Brazilian Journal of Pulmonology

ISSN (on-line): 1806-3756 | ISSN (printed): 1806-3713

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Current Issue: 2011 - Volume 37 - Number 3 (May/June)

ORIGINAL ARTICLE

Is tuberculosis difficult to diagnose in childhood and adolescence?

A tuberculose na infância e na adolescência é difícil de diagnosticar?

 

João Carlos Coelho Filho; Marwal Araújo Caribé; Simone Castro Couto Caldas; Eduardo Martins Netto

 

Abstract

Objective: To determine the sensitivity of the scoring system proposed by the Brazilian National Ministry of Health in 2002 for the diagnosis of tuberculosis in children and adolescents suspected of having the disease. Methods: This was a retrospective study of 316 children and adolescents (0-14 years of age) diagnosed with pulmonary tuberculosis between 1997 and 2007 at the Brazilian Institute for Tuberculosis Research, located in the city of Salvador, Brazil. After reviewing the medical charts and chest X-rays of the patients, we calculated the tuberculosis scores. Results: The majority of the subjects (80.4%) had a history of close household contact with an AFB-positive adult within the last two years. The tuberculin test was negative in 11 subjects (3.5%). According to the scoring system, 251 (79.4%) were very likely to have tuberculosis (score, ≥ 40), 63 (19.9%) were moderately likely to have tuberculosis (score, 30-35), and 2 (0.7%) were unlikely to have tuberculosis (score, ≤ 25). When a cut-off score of 30 was used, the sensitivity of this scoring system was 99.3%. Conclusions: In our sample, the sensitivity of this scoring system was high when the selected cut-off score was employed. If a cut-off score of 40 had been used, 20% of the subjects would not have been treated. Therefore, scores between 30 and 35 are critical for diagnostic confirmation. Judicious clinical evaluation should prevail in the decision of treating these patients. When the cut-off score of 30 is used, 30% of individuals with other pathologies will be treated for tuberculosis. This highlights the need for improved diagnostic methods for tuberculosis.

 

Resumo

Objetivo: Determinar a sensibilidade do sistema de escore proposto pelo Ministério da Saúde do Brasil em 2002 para o diagnóstico de crianças e adolescentes com suspeita de tuberculose. Métodos: Entre 1997 e 2007, 316 crianças e adolescentes (0-14 anos de idade) com diagnóstico de tuberculose pulmonar no Instituto Brasileiro de Investigação da Tuberculose, em Salvador (BA), foram incluídos no presente estudo retrospectivo. Foram revisados os prontuários médicos e as radiografias de tórax dos pacientes, e os escores foram calculados. Resultados: A maioria dos sujeitos (80,4%) tinha história de contato domiciliar com adultos com BAAR positivo nos últimos dois anos. O teste tuberculínico foi negativo em 11 sujeitos (3,5%). Conforme o sistema de escore, 251 (79,4%) muito provavelmente tinham tuberculose (escores ≥ 40), 63 (19,9%) possivelmente tinham tuberculose (escores entre 30 e 35) e 2 (0,7%) pouco provavelmente tinham tuberculose (escores ≤ 25). A sensibilidade desse sistema de escore foi de 99,3%, com um ponto de corte de 30. Conclusões: Em nossa amostra, a sensibilidade do sistema de escore foi alta para o ponto de corte selecionado. Com um ponto de corte de 40, 20% dos sujeitos não teriam sido tratados. Portanto, escores entre 30 e 35 são críticos para a definição diagnóstica. Uma avaliação clínica judiciosa deve prevalecer para a decisão de tratar esses pacientes. Com um ponto de corte de 30, 30% dos indivíduos com outras patologias seriam tratados para tuberculose. Isto enfatiza a necessidade de melhores métodos diagnósticos para a tuberculose.

 

 

Keywords: Tuberculosis/diagnosis; Epidemiology; Diagnostic techniques and procedures.

 

Palavras-chave: Tuberculose/diagnóstico; Epidemiologia; Técnicas e procedimentos diagnósticos.

