We collected individual patient data from observational studies identified through systematic reviews and a public call for data. We included patients meeting WHO eligibility criteria for the shorter regimen: not previously treated with second-line drugs, and with fluoroquinolone- and second-line injectable agent-susceptible RR/MDR-TB. We used propensity score matched, mixed effects meta-regression to calculate adjusted odds ratios and adjusted risk differences (aRDs) for failure or relapse, death within 12 months of treatment initiation and loss to follow-up.
We included 2625 out of 3378 (77.7%) individuals from nine studies of shorter regimens and 2717 out of 13 104 (20.7%) individuals from 53 studies of longer regimens. Treatment success was higher with the shorter regimen than with longer regimens (pooled proportions 80.0% versus 75.3%), due to less loss to follow-up with the former (aRD -0.15, 95% CI -0.17- -0.12). The risk difference for failure or relapse was slightly higher with the shorter regimen overall (aRD 0.02, 95% CI 0-0.05) and greater in magnitude with baseline resistance to pyrazinamide (aRD 0.12, 95% CI 0.07-0.16), prothionamide/ethionamide (aRD 0.07, 95% CI -0.01-0.16) or ethambutol (aRD 0.09, 95% CI 0.04-0.13).
In patients meeting WHO criteria for its use, the standardised shorter regimen was associated with substantially less loss to follow-up during treatment compared with individualised longer regimens and with more failure or relapse in the presence of resistance to component medications. Our findings support the need to improve access to reliable drug susceptibility testing.
Tajikistan has a high burden of rifampicin-resistant TB (RR-TB), with 2,700 new cases estimated for 2021 (28/100,000 population). TB is spread among household members through close interaction and children exposed through household contact progress to disease rapidly and frequently.
METHODS
We retrospectively analysed programmatic data from household contact tracing in Dushanbe over 50 months. We calculated person-years of follow-up, contact tracing yield, number needed to screen (NNS) and number needed to test (NNT) to find one new case, and time to diagnosis.
RESULTS
We screened 6,654 household contacts of 830 RR-TB index cases; 47 new RR-TB cases were detected, 43 in Year 1 and 4 in Years 2 or 3. Ten were aged <5 years; 46/47 had TB symptoms, 34/45 had chest radiographs consistent with TB, 11/35 were Xpert Ultra-positive, 29/32 were tuberculin skin test-positive and 28/47 had positive TB culture and phenotypic drug susceptibility results. The NNS to find one RR-TB case was 141.57 and the NNT was 34.49. The yields for different types of contacts were as follows: 0.7% for screened contacts, 2.9% for tested contacts, 17.0% for symptomatic contacts and 12.1% for symptomatic contacts aged below 5 years.
CONCLUSION
RR-TB household contact tracing was feasible and productive in Tajikistan, a low middle-income country with an inefficient healthcare delivery system.
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.
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.
Countries in the West and Central African regions struggle to offer quality HIV care at scale, despite HIV prevalence being relatively low. In these challenging operating environments, basic health care needs are multiple, systems are highly fragile and conflict disrupts health care. Médecins Sans Frontières (MSF) has been working to integrate HIV care in basic health services in such settings since 2000. We review the implementation of differentiated HIV care and treatment approaches in MSF-supported programmes in South Sudan (RoSS), Central African Republic (CAR) and Democratic Republic of Congo (DRC).
METHODS
A descriptive analysis from CAR, DRC and RoSS programmes reviewing methodology and strategies of HIV care integration between 2010 and 2015 was performed. We describe HIV care models integrated within the provision of general health care and highlight best practices and challenges.
RESULTS
Services included provision of general health care, with out-patient care (range between countries 43,343 and 287,163 consultations/year in 2015) and in-patient care (range 1076–16,595 in 2015). By the end of 2015 antiretroviral therapy (ART) initiations reached 12–255 patients/year. A total of 1101 and 1053 patients were on ART in CAR and DRC, respectively. In RoSS 186 patients were on ART when conflict recommenced late in 2013. While ART initiation and monitoring were mostly clinically driven in the early phase of the programmes, DRC implemented CD4 monitoring and progressively HIV viral load (VL) monitoring during study period. Attacks to health care facilities in CAR and RoSS disrupted service provision temporarily. Programmatic challenges include: competing health priorities influencing HIV care and need to integrate within general health services. Differentiated care approaches that support continuity of care in these programmes include simplification of medical protocols, multi-month ART prescriptions, and community strategies such as ART delivery groups, contingency plans and peer support activities.
CONCLUSIONS
The principles of differentiated HIV care for high-quality ART delivery can successfully be applied in challenging operating environments. However, success heavily depends on specific adaptations to each setting.
In this retrospective study, we evaluated the diagnostic accuracy of molecular tests (MT) for the detection of DR‐TB, compared to the gold standard liquid‐based Drug Susceptibility Testing (DST) in Karakalpakstan.
