Now showing items 21-40 of 3026

    • Clinical perspectives on treatment of rifampicin-resistant/multidrug-resistant TB

      Cox, V; McKenna, L; Acquah, R; Reuter, A; Wasserman, S; Vambe, D; Ustero, P; Udwadia, Z; Trivino-Duran, L; Tommasi, M; et al. (International Union Against Tuberculosis and Lung Disease, 2020-11-01)
      Rapid diagnostics, newer drugs, repurposed medications, and shorter regimens have radically altered the landscape for treating rifampicin-resistant TB (RR-TB) and multidrug-resistant TB (MDR-TB). There are multiple ongoing clinical trials aiming to build a robust evidence base to guide RR/MDR-TB treatment, and both observational studies and programmatic data have contributed to advancing the treatment field. In December 2019, the WHO issued their second ‘Rapid Communication´ related to RR-TB management. This reiterated their prior recommendation that a majority of people with RR/MDR-TB receive all-oral treatment regimens, and now allow for specific shorter duration regimens to be used programmatically as well. Many TB programs need clinical advice as they seek to roll out such regimens in their specific setting. In this Perspective, we highlight our early experiences and lessons learned from working with National TB Programs, adult and pediatric clinicians and civil society, in optimizing treatment of RR/MDR-TB, using shorter, highly-effective, oral regimens for the majority of people with RR/MDR-TB.
    • Bridging research integrity and global health epidemiology (BRIDGE) guidelines: explanation and elaboration

      Alba, S; Lenglet, A; Verdonck, K; Roth, J; Patil, R; Mendoza, W; Juvekar, S; Rumisha, SF (BMJ Publishing Group, 2020-10-28)
      Over the past decade, two movements have profoundly changed the environment in which global health epidemiologists work: research integrity and research fairness. Both ought to be equally nurtured by global health epidemiologists who aim to produce high quality impactful research. Yet bridging between these two aspirations can lead to practical and ethical dilemmas. In the light of these reflections we have proposed the BRIDGE guidelines for the conduct of fair global health epidemiology, targeted at stakeholders involved in the commissioning, conduct, appraisal and publication of global health research. The guidelines follow the conduct of a study chronologically from the early stages of study preparation until the dissemination and communication of findings. They can be used as a checklist by research teams, funders and other stakeholders to ensure that a study is conducted in line with both research integrity and research fairness principles. In this paper we offer a detailed explanation for each item of the BRIDGE guidelines. We have focused on practical implementation issues, making this document most of interest to those who are actually conducting the epidemiological work.
    • Bridging research integrity and global health epidemiology (BRIDGE) statement: guidelines for good epidemiological practice

      Alba, S; Verdonck, K; Lenglet, A; Rumisha, SF; Wienia, M; Teunissen, I; Straetemans, M; Mendoza, W; Jeannetot, D; Weibel, D; et al. (BMJ Publishing Group, 2020-10-28)
      Background Research integrity and research fairness have gained considerable momentum in the past decade and have direct implications for global health epidemiology. Research integrity and research fairness principles should be equally nurtured to produce high-quality impactful research—but bridging the two can lead to practical and ethical dilemmas. In order to provide practical guidance to researchers and epidemiologist, we set out to develop good epidemiological practice guidelines specifically for global health epidemiology, targeted at stakeholders involved in the commissioning, conduct, appraisal and publication of global health research. Methods We developed preliminary guidelines based on targeted online searches on existing best practices for epidemiological studies and sought to align these with key elements of global health research and research fairness. We validated these guidelines through a Delphi consultation study, to reach a consensus among a wide representation of stakeholders. Results A total of 45 experts provided input on the first round of e-Delphi consultation and 40 in the second. Respondents covered a range of organisations (including for example academia, ministries, NGOs, research funders, technical agencies) involved in epidemiological studies from countries around the world (Europe: 19; Africa: 10; North America: 7; Asia: 5; South-America: 3 Australia: 1). A selection of eight experts were invited for a face-to-face meeting. The final guidelines consist of a set of 6 standards and 42 accompanying criteria including study preparation, protocol development, data collection, data management, data analysis, dissemination and communication. Conclusion While guidelines will not by themselves guard global health from questionable and unfair research practices, they are certainly part of a concerted effort to ensure not only mutual accountability between individual researchers, their institutions and their funders but most importantly their joint accountability towards the communities they study and society at large.
    • Comparative Effectiveness of Interventions to Improve the HIV Continuum of Care and HIV Preexposure Prophylaxis in Kenya: A Model-Based Analysis