 

 

Introduction

Tuberculosis is a significant health problem in Brazil, which was ranked as one of the twenty countries in the world with the highest incidence rates of the disease. In 2009, the Brazilian Tuberculosis Control Program reported 85,000 cases of tuberculosis (approximately 45 cases per 100,000 inhabitants) to the World Health Organization (WHO).(1) Between 2005 and 2009, the incidence decreased by 2.9% per year.(1) In Brazil, 7% of reported cases affected children or adolescents (0-14 years of age); in the state of Bahia,(2) this is estimated to be even greater, with 15-20% of the cases affecting children or adolescents.(3) This is thought to be an underestimate of the true prevalence of tuberculosis due to the difficulty of diagnosis. The diagnosis is complex, because quite often the results for AFB are negative.(4) Although there have been technological advances and new, promising tuberculosis diagnostic tests have been developed, which have improved sensitivity and are easy to use, none are readily available in Brazil.(5-13) In 2002, in response to the difficulty in diagnosing tuberculosis, the Brazilian National Ministry of Health (NMH) approved the use of a scoring system to facilitate the identification and treatment of potential cases.(14,15) In 2006, the WHO published a handbook comparing various scoring systems for the diagnosis and treatment of tuberculosis in children and adolescents.(16) In a study published in 2007, Sant'Anna  Hijjar(17) hailed this as a great improvement, because these new guidelines presented a careful review on the diagnosis and treatment in pediatric patients. According to the WHO scoring system, individuals 0-14 years of age are considered "very likely to have tuberculosis" if presenting with at least three of the following: chronic symptoms suggestive of tuberculosis; physical examination revealing symptoms suggestive of tuberculosis; a positive tuberculin test; and chest X-ray findings suggestive of tuberculosis. However, on the basis of a detailed analysis of the systems proposed by Edwards et al.,(18) Sant'Anna  Hijjar(17) did not recommend the use of the WHO scoring system in Brazil. The scoring system proposed by the NMH showed a better balance between sensitivity and specificity (89% and 87%, respectively) than did the WHO scoring system. In addition, Sant'Anna  Hijjar(17) found that the Brazilian scoring system was easier to implement in a health care setting in Brazil, where the tuberculosis/HIV co-infection is less frequent than that reported for African countries.(17) Indeed, another group of authors found that the NMH scoring system was also valuable in HIV-infected children and adolescents.(19)

The objective of the present study was to determine the sensitivity of the NMH scoring system for the diagnosis of tuberculosis in individuals 0-14 years of age.

Methods

This was a retrospective study. Between 1997 and 2007, 4,297 cases of tuberculosis were treated at the Instituto Brasileiro para Investigação da Tuberculose (IBIT, Brazilian Institute for the Tuberculosis Research), located in the city of Salvador, Brazil. The IBIT has an overall cure rate 85% above the cut-off value for good care of tuberculosis patients. Of the 4,297 patients, 381 (9%) were 0-14 years of age. Of those, 56 (14%) were excluded because they were diagnosed with extrapulmonary tuberculosis.
Therefore, the initial sample comprised 325 children and adolescents suspected of having pulmonary tuberculosis. All medical records, as well as chest X-rays, were reviewed by a physician and a nurse, both with more than 20 years of experience, in order to score the patients in accordance with the NMH scoring system.(15,17) Of those 325 patients, 9 were excluded for having unconfirmed diagnoses. Therefore, the final study sample consisted of 316 children and adolescents diagnosed with the pulmonary form of tuberculosis. Data regarding clinical and radiological patient status, evidence of household contacts, chest X-ray findings, tuberculin test results, and nutritional status were collected. This protocol was approved by the Research Ethics Committee of the Federal University of Bahia Climério de Oliveira Maternity Hospital.

Results

Of the 316 patients included in the study, 249 were in the 0-9 age bracket and 67 were in the 10-14 age bracket. The mean age was 6.0 years. There were 176 males (55.7%) and 140 females (44.3%). Table 1 shows the distribution of patients between 1997 and 2007. We found that 205 patients (64%) presented symptoms: fever, cough, adynamia, sputum production, weight loss, or sweating for more than two weeks. The remaining 111 patients (36%) were asymptomatic (Table 2). On chest X-rays, hilar lymph node enlargement or miliary pattern were present in 187 cases (59.2%), and condensation or infiltration for more than two weeks were present in 110 (34.8%). One patient (0.3%) presented with bronchial tuberculosis, normal radiological pattern, and positive culture in BAL fluid.






