi2 = 0.0054Chi2 = 1.6932
      P-value = 0.941P-value = 0.193
      Medical history
      History of antibiotic treatmentChi2 = 0.3191Chi2 = 1.5605
      P-value = 0.853P-value = 0.458
      History of anti-TB treatmentChi2 = 1.4879Chi2 = 2.9893
      P-value = 0.475P-value = 0.224
      Contact with TB patientChi2 = 3.2327Chi2 = 3.2642
      P-value = 0.199P-value = 0.196
      Chronic medical illnessChi2 = 2.1491Chi2 = 2.2547
      P-value = 0.341P-value = 0.324
      Investigation findings
      Chest X-ray finding (n=93)Chi2 = 3.5881Chi2 = 1.1944
      P-value = 0.166P-value = 0.550
      HIV Test (n=249)Chi2 = 2.0891Chi2 = 1.3550
      P-value = 0.352P-value = 0.508
      Erythrocyte sedimentation rate (n=165)Chi2 = 1.2664Chi2 = 0.1212
      P-value = 0.260P-value = 0.728
      TB, Tuberculosis.

      Discussion

      In this facility-based cross-sectional study conducted in Debre Markos Comprehensive Specialized Hospital, we investigated the clinical characteristics and possible associated factors among patients with a cytomorphologic diagnosis of TBL. Among 294 study participants, the majority of them were young adults (aged 15-45 years); this finding is in agreement with other studies (
      • Mathiasen VD
      • Eiset AH
      • Andersen PH
      • Wejse C
      • Lillebaek T.
      Epidemiology of tuberculous lymphadenitis in Denmark: a nationwide register-based study.
      ,
      • Mathiasen VD
      • Andersen PH
      • Johansen IS
      • Lillebaek T
      • Wejse C.
      Clinical features of tuberculous lymphadenitis in a low-incidence country.
      ;
      • Muluye D
      • Biadgo B
      • Woldegerima E
      • Ambachew A.
      Prevalence of tuberculous lymphadenitis in gondar university hospital, Northwest Ethiopia.
      ). This finding may challenge the previous thought of increased incidence of TB among elderlies and infants (
      • Schaaf HS
      • Collins A
      • Bekker A
      • Davies PDO.
      Tuberculosis at extremes of age.
      ).
      The vast majority of our patients with TBL came from rural areas, and this high prevalence is supported by other studies conducted in Bangladesh and Ethiopia (
      • Biadglegne F
      • Tesfaye W
      • Sack U
      • Rodloff AC.
      Tuberculous lymphadenitis in Northern Ethiopia: in a public health and microbiological perspectives.
      ;
      • Kamal MS
      • Hoque MH
      • Chowdhury FR
      • Farzana R.
      Cervical tuberculous lymphadenitis: clinico-demographic profiles of patients in a secondary level hospital of Bangladesh.
      ;
      • Zenebe Y
      • Adem Y
      • Tulu B
      • Mekonnen D
      • Derbie A
      • Mekonnen Z
      • Biadglegne F.
      Tuberculosis lymphadenitis and human immunodeficiency virus co-infections among lymphadenitis patients in Northwest Ethiopia.
      ), suggesting the possibility of zoonotic transmission because close contact with domestic animals and the habit of raw milk ingestion are more commonly seen in rural settings (
      • Gumi B
      • Schelling E
      • Berg S
      • Firdessa R
      • Erenso G
      • Mekonnen W
      • et al.
      Zoonotic transmission of tuberculosis between pastoralists and their livestock in South-East Ethiopia.
      ). Similar to other studies (
      • Abebe G
      • Deribew A
      • Apers L
      • Abdissa A
      • Deribie F
      • Woldemichael K
      • et al.
      Tuberculosis lymphadenitis in Southwest Ethiopia: a community based cross-sectional study.
      ;
      • Fontanilla JM
      • Barnes A
      • Von Reyn CF.
      Current diagnosis and management of peripheral tuberculous lymphadenitis.
      ;
      • Mekonnen D
      • Derbie A
      • Abeje A
      • Shumet A
      • Nibret E
      • Biadglegne F
      • et al.
      Epidemiology of tuberculous lymphadenitis in Africa: a systematic review and meta-analysis.
      ;
      • Taye H
      • Alemu K
      • Mihret A
      • Wood JLN
      • Shkedy Z
      • Berg S
      • Aseffa A
      • consortium ETHICOBOTS
      Factors associated with localization of tuberculosis disease among patients in a high burden country: a health facility-based comparative study in Ethiopia.
      ), most of the patients were female, which can be explained by the immunologic (
      • Bothamley GH
      Genetics and tuberculosis.
      ), social (
      • Kamal MS
      • Hoque MH
      • Chowdhury FR
      • Farzana R.
      Cervical tuberculous lymphadenitis: clinico-demographic profiles of patients in a secondary level hospital of Bangladesh.
      ), and smoking status (
      • Chiang C
      • Slama K
      • Enarson D.
      Associations between tobacco and tuberculosis.
      ) variations.
      Cervical LNs are the most common site of involvement (77.89%); this finding is in agreement with other studies (
      • Mathiasen VD
      • Andersen PH
      • Johansen IS
      • Lillebaek T
      • Wejse C.
      Clinical features of tuberculous lymphadenitis in a low-incidence country.
      ;
      • Mekonnen D
      • Derbie A
      • Abeje A
      • Shumet A
      • Nibret E
      • Biadglegne F
      • et al.
      Epidemiology of tuberculous lymphadenitis in Africa: a systematic review and meta-analysis.
      ;
      • Neelakantan S
      • Nair PP
      • Emmanuel RV
      • Agrawal K.
      Diversities in presentations of extrapulmonary tuberculosis.
      ), partly explained by the lymphohematogenous spread of PTB (
      • Kent DC.
      Tuberculous lymphadenitis: not a localized disease process.
      ) and the hyper-reaction of LNs against previous PTB (
      • Schlossberg DL.
      Tuberculosis and nontuberculous mycobacterial infections.
      ). Most of the LNs in our patients with TBL presented as fluctuant swelling, in contrast to the predominant firm consistency seen in other studies (
