Tuberculosis retreatment in Northern Portugal
C.. Pachecoa,
, E.. Silvaa,b, O.. Oliveiraa,b,c, A.. Carvalhod,e, A.M.. Correiaa,b,c,f, R.. Duarteg,h,i,j
Corresponding author
a Pneumology Department, Hospital de Braga, Portugal
b Pneumology Department, Hospital de Viseu, Portugal
c Institute of Public Health, University of Porto, Porto, Portugal
d Pulmonology Department, Centro Hospitalar de Vila Nova de Gaia/Espinho, EPE, Vila Nova de Gaia, Portugal
e Chest Disease Centre of Vila Nova de Gaia, Vila Nova de Gaia, Portugal
f Public Health Department, Regional North Health Administration, Portugal
g Pulmonology Department, Centro Hospitalar de Vila Nova de Gaia/Espinho, EPE, Vila Nova de Gaia, Portugal
h Chest Disease Centre of Vila Nova de Gaia, Vila Nova de Gaia, Portugal
i Epi Unit, Institute of Public Health, University of Porto, Porto, Portugal
j Epidemiology Department, Medical School, University of Porto, Porto, Portugal
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(A) Chest CT images with cystic and varicose bronchiectasis, as well as peribronchovascular reticulation. (B) Chest CT images confirming the presence of parenchymal densifications, bilateral ground glass opacities and predominance of a mosaic pattern. (C) Photomicrograph illustrating the presence of agglomerates of collagen surrounding the bronchovascular axes with widespread alveolar distension, resulting in concentric narrowing and obliteration. H stain, 100× original magnification. (D) Photomicrograph illustrating the presence of fibroblast proliferation associated with collagen deposition, as well as alveolar and septal rupture and centrilobular emphysema. These features result in constriction of the airway lumen, which is compatible with the definitive diagnosis of constrictive bronchiolitis. H&E stain, 100× original magnification." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "D. Madama, A. Silva, S. Freitas, F. 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The retreatment takes place annually in these centers and the rate is also higher (2.97/100,000 people and 2.45/100,000 people, respectively) than in others in Portugal.<a href="#bib9" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">1</span></a></p><p class="elsevierStylePara">The persistence of tuberculous bacilli in patients who are cured or in those whose treatment was not correctly completed is an important issue.<a href="#bib10" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">2</span></a> Published risk factors for treatment failure or relapse include medical factors like HIV infection, diabetes mellitus, low body weight, cavitation on chest X-ray, high bacterial burden, short duration of treatment, drug resistance, positive culture after two months of treatment and socio-demographic factors like male gender, unemployment, drug abuse, alcoholism, smoking and poor treatment adherence.<a href="#bib10" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">2</span></a><span class="elsevierStyleSup">, </span><a href="#bib11" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">3</span></a><span class="elsevierStyleSup">, </span><a href="#bib17" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">4</span></a><span class="elsevierStyleSup">, </span><a href="#bib13" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">5</span></a></p><p class="elsevierStylePara">Retreatment cases are the leading risk factor for drug resistance if not appropriately and effectively managed, especially in HIV-seronegative patients.<a href="#bib17" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">4</span></a><span class="elsevierStyleSup">, </span><a href="#bib14" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">6</span></a></p><p class="elsevierStylePara">We carried out a study to assess risk factors and outcome for retreatment in TB patients in northern Portugal.</p><p class="elsevierStylePara">The World Health Organization (WHO) standard definition was used for treatment outcome (treatment success, death, failure, default and transferred out).