Of the 316 patients, 254 (80.4%) had a history of close household contact with an AFB-positive adult within the last two years, and 267 (82.2%) presented with adequate nutritional status (weight above the 10th percentile).

The tuberculin test was negative in 11 patients (3.5%). The characteristics of these cases were disseminated tuberculosis, in 2; HIV infection with probable immunosuppression, in 1; a positive culture for Mycobacterium tuberculosis, in 2 (1 of whom was diagnosed with bronchial tuberculosis); corticosteroid treatment for severe bronchial asthma, in 1; presence of fever when the test was performed, in 1; sickle cell anemia, in 1; positive tuberculin test upon retest in the second month of treatment, in 1; and history of household contact as well as clinical and radiological symptoms, which improved after two months of treatment, suggestive of tuberculosis, in 2. Of those 11 patients, 9 were considered cured at the final evaluation. One died due to uncontrolled lymphoma, and 1 abandoned treatment four months later, showing partial improvement in signs and symptoms.

According to the NMH scoring system (Table 3), 251 (79.4%) of the patients in our sample were very likely to have tuberculosis (score, ≥ 40), 63 (19.9%) were moderately likely to have tuberculosis (score, 30-35), and 2 (0.7%) were unlikely to have tuberculosis (score, ≤ 25). When a cut-off score of 30 was used, the sensitivity of the scoring system proposed by the NMH was 99.3%.




One of the patients scoring ≤ 25 on the NMH scoring system was an asymptomatic 10-year-old girl with a history of severe bronchial asthma, who was closely followed by a pediatrician. A chest X-ray showed perihilar condensation, and the tuberculin test was negative (the test became positive-12 mm-upon retest three months after the beginning of treatment). This child had no history of contact with tuberculosis patients. The other was an asymptomatic 4-year-old girl with a history of contact with a tuberculosis patient within the past 2 years; she was finishing treatment for Hodgkin's lymphoma and had normal weight for her age when she presented with hilar lymph node enlargement on a chest X-ray. The tuberculin test was negative. Three months after the initiation of the tuberculosis treatment, the chest X-ray was normal. However, she died during the second round of treatment for uncontrolled lymphoma.

Discussion

The NMH tuberculosis scoring system is meant to be used in children and adolescents with negative AFB results in primary care settings.(15) When a cut-off score of 30 was used, the sensitivity of this scoring system at the IBIT was 99.3%, which is quite high. These results are similar to those found by Sant'Anna et al. in two retrospective studies,(20,21) as well as to those reported by Maciel et al.(22) in a nested control-case study. If only patients with scores ≥ 40 had been considered for treatment, 20% of the patients would not have been treated. In the present study, patients with scores ranging from 30 to 35 points (20.3% of the cohort) represented a critical population for the diagnostic confirmation. In our experience, judicious clinic evaluation should prevail in the decision of whether to treat such patients. The negative predictive value of the proposed scoring system, with the low treatment cut-off score of 30 and with the acceptance of a sensitivity of 70% proposed by Maciel et al.,(22) is problematic. When this cut-off score is used, at least 30% of the patients without tuberculosis (with other pathologies) will receive tuberculosis treatment. This highlights the need for improved diagnostic methods for tuberculosis.

Another important aspect addressed in this study was the importance of the presence of an identifiable household contact with tuberculosis. In this cohort, 79.1% of the parents or guardians of the patients revealed the existence of a close household contact with active tuberculosis. In Brazil, the identification of household contacts of tuberculosis patients needs to be radically improved.(23) The Tuberculosis Control Program in the State of Bahia reported that only 8-25% of the household contacts of tuberculosis patients were investigated between 2004 and 2008. This is representative of the country as a whole, with similar findings in other states, such as Mato Grosso.(24) In addition, the decrease in the incidence rate of tuberculosis in Brazil, according to the WHO, is 2.9%, which is much lower than the ideal 11% reduction that has been achieved in other countries with better treatment control and more efficient contact outreach.(25)


Acknowledgments

The authors would like to thank Miss Choe Le Marchand, who contributed to the preparation of this manuscript, and the staff of the IBIT/José Silveira Foundation for their support.


