The TB REACH Initiative: Supporting TB Elimination Efforts in the Asia-Pacific.

After many years of TB 'control' and incremental progress, the TB community is talking about ending the disease, yet this will only be possible with a shift in the way we approach the TB response. While the Asia-Pacific region has the highest TB burden worldwide, it also has the opportunity to lead the quest to end TB by embracing the four areas laid out in this series: using data to target hotspots, initiating active case finding, provisioning preventive TB treatment, and employing a biosocial approach. The Stop TB Partnership's TB REACH initiative provides a platform to support partners in the development, evaluation and scale-up of new and innovative technologies and approaches to advance TB programs. We present several approaches TB REACH is taking to support its partners in the Asia-Pacific and globally to advance our collective response to end TB.

Finding gaps in TB notifications: spatial analysis of geographical patterns of TB notifications, associations with TB program efforts and social determinants of TB risk in Bangladesh, Nepal and Pakistan.

BACKGROUND: In order to effectively combat Tuberculosis, resources to diagnose and treat TB should be allocated effectively to the areas and population that need them. Although a wealth of subnational data on TB is routinely collected to support local planning, it is often underutilized. Therefore, this study uses spatial analytical techniques and profiling to understand and identify factors underlying spatial variation in TB case notification rates (CNR) in Bangladesh, Nepal and Pakistan for better TB program planning. METHODS: Spatial analytical techniques and profiling was used to identify subnational patterns of TB CNRs at the district level in Bangladesh (N = 64, 2015), Nepal (N = 75, 2014) and Pakistan (N = 142, 2015). A multivariable linear regression analysis was performed to assess the association between subnational CNR and demographic and health indicators associated with TB burden and indicators of TB programme efforts. To correct for spatial dependencies of the observations, the residuals of the multivariable models were tested for unexplained spatial autocorrelation. Spatial autocorrelation among the residuals was adjusted for by fitting a simultaneous autoregressive model (SAR). RESULTS: Spatial clustering of TB CNRs was observed in all three countries. In Bangladesh, TB CNR were found significantly associated with testing rate (0.06%, p < 0.001), test positivity rate (14.44%, p < 0.001), proportion of bacteriologically confirmed cases (- 1.33%, p < 0.001) and population density (4.5*10-3%, p < 0.01). In Nepal, TB CNR were associated with population sex ratio (1.54%, p < 0.01), facility density (- 0.19%, p < 0.05) and treatment success rate (- 3.68%, p < 0.001). Finally, TB CNR in Pakistan were found significantly associated with testing rate (0.08%, p < 0.001), positivity rate (4.29, p < 0.001), proportion of bacteriologically confirmed cases (- 1.45, p < 0.001), vaccination coverage (1.17%, p < 0.001) and facility density (20.41%, p < 0.001). CONCLUSION: Subnational TB CNRs are more likely reflective of TB programme efforts and access to healthcare than TB burden. TB CNRs are better used for monitoring and evaluation of TB control efforts than the TB epidemic. Using spatial analytical techniques and profiling can help identify areas where TB is underreported. Applying these techniques routinely in the surveillance facilitates the use of TB CNRs in program planning.

Health extension workers improve tuberculosis case finding and treatment outcome in Ethiopia: a large-scale implementation study.

BACKGROUND: Tuberculosis (TB) is a major cause of death in Ethiopia. One of the main barriers for TB control is the lack of access to health services. METHODS: We evaluated a diagnostic and treatment service for TB based on the health extension workers (HEW) of the Ethiopian Health Extension Programme in Sidama Zone, with 3.5 million population. We added the services to the HEW routines and evaluated their effect over 4.5 years. 1024 HEWs were trained to identify individuals with symptoms of TB, request sputum samples and prepare smears. Smears were transported to designated laboratories. Individuals with TB were offered treatment at home or the local health post. A second zone (Hadiya) with 1.2 million population was selected as control. We compared TB case notification rates (CNR) and treatment outcomes in the zones 3 years before and 4.5 years after intervention. RESULTS: HEWs identified 216 165 individuals with symptoms and 27 918 (12%) were diagnosed with TB. Smear-positive TB CNR increased from 64 (95% CI 62.5 to 65.8) to 127 (95% CI 123.8 to 131.2) and all forms of TB increased from 102 (95% CI 99.1 to 105.8) to 177 (95% CI 172.6 to 181.0) per 100 000 population in the first year of intervention. In subsequent years, the smear-positive CNR declined by 9% per year. There was no change in CNR in the control area. Treatment success increased from 76% before the intervention to 95% during the intervention. Patients lost to follow-up decreased from 21% to 3% (p<0.001). CONCLUSION: A community-based package significantly increased case finding and improved treatment outcome. Implementing this strategy could help meet the Ethiopian Sustainable Development Goal targets.

