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BMC Research Notes

Open Access

Resistant tuberculosis in Maranhão, Brazil: a case series

  • Kenia Regina Oliveira Maia1,
  • Graça Maria de Castro Viana2Email author,
  • Marcos Antonio Custódio Neto da Silva3,
  • Maria do Desterro Soares Brandão Nascimento4,
  • Victor Lima de Souza5 and
  • Silvio Gomes Monteiro1
BMC Research Notes20169:260

https://doi.org/10.1186/s13104-016-2063-x

Received: 20 November 2015

Accepted: 25 April 2016

Published: 4 May 2016

Abstract

Background

Mycobacterium tuberculosis multidrug resistance, especially against rifampicin and isoniazid, places pulmonary tuberculosis in the list of emerging diseases. The misuse of therapeutic regimens is one of its main predisposing factors.

Case presentation

Four clinical cases (three were brown and one black) with multidrug-resistant tuberculosis, treated in a reference hospital in the state of Maranhão, Brazil, were reported to evaluate the importance of radiological framework on disease evolution.

Conclusion

The clinical framework showed a bad evolution and drug resistance, while radiology showed lung lesions, ranging from exudative infiltrates to lung parenchyma disintegration.

Keywords

TuberculosisAnti-tuberculosis drugsResistance

Background

The adverse effects of anti-tuberculosis drugs are related to the high incidence of noncompliance to treatment [1]. Bacillus’ resistance to anti-tuberculosis drugs is related to wild strain mutations and the mutant selection process during treatment [24] in cases related to discontinuation or irregular treatment with standard regimens. Cases that led to primary resistance or acquired resistance, without contact, have also been found upon using specific drugs [5]. Cavitary tuberculosis cause outbreaks with higher resistance and mutant frequency [2].

This paper shows four clinical cases of patients with multidrug-resistant tuberculosis (MDR-TB) assisted in a reference hospital in the state of Maranhão, Brazil. In addition, the radiological framework importance on disease evolution was assessed.

Case presentation

This paper consists of a retrospective study with 41 confirmed MDR-TB cases in 2003–2010. Only four cases are described in this series, as they had a complete supporting documentation.

Case 1

A 33-year-old man, brown, married, was admitted in October 2006, with a history of Scheme III failure (indicated for therapeutic failure; 2 months with streptomycin, ethionamide, ethambutol and pyrazinamide, and 4 months with ethionamide and ethambutol) and resistance to rifampicin, isoniazid and streptomycin; negative HIV test; chest radiograph showed a right hemithorax fissure rectification and an exudative bronchiectasis lesion in the hemithorax. One year and 1 month later, fibro-atelectatic lesions were observed in the right upper lobe. The patient initiated the MDR-TB treatment 3 years later, having a positive sputum smear for acid-fast bacilli (AFB), confirmed by culture, with an oscillating pattern, and two positive cultures for Mycobacterium tuberculosis, with resistance to isoniazid, rifampicin, streptomycin and ethambutol. MR scheme for MR-X was conducted with ciprofloxacin, clarithromycin and pyrazinamide. Terizidone and bacilloscopies continued with an oscillating pattern. During 2 years and 6 months, two negative cultures were performed, with clinical resolution and radiological pattern of healing (Table 1).

Case 2

A 27-year-old woman, brown, single, student, with a history of irregular treatment with regimen I in 2005 (indicated for new pulmonary and extra-pulmonary tuberculosis cases, except tuberculous meningitis; 2 months with rifampicin, isoniazid and ethambutol, and 4 months with rifampicin and isoniazid). HIV was negative. After 6 months, the patient developed productive cough, fatigue, fever episodes and gastrointestinal symptoms, then resumed with the tuberculostatic medication. The radiological framework showed residual pleural injury. Three years later, a cavitary lesion in the left upper lobe and bilaterally diffuse alveolar infiltrates were found when the enhanced scheme I was repeated, as having a positive sputum smear for AFB. A month later, bilateral lesions were found with cavities in the right upper lobe, positive smear and culture, and then the MDR-TB treatment began. Three months later, the positive culture remained, and a bilateral parenchymal fibrosis to the right was observed. A month later, the radiological examination showed bilaterally diffuse interstitial-alveolar infiltrate. Two months later, the radiological examination showed alveolar lesions in the apices, an atelectasis band to the right and a positive culture. Four years later, decreased lung size, atelectasis bands and cavitary lesions in the upper lobes were found. Three months later, bilateral bronchiectasis areas were observed. After three months, the patient was in a severe general condition. Five years later, a positive smear was found and an alternative scheme began. A month later, bilateral cavitation areas were observed, with right lung reduction. Three months later, radiological pattern persisted and positive smear with sensitivity tests indicating isoniazid and rifampicin resistance were found. Although the patient was treated, the severity evolved without improvement and the patient died 2 months later (Table 1).