References

1. World Health Organization [homepage on the Internet]. Geneva: World Health Organization [cited 2011 Jan 24]. Global tuberculosis control 2010. Available from: http://whqlibdoc.who.int/publications/2010/9789241564069_eng.pdf

2. Rede Intergerencial de Informações para a Saúde -- RIPSA [homepage in the Internet]. Brasília: Ministério da Saúde [cited 2009 Aug 4]. Indicadores e Dados Básicos - Brasil - 2007 Available from: http://tabnet.datasus.gov.br/cgi/idb2007/matriz.htm

3. Marais BJ, Gie RP, Schaaf HS, Hesseling AC, Obihara CC, Nelson LJ, et al. The clinical epidemiology of childhood pulmonary tuberculosis: a critical review of literature from the pre-chemotherapy era. Int J Tuberc Lung Dis. 2004;8(3):278-85.

4. Sant'Anna CC, Orfaliais CT, March Mde F, Conde MB. Evaluation of a proposed diagnostic scoring system for pulmonary tuberculosis in Brazilian children. Int J Tuberc Lung Dis. 2006;10(4):463-5.

5. Boehme C, Molokova E, Minja F, Geis S, Loscher T, Maboko L, et al. Detection of mycobacterial lipoarabinomannan with an antigen-capture ELISA in unprocessed urine of Tanzanian patients with suspected tuberculosis. Trans R Soc Trop Med Hyg. 2005 Dec;99(12):893-900.

6. Coler RN, Skeiky YA, Ovendale PJ, Vedvick TS, Gervassi L, Guderian J, et al. Cloning of a Mycobacterium tuberculosis gene encoding a purified protein derivative protein that elicits strong tuberculosis-specific delayed-type hypersensitivity. J Infect Dis. 2000;182(1):224-33.

7. Gordhan BG, Smith DA, Alderton H, McAdam RA, Bancroft GJ, Mizrahi V. Construction and phenotypic characterization of an auxotrophic mutant of Mycobacterium tuberculosis defective in L-arginine biosynthesis. Infect Immun. 2002;70(6):3080-4.

8. Kashyap RS, Rajan AN, Ramteke SS, Agrawal VS, Kelkar SS, Purohit HJ, et al. Diagnosis of tuberculosis in an Indian population by an indirect ELISA protocol based on detection of Antigen 85 complex: a prospective cohort study. BMC Infect Dis. 2007;7:74.

9. Leyten EM, Lin MY, Franken KL, Friggen AH, Prins C, van Meijgaarden KE, et al. Human T-cell responses to 25 novel antigens encoded by genes of the dormancy regulon of Mycobacterium tuberculosis. Microbes Infect. 2006;8(8):2052-60.

10. Pereira Arias-Bouda LM, Nguyen LN, Ho LM, Kuijper S, Jansen HM, Kolk AH. Development of antigen detection assay for diagnosis of tuberculosis using sputum samples. J Clin Microbiol. 2000;38(6):2278-83.

11. Huang TS, Liu YC, Bair CH, Sy CL, Chen YS, Tu HZ, et al. Detection of M. tuberculosis using DNA chips combined with an image analysis system. Int J Tuberc Lung Dis. 2008;12(1):33-8.

12. Tessema TA, Bjune G, Assefa G, Svenson S, Hamasur B, Bjorvatn B. Clinical and radiological features in relation to urinary excretion of lipoarabinomannan in Ethiopian tuberculosis patients. Scand J Infect Dis. 2002;34(3):167-71.

13. Napolitano DR, Pollock N, Kashino SS, Rodrigues V Jr, Campos-Neto A. Identification of Mycobacterium tuberculosis ornithine carboamyltransferase in urine as a possible molecular marker of active pulmonary tuberculosis. Clin Vaccine Immunol. 2008;15(4):638-43.

14. Brasil. Ministério da Saúde. Fundação Nacional de Saúde; Sociedade Brasileira de Pneumologia e Tisiologia. Controle da Tuberculose: uma proposta de integração ensino serviço. Rio de Janeiro: FUNASA/CRPHF/SBPT; 2002.