Comparative meta-analysis of tuberculosis contact investigation interventions in eleven high burden countries.

BACKGROUND: Screening of household contacts of tuberculosis (TB) patients is a recommended strategy to improve early case detection. While it has been widely implemented in low prevalence countries, the most optimal protocols for contact investigation in high prevalence, low resource settings is yet to be determined. This study evaluated contact investigation interventions in eleven lower and middle income countries and reviewed the association between context or program-related factors and the yield of cases among contacts. METHODS: We reviewed data from nineteen first wave TB REACH funded projects piloting innovations to improve case detection. These nineteen had fulfilled the eligibility criteria: contact investigation implementation and complete data reporting. We performed a cross-sectional analysis of the percentage yield and case notifications for each project. Implementation strategies were delineated and the association between independent variables and yield was analyzed by fitting a random effects logistic regression. FINDINGS: Overall, the nineteen interventions screened 139,052 household contacts, showing great heterogeneity in the percentage yield of microscopy confirmed cases (SS+), ranging from 0.1% to 6.2%). Compared to the most restrictive testing criteria (at least two weeks of cough) the aOR's for lesser (any TB related symptom) and least (all contacts) restrictive testing criteria were 1.71 (95%CI 0.94-3.13) and 6.90 (95% CI 3.42-13.93) respectively. The aOR for inclusion of SS- and extra-pulmonary TB was 0.31 (95% CI 0.15-0.62) compared to restricting index cases to SS+ TB. Contact investigation contributed between <1% and 14% to all SS+ cases diagnosed in the intervention areas. CONCLUSIONS: This study confirms that high numbers of active TB cases can be identified through contact investigation in a variety of contexts. However, design and program implementation factors appear to influence the yield of contact investigation and its concomitant contribution to TB case detection.

A pragmatic approach to measuring, monitoring and evaluating interventions for improved tuberculosis case detection.

The inability to detect all individuals with active tuberculosis has led to a growing interest in new approaches to improve case detection. Policy makers and program staff face important challenges measuring effectiveness of newly introduced interventions and reviewing feasibility of scaling-up successful approaches. While robust research will continue to be needed to document impact and influence policy, it may not always be feasible for all interventions and programmatic evidence is also critical to understand what can be expected in routine settings. The effects of interventions on early and improved tuberculosis detection can be documented through well-designed program evaluations. We present a pragmatic framework for evaluating and measuring the effect of improved case detection strategies using systematically collected intervention data in combination with routine tuberculosis notification data applying historical and contemporary controls. Standardized process evaluation and systematic documentation of program implementation design, cost and context will contribute to explaining observed levels of success and may help to identify conditions needed for success. Findings can then guide decisions on scale-up and replication in different target populations and settings.

A multi-site evaluation of innovative approaches to increase tuberculosis case notification: summary results.

BACKGROUND: Globally, TB notifications have stagnated since 2007, and sputum smear positive notifications have been declining despite policies to improve case detection. We evaluate results of 28 interventions focused on improving TB case detection. METHODS: We measured additional sputum smear positive cases treated, defined as the intervention area's increase in case notification during the project compared to the previous year. Projects were encouraged to select control areas and collect historical notification data. We used time series negative binomial regression for over-dispersed cross-sectional data accounting for fixed and random effects to test the individual projects' effects on TB notification while controlling for trend and control populations. RESULTS: Twenty-eight projects, 19 with control populations, completed at least four quarters of case finding activities, covering a population of 89.2 million. Among all projects sputum smear positive (SS+) TB notifications increased 24.9% and annualized notification rates increased from 69.1 to 86.2/100,000 (p = 0.0209) during interventions. Among the 19 projects with control populations, SS+TB case notifications increased 36.9% increase while in the control populations a 3.6% decrease was observed. Fourteen (74%) of the 19 projects' SS+TB notification rates in intervention areas increased from the baseline to intervention period when controlling for historical trends and notifications in control areas. CONCLUSIONS: Interventions were associated with large increases in TB notifications across many settings, using an array of interventions. Many people with TB are not reached using current approaches. Different methods and interventions tailored to local realities are urgently needed.

Results from early programmatic implementation of Xpert MTB/RIF testing in nine countries.

