To see all articles in this section, click on "browse by Title".

Recent Submissions

  • Cost-effectiveness of new MDR-TB regimens: study protocol for the TB-PRACTECAL economic evaluation substudy.

    Sweeney, S; Gomez, G; Kitson, N; Sinha, A; Yatskevich, N; Staples, S; Moodliar, R; Motlhako, S; Maloma, M; Rassool, M; et al. (BMJ Publishing Group, 2020-10-10)
    Introduction: Current treatment regimens for multidrug-resistant tuberculosis (MDR-TB) are long, poorly tolerated and have poor outcomes. Furthermore, the costs of treating MDR-TB are much greater than those for treating drug-susceptible TB, both for health service and patient-incurred costs. Urgent action is needed to identify short, effective, tolerable and cheaper treatments for people with both quinolone-susceptible and quinolone-resistant MDR-TB. We present the protocol for an economic evaluation (PRACTECAL-EE substudy) alongside an ongoing clinical trial (TB-PRACTECAL) aiming to assess the costs to patients and providers of new regimens, as well as their cost-effectiveness and impact on participant poverty levels. This substudy is based on data from the three countries participating in the main trial. Methods and analysis: Primary cost data will be collected from the provider and patient perspectives, following economic best practice. We will estimate the probability that new MDR-TB regimens containing bedaquiline, pretomanid and linezolid are cost-effective from a societal perspective as compared with the standard of care for MDR-TB patients in Uzbekistan, South Africa and Belarus. Analysis uses a Markov model populated with primary cost and outcome data collected at each study site. We will also estimate the impact of new regimens on prevalence of catastrophic patient costs due to TB. Ethics and dissemination: Ethical approval has been obtained from the London School of Hygiene & Tropical Medicine and Médecins Sans Frontières. Local ethical approval will be sought in each study site. The results of the economic evaluation will be shared with the country health authorities and published in a peer-reviewed journal.
  • Preparedness of outpatient health facilities for ambulatory treatment with all-oral short DR-TB treatment regimens in Zhytomyr, Ukraine: a cross-sectional study.

    Gils, T; Laxmeshwar, C; Duka, M; Malakyan, K; Siomak, OV; Didik, VS; Lytvynenko, N; Terleeva, Y; Donchuk, D; Isaakidis, P (BMC, 2020-09-21)
    Background: Ukraine has a high burden of drug-resistant tuberculosis (DR-TB). Mental health problems, including alcohol use disorder, are common co-morbidities. One in five DR-TB patients has human immunodeficiency virus (HIV). As part of health reform, the country is moving from inpatient care to ambulatory primary care for tuberculosis (TB). In Zhytomyr oblast, Médecins Sans Frontières (MSF) is supporting care for DR-TB patients on all-oral short DR-TB regimens. This study describes the preparedness of ambulatory care facilities in Zhytomyr oblast, Ukraine, to provide good quality ambulatory care. Methods: This is a retrospective analysis of routinely collected programme data. Before discharge of every patient from the hospital, MSF teams assess services available at outpatient facilities using a standardised questionnaire. The assessment evaluates access, human resources, availability of medicines, infection control measures, laboratory and diagnostic services, and psychosocial support. Results: We visited 68 outpatient facilities in 22 districts between June 2018 and September 2019. Twenty-seven health posts, 24 TB-units, 13 ambulatories, two family doctors and one polyclinic, serving 30% of DR-TB patients in the oblast by September 2019, were included. All facilities provided directly observed treatment, but only seven (10%) provided weekend-services. All facilities had at least one medical staff member, but TB-training was insufficient and mostly limited to TB-doctors. TB-treatment and adequate storage space were available in all facilities, but only five (8%) had ancillary medicines. HIV-positive patients had to visit a separate facility to access HIV-care. Personal protective equipment was unavailable in 32 (55%) facilities. Basic laboratory services were available in TB-units, but only four (17%) performed audiometry. Only ten (42%) TB-units had psychosocial support available, and nine (38%) offered psychiatric support. Conclusion: Outpatient facilities in Zhytomyr oblast are not yet prepared to provide comprehensive care for DR-TB patients. Capacity of all facilities needs strengthening with trainings, infection control measures and infrastructure. Integration of psychosocial services, treatment of co-morbidities and adverse events at the same facility are essential for successful decentralisation. The health reform is an opportunity to establish quality, patient-centred care.
  • Person-centred care in practice: perspectives from a short course regimen for multi-drug resistant tuberculosis in Karakalpakstan, Uzbekistan.