<a href="#bib11" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">3</span></a><span class="elsevierStyleSup">, </span><a href="#bib13" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">5</span></a><span class="elsevierStyleSup">, </span><a href="#bib15" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">7</span></a></p><p class="elsevierStylePara">The cases included were all retreatment TB cases (having received previous treatments) reported in 2012 in Northern Portugal and controls were the new cases (having received no previous treatment for TB) that were registered during the same period. Cases and controls were selected from the national database, which integrates the data from the mandatory registration of TB. For each case we randomly selected 2 controls. Risk factors (male sex, age over 40, HIV infection, diabetes mellitus, drug resistance, cavitation on chest X-ray, pulmonary vs. extra-pulmonary TB, unemployment, intravenous drug abuse and alcohol abuse) and outcomes for retreatment cases were compared against those for new cases.</p><p class="elsevierStylePara">We analyzed 57 cases and 118 controls (<a href="#t0005" class="elsevierStyleCrossRefs">Table 1</a>). In the cases, the median age was 48.0 years (range: 27.0–83.0) and 47 patients (82.5%) were male. In controls, the median age was 45.0 years (range: 14.0–85.0) and 67 patients (56.8%) were male.</p><p class="elsevierStylePara">Table 1. Risk factors for retreatment.</p><a name="t0005" class="elsevierStyleCrossRefs"></a><p class="elsevierStylePara"></p><table><tr align="left"><td>Risk factors</td><td>New cases (<span class="elsevierStyleItalic">n</span> = 118)</td><td>Retreatment (<span class="elsevierStyleItalic">n</span> = 57)</td><td colspan="2">Univariate analysis</td><td colspan="2">Multivariate analysis</td></tr><tr align="left"><td> </td><td> </td><td> </td><td>OR* (95% CI)</td><td><span class="elsevierStyleItalic">p</span>-value</td><td>aOR* (95% CI)</td><td><span class="elsevierStyleItalic">p</span>-value</td></tr><tr align="left"><td colspan="7"><span class="elsevierStyleItalic">Age</span></td></tr><tr align="left"><td>≤40 years</td><td>47 (39.8)</td><td>12 (21.1)</td><td>1.0</td><td> </td><td>1.0</td><td> </td></tr><tr align="left"><td>>40 years</td><td>71 (60.2)</td><td>45 (78.9)</td><td>2.48 (1.19–5.18)</td><td>0.015</td><td>3.12 (1.38–7.06)</td><td>0.006</td></tr><tr align="left"><td colspan="7"> </td></tr><tr align="left"><td colspan="7"><span class="elsevierStyleItalic">Sex</span></td></tr><tr align="left"><td>Female</td><td>51 (43.2)</td><td>10 (17.5)</td><td>1.0</td><td> </td><td>1.0</td><td> </td></tr><tr align="left"><td>Male</td><td>67 (56.8)</td><td>47 (82.5)</td><td>3.58 (1.65–7.76)</td><td>0.001</td><td>2.87 (1.25–6.57)</td><td>0.013</td></tr><tr align="left"><td colspan="7"> </td></tr><tr align="left"><td colspan="7"><span class="elsevierStyleItalic">Risk factors</span></td></tr><tr align="left"><td>None</td><td>95 (80.6)</td><td>44 (77.2)</td><td>1.0</td><td> </td><td> </td><td> </td></tr><tr align="left"><td>Alcohol abuse only</td><td>22 (18.6)</td><td>9 (15.8)</td><td>0.88 (0.38–2.08)</td><td>0.776</td><td> </td><td> </td></tr><tr align="left"><td>Injection drug use only</td><td>1 (0.8)</td><td>4 (7.0)</td><td>8.64 (0.94–79.54)</td><td>0.057</td><td> </td><td> </td></tr><tr align="left"><td colspan="7"> </td></tr><tr align="left"><td colspan="7"><span class="elsevierStyleItalic">HIV status</span></td></tr><tr align="left"><td>Negative</td><td>110 (93.2)</td><td>45 (78.9)</td><td>1.0</td><td> </td><td>1.0</td><td> </td></tr><tr align="left"><td>Positive</td><td>8 (6.8)</td><td>12(21.1)</td><td>3.67 (1.41–9.57)</td><td>0.008</td><td>5.31 (1.80–15.66)</td><td>0.002</td></tr><tr align="left"><td colspan="7"> </td></tr><tr align="left"><td colspan="7"><span class="elsevierStyleItalic">Site of disease</span></td></tr><tr align="left"><td>Extra-pulmonary</td><td>18 (15.3)</td><td>2 (3.5)</td><td>1.0</td><td> </td><td>1.0</td><td> </td></tr><tr align="left"><td>Pulmonary</td><td>100 (84.7)</td><td>55 (95.6)</td><td>4.95 (1.11–22.13)</td><td>0.036</td><td>6.56 (1.26–34.22)</td><td>0.026</td></tr><tr align="left"><td colspan="7"> </td></tr><tr align="left"><td colspan="7"><span class="elsevierStyleItalic">Chest radiography</span></td></tr><tr align="left"><td>No cavitation</td><td>65 (55.1)</td><td>29 (50.9)</td><td>1.0</td><td> </td><td> </td><td> </td></tr><tr align="left"><td>Cavitation</td><td>53 (44.9)</td><td>28 (49.1)</td><td>1.18 (0.63–2.23)</td><td>0.601</td><td> </td><td> </td></tr><tr align="left"><td colspan="7"> </td></tr><tr align="left"><td colspan="7"><span class="elsevierStyleItalic">Diabetes Mellitus</span></td></tr><tr align="left"><td>No</td><td>6 (5.1)</td><td>3 (5.3)</td><td>1.0</td><td> </td><td> </td><td> </td></tr><tr align="left"><td>Yes</td><td>112 (94.9)</td><td>54 (94.7)</td><td>1.04 (0.25–4.31)</td><td>0.96</td><td> </td><td> </td></tr><tr align="left"><td colspan="7"> </td></tr><tr align="left"><td colspan="7"><span class="elsevierStyleItalic">Unemployed</span></td></tr><tr align="left"><td>No</td><td>98 (83.1)</td><td>41 (71.9)</td><td>1.0</td><td> </td><td> </td><td> </td></tr><tr align="left"><td>Yes</td><td>20 (16.9)</td><td>16 (28.1)</td><td>1.91 (0.90–4.06)</td><td>0.091</td><td> </td><td> </td></tr><tr align="left"><td colspan="7"> </td></tr><tr align="left"><td colspan="7"><span class="elsevierStyleItalic">MDR TB</span></td></tr><tr align="left"><td>No</td><td>110 (93.2)</td><td>55 (96.5)</td><td>1.0</td><td> </td><td> </td><td> </td></tr><tr align="left"><td>Yes</td><td>8 (6.8)</td><td>2 (3.5)</td><td>0.50 (0.11–2.44)</td><td>0.391</td><td> </td><td> </td></tr></table><p class="elsevierStylePara">The number of cases of pulmonary TB was higher in retreatment group (96.5% vs. 84.7%, <span class="elsevierStyleItalic">p</span> = 0.04). There were no differences when factors such as diabetes mellitus, immunosuppression, drug resistance, unemployment, intravenous drug abuse and alcohol abuse were compared.</p><p class="elsevierStylePara">Male sex (adjusted OR: 2.87, 95% CI: 1.25–6.57, <span class="elsevierStyleItalic">p</span> = 0.013), HIV-positive status (adjusted OR: 5.31, 95% CI: 1.80–15.66, <span class="elsevierStyleItalic">p</span> = 0.002) and age over 40 (adjusted OR: 3.12, 95% CI: 1.38–7.06, <span class="elsevierStyleItalic">p</span> = 0.006) were independent risk factors identified for retreatment (<a href="#t0005" class="elsevierStyleCrossRefs">Table 1</a>). Of the 57 retreatment cases identified, 46 (81%) had been successfully treated in the past.</p><p class="elsevierStylePara">The treatment success rate was lower among patients who had received prior TB treatment than in patients who had never been treated for TB (80.7% vs. 92.5%, <span class="elsevierStyleItalic">p</span> = 0.04). In retreatment group 6 patients (10.5%) died while 7 patients (5.9%) died among the new cases, although this was not a statistically significant difference (<span class="elsevierStyleItalic">p</span> = 0.36) (<a href="#t0010" class="elsevierStyleCrossRefs">Table 2</a>).</p><p class="elsevierStylePara">Table 2. Patients outcome.</p><a name="t0010" class="elsevierStyleCrossRefs"></a><p class="elsevierStylePara"></p><table><tr align="left"><td>Categories</td><td>Treatment success</td><td colspan="3">Poor outcome</td><td><span class="elsevierStyleItalic">p</span>-Value</td></tr><tr align="left"><td> </td><td>Treatment completed</td><td>Died</td><td>Failed</td><td>Defaulted</td><td> </td></tr><tr align="left"><td colspan="6"><span class="elsevierStyleItalic">Treatment history</span></td></tr><tr align="left"><td>Never treated for TB</td><td>109 (92.5)</td><td>7 (5.9)</td><td>1 (0.8)</td><td>1 (0.8)</td><td>0.04</td></tr><tr align="left"><td>Previously treated for TB</td><td>46 (80.7)</td><td>6 (10.5)</td><td>3 (5.2)</td><td>2 (3.6)</td><td> </td></tr><tr align="left"><td>Total</td><td>155 (88.5)</td><td>13 (7.4)</td><td>4 (2.3)</td><td>3 (1.8)</td><td> </td></tr></table><p class="elsevierStylePara">Male sex appears as a risk factor for retreatment, in ours and in other studies.<a href="#bib10" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">2</span></a><span class="elsevierStyleSup">, </span><a href="#bib11" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">3</span></a><span class="elsevierStyleSup">, </span><a href="#bib17" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">4</span></a><span class="elsevierStyleSup">, </span><a href="#bib16" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">8</span></a> Although it is not fully understood why this is a risk factor for retreatment of tuberculosis, it is thought that this may be due to habits associated more to men than women as smoking, intravenous drug abuse and alcohol abuse.</p><p class="elsevierStylePara">Dooley et al.<a href="#bib11" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">3</span></a> commented that although retreatment guidelines are often the same for patients with failure of, default from, or relapse after initial treatment, these groups may benefit from different management strategies.