BACKGROUND: The Xpert MTB/RIF assay has garnered significant interest as a sensitive and rapid diagnostic tool to improve detection of sensitive and drug resistant tuberculosis. However, most existing literature has described the performance of MTB/RIF testing only in study conditions; little information is available on its use in routine case finding. TB REACH is a multi-country initiative focusing on innovative ways to improve case notification. METHODS: We selected a convenience sample of nine TB REACH projects for inclusion to cover a range of implementers, regions and approaches. Standard quarterly reports and machine data from the first 12 months of MTB/RIF implementation in each project were utilized to analyze patient yields, rifampicin resistance, and failed tests. Data was collected from September 2011 to March 2013. A questionnaire was implemented and semi-structured interviews with project staff were conducted to gather information on user experiences and challenges. RESULTS: All projects used MTB/RIF testing for people with suspected TB, as opposed to testing for drug resistance among already diagnosed patients. The projects placed 65 machines (196 modules) in a variety of facilities and employed numerous case-finding strategies and testing algorithms. The projects consumed 47,973 MTB/RIF tests. Of valid tests, 7,195 (16.8%) were positive for MTB. A total of 982 rifampicin resistant results were found (13.6% of positive tests). Of all tests conducted, 10.6% failed. The need for continuous power supply was noted by all projects and most used locally procured solutions. There was considerable heterogeneity in how results were reported and recorded, reflecting the lack of standardized guidance in some countries. CONCLUSIONS: The findings of this study begin to fill the gaps among guidelines, research findings, and real-world implementation of MTB/RIF testing. Testing with Xpert MTB/RIF detected a large number of people with TB that routine services failed to detect. The study demonstrates the versatility and impact of the technology, but also outlines various surmountable barriers to implementation. The study is not representative of all early implementer experiences with MTB/RIF testing but rather provides an overview of the shared issues as well as the many different approaches to programmatic MTB/RIF implementation.

Individual and community perceptions of surgical care in Sierra Leone.

OBJECTIVES: To determine themes and beliefs that influence health-seeking behaviour and barriers to accessing surgical care. METHODS: In January 2012 in Western Area Province of Sierra Leone, six Focus Group Discussions (FGDs) were conducted. The FDGs consisted of three male only and three female only groups in an urban, a slum and a rural setting. Researchers investigated a wide range of topics including definitions of surgery, types of surgical procedures, trust, quality of care, human resources, post-operative care, permission-seeking and traditional beliefs. RESULTS: Although many individual beliefs were expressed, common fears were as follows: becoming half human after surgery; complications from procedures; stigma from having a scar; and financial burdens resulting from the cost of care. Participants also expressed concern about the quality of the care available in Sierra Leone. CONCLUSIONS: The concept of being half human after surgery, previously not documented in the literature, is noteworthy and should be explored more fully. Qualitative research in other parts of Sierra Leone and other LMICs into beliefs of the local population could improve programmes for access and delivery of surgical care.

Female health and family planning in Sierra Leone.

OBJECTIVE: To describe the current status of access to maternal care, family planning use, and place of delivery in Sierra Leone, one of the poorest countries in the world with one of the highest maternal mortality rates. METHODS: Data from the Surgeons OverSeas Assessment of Surgical Need, a cross-sectional two-stage cluster-based household survey conducted in Sierra Leone in 2012, were analyzed to determine access to maternal care, family planning use, and location of delivery. RESULTS: Of 3,318 females of reproductive age (12-50 years of age), 1,205 participants were interviewed in depth. Twenty percent (95% confidence interval [CI] 17.9-22.5) of respondents reported using family planning methods; injectables were the most frequently used method. Fifty-nine percent (95% CI 54.0-63.0) of the recalled deliveries took place outside of a health facility. Of the total births, 1.9% (95% CI 1.3-2.5) were reportedly delivered by cesarean and 0.4% (9/2,316) with instrumental delivery. There were 53 reported maternal deaths in the 12 months before the survey, resulting in a maternal mortality rate of 1,600 per 100,000 females per year. Of the maternal deaths, 30 females (56.6%) did not receive any type of modern health care with 53% (16/30) of families citing financial constraints. CONCLUSION: This study reaffirms a low family planning uptake and very low instrument deliveries and cesarean delivery rates in Sierra Leone. Additionally, financial barriers hinder access to health care and indicate that the free health care initiative for pregnant females is not yet fully covering the reproductive needs of the females of Sierra Leone. LEVEL OF EVIDENCE: III.

Innovative community-based approaches doubled tuberculosis case notification and improve treatment outcome in Southern Ethiopia.