    Horter, S; Stringer, B; Gray, N; Parpieva, N; Safaev, K; Tigay, Z; Singh, J; Achar, J (BMC, 2020-09-16)
    Introduction: Person-centred care, an internationally recognised priority, describes the involvement of people in their care and treatment decisions, and the consideration of their needs and priorities within service delivery. Clarity is required regarding how it may be implemented in practice within different contexts. The standard multi-drug resistant tuberculosis (MDR-TB) treatment regimen is lengthy, toxic and insufficiently effective. 2019 World Health Organisation guidelines include a shorter (9-11-month) regimen and recommend that people with MDR-TB be involved in the choice of treatment option. We examine the perspectives and experiences of people with MDR-TB and health-care workers (HCW) regarding person-centred care in an MDR-TB programme in Karakalpakstan, Uzbekistan, run by Médecins Sans Frontières and the Ministry of Health. Methods: A qualitative study comprising 48 interviews with 24 people with MDR-TB and 20 HCW was conducted in June-July 2019. Participants were recruited purposively to include a range of treatment-taking experiences and professional positions. Interview data were analysed thematically using coding to identify emerging patterns, concepts, and categories relating to person-centred care, with Nvivo12. Results: People with MDR-TB were unfamiliar with shared decision-making and felt uncomfortable taking responsibility for their treatment choice. HCW were viewed as having greater knowledge and expertise, and patients trusted HCW to act in their best interests, deferring the choice of appropriate treatment course to them. HCW had concerns about involving people in treatment choices, preferring that doctors made decisions. People with MDR-TB wanted to be involved in discussions about their treatment, and have their preference sought, and were comfortable choosing whether treatment was ambulatory or hospital-based. Participants felt it important that people with MDR-TB had knowledge and understanding about their treatment and disease, to foster their sense of preparedness and ownership for treatment. Involving people in their care was said to motivate sustained treatment-taking, and it appeared important to have evidence of treatment need and effect. Conclusions: There is a preference for doctors choosing the treatment regimen, linked to shared decision-making unfamiliarity and practitioner-patient knowledge imbalance. Involving people in their care, through discussions, information, and preference-seeking could foster ownership and self-responsibility, supporting sustained engagement with treatment.
  • Translating drug resistant tuberculosis treatment guidelines to reality in war-torn Kandahar, Afghanistan: A retrospective cohort study.

    Mesic, A; Khan, WH; Lenglet, A; Lynen, L; Ishaq, S; Phyu, EHH; Mar, HT; Oraegbu, A; Seddiq, MK; Amirzada, HK; et al. (Public Library of Sciences, 2020-08-21)
    Introduction: Afghanistan is affected by one of the world's longest protracted armed conflicts, frequent natural disasters, disease outbreaks and large population movements and it suffers from a high burden of tuberculosis (TB), including rifampicin-resistant TB (RR-TB). The study shows Médecins Sans Frontières' experiences with care for patients with RR-TB in Kandahar Province. We describe the uptake of RR-TB treatment, how World Health Organisation criteria for the choice between the short and an individualized regimen were implemented, and treatment outcomes. Methods: This is a retrospective cohort analysis of routinely collected data from RR-TB patients enrolled in care from 2016 until 2019. Descriptive analysis was performed to present characteristics of patients and treatment outcomes. Multivariable Cox analysis was performed to identify risk factors for having an unfavourable treatment outcome. Results: Out of 146 enrolled RR-TB patients, 112 (76.7%) started treatment: 41 (36.6%) and 71 (63.4%) with the short and individualized treatment regimen, respectively. Of 82 with results for fluoroquinolone susceptibility, 39 (47.6%) had fluoroquinolone-resistant TB. Seven patients with initially fluoroquinolone-resistant TB and three pregnant women started the short regimen and 18 patients eligible for the short regimen started the injectable-free individualized regimen. Overall, six-month smear and culture conversion were 98.7% and 97.1%, respectively; treatment success was 70.1%. Known initial fluoroquinolone resistance (aHR 3.77, 95%CI:1.53-9.27) but not choice of regimen predicted having an unfavourable outcome. Conclusion: Even though criteria for the choice of treatment regimen were not applied strictly, we have achieved acceptable outcomes in this cohort. To expand RR-TB care, treatment regimens should fit provision at primary health care level and take patient preferences into account.
  • 'She is like my mother': Community-based care of drug-resistant tuberculosis in rural Eswatini.