Case 3

A 38-year-old woman, black, homemaker. Chest radiography showed diffuse interstitial-alveolar infiltrates with pulmonary parenchyma, bubbles and bronchiectasis in the upper lobes. The treatment with scheme I began in 2006. It was abandoned, and the patient resumed treatment 1 year later with an enhanced scheme I. After a few months, the patient stopped taking medication, and the treatment resumed with the MDR-TB regimen. Three months later, being the smear positive, a positive culture for M. tuberculosis was observed in the susceptibility test, showing resistance to isoniazid and rifampicin. Six months later, Mycobacterium hodleri was identified by PCR. Seven months later, a radiograph showed large pneumatoceles in the upper lobes, left apical bronchiectasis, and fibro-exudative and cavitary lesions in the upper segments of lower lobes. Three months later, the patient was discharged after the cure of MDR-TB, returning repeatedly for 10 months, when the AFB smear was positive. Chest radiograph showed bubbles, bronchiectasis and fibrous residual lesions in the upper lobes (Table 1).

Case 4

An 18-year-old woman, brown, single, peasant. She started the regimen I treatment in 2003, and abandoned it. One year later, the treatment was resumed with the enhanced scheme I, showing therapeutic failure. One year later, the MDR-TB treatment began. Two years later, the patient was treated for MDR-X tuberculosis. Bacilloscopy oscillated during the course of treatment. The culture trials conducted during treatment were positive for M. tuberculosis, showing a resistance to isoniazid, rifampicin and ethambutol. Six months later, a chest radiograph showed alveolar infiltrates in the left lung base. A year and 10 months later, the radiograph showed left lung parenchymal destruction, with cavitary lesions in the right upper lobe (Table 1).
Table 1

Clinical characteristics of patients with documented multidrug-resistant tuberculosis (MDR-TB)

Patient

Age

Tuberculosis duration, years

Drugs to which the patient was resistanta

Severe CXR findingsb

Time to smear conversion, months

Adverse reactions to the treatment

1

33

3

INH, Rif, Eth, Stm

No

12

None

2

27

5

INH, Rif

Yes

GI

3

38

4

INH, Rif

Yes

None

4

18

7

INH, Rif, Eth

Yes

None

CXR chest radiograph, Eth ethambutol, INH isoniazid, Rif rifampin, Stm streptomycin, GI gastrointestinal

aPatients were tested for resistance to Eth, INH, Rif, PZA, Stm, Km, Cm, and Tha, as well as resistance to ciprofloxacin and cycloserine

bCavitary and bilateral lesions

Discussion

Although the literature describes a high toxicity of drugs used in the MDR-TB treatment [6], adverse effects were only observed in one case (25 %).

Through the report of four cases, the presence of severe pulmonary lesions with irreversible characteristics was radiographically evident, usually beginning with exudative lesions and parenchymal lung destruction. Case 3 shows a concomitant infection by M. hodleri, with very exuberant lung lesions. All patients described abandoned treatment, and had cavitary and fibro residual lesions and treatment failure, and showed no HIV coinfection, which is an association commonly described in the literature [7].

Chest radiography predicts tuberculosis prognosis by evaluating pulmonary lesions [7], and it is still the most used imaging method [8]. Cavitary lesions and residual fibrosis found related to multidrug resistance corroborate the literature [2].

In this study, 7.3 % of MDR-TB and 2.4 % of XDR were found, values lower than those reported for the USA. Marks et al. [9] found a prevalence of 36 % of MDR-TB and 56 % of XDR-TB in 2005–2007 [9]. Regarding drugs, resistance to rifampicin and isoniazid, as well as age (young adults), supported the findings of a study conducted in Congo [10].

In summary, MDR-TB is a major public health problem in Brazil, especially in poor areas such as the Brazilian North and Northeast.

Abbreviations

AFB: 

acid-fast bacilli

HIV: 

human immunodeficiency virus

MDR-TB: 

multidrug-resistant tuberculosis

XDR: 

extensively drug-resistant tuberculosis

Declarations

Authors’ contributions

KROM participated in data collection and interpretation, critically revised the manuscript and contributed to the writing of the manuscript. GMCV participated in data collection and interpretation, contributed to the writing of the manuscript and critically revised the manuscript. SGM participated in data collection and interpretation and critically revised the manuscript. MACNS contributed to the writing and drafting of the manuscript, and critically revised the manuscript. MDSBN contributed to the writing and drafting of the manuscript and critically revised the manuscript. VLS contributed in drafting the manuscript and critically revised it. All authors read and approved the final manuscript.