      Luong Nguyen, LB; Freedberg, KA; Wanjala, S; Maman, D; Szumilin, E; Mendiharat, P; Yazdanpanah, Y (Oxford University Press, 2020-10-27)
      Background In Western Kenya up to one-quarter of the adult population was human immunodeficiency virus (HIV)-infected in 2012. The Ministry of Health, Médecins Sans Frontières, and partners implemented an HIV program that surpassed the 90-90-90 UNAIDS targets. In this generalized epidemic, we compared the effectiveness of preexposure prophylaxis (PrEP) with improving continuum of care. Methods We developed a dynamic microsimulation model to project HIV incidence and infections averted to 2030. We modeled 3 strategies compared to a 90-90-90 continuum of care base case: (1) scaling up the continuum of care to 95-95-95, (2) PrEP targeting young adults with 10% coverage, and (3) scaling up to 95-95-95 and PrEP combined. Results In the base case, by 2030 HIV incidence was 0.37/100 person-years. Improving continuum levels to 95-95-95 averted 21.5% of infections, PrEP averted 8.0%, and combining 95-95-95 and PrEP averted 31.8%. Sensitivity analysis showed that PrEP coverage had to exceed 20% to avert as many infections as reaching 95-95-95. Conclusions In a generalized HIV epidemic with continuum of care levels at 90-90-90, improving the continuum to 95-95-95 is more effective than providing PrEP. Continued improvement in the continuum of care will have the greatest impact on decreasing new HIV infections.
    • Standardized Protocol Items Recommendations for Observational Studies (SPIROS) for Observational Study Protocol Reporting Guidelines: Protocol for a Delphi Study

      Mahajan, R; Burza, S; Bouter, LM; Sijtsma, K; Knottnerus, A; Kleijnen, J; Dael, PV; Zeegers, MP (JMIR Publications, 2020-10-21)
      Background: Approximately 90% of currently published clinical and public health research is in the form of observational studies. Having a detailed and registered study protocol prior to data collection is important in any empirical study. Without this, there is no reliable way to assess the occurrence of publication bias, outcome reporting bias, and other protocol deviations. However, there is currently no solid guidance available on the information that a protocol for an observational study should contain. Objective: The aim of this study is to formulate the Standardized Protocol Items Recommendations for Observational Studies (SPIROS) reporting guidelines, which focus on 3 main study designs of analytical epidemiology: cohort, case-control, and cross-sectional studies. Methods: A scoping review of published protocol papers of observational studies in epidemiology will identify candidate items for the SPIROS reporting guidelines. The list of items will be extended with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist items and recommendations from the SPIROS steering committee. This long list serves as the basis for a 2-round Delphi survey among experts to obtain consensus on which items to include. Each candidate item from the long list will be rated on a 5-point Likert scale to assess relevance for inclusion in the SPIROS reporting guidelines. Following the Delphi survey, an expert-driven consensus workshop will be convened to finalize the reporting guidelines. Results: A scoping review of published observational study protocols has been completed, with 59 candidate items identified for inclusion into the Delphi survey, itself launched in early 2020. Conclusions: This project aims to improve the timeliness, completeness, and clarity of study protocols of observational studies in analytical epidemiology by producing expert-based recommendations of items to be addressed. These reporting guidelines will facilitate and encourage researchers to prepare and register study protocols of sufficient quality prior to data collection in order to improve the transparency, reproducibility, and quality of observational studies.
    • One step forward: Successful end-of-treatment outcomes of drug-resistant TB patients who received concomitant bedaquiline and delamanid in Mumbai, India