    Burtscher, D; Juul Bjertrup, P; Vambe, D; Dlamini, V; Mmema, N; Ngwenya, S; Rusch, B; Kerschberger, B (Routledge, 2020-08-20)
    Patients with drug-resistant tuberculosis (DR-TB) have received community-based care in Eswatini since 2009. Trained and compensated community treatment supporters (CTSs) provide directly observed therapy (DOT), injectables and psychological support. We examined the acceptability of this model of care among DR-TB patients, including the perspective of family members of DR-TB patients and their CTSs in relation to the patient's experience of care and quality of life. This qualitative research was conducted in rural Eswatini in February 2018. DR-TB patients, CTSs and family members participated in in-depth interviews, paired interviews, focus group discussions and PhotoVoice. Data were thematically analysed and coded, and themes were extracted. Methodological triangulation enhanced the interpretation. All patients and CTSs and most family members considered community-based DR-TB care to be supportive. Positive aspects were emotional support, trust and dedicated individual care, including enabling practical, financial and social factors. Concerns were related to social and economic problems within the family and fears about infection risks for the family and the CTSs. Community-based DR-TB care was acceptable to patients, family members and CTSs. To reduce family members' fears of TB infection, information and sensitisation within the family and constant follow-up appear crucial.
  • Mortality in adults with multidrug-resistant tuberculosis and HIV by antiretroviral therapy and tuberculosis drug use: an individual patient data meta-analysis.

    Bisson, GP; Bastos, M; Campbell, JR; Bang, D; Brust, JC; Isaakidis, P; Lange, C; Menzies, D; Migliori, GB; Pape, JW; et al. (Elsevier, 2020-08-08)
    Background: HIV-infection is associated with increased mortality during multidrug-resistant tuberculosis treatment, but the extent to which the use of antiretroviral therapy (ART) and anti-tuberculosis medications modify this risk are unclear. Our objective was to evaluate how use of these treatments altered mortality risk in HIV-positive adults with multidrug-resistant tuberculosis. Methods: We did an individual patient data meta-analysis of adults 18 years or older with confirmed or presumed multidrug-resistant tuberculosis initiating tuberculosis treatment between 1993 and 2016. Data included ART use and anti-tuberculosis medications grouped according to WHO effectiveness categories. The primary analysis compared HIV-positive with HIV-negative patients in terms of death during multidrug-resistant tuberculosis treatment, excluding those lost to follow up, and was stratified by ART use. Analyses used logistic regression after exact matching on country World Bank income classification and drug resistance and propensity-score matching on age, sex, geographic site, year of multidrug-resistant tuberculosis treatment initiation, previous tuberculosis treatment, directly observed therapy, and acid-fast-bacilli smear-positivity to obtain adjusted odds ratios (aORs) and 95% CIs. Secondary analyses were conducted among those with HIV-infection. Findings: We included 11 920 multidrug-resistant tuberculosis patients. 2997 (25%) were HIV-positive and on ART, 886 (7%) were HIV-positive and not on ART, and 1749 (15%) had extensively drug-resistant tuberculosis. By use of HIV-negative patients as reference, the aOR of death was 2·4 (95% CI 2·0-2·9) for all patients with HIV-infection, 1·8 (1·5-2·2) for HIV-positive patients on ART, and 4·2 (3·0-5·9) for HIV-positive patients with no or unknown ART. Among patients with HIV, use of at least one WHO Group A drug and specific use of moxifloxacin, levofloxacin, bedaquiline, or linezolid were associated with significantly decreased odds of death. Interpretation: Use of ART and more effective anti-tuberculosis drugs is associated with lower odds of death among HIV-positive patients with multidrug-resistant tuberculosis. Access to these therapies should be urgently pursued.
  • Culture Conversion in Patients Treated with Bedaquiline and/or Delamanid: A Prospective Multi-country Study.

