Lucie Blok

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.

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

BackgroundThe 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.MethodsWe 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.ResultsAll 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.ConclusionsThe 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.

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.

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.

Individual and community perceptions of surgical care in Sierra Leone

To determine themes and beliefs that influence health‐seeking behaviour and barriers to accessing surgical care.

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

BackgroundHealth 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.MethodsA 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.ResultsHealth 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.ConclusionsAlthough 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.

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.