Journal Article > ResearchFull Text
Int J Tuberc Lung Dis. 2017 March 1; Volume 21 (Issue 3); 314-319.; DOI:10.5588/ijtld.16.0661
Huerga H, Bastard M, Kamene M, Wanjala S, Arnold A, et al.
Int J Tuberc Lung Dis. 2017 March 1; Volume 21 (Issue 3); 314-319.; DOI:10.5588/ijtld.16.0661
SETTING
In March 2006, the first multidrug-resistant tuberculosis (MDR-TB) treatment programme was implemented in Kenya.
OBJECTIVE
To describe patients' treatment outcomes and adverse events.
DESIGN
A retrospective case note review of patients started on MDR-TB treatment at two Médecins Sans Frontières-supported sites and the national referral hospital of Kenya was undertaken. Sites operated an ambulatory model of care. Patients were treated for a minimum of 24 months with at least 4-5 drugs for the intensive phase of treatment, including an injectable agent.
RESULTS
Of 169 patients, 25.6% were human immunodeficiency virus (HIV) positive and 89.3% were culture-positive at baseline. Adverse events occurred in 67.4% of patients: 45.9% had nausea/vomiting, 43.9% electrolyte disturbance, 41.8% dyspepsia and 31.6% hypothyroidism. The median time to culture conversion was 2 months. Treatment outcomes were as follows: 76.6% success, 14.5% deaths, 8.3% lost to follow-up and 0.7% treatment failure. HIV-positive individuals (adjusted odds ratio [aOR] 3.51, 95% confidence interval [CI] 1.12-11.03) and women (aOR 2.73, 95%CI 1.01-7.39) had a higher risk of unfavourable outcomes, while the risk was lower in those with culture conversion at 6 months (aOR 0.11, 95%CI 0.04-0.32).
CONCLUSION
In Kenya, where an ambulatory model of care is used for MDR-TB treatment, treatment success was high, despite high rates of HIV. Almost half of the patients experienced electrolyte disturbance and one third had hypothyroidism; this supports the view that systematic regular biochemical monitoring is needed in Kenya.
In March 2006, the first multidrug-resistant tuberculosis (MDR-TB) treatment programme was implemented in Kenya.
OBJECTIVE
To describe patients' treatment outcomes and adverse events.
DESIGN
A retrospective case note review of patients started on MDR-TB treatment at two Médecins Sans Frontières-supported sites and the national referral hospital of Kenya was undertaken. Sites operated an ambulatory model of care. Patients were treated for a minimum of 24 months with at least 4-5 drugs for the intensive phase of treatment, including an injectable agent.
RESULTS
Of 169 patients, 25.6% were human immunodeficiency virus (HIV) positive and 89.3% were culture-positive at baseline. Adverse events occurred in 67.4% of patients: 45.9% had nausea/vomiting, 43.9% electrolyte disturbance, 41.8% dyspepsia and 31.6% hypothyroidism. The median time to culture conversion was 2 months. Treatment outcomes were as follows: 76.6% success, 14.5% deaths, 8.3% lost to follow-up and 0.7% treatment failure. HIV-positive individuals (adjusted odds ratio [aOR] 3.51, 95% confidence interval [CI] 1.12-11.03) and women (aOR 2.73, 95%CI 1.01-7.39) had a higher risk of unfavourable outcomes, while the risk was lower in those with culture conversion at 6 months (aOR 0.11, 95%CI 0.04-0.32).
CONCLUSION
In Kenya, where an ambulatory model of care is used for MDR-TB treatment, treatment success was high, despite high rates of HIV. Almost half of the patients experienced electrolyte disturbance and one third had hypothyroidism; this supports the view that systematic regular biochemical monitoring is needed in Kenya.
Journal Article > ResearchAbstract
Pediatr Infect Dis J. 2017 August 2; Volume 37 (Issue 2); 147-152.; DOI:10.1097/INF.0000000000001727
Bonnet MMB, Nansumba M, Bastard M, Orikiriza P, Kyomugasho N, et al.
Pediatr Infect Dis J. 2017 August 2; Volume 37 (Issue 2); 147-152.; DOI:10.1097/INF.0000000000001727
BACKGROUND
Mortality among children with presumptive tuberculosis (TB) empiric TB treatment can be high. We describe the predictors of death among children with presumptive TB, and the relation between treatment and mortality.