      • Bothamley GH
      Genetics and tuberculosis.
      ). This could be explained by the delayed arrival of patients to the health facility (
      • Mathiasen VD
      • Hansen AK
      • Eiset AH
      • Lillebaek T
      • Wejse C.
      Delays in the diagnosis and treatment of tuberculous lymphadenitis in low-incidence countries: a systematic review.
      ), resulting in the late “Jones and Campbell stage” of the disease (
      • Gandhare A
      • Mahashur A.
      Tuberculosis of the lymph nodes: many facets, many hues.
      ).
      Around 5% of our study participants had a history of anti-TB treatment, which is lower in prevalence than the 9.1% (
      • Metaferia Y
      • Seid A
      • Fenta GM
      • Gebretsadik D.
      Assessment of extrapulmonary tuberculosis using gene Xpert MTB/RIF assay and fluorescent microscopy and its risk factors at Dessie referral hospital, Northeast Ethiopia.
      ) and 12% (
      • Mekonnen D
      • Derbie A
      • Abeje A
      • Shumet A
      • Nibret E
      • Biadglegne F
      • et al.
      Epidemiology of tuberculous lymphadenitis in Africa: a systematic review and meta-analysis.
      ) findings in other studies conducted in Africa. Among our study participants, only a quarter of patients had contact with known or suspected patients with TB, and this is similar to other studies conducte.d in Ethiopia (
      • Berg S
      • Schelling E
      • Hailu E
      • Firdessa R
      • Gumi B
      • Erenso G
      • Hussein J
      • et al.
      Investigation of the high rates of extrapulmonary tuberculosis in Ethiopia reveals no single driving factor and minimal evidence for zoonotic transmission of Mycobacterium bovis infection.
      ;
      • Zenebe Y
      • Adem Y
      • Tulu B
      • Mekonnen D
      • Derbie A
      • Mekonnen Z
      • Biadglegne F.
      Tuberculosis lymphadenitis and human immunodeficiency virus co-infections among lymphadenitis patients in Northwest Ethiopia.
      ). This might signify looking for nonairborne transmission dynamics.
      In contrast to other study findings (
      • Mathiasen VD
      • Andersen PH
      • Johansen IS
      • Lillebaek T
      • Wejse C.
      Clinical features of tuberculous lymphadenitis in a low-incidence country.
      ;
      • Metaferia Y
      • Seid A
      • Fenta GM
      • Gebretsadik D.
      Assessment of extrapulmonary tuberculosis using gene Xpert MTB/RIF assay and fluorescent microscopy and its risk factors at Dessie referral hospital, Northeast Ethiopia.
      ;
      • Taye H
      • Alemu K
      • Mihret A
      • Wood JLN
      • Shkedy Z
      • Berg S
      • Aseffa A
      • consortium ETHICOBOTS
      Factors associated with localization of tuberculosis disease among patients in a high burden country: a health facility-based comparative study in Ethiopia.
      ), we have found a very low level of comorbidity with other chronic medical illnesses in our patients with TBL. The HIV positivity rate in patients with TBL was 5.6%, which is consistent with another study conducted in Denmark (
      • Mathiasen VD
      • Andersen PH
      • Johansen IS
      • Lillebaek T
      • Wejse C.
      Clinical features of tuberculous lymphadenitis in a low-incidence country.
      ).
      In this study, constitutional symptoms were seen in nearly half of the cases, which are slightly lower than findings in other studies (
      • Gupta V
      • Bhake A.
      Clinical and cytological features in diagnosis of peripheral tubercular lymphadenitis - a hospital-based study from central India.
      ;
      • Mathiasen VD
      • Andersen PH
      • Johansen IS
      • Lillebaek T
      • Wejse C.
      Clinical features of tuberculous lymphadenitis in a low-incidence country.
      ). Nearly 27% of patients complained of cough of more than 2 weeks duration, which is similar to a finding in another study (
      • Mekonnen D
      • Derbie A
      • Abeje A
      • Shumet A
      • Nibret E
      • Biadglegne F
      • et al.
      Epidemiology of tuberculous lymphadenitis in Africa: a systematic review and meta-analysis.
      ); however, this finding is higher than in another study conducted in Northern Ethiopia (
      • Biadglegne F
      • Tesfaye W
      • Sack U
      • Rodloff AC.
      Tuberculous lymphadenitis in Northern Ethiopia: in a public health and microbiological perspectives.
      ).
      The radiologic suggestion of PTB was made in only 10.75%, which is significantly lower than the findings in Germany (
      • Singh DD
      • Vogel M
      • Müller-Stöver I
      • El Scheich T
      • Winzer M
      • Göbels S
      • et al.
      TB or not TB? Difficulties in the diagnosis of tuberculosis in HIV-negative immigrants to Germany.
      ). This may suggest the occurrence of tubercular lymphadenitis through direct exposure to infection rather than an extension from pulmonary focus (
      • Deveci HS
      • Kule M
      • Kule ZA
      • Habesoglu TE.
      Diagnostic challenges in cervical tuberculous lymphadenitis: a review.
      ). ESR elevation was noted in about 80%, which is similar to the 75% findings in Germany (
      • Singh DD
      • Vogel M
      • Müller-Stöver I
      • El Scheich T
      • Winzer M
      • Göbels S
      • et al.
      TB or not TB? Difficulties in the diagnosis of tuberculosis in HIV-negative immigrants to Germany.
      ), of which extreme ESR elevation of ≥100 mm/hour was seen in about half of the patients. The mean ESR of all our participants was 78.64 mm/hour. No statistically significant difference in mean ESR values was seen between age groups, distribution pattern, HIV status, and the presence of constitutional symptoms.