    Franke, MF; Khan, P; Hewison, C; Khan, U; Huerga, H; Seung, KJ; Rich, ML; Zarli, K; Samieva, N; Oyewusi, L; et al. (ATS Journals, 2020-07-24)
    Background Bedaquiline and delamanid offer the possibility of more effective and less toxic multidrug-resistant tuberculosis (MDR-TB) treatment. With this treatment, however, some patients, remain at high risk for an unfavorable treatment outcome. The endTB observational study is the largest multicountry cohort of patients with rifampin-resistant/MDR-TB treated in routine care, according to WHO guidance, with delamanid- and/or bedaquiline-containing regimens. We report frequency of sputum culture conversion within six-months of treatment initiation and risk factors for non-conversion. Methods We included patients with a positive baseline culture who initiated a first endTB regimen prior to April 2018. Two consecutive negative cultures collected > 15 days apart constituted culture conversion. We used generalized mixed models to derive marginal predictions for the probability of culture conversion in key subgroups. Findings 1,109 patients initiated a multidrug treatment containing bedaquiline (63%), delamanid (27%) or both (10%). Of these, 939 (85%) experienced culture conversion within six months. In adjusted analyses, patients with HIV had a lower probability of conversion (0·73 [95% CI: 0·62, 0·84]) than patients without HIV (0·84 [95% CI: 0·79, 0·90]; p=0·03). Patients with both cavitary disease and highly positive sputum smear had a lower probability of conversion (0·68 [95% CI: 0·57, 0·79]) relative to patients without either (0·89; 95% CI: 0·84, 0·95; p=0·0004). Hepatitis C infection, diabetes mellitus/glucose intolerance, and baseline resistance were not associated with conversion. Interpretation Frequent sputum conversion in patients with rifampin-resistant/MDR-TB who were treated with bedaquiline and/or delamanid underscores the need for urgent expanded access to these drugs. There is a need to optimize treatment for patients with HIV and extensive disease.
  • Bedaquiline and delamanid for drug-resistant tuberculosis: a clinician's perspective

    Guglielmetti, L; Chiesi, S; Eimer, J; Dominguez, J; Masini, T; Varaine, F; Veziris, N; Ader, F; Robert, J (Future Medicine, 2020-07-23)
    Drug-resistant tuberculosis (TB) represents a substantial threat to the global efforts to control this disease. After decades of stagnation, the treatment of drug-resistant TB is undergoing major changes: two drugs with a new mechanism of action, bedaquiline and delamanid, have been approved by stringent regulatory authorities and are recommended by the WHO. This narrative review summarizes the evidence, originating from both observational studies and clinical trials, which is available to support the use of these drugs, with a focus on special populations. Areas of uncertainty, including the use of the two drugs together or for prolonged duration, are discussed. Ongoing clinical trials are aiming to optimize the use of bedaquiline and delamanid to shorten the treatment of drug-resistant TB.
  • Correspondence regarding "Delamanid for rifampicin-resistant tuberculosis: a retrospective study from South Africa".

    Mohr-Holland, E; Reuter, A; Hughes, J; Daniels, J; Beko, B; Makhanda, G; De Avezedo, V; Kock, Y; Cox, H; Furin, J; et al. (European Respiratory Society, 2020-07-23)
  • The problem with vitamin D supplementation for tuberculosis