METHODS
A prospective cohort of children with presumptive TB who underwent clinical assessment, chest radiograph, tuberculin skin test and sputum bacterial tests for TB was followed up for 3 months. TB diagnosis was based on mycobacterial, clinical and radiologic findings. Predictors of deaths were determined using cox regression model.
RESULTS
Of 360 children included in the analysis, 31.4% were younger than 2 years; 31.6% were HIV infected and 11.3% were severely malnourished. One hundred forty (38.9%) were diagnosed with TB, 18 (13%) of whom were bacteriologically confirmed. At 3 months of follow up, 25 of 360 (6.9%) children had died: 15 of 140 (10.7%) were receiving TB treatment versus 10 of 220 (4.5%) were not receiving treatment (P = 0.025). Severely malnourished children [adjusted hazard ratio (aHR), 9.86; 95% confidence interval (CI): 3.11-31.23] and those with chest radiographs suggestive of TB (aHR, 4.20; 95% CI: 0.93-19.01) were more likely to die. Children receiving empiric TB treatment had an increased risk of death (aHR, 2.37; 95% CI: 1.01-5.55) compared with children without treatment after adjustment for age, sex, HIV status and Bacillus Calmette-Guérin (BCG) vaccination.
CONCLUSIONS
The high mortality in children receiving empirically TB treatment highlights the difficulty in diagnosing childhood TB, the increased likelihood of starting treatment in critically ill children and in children with chronic disease, and the possibility of misdiagnosis. It strengthens the need to invest further in early TB detection and diagnosing nonsevere illness.
Mortality among children with presumptive tuberculosis (TB) empiric TB treatment can be high. We describe the predictors of death among children with presumptive TB, and the relation between treatment and mortality.
METHODS
A prospective cohort of children with presumptive TB who underwent clinical assessment, chest radiograph, tuberculin skin test and sputum bacterial tests for TB was followed up for 3 months. TB diagnosis was based on mycobacterial, clinical and radiologic findings. Predictors of deaths were determined using cox regression model.
RESULTS
Of 360 children included in the analysis, 31.4% were younger than 2 years; 31.6% were HIV infected and 11.3% were severely malnourished. One hundred forty (38.9%) were diagnosed with TB, 18 (13%) of whom were bacteriologically confirmed. At 3 months of follow up, 25 of 360 (6.9%) children had died: 15 of 140 (10.7%) were receiving TB treatment versus 10 of 220 (4.5%) were not receiving treatment (P = 0.025). Severely malnourished children [adjusted hazard ratio (aHR), 9.86; 95% confidence interval (CI): 3.11-31.23] and those with chest radiographs suggestive of TB (aHR, 4.20; 95% CI: 0.93-19.01) were more likely to die. Children receiving empiric TB treatment had an increased risk of death (aHR, 2.37; 95% CI: 1.01-5.55) compared with children without treatment after adjustment for age, sex, HIV status and Bacillus Calmette-Guérin (BCG) vaccination.
CONCLUSIONS
The high mortality in children receiving empirically TB treatment highlights the difficulty in diagnosing childhood TB, the increased likelihood of starting treatment in critically ill children and in children with chronic disease, and the possibility of misdiagnosis. It strengthens the need to invest further in early TB detection and diagnosing nonsevere illness.
Journal Article > Short ReportFull Text
Clin Infect Dis. 2019 November 2; Volume 71 (Issue 2); 415-418.; DOI:10.1093/cid/ciz1084
Seung KJ, Khan PY, Franke MF, Ahmed SM, Aiylchiev S, et al.
Clin Infect Dis. 2019 November 2; Volume 71 (Issue 2); 415-418.; DOI:10.1093/cid/ciz1084
Delamanid should be effective against highly resistant strains of Mycobacterium tuberculosis, but uptake has been slow globally. In the endTB (expand new drug markets for TB) Observational Study, which enrolled a large, heterogeneous cohorts of patients receiving delamanid as part of a multidrug regimen, 80% of participants experienced sputum culture conversion within 6 months.
Journal Article > LetterFull Text
Am J Respir Crit Care Med. 2015 February 1; Volume 191 (Issue 3); 355-358.; DOI:10.1164/rccm.201407-1302LE
Bastard M, Bonnet MMB, du Cros PAK, Khamraev AK, Hayrapetyan A, et al.