      Das, M; Dalal, A; Laxmeshwar, C; Ravi, S; Mamnoon, F; Meneguim, AC; Paryani, R; Mathur, T; Singh, P; Mansoor, H; et al. (Oxford University Press, 2020-10-20)
      Background Médecins Sans Frontières clinic in Mumbai, India has been providing concomitant Bedaquiline (BDQ) and Delamanid (DLM) in treatment regimen for patients with drug-resistant tuberculosis (DR-TB) and limited therapeutic options, referred from other healthcare institutions, since 2016. The study documents the end-of-treatment outcomes, culture-conversion rates, and serious adverse events (SAEs) during treatment. Methods This was a retrospective cohort study based on routinely collected programme data. In clinic, treatment regimens are designed based on culture-drug sensitivity test patterns, previous drug-exposures and are provided for 20-22 months. The BDQ and DLM are extended beyond 24 weeks as off-label use. Patients who initiated DR-TB treatment including BDQ and DLM (concomitantly for at least 4 weeks) during February2016-February2018 were included. Result Of the 70 patients included, the median (IQR) age was 25(22-32) years and 56% were females. All except one were fluoroquinolone resistant. The median(IQR) duration of exposure to BDQ and DLM was 77(43-96) weeks. Thirty-nine episodes of serious-adverse-events(SAEs) were reported among 30(43%) patients, including five instances of QTc prolongation-assessed as possibly related to BDQ and/or DLM. Majority(69%) had culture conversion before 24 weeks of treatment. In 61(87%), use of BDQ and DLM was extended beyond 24 weeks. Successful end-of-treatment outcomes were reported in 49(70%) patients. Conclusion The successful treatment outcomes of this cohort show that regimens including concomitant bedaquiline and delamanid for longer than 24 weeks are effective and can be safely administered on ambulatory basis. National TB programmes globally should scale up access to life saving DR-TB regimens with new drugs.
    • Outdoor Residual Insecticide Spraying (ODRS), a New Approach for the Control of the Exophilic Vectors of Human Visceral Leishmaniasis: Phlebotomus orientalis in East Africa

      Elnaiem, DA; Dakein, O; Alawad, AM; Alsharif, B; Khogali, A; Jibreel, T; Osman, OF; Has'san, H; Atia, AM; Elhag, M; et al. (Public Library of Sciences, 2020-10-20)
      Visceral Leishmaniasis (VL) due to Leishmania donovani is a neglected protozoan parasitic disease in humans, which is usually fatal if untreated. Phlebotomus orientalis, the predominant VL vector in East Africa, is a highly exophilic/exophagic species that poses a major challenge to current Integrated Vector Management (IVM). Here we report results of pilot studies conducted in rural villages in Gedarif state, Sudan, to evaluate outdoor residual spraying of 20mg active ingredient (a.i.) /m2 deltamethrin insecticide applied to the characteristic household compound boundary reed fence and to the outside of household buildings (Outdoor Residual Insecticide Spraying, ODRS), and as an alternative, spraying restricted to the boundary fence only (Restricted Outdoor Residual Insecticide Spraying, RODRS). Four to six clusters of 20 households were assigned to insecticide treatments or control in three experiments. Changes in sand fly numbers were monitored over 2,033 trap-nights over 43–76 days follow-up in four sentinel houses per cluster relative to unsprayed control clusters. Sand fly numbers were monitored by sticky traps placed on the ground on the inside (“outdoor”) and the outside (“peridomestic”) of the boundary fence, and by CDC light traps suspended outdoors in the household compound. The effects of ODRS on sand fly numbers inside sleeping huts were monitored by insecticide knockdown. After a single application, ODRS reduced P. orientalis abundance by 83%-99% in outdoor and peridomestic trap locations. ODRS also reduced numbers of P. orientalis found resting inside sleeping huts. RODRS reduced outdoor and peridomestic P. orientalis by 60%-88%. By direct comparison, RODRS was 58%-100% as effective as ODRS depending on the trapping method. These impacts were immediate on intervention and persisted during follow-up, representing a large fraction of the P. orientalis activity season. Relative costs of ODRS and RODRS delivery were $5.76 and $3.48 per household, respectively. The study demonstrates the feasibility and high entomological efficacy of ODRS and RODRS, and the expected low costs relative to current IVM practises. These methods represent novel sand fly vector control tools against predominantly exophilic/exophagic sand fly vectors, aimed to lower VL burdens in Sudan, with potential application in other endemic regions in East Africa.
    • Cost-effectiveness of screening and treatment using direct-acting antivirals for chronic Hepatitis C virus in a primary care setting in Karachi, Pakistan