15. Ministério da Saúde [homepage on the Internet]. Brasília: Ministério da Saúde [cited 2011 Jan 14]. Manual de Recomendações para o Controle da Tuberculose no Brasil. [Adobe Acrobat document, 186p.] Available from: http://portal.saude.gov.br/portal/arquivos/pdf/manual_de_recomendacoes_controle_tb_novo.pdf

16. World Health Organization. Guidance for national tuberculosis programmes on the management of tuberculosis in children. Geneva: World Health Organization; 2006.

17. Sant'Anna CC, Hijjar MA. Recent contribution of the World Health Organization to control childhood tuberculosis [Article in Portuguese]. Rev Saude Publica. 2007;41 Suppl 1:117-20.

18. Edwards DJ, Kitetele F, Van Rie A. Agreement between clinical scoring systems used for the diagnosis of pediatric tuberculosis in the HIV era. Int J Tuberc Lung Dis. 2007;11(3):263-9.

19. Pedrozo C, Sant'Anna CC, March Mde F, Lucena SC. Efficacy of the scoring system, recommended by the Brazilian National Ministry of Health, for the diagnosis of pulmonary tuberculosis in children and adolescents, regardless of their HIV status. J Bras Pneumol. 2010;36(1):92-8.

20. Sant'Anna CC, Orfaliais CT, March Mde F. A retrospective
evaluation of a score system adopted by the Ministry of Health, Brazil in the diagnosis of pulmonary tuberculosis in childhood: a case control study. Rev Inst Med Trop Sao Paulo. 2003;45(2):103-5.

21. Sant'Anna CC, Santos MA, Franco R. Diagnosis of pulmonary tuberculosis by score system in children and adolescents: a trial in a reference center in Bahia, Brazil. Braz J Infect Dis. 2004;8(4):305-10.

22. Maciel EL, Dietze R, Silva RE, Hadad DJ, Struchiner CJ. Evaluation of a scoring system recommended by the Brazilian Ministry of Health for the diagnosis of childhood tuberculosis [Article in Portuguese]. Cad Saude Publica. 2008;24(2):402-8.

23. Lemos AC, Matos ED, Pedral-Sampaio DB, Netto EM. Risk of tuberculosis among household contacts in Salvador, Bahia. Braz J Infect Dis. 2004;8(6):424-30.

24. Hartwig SV, Ignotti E, Oliveira BF, Pereira HC, Scatena JH. Evaluation of surveillance of contacts of new tuberculosis cases in the state of Mato Grosso - Brazil. J Bras Pneumol. 2008;34(5):298-303.

25. Rieder HL, Cauthen GM, Comstock GW, Snider DE Jr. Epidemiology of tuberculosis in the United States. Epidemiol Rev. 1989;11:79-98.




* Study carried out at the José Silveira Foundation, Salvador, Brazil.
Correspondence to: João Carlos Coelho Filho. Ladeira do Campo Santo, s/n, Federação, CEP 40210-320, Salvador, BA, Brazil.
Tel. 55 71 3504-5295. Fax: 55 71 3504 5273. E-mail: patologia@fjs.org.br
Financial support: None.
Submitted: 11 November 2010. Accepted, after review: 11 March 2011.
** A versão completa em português deste artigo está disponível em www.jornaldepneumologia.com.br



About the authors

João Carlos Coelho Filho
Pathologist. Laboratory of Pathology, José Silveira Foundation, Salvador, Brazil.

Marwal Araújo Caribé
Pediatrician. Instituto Brasileiro para Investigação da Tuberculose - IBIT, Brazilian Institute for the Tuberculosis Research - José Silveira Foundation, Salvador, Brazil.

Simone Castro Couto Caldas
Nurse Researcher. Instituto Brasileiro para Investigação da Tuberculose - IBIT, Brazilian Institute for the Tuberculosis Research - José Silveira Foundation, Salvador, Brazil.

Eduardo Martins Netto
Professor of Biostatistics. Universidade Federal da Bahia - UFBA, Federal University of Bahia - Salvador, Brazil.

 

 


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