    Reuter, A; Furin, J (Elsevier, 2020-07-01)
    “We were hungry all the time”, is the first thing a 28-year-old tuberculosis survivor from rural Haiti told one of us (JF) when asked in 2017 about his experience of being treated for the disease. This patient had been cutting sugar cane to support his family of seven—all of whom lived in a one-room shack—but had to stop his gruelling labour once he became sick with tuberculosis, both because of his physical symptoms and because he had to go to the clinic daily for directly observed therapy. Without his income, his family fell into ruin and the pressing need to feed his children became his most urgent priority. “It was hard to take my treatment when the little ones were holding their bellies and crying. We lost so much to TB.”
  • Systematic or test-guided treatment for tuberculosis in HIV-infected adults

    Blanc, FX; Badje, AD; Bonnet, M; Gabillard, D; Messou, E; Muzoora, C; Samreth, S; Nguyen, BD; Borand, L; Domergue, A; et al. (Massachusetts Medical Society, 2020-06-18)
    Background: In regions with high burdens of tuberculosis and human immunodeficiency virus (HIV), many HIV-infected adults begin antiretroviral therapy (ART) when they are already severely immunocompromised. Mortality after ART initiation is high in these patients, and tuberculosis and invasive bacterial diseases are common causes of death. Methods: We conducted a 48-week trial of empirical treatment for tuberculosis as compared with treatment guided by testing in HIV-infected adults who had not previously received ART and had CD4+ T-cell counts below 100 cells per cubic millimeter. Patients recruited in Ivory Coast, Uganda, Cambodia, and Vietnam were randomly assigned in a 1:1 ratio to undergo screening (Xpert MTB/RIF test, urinary lipoarabinomannan test, and chest radiography) to determine whether treatment for tuberculosis should be started or to receive systematic empirical treatment with rifampin, isoniazid, ethambutol, and pyrazinamide daily for 2 months, followed by rifampin and isoniazid daily for 4 months. The primary end point was a composite of death from any cause or invasive bacterial disease within 24 weeks (primary analysis) or within 48 weeks after randomization. Results: A total of 522 patients in the systematic-treatment group and 525 in the guided-treatment group were included in the analyses. At week 24, the rate of death from any cause or invasive bacterial disease (calculated as the number of first events per 100 patient-years) was 19.4 with systematic treatment and 20.3 with guided treatment (adjusted hazard ratio, 0.95; 95% confidence interval [CI], 0.63 to 1.44). At week 48, the corresponding rates were 12.8 and 13.3 (adjusted hazard ratio, 0.97 [95% CI, 0.67 to 1.40]). At week 24, the probability of tuberculosis was lower with systematic treatment than with guided treatment (3.0% vs. 17.9%; adjusted hazard ratio, 0.15; 95% CI, 0.09 to 0.26), but the probability of grade 3 or 4 drug-related adverse events was higher with systematic treatment (17.4% vs. 7.2%; adjusted hazard ratio 2.57; 95% CI, 1.75 to 3.78). Serious adverse events were more common with systematic treatment. Conclusions: Among severely immunosuppressed adults with HIV infection who had not previously received ART, systematic treatment for tuberculosis was not superior to test-guided treatment in reducing the rate of death or invasive bacterial disease over 24 or 48 weeks and was associated with more grade 3 or 4 adverse events. (Funded by the Agence Nationale de Recherches sur le Sida et les Hépatites Virales; STATIS ANRS 12290 ClinicalTrials.gov number, NCT02057796.).
  • Yield of Systematic Longitudinal Screening of Household Contacts of Pre-Extensively Drug Resistant (PreXDR) and Extensively Drug Resistant (XDR) Tuberculosis Patients in Mumbai, India