Acknowledgements

We would like to thank Presidente Vargas Hospital for providing the data from patients involved in this study.

Availability of data and materials

The data supporting the conclusions of this paper are included in the paper (and its additional files).

Competing interests

The authors declare that they have no competing interests.

Ethics (and consent)

A free and informed consent was obtained from all patients that participated in this study. The study was approved by the Ethics Committee of the State Department of Health, according to the Resolution no. 466/2012 of the National Health Council.

Publishing consent

A written informed consent was obtained from all patients concerning the publication of the case report and accompanying tables from all four patients. In the case of patients that died, a written informed consent was obtained for the publication of this case report and any accompanying tables from the next of kin of the patients.

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Authors’ Affiliations

(1)
Graduate Program in Parasitic Biology, University CEUMA
(2)
Nucleus of Basic and Applied Immunology, Department of Pathology, Federal University of Maranhão
(3)
Medicine School, Federal University of Maranhão, Scientific Scholarship of CNPq
(4)
Graduate Program in Adult and Child Health, Nucleus of Basic and Applied Immunology, Department of Pathology, Federal University of Maranhão
(5)
Medicine School, Federal University of Maranhão

References

  1. Maciel ELN, Guidoni LM, Favero JL, Hadad DJ, Molino LP, Jonhson JL, Dietze R. Efeitos adversos causados pelo novo esquema de tratamento de tuberculose preconizado pelo Ministério da Saúde do Brasil. J Bras Pneumol. 2010;36(2):232–8.View ArticlePubMedGoogle Scholar
  2. Campos HS. Mycobacterium tuberculosis resistente, de onde vem a resistência? Rev Bras Anál Clín. 2005;37(3):157–61.Google Scholar
  3. Marques M, Cunha EAT, Ruffino-Netto A, Andrade SMO. Drug rsistance profile of Mycobacterium tuberculosis in the state of Mato Grosso do Sul, Brazil, 2000–2006. J Bras Pneumol. 2010;36(2):224–31.PubMedGoogle Scholar
  4. Cunha EAT, Marques M, Leite CQF, Junqueira CT, Arão CAB, Costa IP. The contribution of the public health central laboratory of Mato Grosso do Sul to the diagnosis of tuberculosis and identification of antituberculosis drug-resistance. BBAC. 2009;41(3):191–6.Google Scholar
  5. Rocha JL, Dacolmo MP, Borga L, Fedele D, Marques MG. Tuberculose multirresistente. Pulmão RJ. 2008;17(1):27–32.Google Scholar
  6. Shim TS, Jo KW. Medical treatment of pulmonary multidrug-resistant tuberculosis. Infect Chemother. 2013;45(4):367–74 (Epub 2013 Dec 27).View ArticlePubMedPubMed CentralGoogle Scholar
  7. Santa Cruz RC, Albuquerque MFPM, Campelo ARL, Silva EJC, Mazza E, Menezes RC, Kosminsky S. Pulmonary tuberculosis: association between extent of residual pulmonary lesion and alteration in the lung function. Rev Assoc Med Bras. 2008;54(5):406–10.Google Scholar
  8. Bombarda S, Figueiredo CM, Funari MBG, Soares JRJ, Seiscento M, Terra FM. Imagem em tuberculose pulmonar. J. Pneumol. 2001;27(6):329–40.View ArticleGoogle Scholar
  9. Marks SM, Flood J, Seaworth B, Hirsch-Moverman Y, Armstrong L, Mase S, Salcedo K, Oh P, Graviss EA, Colson PW, Armitige L, Revuelta M, Sheeran K, TB Epidemiologic Studies Consortium. Treatment practices, outcomes, and costs of multidrug-resistant and extensively drug-resistant tuberculosis, United States, 2005–2007. Emerg Infect Dis. 2014;20(5):812–21.View ArticlePubMedPubMed CentralGoogle Scholar
  10. Kaswa MK, Bisuta S, Kabuya G, Lunguya O, Ndongosieme A, Muyembe JJ, Van Deun A, Boelaert M. Multi drug resistant tuberculosis in mosango, a rural area in the democratic republic of congo. PLoS ONE. 2014;9(4):e94618. doi:10.1371/journal.pone.0094618.View ArticlePubMedPubMed CentralGoogle Scholar

Copyright

© Maia et al. 2016

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