Am J Respir Crit Care Med. 2015 February 1; Volume 191 (Issue 3); 355-358.; DOI:10.1164/rccm.201407-1302LE
Journal Article > ResearchFull Text
PLOS One. 2012 March 12; Volume 7 (Issue 3); DOI:10.1371/journal.pone.0032140
Nackers F, Huerga H, Espie E, Aloo AO, Bastard M, et al.
PLOS One. 2012 March 12; Volume 7 (Issue 3); DOI:10.1371/journal.pone.0032140
Good adherence to treatment is crucial to control tuberculosis (TB). Efficiency and feasibility of directly observed therapy (DOT) under routine program conditions have been questioned. As an alternative, Médecins sans Frontières introduced self-administered therapy (SAT) in several TB programs. We aimed to measure adherence to TB treatment among patients receiving TB chemotherapy with fixed dose combination (FDC) under SAT at the Homa Bay district hospital (Kenya). A second objective was to compare the adherence agreement between different assessment tools.
Journal Article > ResearchFull Text
Nat Commun. 2024 May 9; Volume 15 (Issue 1); 3927.; DOI:10.1038/s41467-024-48077-8
Kho S, Seung KJ, Huerga H, Bastard M, Khan PY, et al.
Nat Commun. 2024 May 9; Volume 15 (Issue 1); 3927.; DOI:10.1038/s41467-024-48077-8
Sputum culture reversion after conversion is an indicator of tuberculosis (TB) treatment failure. We analyze data from the endTB multi-country prospective observational cohort (NCT03259269) to estimate the frequency (primary endpoint) among individuals receiving a longer (18-to-20 month) regimen for multidrug- or rifampicin-resistant (MDR/RR) TB who experienced culture conversion. We also conduct Cox proportional hazard regression analyses to identify factors associated with reversion, including comorbidities, previous treatment, cavitary disease at conversion, low body mass index (BMI) at conversion, time to conversion, and number of likely-effective drugs. Of 1,286 patients, 54 (4.2%) experienced reversion, a median of 173 days (97-306) after conversion. Cavitary disease, BMI < 18.5, hepatitis C, prior treatment with second-line drugs, and longer time to initial culture conversion were positively associated with reversion. Reversion was uncommon. Those with cavitary disease, low BMI, hepatitis C, prior treatment with second-line drugs, and in whom culture conversion is delayed may benefit from close monitoring following conversion.
Journal Article > ResearchFull Text
Open Forum Infect Dis. 2020 December 23; Volume 8 (Issue 2); ofaa639.; DOI:10.1093/ofid/ofaa639
Huerga H, Rucker SCM, Bastard M, Mpunga J, Amoros Quiles I, et al.
Open Forum Infect Dis. 2020 December 23; Volume 8 (Issue 2); ofaa639.; DOI:10.1093/ofid/ofaa639
BACKGROUND
Diagnosing tuberculosis (TB), the leading cause of death in people with HIV, remains a challenge in resource-limited countries. We assessed TB diagnosis using a strategy that included systematic urine lipoarabinomannan (LAM) testing for all HIV patients hospitalized in the medical wards and 6-month mortality according to the LAM result.
METHODS
This prospective, observational study included adult HIV patients hospitalized in the medical wards of a public district hospital in Malawi regardless of their TB symptoms or CD4 count. Each patient had a clinical examination and Alere Determine TB-LAM, sputum microscopy, sputum GeneXpert MTB/RIF (Xpert), chest X-ray, and CD4 count were systematically requested.
RESULTS
Among 387 inpatients, 54% had a CD4<200 cells/µL, 64% had presumptive TB and 90% had ≥1 TB symptom recorded in the medical file. LAM results were available for 99.0% of the patients, microscopy for 62.8% and Xpert for 60.7%. In total, 26.1% (100/383) had LAM-positive results, 48% (48/100) of which were grades 2-4. Any TB laboratory test result was positive in 30.8% (119/387). Among patients with no Xpert result, 28.5% (43/151) were LAM-positive. Cumulative 6-months mortality was 40.1% (151/377): 50.5% (49/97) in LAM-positives and 36.2% (100/276) in LAM-negatives, p=0.013. In multivariable regression analyses, LAM-positive patients had higher risk of mortality than LAM-negatives (aOR: 2.5, 95%CI: 1.1-5.8, p=0.037).
CONCLUSIONS
In resource-limited hospital medical wards with high TB prevalence, a diagnostic strategy including systematic urine-LAM testing for all HIV patients is an easily implementable strategy that identifies a large proportion of patients with TB at risk of death.