    Paryani, RH; Gupta, V; Singh, P; Verma, M; Sheikh, S; Yadav, R; Mansoor, H; Kalon, S; Selvaraju, S; Das, M; et al. (MDPI, 2020-05-26)
    While risk of tuberculosis (TB) is high among household contacts (HHCs) of pre-extensively drug resistant (pre-XDR) TB and XDR-TB, data on yield of systematic longitudinal screening are lacking. We aim to describe the yield of systematic longitudinal TB contact tracing among HHCs of patients with pre-XDR-TB and XDR-TB. At the Médecins Sans Frontières (MSF) clinic, Mumbai, India a cohort comprising 518 HHCs of 109 pre-XDR and XDR index cases was enrolled between January 2016 and June 2018. Regular HHC follow-ups were done till one year post treatment of index cases. Of 518 HHCs, 23 had TB (21 on TB treatment and two newly diagnosed) at the time of first visit. Of the rest, 19% HHCs had no follow-ups. Fourteen (3.5%) TB cases were identified among 400 HHCs; incidence rate: 2072/100,000 person-years (95% CI: 1227-3499). The overall yield of household contact tracing was 3% (16/518). Of 14 who were diagnosed with TB during follow-up, six had drug susceptible TB (DSTB); six had pre-XDR-TB and one had XDR-TB. Five of fourteen cases had resistance patterns concordant with their index case. In view of the high incidence of TB among HHCs of pre-XDR and XDR-TB cases, follow-up of HHCs for at least the duration of index cases' treatment should be considered.
  • Improving pediatric TB diagnosis in North Kivu (DR Congo), focusing on a clinical algorithm including targeted Xpert MTB/RIF on gastric aspirates

    Van Brusselen, D; Simons, E; Luendo, T; Luendo, T; Habarugira, D; Ngowa, J; Mitutso, NN; Moluh, Z; Steenssens, M; Seguin, R; et al. (BMC, 2020-05-14)
    Background The incidence of tuberculosis (TB) in the Democratic Republic of the Congo (DRC) is 323/100,000. A context of civil conflict, internally displaced people and mining activities suggests a higher regional TB incidence in North Kivu. Médecins Sans Frontières (MSF) supports the General Reference Hospital of Masisi, North Kivu, covering a population of 520,000, with an elevated rate of pediatric malnutrition. In July 2017, an adapted MSF pediatric TB diagnostic algorithm, including Xpert MTB/RIF on gastric aspirates (GAs), was implemented. The aim of this study was to evaluate whether the introduction of this clinical pediatric TB diagnostic algorithm influenced the number of children started on TB treatment. Methods We performed a retrospective analysis of pediatric TB cases started on treatment in the inpatient therapeutic feeding centre (ITFC) and the pediatric ward. We compared data collected in the second half (July to December) of 2016 (before introduction of the new diagnostic algorithm) and the second half of 2017. For the outcome variables the difference between the two years was calculated by a Pearson Chi-square test. Results In 2017, 94 GAs were performed, compared to none in 2016. Twelve percent (11/94) of samples were Xpert MTB/RIF positive. Sixty-eight children (2.9% of total exits) aged between 3 months and 15 years started TB treatment in 2017, compared to 19 (1.4% of total exits) in 2016 (p 0.002). The largest increase in pediatric TB diagnoses in 2017 occurred in patients with a negative Xpert MTB/RIF result, but clinically highly suggestive of TB according to the newly introduced diagnostic algorithm. Fifty-two (3.1%) children under five years old started treatment in 2017, as compared to 14 (1.3%) in 2016 (p 0.004). The increase was less pronounced and not statistically significant in older patients: sixteen children (2.6%) above 5 years old started TB treatment in 2017 as compared to five (1.3%) in 2016 (p 0.17). Conclusion After the introduction of an adapted clinical pediatric TB diagnostic algorithm, including Xpert MTB/RIF on gastric aspirates, we observed a significant increase in the number of children – especially under 5 years old – started on TB treatment, mostly on clinical grounds. Increased ‘clinician awareness’ of pediatric TB likely played an important role.
  • The ethical imperative to relieve suffering for people with tuberculosis by ensuring access to palliative care