</p><p class="elsevierStylePara">The number of cases of pulmonary TB was also higher in the retreatment group, although there are no studies in the literature that can explain this result.</p><p class="elsevierStylePara">In our population there were no differences when comparing factors such as diabetes mellitus, drug resistance, unemployment, intravenous drug abuse and alcoholism.</p><p class="elsevierStylePara">The low rate of multi drug resistance (MDR) TB in the retreatment group and the fact that there were no statistically significant differences when compared with the control group suggests that these patients may not have been exposed to many drugs in the past or that they had had a complete treatment, which was also noted by Kritski et al. in their population.<a href="#bib14" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">6</span></a></p><p class="elsevierStylePara">Despite this result, the treatment success rate was lower among patients who had received prior TB treatment than in patients who had never been treated for TB.</p><p class="elsevierStylePara">Identifying local patient characteristics that confer higher risk of relapse, failure or default from primary TB treatment may help inform country-specific prevention strategies aiming to reduce the need for retreatment, resulting in cost savings and diminished morbidity and transmission.</p><a name="sec0005" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Conflict of interest</span><p class="elsevierStylePara">The authors have no conflicts of interest to declare.</p><p class="elsevierStylePara">Corresponding author. ceciliafpacheco@gmail.com</p>" "pdfFichero" => "320v21n03a90418847pdf001.pdf" "tienePdf" => true "bibliografia" => array:2 [ "titulo" => "Bibliography" "seccion" => array:1 [ 0 => array:1 [ "bibliografiaReferencia" => array:8 [ 0 => array:3 [ "identificador" => "bib9" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Programa Nacional de Luta Contra a Tuberculose – Ponto da situação epidemiológica e de desempenho. 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| Year/Month | Html | Total | |
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| 2024 November | 9 | 6 | 15 |
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| 2020 December | 25 | 11 | 36 |
| 2020 November | 26 | 16 | 42 |
| 2020 October | 27 | 16 | 43 |
| 2020 September | 34 | 20 | 54 |
| 2020 August | 49 | 20 | 69 |
| 2020 July | 51 | 22 | 73 |
| 2020 June | 52 | 17 | 69 |
| 2020 May | 51 | 18 | 69 |
| 2020 April | 52 | 30 | 82 |
| 2020 March | 52 | 19 | 71 |
| 2020 February | 57 | 46 | 103 |
| 2020 January | 52 | 13 | 65 |
| 2019 December | 45 | 14 | 59 |
| 2019 November | 46 | 16 | 62 |
| 2019 October | 58 | 22 | 80 |
| 2019 September | 55 | 16 | 71 |
| 2019 August | 136 | 9 | 145 |
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| 2019 June | 165 | 14 | 179 |
| 2019 May | 122 | 14 | 136 |
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| 2019 March | 161 | 18 | 179 |
| 2019 February | 154 | 7 | 161 |
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| 2018 December | 93 | 11 | 104 |
| 2018 November | 41 | 1 | 42 |
| 2018 October | 55 | 8 | 63 |
| 2018 September | 29 | 9 | 38 |
| 2018 August | 42 | 30 | 72 |
| 2018 July | 30 | 16 | 46 |
| 2018 June | 35 | 14 | 49 |
| 2018 May | 47 | 16 | 63 |
| 2018 April | 63 | 15 | 78 |
| 2018 March | 78 | 22 | 100 |
| 2018 February | 48 | 8 | 56 |
| 2018 January | 64 | 7 | 71 |
| 2017 December | 74 | 24 | 98 |
| 2017 November | 13 | 9 | 22 |
| 2017 October | 19 | 10 | 29 |
| 2017 September | 11 | 17 | 28 |
| 2017 August | 24 | 14 | 38 |
| 2017 July | 12 | 12 | 24 |
| 2017 June | 14 | 16 | 30 |
| 2017 May | 32 | 17 | 49 |
| 2017 April | 9 | 16 | 25 |
| 2017 March | 25 | 11 | 36 |
| 2017 February | 4 | 11 | 15 |
| 2017 January | 9 | 10 | 19 |
| 2016 December | 7 | 4 | 11 |
| 2016 November | 8 | 3 | 11 |
| 2016 October | 14 | 1 | 15 |
| 2016 September | 4 | 1 | 5 |
| 2016 August | 5 | 4 | 9 |
| 2016 July | 1 | 8 | 9 |
| 2016 June | 0 | 5 | 5 |
| 2016 May | 0 | 7 | 7 |
| 2016 April | 21 | 1 | 22 |
| 2016 March | 24 | 21 | 45 |
| 2016 February | 52 | 27 | 79 |
| 2016 January | 35 | 21 | 56 |
| 2015 December | 36 | 23 | 59 |
| 2015 November | 20 | 11 | 31 |
| 2015 October | 25 | 20 | 45 |
| 2015 September | 49 | 16 | 65 |
| 2015 August | 59 | 40 | 99 |
| 2015 July | 45 | 26 | 71 |
| 2015 June | 52 | 26 | 78 |
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