      Mafirakureva, N; Lim, AG; Khalid, GG; Aslam, K; Campbell, L; Zahid, H; Van den Bergh, R; Falq, G; Fortas, C; Wailly, Y; et al. (Wiley, 2020-10-14)
      abilistic sensitivity analyses (PSA). The ICER for implementing testing and treatment compared to no programme was US$450/DALY averted, with 100% of PSA runs falling below the per capita Gross Domestic Product threshold for cost-effective interventions for Pakistan (US$1,422). The ICER increased to US$532/DALY averted assuming national HCV seroprevalence (5.5% versus 33% observed in the intervention). If the cost of liver disease care was included (adapted from resource use data from Cambodia which has similar GDP to Pakistan), the ICER dropped to US$148/DALY, while it became cost-saving if a recently negotiated reduced drug cost of $75/treatment course was assumed (versus $282 in base-case) in addition to cost of liver disease care. In conclusion, screening and DAA treatment for HCV infection are expected to be highly cost-effective in Pakistan, supporting the expansion of similar screening and treatment programmes across Pakistan.
    • 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.
    • Extended use or reuse of single-use surgical masks and filtering face-piece respirators during the coronavirus disease 2019 (COVID-19) pandemic: A rapid systematic review.

      Toomey, E; Conway, Y; Burton, C; Smith, S; Smalle, M; Chan, X; Adisesh, A; Tanveer, S; Ross, L; Thomson, I; et al. (Cambridge University Press, 2020-10-08)
      Background: Shortages of personal protective equipment during the coronavirus disease 2019 (COVID-19) pandemic have led to the extended use or reuse of single-use respirators and surgical masks by frontline healthcare workers. The evidence base underpinning such practices warrants examination. Objectives: To synthesize current guidance and systematic review evidence on extended use, reuse, or reprocessing of single-use surgical masks or filtering face-piece respirators. Data sources: We used the World Health Organization, the European Centre for Disease Prevention and Control, the US Centers for Disease Control and Prevention, and Public Health England websites to identify guidance. We used Medline, PubMed, Epistemonikos, Cochrane Database, and preprint servers for systematic reviews. Methods: Two reviewers conducted screening and data extraction. The quality of included systematic reviews was appraised using AMSTAR-2. Findings were narratively synthesized. Results: In total, 6 guidance documents were identified. Levels of detail and consistency across documents varied. They included 4 high-quality systematic reviews: 3 focused on reprocessing (decontamination) of N95 respirators and 1 focused on reprocessing of surgical masks. Vaporized hydrogen peroxide and ultraviolet germicidal irradiation were highlighted as the most promising reprocessing methods, but evidence on the relative efficacy and safety of different methods was limited. We found no well-established methods for reprocessing respirators at scale. Conclusions: Evidence on the impact of extended use and reuse of surgical masks and respirators is limited, and gaps and inconsistencies exist in current guidance. Where extended use or reuse is being practiced, healthcare organizations should ensure that policies and systems are in place to ensure these practices are carried out safely and in line with available guidance.
    • Impact of the implementation of new guidelines on the management of patients with HIV infection at an advanced HIV clinic in Kinshasa, Democratic Republic of Congo (DRC).

      Mangana, F; Massaquoi, L D; Moudachirou, R; Harrison, R; Kaluangila, T; Mucinya, G; Ntabugi, N; van Cutsem, G; Burton, R; Isaakidis, P (BMC, 2020-10-07)
      Background: HIV continues to be the main determinant morbidity with high mortality rates in Sub-Saharan Africa, with a high number of patients being late presenters with advanced HIV. Clinical management of advanced HIV patients is thus complex and requires strict adherence to updated, empirical and simplified guidelines. The current study investigated the impact of the implementation of a new clinical guideline on the management of advanced HIV in Kinshasa, Democratic Republic of Congo (DRC). Methods: A retrospective analysis of routine clinical data of advanced HIV patients was conducted for the periods; February 2016 to March 2017, before implementation of new guidelines, and November 2017 to July 2018, after the implementation of new guidelines. Eligible patients were patients with CD4 < 200 cell/μl and presenting with at least 1 of 4 opportunistic infections. Patient files were reviewed by a medical doctor and a committee of 3 other doctors for congruence. Statistical significance was set at 0.05%. Results: Two hundred four and Two hundred thirty-one patients were eligible for inclusion before and after the implementation of new guidelines respectively. Sex and age distributions were similar for both periods, and median CD4 were 36 & 52 cell/μl, before and after the new guidelines implementation, respectively. 40.7% of patients had at least 1 missed/incorrect diagnosis before the new guidelines compared to 30% after new guidelines, p < 0.05. Clinical diagnosis for TB and toxoplasmosis were also much improved after the implementation of new guidelines. In addition, only 63% of patients had CD4 count test results before the new guidelines compared to 99% of patients after new guidelines. Death odds after the implementation of new guidelines were significantly lower than before new guidelines in a multivariate regression model that included patients CD4 count and 10 other covariates, p < 0.05. Conclusions: Simplification and implementation of a new and improved HIV clinical guideline coupled with the installation of laboratory equipment and point of care tests potentially helped reduce incorrect diagnosis and improve clinical outcomes of patients with advanced HIV. Regulating authorities should consider developing simplified versions of guidelines followed by the provision of basic diagnostic equipment to health centers.
    • Offering care for victims of torture among a migrant population in a transit country: a descriptive study in a dedicated clinic from January 2017 to June 2019.