Diagnosing tuberculosis (TB), the leading cause of death in people with HIV, remains a challenge in resource-limited countries. We assessed TB diagnosis using a strategy that included systematic urine lipoarabinomannan (LAM) testing for all HIV patients hospitalized in the medical wards and 6-month mortality according to the LAM result.
METHODS
This prospective, observational study included adult HIV patients hospitalized in the medical wards of a public district hospital in Malawi regardless of their TB symptoms or CD4 count. Each patient had a clinical examination and Alere Determine TB-LAM, sputum microscopy, sputum GeneXpert MTB/RIF (Xpert), chest X-ray, and CD4 count were systematically requested.
RESULTS
Among 387 inpatients, 54% had a CD4<200 cells/µL, 64% had presumptive TB and 90% had ≥1 TB symptom recorded in the medical file. LAM results were available for 99.0% of the patients, microscopy for 62.8% and Xpert for 60.7%. In total, 26.1% (100/383) had LAM-positive results, 48% (48/100) of which were grades 2-4. Any TB laboratory test result was positive in 30.8% (119/387). Among patients with no Xpert result, 28.5% (43/151) were LAM-positive. Cumulative 6-months mortality was 40.1% (151/377): 50.5% (49/97) in LAM-positives and 36.2% (100/276) in LAM-negatives, p=0.013. In multivariable regression analyses, LAM-positive patients had higher risk of mortality than LAM-negatives (aOR: 2.5, 95%CI: 1.1-5.8, p=0.037).
CONCLUSIONS
In resource-limited hospital medical wards with high TB prevalence, a diagnostic strategy including systematic urine-LAM testing for all HIV patients is an easily implementable strategy that identifies a large proportion of patients with TB at risk of death.
Journal Article > ResearchAbstract
Trop Med Int Health. 2012 October 11; Volume 17 (Issue 12); DOI:10.1111/j.1365-3156.2012.03095.x
Mueller YK, Bastard M, Ehounou G, Itama J, Quere M, et al.
Trop Med Int Health. 2012 October 11; Volume 17 (Issue 12); DOI:10.1111/j.1365-3156.2012.03095.x
Objective To assess the effectiveness of blood transfusions in a hospital of north-eastern Democratic Republic of the Congo. Methods Prospective study of children admitted for severe anaemia. During admission, data were collected on clinical condition and haemoglobin levels, before and after blood transfusion. A linear regression model was built to explore factors associated with haemoglobin level after transfusion. Risk factors for mortality were explored through multivariate logistic regression. Results Haemoglobin level (Hb) was below 4 g/dl in 35% (230/657), between 4 and 6 g/dl in 58% (348/657) and at least 6 g/dl in another 6% (43/657) of the transfused children. A transfusion of 15 ml/kg of whole blood increased the Hb from 4.4 to 7.8 g/dl. Haemoglobin level after transfusion was associated with baseline Hb, quantity of delivered blood and history of previous transfusions. Overall case-fatality rate was 5.6% (37/657). Risk factors for deaths were co-morbidities such as chest infection, meningitis or malnutrition, Hb ≥ 6 g/dl, impaired consciousness or jugular venous distention on admission, and provenance. Conclusion Transfusion was a frequent practice, the use of which could clearly have been rationalised. While indications should be restricted, quantities of transfused blood should be adapted to needs.
Journal Article > ResearchFull Text
Clin Infect Dis. 2024 January 25; Volume 78 (Issue 1); 164-171.; DOI:10.1093/cid/ciad589
Sauer SM, Mitnick CD, Khan UT, Hewison CCH, Bastard M, et al.
Clin Infect Dis. 2024 January 25; Volume 78 (Issue 1); 164-171.; DOI:10.1093/cid/ciad589
BACKGROUND
Quantification of recurrence risk following successful treatment is crucial to evaluating regimens for multidrug- or rifampicin-resistant (MDR/RR) tuberculosis (TB). However, such analyses are complicated when some patients die or become lost during post-treatment-follow-up.
METHODS
We analyzed data on 1,991 patients who successfully completed a longer MDR/RR-TB regimen containing bedaquiline and/or delamanid between 2015 and 2018 in 16 countries. Using five approaches for handling post-treatment deaths, we estimated the six-month post-treatment TB recurrence risk overall, and by HIV status. We used inverse-probability-weighting to account for patients with missing follow-up and investigated the impact of potential bias from excluding these patients without applying inverse-probability weights.