BACKGROUND: TB Control Programmes rely on passive case-finding to detect cases. TB notification remains low in Ethiopia despite major expansion of health services. Poor rural communities face many barriers to service access. METHODS AND FINDINGS: A community-based intervention package was implemented in Sidama zone, Ethiopia. The package included advocacy, training, engaging stakeholders and communities and active case-finding by female Health Extension Workers (HEWs) at village level. HEWs conducted house-to-house visits, identified individuals with a cough for two or more weeks, with or without other symptoms, collected sputum, prepared smears and supervised treatment. Supervisors transported smears for microscopy, started treatment, screened contacts and initiated Isoniazid preventive therapy (IPT) for children. Outcomes were compared with the pre-implementation period and a control zone. Qualitative research was conducted to understand community and provider perceptions and experiences. HEWs screened 49,857 symptomatic individuals (60% women) from October 2010 to December 2011. 2,262 (4·5%) had smear-positive TB (53% women). Case notification increased from 64 to 127/100,000 population/year resulting in 5,090 PTB+ and 7,071 cases of all forms of TB. Of 8,005 contacts visited, 1,949 were symptomatic, 1,290 symptomatic were tested and 69 diagnosed with TB. 1,080 children received IPT. Treatment success for smear-positive TB increased from 77% to 93% and treatment default decreased from 11% to 3%. Service users and providers found the intervention package highly acceptable. CONCLUSIONS: Community-based interventions made TB diagnostic and treatment services more accessible to the poor, women, elderly and children, doubling the notification rate and improving treatment outcome. This approach could improve TB diagnosis and treatment in other high burden settings.

How countries cope with competing demands and expectations: perspectives of different stakeholders on priority setting and resource allocation for health in the era of HIV and AIDS.

BACKGROUND: Health systems have experienced unprecedented stress in recent years, and as yet no consensus has emerged as to how to deal with the multiple burden of disease in the context of HIV and AIDS and other competing health priorities. Priority setting is essential, yet this is a complex, multifaceted process. Drawing on a study conducted in five African countries, this paper explores different stakeholders' perceptions of health priorities, how priorities are defined in practice, the process of resource allocation for HIV and Health and how different stakeholders perceive this. METHODS: A sub-analysis was conducted of selected data from a wider qualitative study that explored the interactions between health systems and HIV and AIDS responses in five sub-Saharan countries (Burkina Faso, the Democratic Republic of Congo, Ghana, Madagascar and Malawi). Key background documents were analysed and semi-structured interviews (n = 258) and focus group discussions (n = 45) were held with representatives of communities, health personnel, decision makers, civil society representatives and development partners at both national and district level. RESULTS: Health priorities were expressed either in terms of specific health problems and diseases or gaps in service delivery requiring a strengthening of the overall health system. In all five countries study respondents (with the exception of community members in Ghana) identified malaria and HIV as the two top health priorities. Community representatives were more likely to report concerns about accessibility of services and quality of care. National level respondents often referred to wider systemic challenges in relation to achieving the Millennium Development Goals (MDGs). Indeed, actual priority setting was heavily influenced by international agendas (e.g. MDGs) and by the ways in which development partners were supporting national strategic planning processes. At the same time, multi-stakeholder processes were increasingly used to identify priorities and inform sector-wide planning, whereby health service statistics were used to rank the burden of disease. However, many respondents remarked that health system challenges are not captured by such statistics.In all countries funding for health was reported to fall short of requirements and a need for further priority setting to match actual resource availability was identified. Pooled health sector funds have been established to some extent, but development partners' lack of flexibility in the allocation of funds according to country-generated priorities was identified as a major constraint. CONCLUSIONS: Although we found consensus on health priorities across all levels in the study countries, current funding falls short of addressing these identified areas. The nature of external funding, as well as programme-specific investment, was found to distort priority setting. There are signs that existing interventions have had limited effects beyond meeting the needs of disease-specific programmes. A need for more comprehensive health system strengthening (HSS) was identified, which requires a strong vision as to what the term means, coupled with a clear strategy and commitment from national and international decision makers in order to achieve stated goals. Prospective studies and action research, accompanied by pilot programmes, are recommended as deliberate strategies for HSS.

Measuring workload for tuberculosis service provision at primary care level: a methodology.

We developed and piloted a methodology to establish TB related work load at primary care level for clinical and laboratory staff. Workload is influenced by activities to be implemented, time to perform them, their frequency and patient load. Of particular importance is the patient pathway for diagnosis and treatment and the frequency of clinic visits. Using observation with checklists, clocking, interviews and review of registers, allows assessing the contribution of different factors on the workload.