      Keshk, M; Harrison, R; Kizito, W; Psarra, C; Owiti, P; Timire, C; Camacho, MM; De Maio, G; Safwat, H; Matboly, A; et al. (Oxford University Press, 2020-10-06)
      Background: Medecins Sans Frontieres set up a clinic to provide multidisciplinary care to a vulnerable migrant population experiencing torture. We describe the population accessing care, the characteristics of care provided and patient outcomes. Methods: A descriptive retrospective cohort study of patients enrolled in care during January 2017-June 2019 was conducted. Results: Of 2512 victims of torture cases accessing the clinic, the male: female ratio was 1:1. About 67% of patients received medical care, mostly for chronic pain treatment. About 73% of patients received mental healthcare, 37% received physiotherapy and 33% received social support care; 49% came to the clinic upon the recommendation of a friend or family member. The discharge with improvement rate ranged from 23% in the mental health service to 9% in the sociolegal service. Patients retained in care had a median IQR of 3 (2-4) follow-up visits for medical care, 4 (2-7) for mental health, 6 (3-10) for physiotherapy and 2 (1-4) for sociolegal. Conclusion: Care for victims of torture cases among vulnerable migrants is complex. For those who did receive care that led to an improvement in their condition, their care models have been described, to allow its implementation in other non-specialised settings.
    • Lived experiences of palliative care among people living with HIV/AIDS: a qualitative study from Bihar, India.

      Nair, M; Kumar, P; Mahajan, R; Harshana, A; Richardson, K; Moreto-Planas, L; Burza, S (BMJ Publishing Group, 2020-10-05)
      Objectives: This study aimed to assess the lived experiences of palliative care among critically unwell people living with HIV/AIDS (PLHA), caregivers and relatives of deceased patients. It also aimed to understand the broader palliative care context in Bihar. Design: This was an exploratory, qualitative study which used thematic analysis of semistructured, in-depth interviews as well as a focus group discussion. Setting: All interviews took place in a secondary care hospital in Patna, Bihar which provides holistic care to critically unwell PLHA. Participants: We purposively selected 29 participants: 10 critically unwell PLHA, 5 caregivers of hospitalised patients, 7 relatives of deceased patients who were treated in the secondary care hospital and 7 key informants from community-based organisations. Results: Critically ill PLHA emphasised the need for psychosocial counselling and opportunities for social interaction in the ward, as well as a preference for components of home-based palliative care, even though they were unfamiliar with actual terms such as 'palliative care' and 'end-of-life care'. Critically unwell PLHA generally expressed preference for separate, private inpatient areas for end-of-life care. Relatives of deceased patients stated that witnessing patients' deaths caused trauma for other PLHA. Caregivers and relatives of deceased patients felt there was inadequate time and space for grieving in the hospital. While both critically ill PLHA and relatives wished that poor prognosis be transparently disclosed to family members, many felt it should not be disclosed to the dying patients themselves. Conclusions: Despite expected high inpatient fatality rates, PLHA in Bihar lack access to palliative care services. PLHA receiving end-of-life care in hospitals should have a separate dedicated area, with adequate psychosocial counselling and activities to prevent social isolation. Healthcare providers should make concerted efforts to inquire, understand and adapt their messaging on prognosis and end-of-life care based on patients' preferences.
    • Lessons Learned From Helping Babies Survive in Humanitarian Settings.