RESULTS
The estimated TB recurrence risk was 7.4 per 1000 (95% confidence interval (CI): 3.5,12.9) when deaths were handled as non-recurrences, and 7.6 per 1000 (95% CI: 3.6,13.1) when deaths were censored and inverse-probability weights were applied to account for the excluded deaths. The estimated risk of composite recurrence outcomes were 25.5 (95% CI: 15.4,38.1), 11.7 (95% CI: 6.5,18.3), and 8.6 (95% CI: 4.2,14.6) per 1000 for recurrence or 1) any death, 2) death with unknown or TB-related cause, 3) TB-related death, respectively. Corresponding relative risks for HIV status varied in direction and magnitude. Exclusion of patients with missing follow-up without inverse-probability-weighting had a small impact on estimates.
CONCLUSIONS
The estimated six-month TB recurrence risk was low, and the association with HIV status was inconclusive due to few recurrence events. Estimation of post-treatment recurrence will be enhanced by explicit assumptions about deaths and appropriate adjustment for missing follow-up data.
Quantification of recurrence risk following successful treatment is crucial to evaluating regimens for multidrug- or rifampicin-resistant (MDR/RR) tuberculosis (TB). However, such analyses are complicated when some patients die or become lost during post-treatment-follow-up.
METHODS
We analyzed data on 1,991 patients who successfully completed a longer MDR/RR-TB regimen containing bedaquiline and/or delamanid between 2015 and 2018 in 16 countries. Using five approaches for handling post-treatment deaths, we estimated the six-month post-treatment TB recurrence risk overall, and by HIV status. We used inverse-probability-weighting to account for patients with missing follow-up and investigated the impact of potential bias from excluding these patients without applying inverse-probability weights.
RESULTS
The estimated TB recurrence risk was 7.4 per 1000 (95% confidence interval (CI): 3.5,12.9) when deaths were handled as non-recurrences, and 7.6 per 1000 (95% CI: 3.6,13.1) when deaths were censored and inverse-probability weights were applied to account for the excluded deaths. The estimated risk of composite recurrence outcomes were 25.5 (95% CI: 15.4,38.1), 11.7 (95% CI: 6.5,18.3), and 8.6 (95% CI: 4.2,14.6) per 1000 for recurrence or 1) any death, 2) death with unknown or TB-related cause, 3) TB-related death, respectively. Corresponding relative risks for HIV status varied in direction and magnitude. Exclusion of patients with missing follow-up without inverse-probability-weighting had a small impact on estimates.
CONCLUSIONS
The estimated six-month TB recurrence risk was low, and the association with HIV status was inconclusive due to few recurrence events. Estimation of post-treatment recurrence will be enhanced by explicit assumptions about deaths and appropriate adjustment for missing follow-up data.
Journal Article > CommentaryFull Text
Int J Tuberc Lung Dis. 2020 October 1; Volume 24 (Issue 10); 1081-1086.; DOI:10.5588/ijtld.20.0141
Seung KJ, Khan UT, Varaine FFV, Ahmed SM, Bastard M, et al.
Int J Tuberc Lung Dis. 2020 October 1; Volume 24 (Issue 10); 1081-1086.; DOI:10.5588/ijtld.20.0141
In 2015, the initiative Expand New Drug Markets for TB (endTB) began, with the objective of reducing barriers to access to the new and repurposed TB drugs. Here we describe the major implementation challenges encountered in 17 endTB countries. We provide insights on how national TB programmes and other stakeholders can scale-up the programmatic use of new and repurposed TB drugs, while building scientific evidence about their safety and efficacy. For any new drug or diagnostic, multiple market barriers can slow the pace of scale-up. During 2015–2019, endTB was successful in increasing the number of patients receiving new and repurposed TB drugs in 17 countries. The endTB experience has many lessons, which are relevant to country level introduction of new TB drugs, as well as non-TB drugs and diagnostics. For example: the importation of TB drugs is possible even in the absence of registration; emphasis on good clinical monitoring is more important than pharmacovigilance reporting; national guidelines and expert committees can both facilitate and hinder innovative practice; clinicians use new and repurposed TB drugs when they are available; data collection to generate scientific evidence requires financial and human resources; pilot projects can drive national scale-up.