METHODS
A total of 6,670 specimens received in the Republican TB No 1 Hospital Laboratory of Karakalpakstan between January and July 2017 from new and retreatment patients were analyzed. Samples were tested using Xpert MTB/RIF and line probe assays (LPA) for the detection of mutations associated with resistance. The sensitivity and specificity of MTs were calculated relative to results based on DST.
RESULTS
The accuracy of MT for detection of rifampicin resistance was high, with sensitivity and specificity over 98%. However, we observed reduced sensitivity of LPA for detection of resistance; 86% for isoniazid (95%CI 82‐90%), 86% for fluoroquinolones (95%CI 68‐96%), 70% for capreomycin (95%CI 46‐88%) and 23% for kanamycin (95%CI 13‐35%).
CONCLUSIONS
We show that MTs are a useful tool for rapid and safe diagnosis of DR‐TB, however, clinicians should be aware of their limitations. Although detection of rifampicin resistance was highly accurate, our data suggests that resistance mutations circulating in the Republic of Karakalpakstan for other drugs were not detected by the methods used here. This merits further investigation.
Person-centred care (PCC) is an internationally recognised priority, and a key underlying principle within MSF projects. PCC ensures that people are involved in their care and treatment decisions, and considers individuals' needs and priorities within service delivery. Clarity is required regarding how this may be implemented within different contexts. Multidrug-resistant tuberculosis (MDR-TB) treatment is lengthy, toxic and insufficiently effective, with recent developments changing the treatment landscape. WHO’s 2019 treatment guidelines include a shorter, 9-11 month-long treatment regimen, and recommends that people with MDR-TB should be involved in the decision around treatment option. We examine what PCC can look like in practice, through the perspectives and experiences of people with MDR-TB and health care workers (HCW) in Karakalpakstan, Uzbekistan.
METHODS
We carried out a qualitative study, comprising 48 interviews with people with MDR-TB (n=24; including repeat interviews with three participants) and healthcare workers (n=20), in Karakalpakstan in June-July 2019. In this setting, MSF and the Ministry of Health collaboratively have provided TB care since 1998. 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 (QSR International, Melbourne, Australia).
ETHICS
This study was approved by the ethics committees of Uzbekistan and the MSF Ethics Review Board.
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 to them to choose the appropriate treatment. HCW distrusted the effectiveness and appropriateness of the shorter treatment regimen, which may influence who is offered this option. Additionally, HCW had concerns about involving people in treatment choices, preferring that the doctor decide. However, people with MDR-TB wanted to be involved in discussions about their treatment, to have their preference sought, and were comfortable choosing the treatment location, whether ambulatory or hospital-based. Participants felt it important that people with MDR-TB have increased knowledge and understanding about their treatment and disease, to foster their sense of preparedness and ownership of treatment. Involving people in their care was said to motivate sustained treatment-taking, which some felt directly observed treatment (DOT) delivery could undermine.
CONCLUSIONS
There was a preference for doctors choosing the treatment regimen, linked to unfamiliarity with shared decision-making and an imbalance between the perceived knowledge base of practitioners and patients. Involving people in their care, through discussions, information, and preference seeking could foster better ownership and self-responsibility, supporting sustained engagement with treatment, which DOT may contradict. These findings are important with MSF operations working to achieve PCC in practice, highlighting the need for approaches that are context specific and adapted to individuals’ preferences. Programmes should consider more person-centred approaches to treatment delivery, such as community or family DOT.
CONFLICTS OF INTEREST
None declared
Background
Isoniazid (INH, H) resistance is the most common drug-resistant TB pattern, with treatment success rates lower than those in drug-susceptible TB. The WHO recommends a 6-month regimen of rifampicin (RIF, R), ethambutol (EMB, E), pyrazinamide (PZA, Z), and levofloxacin (Lfx) (6REZLfx) for INH-resistant, RIF-susceptible TB (HRRS-TB). Uzbekistan has a high burden of TB (62/100,000 population) and multidrug-resistant TB (12/100,000 population).
Methods
We conducted a retrospective, descriptive study of microbiologically confirmed HRRS-TB using routinely collected programmatic data from 2009 to 2020.
Results
We included 854 HRRS-TB cases. Treatment success was 80.2% overall. For REZLfx, the treatment success rate was 92.0% over a short treatment duration, with no amplifications to RIF or second-line anti-TB drug resistance. We documented 46 regimens with REZLfx plus linezolid (success 87.0%) and 539 regimens using kanamycin or capreomycin (success 76.6%). We identified 37 treatment failures (4.3%), 30 deaths (3.5%), 25 resistance amplifications (2.9%), including eight to RIF (0.9%), and 99 lost to follow-up (LTFU) cases (11.6%). Unsuccessful outcomes were more common with older age, diabetes, chest X-ray cavities, smear positivity, smear-positive persistence, and male sex. LTFU was more common with injection-containing regimens.
Conclusions
REZLfx is a safe and effective first-line treatment for INH-resistant, RIF-susceptible TB. Treatment success was lower and LTFU was higher for injection-containing regimens.