    Harding, R; Snyman, L; Ostgathe, C; Odell, S; Gwyther, L (International Union Against Tuberculosis and Lung Disease, 2020-05-01)
    Patients diagnosed with tuberculosis (TB) continue to experience clinical uncertainty and high mortality and to bear a high burden of symptoms and other concerns. Additional concerns may be family support needs and stigma, particularly the latter, as TB and human immunodeficiency virus (HIV) coinfection are common. Human rights covenants, global health policy and the End TB Strategy all recommend palliative care as an essential component of care services. As established in the resolution adopted by the World Health Assembly (WHA) on ‘‘Strengthening of palliative care as a component of comprehensive care throughout the life course’’, there is a ‘‘need for palliative care across disease groups (non-communicable diseases, and infectious diseases, including HIV and multidrug-resistant tuberculosis), and across all age groups’’. We address the ethical imperative to respect the dignity and fundamental rights of people with TB by providing palliative care. We review the evidence for the need for person-centred palliative care and highlight novel models that utilise the skills and training functions of specialist palliative care to achieve better care. We outline simple recommendations for the delivery of specialist and generalist palliative care, offer suggestions on how to ensure optimal coverage by enabling access to appropriate good-quality palliative care at all points of the health system, including alongside treatment. Finally, we set out the current priorities for research and policy to ensure that quality care is delivered to all who need it irrespective of treatment outcome, to minimise distress and to optimise engagement in treatment and care.
  • A case report of a child with probable drug resistant tuberculous pericarditis with a review of challenges involved in diagnosis, treatment and follow up of children with DR-TB pericarditis

    Swaminathan, Aravind; du Cros, Philipp; Achar, Jay; Kliescikova, Jarmila; Mirgayosieva, Shamsiya; Pirmahmadzoda, Bobojon; Médecins Sans Frontières, Dushanbe, Tajikistan; Paediatric Intensive Care Unit, Great Ormond Street Hospital, London, UK; Médecins Sans Frontières, Manson Unit, London, UK; Médecins Sans Frontières, Dushanbe, Tajikistan; National Tuberculoofsis Programme, Ministry of Health and Social Protection of the Republic Tajikistan, Dushanbe, Tajikistan. (2020-04-22)
    Background: There are unique challenges in the diagnosis and management of multi drug resistant tuberculosis (MDR-TB) in children. It is difficult to obtain confirmatory microbiological diagnosis in TB pericarditis. It is essential to differentiate between drug sensitive and drug resistant forms of TB as it has a major bearing on the regimen used, and inappropriate TB treatment combined with steroid use for pericarditis can lead to deterioration. With lack of samples, the treatment decision relies on the drug resistance pattern of the close contact if available. Therapeutic challenges of MDR-TB management in a child involve use of toxic drugs that need to be judiciously handled. We report a 2 years 4 months old male child who was diagnosed with TB pericarditis and treated based on the resistance pattern of his mother who was on treatment for pulmonary MDR-TB. Case presentation: This 2 years 4 months old male child was diagnosed with TB involving his pericardium. Getting him started on an appropriate regimen was delayed due to the difficulty in establishing microbiological confirmation and drug susceptibility. He was commenced on a regimen based on his mother’s drug resistance pattern and required surgery due to cardiac failure during the course of his treatment. He successfully completed 2 years of therapy. Conclusions: This child’s case demonstrates that despite unique challenges in diagnosis and management of drug resistant extra pulmonary tuberculosis in children, treatment of even complex forms can be successful. The need for high suspicion of MDR-TB, especially when there is close contact with pulmonary TB, careful design of an effective regimen that is tolerated by the child, indications for invasive surgical management of pericarditis, appropriate follow-up and management of adverse effects are emphasised.
  • A case report of a child with probable drug resistant tuberculous pericarditis with a review of challenges involved in diagnosis, treatment and follow up of children with DR-TB pericarditis