Risk of acquired drug resistance during short-course directly observed treatment of tuberculosis in an area with high levels of drug resistance.

BACKGROUND: Data on the performance of standardized short-course directly observed treatment (DOTS) of tuberculosis (TB) in areas with high levels of drug resistance and on the potential impact of DOTS on amplification of resistance are limited. Therefore, we analyzed treatment results from a cross-sectional sample of patients with TB enrolled in a DOTS program in an area with high levels of drug resistance in Uzbekistan and Turkmenistan in Central Asia. METHODS: Sputum samples for testing for susceptibility to 5 first-line drugs and for molecular typing were obtained from patients starting treatment in 8 districts. Patients with sputum smear results positive for TB at the end of the intensive phase of treatment and/or at 2 months into the continuation phase were tested again. RESULTS. Among 382 patients with diagnoses of TB, 62 did not respond well to treatment and were found to be infected with an identical Mycobacterium tuberculosis strain when tested again; 19 of these patients had strains that developed new or additional drug resistance. Amplification occurred in only 1.2% of patients with initially susceptible or monoresistant TB strains, but it occurred in 17% of those with polyresistant strains (but not multidrug-resistant strains, defined as strains with resistance to at least isoniazid and rifampicin) and in 7% of those with multidrug-resistant strains at diagnosis. Overall, 3.5% of the patients not initially infected with multidrug-resistant TB strains developed such strains during treatment. Amplification of resistance, however, was found only in polyresistant Beijing genotype strains. CONCLUSIONS: High levels of amplification of drug resistance demonstrated under well-established DOTS program conditions reinforce the need for implementation of DOTS-Plus for multidrug-resistant TB in areas with high levels of drug resistance. The strong association of Beijing genotype and amplification in situations of preexisting resistance is striking and may underlie the strong association between this genotype and drug resistance.

Tuberculosis recurrence and mortality after successful treatment: impact of drug resistance.

BACKGROUND: The DOTS (directly observed treatment short-course) strategy for tuberculosis (TB) control is recommended by the World Health Organization globally. However, there are few studies of long-term TB treatment outcomes from DOTS programs in high-burden settings and particularly settings of high drug resistance. A DOTS program was implemented progressively in Karakalpakstan, Uzbekistan starting in 1998. The total case notification rate in 2003 was 462/100,000, and a drug resistance survey found multidrug-resistant (MDR) Mycobacterium tuberculosis strains among 13% of new and 40% of previously treated patients. A retrospective, observational study was conducted to assess the capacity of standardized short-course chemotherapy to effectively cure patients with TB in this setting. METHODS AND FINDINGS: Using routine data sources, 213 patients who were sputum smear-positive for TB, included in the drug resistance survey and diagnosed consecutively in 2001-2002 from four districts, were followed up to a median of 22 months from diagnosis, to determine mortality and subsequent TB rediagnosis. Valid follow-up data were obtained for 197 (92%) of these patients. Mortality was high, with an average of 15% (95% confidence interval, 11% to 19%) dying per year after diagnosis (6% of 73 pansusceptible cases and 43% of 55 MDR TB cases also died per year). While 73 (74%) of the 99 new cases were "successfully" treated, 25 (34%) of these patients were subsequently rediagnosed with recurrent TB (13 were smear-positive on rediagnosis). Recurrence ranged from ten (23%) of 43 new, pansusceptible cases to six (60%) of ten previously treated MDR TB cases. MDR M. tuberculosis infection and previous TB treatment predicted unsuccessful DOTS treatment, while initial drug resistance contributed substantially to both mortality and disease recurrence after successful DOTS treatment. CONCLUSIONS: These results suggest that specific treatment of drug-resistant TB is needed in similar settings of high drug resistance. High disease recurrence after successful treatment, even for drug-susceptible cases, suggests that at least in this setting, end-of-treatment outcomes may not reflect the longer-term status of patients, with consequent negative impacts for patients and for TB control.

Refugee Health: An approach to emergency situations

Ce livre est une réalisation collective des différentes sections de Médecins Sans Frontières (MSF), et a été écrit pour consolider la vaste expérience de MSF dans les programmes de réfugiés. Ce document traite des réfugiés et des personnes déplacées, et de ce quÆun organisme de santé peut faire pour soulager leurs souffrances. Il met l'accent sur ​​les politiques plutôt que sur les aspects pratiques, et vise à servir de guide aux décideurs.