      Amsalu, R; Schute-Hillen, C; Garcia, DM; Lafferty, N; Morris, CN; Gee, S; Akseer, N; Scudder, E; Sami, S; Barasa, SO; et al. (American Academy of Pediatrics, 2020-10-01)
      Humanitarian crises, driven by disasters, conflict, and disease epidemics, have profound effects on society, including on people's health and well-being. Occurrences of conflict by state and nonstate actors have increased in the last 2 decades: by the end of 2018, an estimated 41.3 million internally displaced persons and 20.4 million refugees were reported worldwide, representing a 70% increase from 2010. Although public health response for people affected by humanitarian crisis has improved in the last 2 decades, health actors have made insufficient progress in the use of evidence-based interventions to reduce neonatal mortality. Indeed, on average, conflict-affected countries report higher neonatal mortality rates and lower coverage of key maternal and newborn health interventions compared with non-conflict-affected countries. As of 2018, 55.6% of countries with the highest neonatal mortality rate (≥30 per 1000 live births) were affected by conflict and displacement. Systematic use of new evidence-based interventions requires the availability of a skilled health workforce and resources as well as commitment of health actors to implement interventions at scale. A review of the implementation of the Helping Babies Survive training program in 3 refugee responses and protracted conflict settings identify that this training is feasible, acceptable, and effective in improving health worker knowledge and competency and in changing newborn care practices at the primary care and hospital level. Ultimately, to improve neonatal survival, in addition to a trained health workforce, reliable supply and health information system, community engagement, financial support, and leadership with effective coordination, policy, and guidance are required.
    • People-centred surveillance: a narrative review of community-based surveillance among crisis-affected populations.

      Ratnayake, R; Tammaro, M; Tiffany, A; Kongelf, A; Polonsky, JA; McClelland, A (Elsevier, 2020-10-01)
      Outbreaks of disease in settings affected by crises grow rapidly due to late detection and weakened public health systems. Where surveillance is underfunctioning, community-based surveillance can contribute to rapid outbreak detection and response, a core capacity of the International Health Regulations. We reviewed articles describing the potential for community-based surveillance to detect diseases of epidemic potential, outbreaks, and mortality among populations affected by crises. Surveillance objectives have included the early warning of outbreaks, active case finding during outbreaks, case finding for eradication programmes, and mortality surveillance. Community-based surveillance can provide sensitive and timely detection, identify valid signals for diseases with salient symptoms, and provide continuity in remote areas during cycles of insecurity. Effectiveness appears to be mediated by operational requirements for continuous supervision of large community networks, verification of a large number of signals, and integration of community-based surveillance within the routine investigation and response infrastructure. Similar to all community health systems, community-based surveillance requires simple design, reliable supervision, and early and routine monitoring and evaluation to ensure data validity. Research priorities include the evaluation of syndromic case definitions, electronic data collection for community members, sentinel site designs, and statistical techniques to counterbalance false positive signals.
    • “You said the hospital can't be bombed”

      Garcia-Mingo, A; Abbara, A; Roy, RB (Elsevier, 2020-10-01)
    • Setting up pharmacovigilance based on available endTB Project data for bedaquiline

      Lachenal, N; Hewison, C; Mitnick, C; Lomtadze, N; Coutisson, S; Osso, E; Ahmed, S; Leblanc, G; Islam, S; Atshemyan, H; et al. (International Union Against Tuberculosis and Lung Disease, 2020-10-01)
      SETTING: Active pharmacovigilance (PV) is recommended for TB programmes, notably for multidrug-resistant TB (MDR-TB) patients treated with new drugs. Launched with the support of UNITAID in April 2015, endTB (Expand New Drug markets for TB) facilitated treatment with bedaquiline (BDQ) and/or delamanid of >2600 patients in 17 countries, and contributed to the creation of a central PV unit (PVU). OBJECTIVE: To explain the endTB PVU process by describing the serious adverse events (SAEs) experienced by patients who received BDQ-containing regimens. DESIGN: The overall PV strategy was in line with the ‘advanced´ WHO active TB drug safety monitoring and management (aDSM) system. All adverse events (AEs) of clinical significance were followed up; the PVU focused on signal detection from SAEs. RESULTS and CONCLUSION: Between 1 April 2015 and 31 March 2019, the PVU received and assessed 626 SAEs experienced by 417 BDQ patients. A board of MDR-TB/PV experts reviewed unexpected and possibly drug-related SAEs to detect safety signals. The experts communicated on clusters of risks factors, notably polypharmacy and off-label drug use, encouraging a patient-centred approach of care. Organising advanced PV in routine care is possible but demanding. It is reasonable to expect local/national programmes to focus on clinical management, and to limit reporting to aDSM systems to key data, such as the SAEs.
    • Bedaquiline and delamanid result in low rates of unfavourable outcomes among TB patients in Eswatini