    Swaminathan, A; du Cros, P; Achar, J; Kliescikova, J; Mirgayosieva, S; Pirmahmadzoda, B (BMC, 2020-04-22)
    Background: There are unique challenges in the diagnosis and management of multi drug resistant tuberculosis (MDR-TB) in children. It is difficult to obtain confirmatory microbiological diagnosis in TB pericarditis. It is essential to differentiate between drug sensitive and drug resistant forms of TB as it has a major bearing on the regimen used, and inappropriate TB treatment combined with steroid use for pericarditis can lead to deterioration. With lack of samples, the treatment decision relies on the drug resistance pattern of the close contact if available. Therapeutic challenges of MDR-TB management in a child involve use of toxic drugs that need to be judiciously handled. We report a 2 years 4 months old male child who was diagnosed with TB pericarditis and treated based on the resistance pattern of his mother who was on treatment for pulmonary MDR-TB. Case presentation: This 2 years 4 months old male child was diagnosed with TB involving his pericardium. Getting him started on an appropriate regimen was delayed due to the difficulty in establishing microbiological confirmation and drug susceptibility. He was commenced on a regimen based on his mother's drug resistance pattern and required surgery due to cardiac failure during the course of his treatment. He successfully completed 2 years of therapy. Conclusions: This child's case demonstrates that despite unique challenges in diagnosis and management of drug resistant extra pulmonary tuberculosis in children, treatment of even complex forms can be successful. The need for high suspicion of MDR-TB, especially when there is close contact with pulmonary TB, careful design of an effective regimen that is tolerated by the child, indications for invasive surgical management of pericarditis, appropriate follow-up and management of adverse effects are emphasised.
  • Treating drug-resistant tuberculosis infection: no more excuses

    Reuter, A; Furin, J (Oxford University Press, 2020-04-08)
  • Drug-associated adverse events in the treatment of multidrug-resistant tuberculosis: an individual patient data meta-analysis

    Lan, Z; Ahmad, N; Baghaei, P; Barkane, L; Benedetti, A; Brode, SK; Brust, JCM; Campbell, JR; Chang, VWL; Falzon, D; et al. (Elsevier, 2020-03-17)
    BACKGROUND: Treatment of multidrug-resistant tuberculosis requires long-term therapy with a combination of multiple second-line drugs. These drugs are associated with numerous adverse events that can cause severe morbidity, such as deafness, and in some instances can lead to death. Our aim was to estimate the absolute and relative frequency of adverse events associated with different tuberculosis drugs to provide useful information for clinicians and tuberculosis programmes in selecting optimal treatment regimens. METHODS: We did a meta-analysis using individual-level patient data that were obtained from studies that reported adverse events that resulted in permanent discontinuation of anti-tuberculosis medications. We used a database created for our previous meta-analysis of multidrug-resistant tuberculosis treatment and outcomes, for which we did a systematic review of literature published between Jan 1, 2009, and Aug 31, 2015 (updated April 15, 2016), and requested individual patient-level information from authors. We also considered for this analysis studies contributing patient-level data in response to a public call made by WHO in 2018. Meta-analysis for proportions and arm-based network meta-analysis were done to estimate the incidence of adverse events for each tuberculosis drug. FINDINGS: 58 studies were identified, including 50 studies from the updated individual patient data meta-analysis for multidrug-resistant tuberculosis treatment. 35 of these studies, with 9178 patients, were included in our analysis. Using meta-analysis of proportions, drugs with low risks of adverse event occurrence leading to permanent discontinuation included levofloxacin (1·3% [95% CI 0·3-5·0]), moxifloxacin (2·9% [1·6-5·0]), bedaquiline (1·7% [0·7-4·2]), and clofazimine (1·6% [0·5-5·3]). Relatively high incidence of adverse events leading to permanent discontinuation was seen with three second-line injectable drugs (amikacin: 10·2% [6·3-16·0]; kanamycin: 7·5% [4·6-11·9]; capreomycin: 8·2% [6·3-10·7]), aminosalicylic acid (11·6% [7·1-18·3]), and linezolid (14·1% [9·9-19·6]). Risk of bias in selection of studies was judged to be low because there were no important differences between included and excluded studies. Variability between studies was significant for most outcomes analysed. INTERPRETATION: Fluoroquinolones, clofazimine, and bedaquiline had the lowest incidence of adverse events leading to permanent drug discontinuation, whereas second-line injectable drugs, aminosalicylic acid, and linezolid had the highest incidence. These results suggest that close monitoring of adverse events is important for patients being treated for multidrug-resistant tuberculosis. Our results also underscore the urgent need for safer and better-tolerated drugs to reduce morbidity from treatment itself for patients with multidrug-resistant tuberculosis.
  • WHO 2019 guidelines on drug-resistant tuberculosis treatment: based on evidence or expert opinion?

    Guglielmetti, L; Huerga, H; Khan, U; Varaine, F (European Respiratory Society, 2020-03-05)

View more