      Conclusion

      In this study, we described the clinicoepidemiologic characteristics of TBL. Our findings outlined that TBL was most common among young adults residing in rural areas. Cervical LN involvement and fluctuant consistency were the most frequent pattern of presentation. Constitutional symptoms were infrequent among patients with TBL. Chronic cough and radiologic findings of PTB were uncommon. Most patients with TBL had neither contact with known patients with TB nor a history of anti-TB treatment. The majority of patients showed raised ESRl; one-third of whom displayed an extreme elevation of ≥100 mm/hour. Comorbidity with HIV and other chronic medical illnesses was rare in patients with TBL.
      In summary, this study highlighted that fluctuant swellings on the neck, especially in young adults aged 15-30 years, should elicit strong suspicion of TBL, even in the absence of constitutional symptoms. ESR elevations strongly complement the diagnosis of TBL. The rare occurrence of chronic cough and radiologic features of PTB as well as the paucity of contact history with PTB, suggest the possibility of nonairborne transmission for TBL. The lower prevalence of HIV and other chronic medical illnesses in our patients may hint at the presence of other predisposing factors.

      Recommendation

      The authors recommend that health professionals in high TB burden countries to have a high degree of suspicion of TBL even in the absence of constitutional symptoms or known predisposing factors and to incorporate ESR evaluation as a diagnostic adjunct. The authors would like to suggest researchers to further investigate the transmission patterns and predisposing factors of TBL.

      Funding

      This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

      Ethical approval and informed consent

      This study has been approved by the Research Ethical Review Committee of the School of Medicine, Debre Markos University (S/R/C/44/08/12). Before the main data collection, written informed consent was acquired after the studies were well explained. The laboratory procedure done with the essence of beneficence and the data were kept confidential.

      Author contributions

      WA, TE, YS, and BM conceived the study, conducted data analysis, and designed and wrote the manuscript for publication. All the authors critically read and approved the final manuscript.

      Consent for publication

      Not applicable.

      Availability of data and materials

      Supporting data for the current study are available from the corresponding author on reasonable request.

      Declaration of Competing Interest

      The authors have no competing interests to declare.

      Acknowledgments

      The authors would like to thank Debre Markos University for arranging this program and giving the authors the opportunity to go through the identification of the health problems and to take part in problem-solving activities.

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