      Vambe, D; Kay, AW; Furin, J; Howard, AA; Dlamini, T; Shabangu, A; Hassen, F; Masuku, S; Maha, O; Wawa, C; et al. (International Union Against Tuberculosis and Lung Disease, 2020-10-01)
      SETTING: Since 2015, Eswatini has been scaling up bedaquiline (BDQ) and delamanid (DLM) based drug-resistant TB treatment regimens under programmatic conditions. OBJECTIVE: Identification of factors associated with treatment outcomes in patients receiving BDQ and/or DLM either as a new treatment initiation or drug substitution. DESIGN: This is a retrospective cohort study of patients receiving BDQ and/or DLM in Eswatini between March 2015 and October 2018. We describe factors associated with unfavourable treatment outcomes (death, lost to follow-up, treatment failure and amplification of resistance) and culture conversion using multivariable flexible parametric survival and competing-risks regression analyses. RESULTS: Of 352 patients receiving BDQ and/or DLM, 7.8% and 21.2% had an unfavourable treatment outcome at 6 and 24 months, respectively. Predictors were age ≥ 60 years (adjusted hazard ratio aHR 4.49, 95%CI 1.61–12.57) vs. age 20–39 years, and a treatment regimen combining both drugs (aHR 4.49, 95%CI 1.61–12.57) vs. BDQ only. The probability of culture conversion was increased for two health facilities and patients with a poly resistance profile (adjusted sub-hazard ratio 2.01, 95%CI 1.13–3.59) vs. multidrug resistance. CONCLUSION: Single use of BDQ or DLM was associated with low rates of unfavourable outcomes, suggesting that these medications may be effectively adopted at scale under routine programmatic conditions. Combined use of BDQ and DLM was a risk factor for unfavourable outcomes and should prompt for collection of more data on the combined use of these medications.
    • Introducing new and repurposed TB drugs: the endTB experience

      Seung, KJ; Khan, U; Varaine, F; Ahmed, S; Bastard, M; Cloez, S; Damtew, D; Franke, MF; Herboczek, K; Huerga, H; et al. (International Union Against Tuberculosis and Lung Disease, 2020-10-01)
      n 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.
    • Implementing novel regimens for drug-resistant TB in South Africa: what can the world learn?

      Ndjeka, N; Hughes, J; Reuter, A; Conradie, F; Enwerem, M; Ferreira, H; Ismail, N; Kock, Y; Master, I; Meintjes, G; et al. (International Union Against Tuberculosis and Lung Disease, 2020-10-01)
      Worldwide uptake of new drugs in the treatment of rifampicin-resistant tuberculosis (RR-TB) has been extremely low. In June 2018, ahead of the release of the updated WHO guidelines for the management of RR-TB, South Africa announced that bedaquiline (BDQ) would be provided to virtually all RR-TB patients on shorter or longer regimens. South Africa has been the global leader in accessing BDQ for patients with RR-TB, who now represent 60% of the global BDQ cohort. The use of BDQ within a shorter modified regimen has generated the programmatic data underpinning the most recent change in WHO guidelines endorsing a shorter, injectable-free regimen. Progressive policies on access to new drugs have resulted in improved favourable outcomes and a reduction in mortality among RR-TB patients in South Africa. This supported global policy change. The strategies underpinning these bold actions include close collaboration between the South African National TB Programme and partners, introduction of new TB diagnostic tools in closely monitored conditions and the use of locally generated programmatic evidence to inform country policy changes. In this paper, we summarise a decade´s work that led to the bold decision to use a modified, short, injectable-free regimen with BDQ and linezolid under carefully monitored programmatic conditions.